Trial Outcomes & Findings for Recombinant FSH Investigation in the Treatment of Infertility With Assisted Reproductive Technology (ART) (RITA-2) (NCT NCT03738618)
NCT ID: NCT03738618
Last Updated: 2024-01-18
Results Overview
Defined as at least one intrauterine viable fetus 8-9 weeks after transfer. Data in this endpoint are presented for the fresh cycle and the cryopreserved cycles.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
588 participants
Primary outcome timeframe
8-9 weeks after transfer (up to approximately 16 months after start of stimulation)
Results posted on
2024-01-18
Participant Flow
The trial was performed in 24 investigational sites in 18 states of the United States between Oct 2018 to Dec 2020.
In total, 666 participants were screened of which 588 participants were randomized. Of the randomized participants, 587 participants were exposed to the investigational medicinal product (IMP): 533 to FE 999049 (Follitropin Delta) and 54 to Placebo. One participant was randomization failure and did not receive the IMP.
Participant milestones
| Measure |
FE 999049 (Follitropin Delta)
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Overall Study
STARTED
|
534
|
54
|
|
Overall Study
Modified Intention-to-treat (mITT)
|
533
|
54
|
|
Overall Study
COMPLETED
|
502
|
54
|
|
Overall Study
NOT COMPLETED
|
32
|
0
|
Reasons for withdrawal
| Measure |
FE 999049 (Follitropin Delta)
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Overall Study
Protocol deviation
|
23
|
0
|
|
Overall Study
Adverse Event
|
4
|
0
|
|
Overall Study
Lost to Follow-up
|
2
|
0
|
|
Overall Study
Randomization failure
|
1
|
0
|
|
Overall Study
Participant relocated, unable to continue in trial
|
1
|
0
|
|
Overall Study
Participant did not show to visit (stimulation day 12)
|
1
|
0
|
Baseline Characteristics
Recombinant FSH Investigation in the Treatment of Infertility With Assisted Reproductive Technology (ART) (RITA-2)
Baseline characteristics by cohort
| Measure |
FE 999049 (Follitropin Delta)
n=533 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
n=54 Participants
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
Total
n=587 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
37.7 years
STANDARD_DEVIATION 2.1 • n=99 Participants
|
37.9 years
STANDARD_DEVIATION 2.1 • n=107 Participants
|
37.7 years
STANDARD_DEVIATION 2.1 • n=206 Participants
|
|
Sex: Female, Male
Female
|
533 Participants
n=99 Participants
|
54 Participants
n=107 Participants
|
587 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
57 Participants
n=99 Participants
|
9 Participants
n=107 Participants
|
66 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
476 Participants
n=99 Participants
|
45 Participants
n=107 Participants
|
521 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
2 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Asian
|
57 Participants
n=99 Participants
|
5 Participants
n=107 Participants
|
62 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
5 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
5 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Black or African American
|
70 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
74 Participants
n=206 Participants
|
|
Race (NIH/OMB)
White
|
398 Participants
n=99 Participants
|
45 Participants
n=107 Participants
|
443 Participants
n=206 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Body mass index (BMI)
|
27.0 kg/m^2
STANDARD_DEVIATION 5.1 • n=99 Participants
|
27.9 kg/m^2
STANDARD_DEVIATION 5.1 • n=107 Participants
|
27.0 kg/m^2
STANDARD_DEVIATION 5.1 • n=206 Participants
|
|
Primary infertility
|
226 participants
n=99 Participants
|
26 participants
n=107 Participants
|
252 participants
n=206 Participants
|
|
Duration of infertility
|
42.7 months
STANDARD_DEVIATION 37.6 • n=99 Participants
|
45.9 months
STANDARD_DEVIATION 43.2 • n=107 Participants
|
43.0 months
STANDARD_DEVIATION 38.1 • n=206 Participants
|
|
Primary reason for infertility
Unexplained infertility
|
251 Participants
n=99 Participants
|
28 Participants
n=107 Participants
|
279 Participants
n=206 Participants
|
|
Primary reason for infertility
Tubal infertility
|
120 Participants
n=99 Participants
|
7 Participants
n=107 Participants
|
127 Participants
n=206 Participants
|
|
Primary reason for infertility
Mild male factor
|
50 Participants
n=99 Participants
|
5 Participants
n=107 Participants
|
55 Participants
n=206 Participants
|
|
Primary reason for infertility
Moderate male factor
|
62 Participants
n=99 Participants
|
8 Participants
n=107 Participants
|
70 Participants
n=206 Participants
|
|
Primary reason for infertility
Severe male factor
|
27 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
31 Participants
n=206 Participants
|
|
Primary reason for infertility
Endometriosis stage I/II
|
20 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
22 Participants
n=206 Participants
|
|
Primary reason for infertility
Endometriosis stage III/IV
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Primary reason for infertility
Other
|
2 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: 8-9 weeks after transfer (up to approximately 16 months after start of stimulation)Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
Defined as at least one intrauterine viable fetus 8-9 weeks after transfer. Data in this endpoint are presented for the fresh cycle and the cryopreserved cycles.
Outcome measures
| Measure |
FE 999049 (Follitropin Delta)
n=533 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
n=54 Participants
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Cumulative Ongoing Pregnancy Rate After the Fresh Cycle and Cryopreserved Cycles Initiated Within 12 Months From the Start of Controlled Ovarian Stimulation (COS)
|
43.3 percentage of participants
|
0.0 percentage of participants
|
SECONDARY outcome
Timeframe: 8-9 weeks after transfer (up to approximately 16 months after start of stimulation)Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
Defined as at least one intrauterine viable fetus 8-9 weeks after transfer. Data in this endpoint are presented for the fresh cycle and the cryopreserved cycles.
Outcome measures
| Measure |
FE 999049 (Follitropin Delta)
n=533 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
n=54 Participants
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Ongoing Pregnancy Rate in the Fresh Cycle and in the Cryopreserved Cycles
Fresh cycle
|
22.0 percentage of participants
|
0.0 percentage of participants
|
|
Ongoing Pregnancy Rate in the Fresh Cycle and in the Cryopreserved Cycles
Cryopreserved cycles
|
47.8 percentage of participants
|
0 percentage of participants
|
SECONDARY outcome
Timeframe: 8-9 weeks after transfer (up to approximately 16 months after start of stimulation)Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
Time from start of COS to ongoing pregnancy, including both the fresh and cryopreserved cycles. In the placebo group, no participants achieved an ongoing pregnancy either after 12 calendar months or after 12 study months.
Outcome measures
| Measure |
FE 999049 (Follitropin Delta)
n=533 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Time From Start of COS to Ongoing Pregnancy Across the Fresh and Cryopreserved Cycles, Including Duration
Total number of days until ongoing pregnancy 12 study months
|
134.7 days
Standard Deviation 87.2
|
—
|
|
Time From Start of COS to Ongoing Pregnancy Across the Fresh and Cryopreserved Cycles, Including Duration
Total number of days until ongoing pregnancy 12 calendar months
|
130.1 days
Standard Deviation 77.8
|
—
|
SECONDARY outcome
Timeframe: 8-9 weeks after transfer (up to approximately 16 months after start of stimulation)Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
Time from start of COS to ongoing pregnancy, including both the fresh and cryopreserved cycles, measured in number of cycles before achieving ongoing pregnancy. In the placebo group, no participants achieved an ongoing pregnancy either after 12 calendar months or after 12 study months.
Outcome measures
| Measure |
FE 999049 (Follitropin Delta)
n=234 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Time From Start of COS to Ongoing Pregnancy Across the Fresh and Cryopreserved Cycles, Measured in Number of Cycles Before Achieving Ongoing Pregnancy
Number of cycles until ongoing pregnancy 12 study months
|
1.8 Cycles
Standard Deviation 1.0
|
—
|
|
Time From Start of COS to Ongoing Pregnancy Across the Fresh and Cryopreserved Cycles, Measured in Number of Cycles Before Achieving Ongoing Pregnancy
Number of cycles until ongoing pregnancy 12 calendar months
|
1.7 Cycles
Standard Deviation 1.0
|
—
|
SECONDARY outcome
Timeframe: 8-9 weeks after transfer (up to approximately 16 months after start of stimulation)Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
Defined as the number of intrauterine viable fetuses 8-9 weeks after transfer divided by number of blastocysts transferred. Data in this endpoint are presented for the fresh cycle, the cryopreserved cycles, and all cycles. One participant can contribute with a range from zero to multiple blastocysts. Data is not shown for placebo arm because no subjects underwent blastocyst transfer in the fresh cycle or cryopreserved cycles. '%' in the unit of measure refers to 'percentage'.
Outcome measures
| Measure |
FE 999049 (Follitropin Delta)
n=750 Blastocysts
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Ongoing Implantation Rate in the Fresh Cycle, the Cryopreserved Cycles and Cumulatively
Fresh cycle
|
32.7 % of viable fetus/blastocyst transfer
|
—
|
|
Ongoing Implantation Rate in the Fresh Cycle, the Cryopreserved Cycles and Cumulatively
Cryopreserved cycles
|
30.6 % of viable fetus/blastocyst transfer
|
—
|
|
Ongoing Implantation Rate in the Fresh Cycle, the Cryopreserved Cycles and Cumulatively
All cycles
|
31.6 % of viable fetus/blastocyst transfer
|
—
|
SECONDARY outcome
Timeframe: 5-6 weeks after transfer (up to approximately 15 months after start of stimulation)Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
Defined at least one gestational sac 5-6 weeks after transfer. Data in this endpoint are presented for the fresh cycle, the cryopreserved cycles, and all cycles.
Outcome measures
| Measure |
FE 999049 (Follitropin Delta)
n=533 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
n=54 Participants
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Clinical Pregnancy Rate in the Fresh Cycle, the Cryopreserved Cycles and Cumulatively
Fresh cycle
|
26.8 percentage of participants
|
0.0 percentage of participants
|
|
Clinical Pregnancy Rate in the Fresh Cycle, the Cryopreserved Cycles and Cumulatively
Cryopreserved cycles
|
58.0 percentage of participants
|
0 percentage of participants
|
|
Clinical Pregnancy Rate in the Fresh Cycle, the Cryopreserved Cycles and Cumulatively
All cycles
|
52.0 percentage of participants
|
0.0 percentage of participants
|
SECONDARY outcome
Timeframe: 5-6 weeks after transfer (up to approximately 15 months after start of stimulation)Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
Defined at least one intrauterine gestational sac with fetal heart beat 5-6 weeks after transfer. Data in this endpoint are presented for the fresh cycle, the cryopreserved cycles, and all cycles.
Outcome measures
| Measure |
FE 999049 (Follitropin Delta)
n=533 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
n=54 Participants
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Vital Pregnancy Rate in the Fresh Cycle, the Cryopreserved Cycles and Cumulatively
All cycles
|
45.6 percentage of participants
|
0.0 percentage of participants
|
|
Vital Pregnancy Rate in the Fresh Cycle, the Cryopreserved Cycles and Cumulatively
Fresh cycle
|
23.5 percentage of participants
|
0.0 percentage of participants
|
|
Vital Pregnancy Rate in the Fresh Cycle, the Cryopreserved Cycles and Cumulatively
Cryopreserved cycles
|
49.4 percentage of participants
|
0 percentage of participants
|
SECONDARY outcome
Timeframe: 5-6 weeks after transfer (up to approximately 15 months after start of stimulation)Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
Defined as the number of gestational sacs 5-6 weeks after transfer divided by number of blastocysts transferred. The endpoint are presented for the fresh cycle, the cryopreserved cycles, and all cycles. One participant can contribute with a range from zero to multiple blastocysts. Data is not shown for placebo arm because no subjects underwent blastocyst transfer in the fresh cycle or cryopreserved cycles. '%' in the unit of measure refers to 'percentage'.
Outcome measures
| Measure |
FE 999049 (Follitropin Delta)
n=750 Blastocysts
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Implantation Rate in the Fresh Cycle, the Cryopreserved Cycles and Cumulatively
Fresh cycle
|
40.4 % gestational sacs/blastocyst transfer
|
—
|
|
Implantation Rate in the Fresh Cycle, the Cryopreserved Cycles and Cumulatively
Cryopreserved cycles
|
40.2 % gestational sacs/blastocyst transfer
|
—
|
|
Implantation Rate in the Fresh Cycle, the Cryopreserved Cycles and Cumulatively
All cycles
|
40.3 % gestational sacs/blastocyst transfer
|
—
|
SECONDARY outcome
Timeframe: 10-14 days after transfer (up to approximately 14 months after start of stimulation)Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
Defined as positive serum βhCG test 10-14 days after transfer. Data in this endpoint are presented for the fresh cycle, the cryopreserved cycles, and all cycles.
Outcome measures
| Measure |
FE 999049 (Follitropin Delta)
n=533 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
n=54 Participants
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Positive Beta Human Chorionic Gonadotropin (βhCG) Rate in the Fresh Cycle, the Cryopreserved Cycles and Cumulatively
Fresh cycle
|
32.1 percentage of participants
|
0.0 percentage of participants
|
|
Positive Beta Human Chorionic Gonadotropin (βhCG) Rate in the Fresh Cycle, the Cryopreserved Cycles and Cumulatively
Cryopreserved cycles
|
65.3 percentage of participants
|
0 percentage of participants
|
|
Positive Beta Human Chorionic Gonadotropin (βhCG) Rate in the Fresh Cycle, the Cryopreserved Cycles and Cumulatively
All cycles
|
58.9 percentage of participants
|
0.0 percentage of participants
|
SECONDARY outcome
Timeframe: Up to 5 days after oocyte retrieval (up to 27 days after start of stimulation)Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
Data in this endpoint are presented for the fresh cycle.
Outcome measures
| Measure |
FE 999049 (Follitropin Delta)
n=533 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
n=54 Participants
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Proportion of Subjects in the Fresh Cycle With Triggering of Final Follicular Maturation (With hCG, With GnRH Agonist, and in Total), Cycle Cancellation and Transfer Cancellation
Triggering drug (hCG)
|
79.5 percentage of participants
|
1.9 percentage of participants
|
|
Proportion of Subjects in the Fresh Cycle With Triggering of Final Follicular Maturation (With hCG, With GnRH Agonist, and in Total), Cycle Cancellation and Transfer Cancellation
Triggering drug (GnRH agonist)
|
15.0 percentage of participants
|
0.0 percentage of participants
|
|
Proportion of Subjects in the Fresh Cycle With Triggering of Final Follicular Maturation (With hCG, With GnRH Agonist, and in Total), Cycle Cancellation and Transfer Cancellation
Triggering drug (None)
|
5.4 percentage of participants
|
98.1 percentage of participants
|
|
Proportion of Subjects in the Fresh Cycle With Triggering of Final Follicular Maturation (With hCG, With GnRH Agonist, and in Total), Cycle Cancellation and Transfer Cancellation
Cycle cancellation
|
5.4 percentage of participants
|
98.1 percentage of participants
|
|
Proportion of Subjects in the Fresh Cycle With Triggering of Final Follicular Maturation (With hCG, With GnRH Agonist, and in Total), Cycle Cancellation and Transfer Cancellation
Transfer cancellation
|
31.5 percentage of participants
|
1.9 percentage of participants
|
SECONDARY outcome
Timeframe: On stimulation day 5Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
The total number of follicles and the number of follicles per size category are reported.
Outcome measures
| Measure |
FE 999049 (Follitropin Delta)
n=532 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
n=54 Participants
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Number of Follicles on Stimulation Day 5
Total number of follicles
|
14.8 number of follicles
Standard Deviation 8.4
|
12.5 number of follicles
Standard Deviation 8.0
|
|
Number of Follicles on Stimulation Day 5
Follicles >= 12 mm
|
1.7 number of follicles
Standard Deviation 1.8
|
0.4 number of follicles
Standard Deviation 0.6
|
|
Number of Follicles on Stimulation Day 5
Follicles >= 17 mm
|
0.0 number of follicles
Standard Deviation 0.2
|
0.0 number of follicles
Standard Deviation 0.2
|
SECONDARY outcome
Timeframe: At end-of-stimulation (up to 20 stimulation days)Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
The total number of follicles and the number of follicles per size category are reported.
Outcome measures
| Measure |
FE 999049 (Follitropin Delta)
n=532 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
n=54 Participants
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Number of Follicles at End-of-stimulation
Total number of follicles
|
17.4 number of follicles
Standard Deviation 10.0
|
13.6 number of follicles
Standard Deviation 9.5
|
|
Number of Follicles at End-of-stimulation
Follicles >= 12 mm
|
10.1 number of follicles
Standard Deviation 6.3
|
0.8 number of follicles
Standard Deviation 0.7
|
|
Number of Follicles at End-of-stimulation
Follicles >= 17 mm
|
3.6 number of follicles
Standard Deviation 2.3
|
0.4 number of follicles
Standard Deviation 0.5
|
SECONDARY outcome
Timeframe: On stimulation day 5Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
Counted by ultrasound for the right and left ovary for each participant.
Outcome measures
| Measure |
FE 999049 (Follitropin Delta)
n=532 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
n=54 Participants
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Size of Follicles on Stimulation Day 5
Largest follicle (mm)
|
12.4 mm
Standard Deviation 2.3
|
10.8 mm
Standard Deviation 2.5
|
|
Size of Follicles on Stimulation Day 5
Average size of 2 largest follicles (mm)
|
11.8 mm
Standard Deviation 2.1
|
9.8 mm
Standard Deviation 1.9
|
SECONDARY outcome
Timeframe: At end-of-stimulation (up to 20 stimulation days)Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
Counted by ultrasound for the right and left ovary for each participant.
Outcome measures
| Measure |
FE 999049 (Follitropin Delta)
n=532 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
n=54 Participants
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Size of Follicles at End-of-stimulation
Largest follicle (mm)
|
19.8 mm
Standard Deviation 2.7
|
14.1 mm
Standard Deviation 5.1
|
|
Size of Follicles at End-of-stimulation
Average size of 2 largest follicles (mm)
|
18.9 mm
Standard Deviation 2.6
|
11.5 mm
Standard Deviation 3.3
|
SECONDARY outcome
Timeframe: On day of oocyte retrieval (up to 22 days after start of stimulation)Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
The number of oocytes retrieved was recorded at the oocyte retrieval visit.
Outcome measures
| Measure |
FE 999049 (Follitropin Delta)
n=533 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
n=54 Participants
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Number of Oocytes Retrieved
|
11.3 number of oocytes retrieved
Standard Deviation 8.9
|
0.0 number of oocytes retrieved
Standard Deviation 0.1
|
SECONDARY outcome
Timeframe: On day of oocyte retrieval (up to 22 days after start of stimulation)Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
Grouped according to the number of oocytes retrieved. Participants with cycle cancellation due to poor ovarian response are included in the \<4 oocytes group.
Outcome measures
| Measure |
FE 999049 (Follitropin Delta)
n=532 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
n=54 Participants
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Proportion of Subjects With <4, 4-7, 8-14, 15-19 and ≥20 Oocytes Retrieved
<4 oocytes retrieved
|
14.6 percentage of participants
|
100 percentage of participants
|
|
Proportion of Subjects With <4, 4-7, 8-14, 15-19 and ≥20 Oocytes Retrieved
4-7 oocytes retrieved
|
23.5 percentage of participants
|
0 percentage of participants
|
|
Proportion of Subjects With <4, 4-7, 8-14, 15-19 and ≥20 Oocytes Retrieved
8-14 oocytes retrieved
|
33.8 percentage of participants
|
0 percentage of participants
|
|
Proportion of Subjects With <4, 4-7, 8-14, 15-19 and ≥20 Oocytes Retrieved
15-19 oocytes retrieved
|
15.2 percentage of participants
|
0 percentage of participants
|
|
Proportion of Subjects With <4, 4-7, 8-14, 15-19 and ≥20 Oocytes Retrieved
>=20 oocytes retrieved
|
12.9 percentage of participants
|
0 percentage of participants
|
SECONDARY outcome
Timeframe: On day of oocyte retrieval (up to 22 days after start of stimulation)Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
The number of MII oocytes to oocytes retrieved for participants where all oocytes were inseminated using ICSI are presented.
Outcome measures
| Measure |
FE 999049 (Follitropin Delta)
n=394 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
n=1 Participants
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Number of Metaphase II Oocytes
|
8.8 number of MII oocytes
Standard Deviation 6.7
|
1.0 number of MII oocytes
Standard Deviation 0
|
SECONDARY outcome
Timeframe: On day 1 after oocyte retrieval (up to 23 days after start of stimulation)Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
An oocyte was defined as fertilized if it had 2 pronuclei (2PN) at 19h (±2h).
Outcome measures
| Measure |
FE 999049 (Follitropin Delta)
n=533 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
n=54 Participants
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Number of Fertilized Oocytes
|
6.4 oocytes (number of fertilized oocytes)
Standard Deviation 5.7
|
0.0 oocytes (number of fertilized oocytes)
Standard Deviation 0.1
|
SECONDARY outcome
Timeframe: On day 1 after oocyte retrieval (up to 23 days after start of stimulation)Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
The fertilization rate was defined as the number of 2PN oocytes divided by the number of oocytes retrieved. Fertilization rate relative to oocytes retrieved has been reported.
Outcome measures
| Measure |
FE 999049 (Follitropin Delta)
n=497 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
n=1 Participants
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Fertilization Rate
|
56.4 percentage of fertilized oocytes
Standard Deviation 23.3
|
100.0 percentage of fertilized oocytes
Standard Deviation 0
|
SECONDARY outcome
Timeframe: On day 5 after oocyte retrievalPopulation: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
Number of blastocysts (total and good-quality) on Day 5 are presented. The quality evaluation of blastocysts consisted of assessment of three parameters, as per the Gardner \& Schoolcraft system: blastocyst expansion and hatching status (graded: 1-6), inner cell mass (graded: A-D) and trophectoderm (graded: A-D). A good-quality blastocyst was defined as a blastocyst of grade 3BB or higher.
Outcome measures
| Measure |
FE 999049 (Follitropin Delta)
n=533 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
n=54 Participants
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Number and Quality of Blastocysts on Day 5 After Oocyte Retrieval
Number of blastocysts on day 5
|
3.7 blastocysts
Standard Deviation 4.0
|
0.0 blastocysts
Standard Deviation 0.0
|
|
Number and Quality of Blastocysts on Day 5 After Oocyte Retrieval
Number of good-quality blastocysts on day 5
|
2.3 blastocysts
Standard Deviation 3.0
|
0.0 blastocysts
Standard Deviation 0.0
|
SECONDARY outcome
Timeframe: On stimulation day 5Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
Mean endometrial thickness is reported.
Outcome measures
| Measure |
FE 999049 (Follitropin Delta)
n=533 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
n=54 Participants
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Endometrial Thickness on Stimulation Day 5
|
8.0 mm
Standard Deviation 2.1
|
6.2 mm
Standard Deviation 1.9
|
SECONDARY outcome
Timeframe: At end-of-stimulation (up to 20 stimulation days)Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
Mean endometrial thickness is reported.
Outcome measures
| Measure |
FE 999049 (Follitropin Delta)
n=532 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
n=54 Participants
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Endometrial Thickness at End-of-stimulation
|
10.6 mm
Standard Deviation 2.5
|
7.8 mm
Standard Deviation 2.3
|
SECONDARY outcome
Timeframe: On stimulation day 5Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
The distribution of participants with hypoechogenic, isoechogenic, or hyperechogenic endometrium is reported
Outcome measures
| Measure |
FE 999049 (Follitropin Delta)
n=533 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
n=54 Participants
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Echogenicity Pattern on Stimulation Day 5
Hypoechogenic
|
64.2 percentage of participants
|
57.4 percentage of participants
|
|
Echogenicity Pattern on Stimulation Day 5
Isoechogenic
|
6.4 percentage of participants
|
5.6 percentage of participants
|
|
Echogenicity Pattern on Stimulation Day 5
Hyperechogenic
|
28.7 percentage of participants
|
33.3 percentage of participants
|
|
Echogenicity Pattern on Stimulation Day 5
Not possible to evaluate
|
0.8 percentage of participants
|
3.7 percentage of participants
|
SECONDARY outcome
Timeframe: At end-of-stimulation (up to 20 stimulation days)Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
The distribution of participants with hypoechogenic, isoechogenic, or hyperechogenic endometrium is reported.
Outcome measures
| Measure |
FE 999049 (Follitropin Delta)
n=532 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
n=54 Participants
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Echogenicity Pattern at End-of-stimulation
Hypoechogenic
|
68.0 percentage of participants
|
68.5 percentage of participants
|
|
Echogenicity Pattern at End-of-stimulation
Isoechogenic
|
3.2 percentage of participants
|
3.7 percentage of participants
|
|
Echogenicity Pattern at End-of-stimulation
Hyperechogenic
|
28.4 percentage of participants
|
25.9 percentage of participants
|
|
Echogenicity Pattern at End-of-stimulation
Not possible to evaluate
|
0.4 percentage of participants
|
1.9 percentage of participants
|
SECONDARY outcome
Timeframe: On day of oocyte retrieval up to 12 months after start of COSPopulation: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
Defined as the number of blastocysts transferred or cryopreserved divided by the number of oocytes retrieved. Data in this endpoint are presented for the cryopreserved cycles.
Outcome measures
| Measure |
FE 999049 (Follitropin Delta)
n=497 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
n=1 Participants
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Oocyte Utilization Rate
|
30.6 blastocysts/oocyte retrieved
Standard Deviation 21.2
|
0.0 blastocysts/oocyte retrieved
Standard Deviation 0
|
SECONDARY outcome
Timeframe: 8-9 weeks after transferPopulation: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
Defined as the cumulative number of ongoing pregnancies per oocyte retrieved. Data in this endpoint are presented for the cryopreserved cycles. The unit of measure for this endpoint is 'cumulative ongoing pregnancies/oocyte retrieved'.
Outcome measures
| Measure |
FE 999049 (Follitropin Delta)
n=497 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
n=1 Participants
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Oocyte Efficiency Index
|
4.5 ongoing pregnancies/oocyte retrieved
Standard Deviation 6.4
|
0.0 ongoing pregnancies/oocyte retrieved
Standard Deviation 0
|
SECONDARY outcome
Timeframe: 0 hour (+0.5 hour) after thawingPopulation: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
Data in this endpoint are presented for the cryopreserved cycles. The unit is number of blastocysts with observations. One participant can contribute with a range from zero to multiple blastocysts.
Outcome measures
| Measure |
FE 999049 (Follitropin Delta)
n=394 Number of blastocyst warmed
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Percentage of Blastocysts Surviving Cryopreservation
|
98.5 percentage of blastocysts
|
—
|
SECONDARY outcome
Timeframe: 2.5 hour (±0.5 hour) after thawingPopulation: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
Data in this endpoint are presented for the cryopreserved cycles. The unit is number of blastocysts with observations. One participant can contribute with a range from zero to multiple blastocysts.
Outcome measures
| Measure |
FE 999049 (Follitropin Delta)
n=394 Number of blastocyst warmed
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Percentage of Blastocysts With Re-expansion After Cryopreservation
|
97.2 percentage of blastocysts
|
—
|
SECONDARY outcome
Timeframe: Up to 12 months after start of stimulationPopulation: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
The total number of cryopreserved cycles initiated are reported. Data in this endpoint are presented for the cryopreserved cycles. One participant can contribute with a range from zero to multiple blastocysts.
Outcome measures
| Measure |
FE 999049 (Follitropin Delta)
n=428 Cryopreserved cycles initiated
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Number of Cryopreserved Cycles Initiated Within 12 Months From the Start of COS
Programmed cycles initiated
|
92.1 Percentages of cycles
|
—
|
|
Number of Cryopreserved Cycles Initiated Within 12 Months From the Start of COS
Natural cycles initiated
|
7.9 Percentages of cycles
|
—
|
SECONDARY outcome
Timeframe: Up to 12 months after start of stimulationPopulation: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
The total number of cryopreserved cycles with blastocyst transfer are reported. Data in this endpoint are presented for the cryopreserved cycles. One participant can contribute with a range from zero to multiple blastocysts.
Outcome measures
| Measure |
FE 999049 (Follitropin Delta)
n=375 Cryopreserved cycles with transfer
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Number of Cryopreserved Cycles With Blastocyst Transfer
Programmed cycles with transfer
|
92.8 Percentages of cycles
|
—
|
|
Number of Cryopreserved Cycles With Blastocyst Transfer
Natural cycles with transfer
|
7.2 Percentages of cycles
|
—
|
SECONDARY outcome
Timeframe: From screening to the day of oocyte retrieval (up to 22 days after start of stimulation)Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment. No circulating concentrations of AMH were assessed for the oocyte retrieval visit for the placebo arm, because no participants who received placebo became pregnant.
Blood samples for analysis of circulating concentrations of AMH were drawn. The median and inter-quartile range (IQR) of AMH levels on stimulation day 1, stimulation day 5, end-of-stimulation visit and oocyte retrieval visit are presented.
Outcome measures
| Measure |
FE 999049 (Follitropin Delta)
n=533 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
n=54 Participants
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Circulating Concentrations of Anti-mullerian Hormone (AMH)
Stimulation day 1
|
13.2 pmol/L
Interval 7.2 to 20.9
|
11.3 pmol/L
Interval 6.7 to 18.3
|
|
Circulating Concentrations of Anti-mullerian Hormone (AMH)
Stimulation day 5
|
10.9 pmol/L
Interval 5.6 to 17.5
|
13.1 pmol/L
Interval 6.6 to 19.6
|
|
Circulating Concentrations of Anti-mullerian Hormone (AMH)
End-of-stimulation visit
|
6.4 pmol/L
Interval 3.6 to 10.5
|
14.6 pmol/L
Interval 7.0 to 21.5
|
|
Circulating Concentrations of Anti-mullerian Hormone (AMH)
Oocyte retrieval visit
|
5.0 pmol/L
Interval 2.9 to 8.0
|
—
|
SECONDARY outcome
Timeframe: From screening to the day of oocyte retrieval (up to 22 days after start of stimulation)Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
Blood samples for analysis of circulating concentrations of FSH were drawn. The median and IQR of FSH levels on stimulation day 1, stimulation day 5, end-of-stimulation visit and oocyte retrieval visit are presented.
Outcome measures
| Measure |
FE 999049 (Follitropin Delta)
n=530 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
n=53 Participants
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Circulating Concentrations of Follicle-stimulating Hormone (FSH)
Stimulation day 1
|
8.7 IU/L
Interval 7.4 to 10.6
|
8.9 IU/L
Interval 7.4 to 10.5
|
|
Circulating Concentrations of Follicle-stimulating Hormone (FSH)
Stimulation day 5
|
20.5 IU/L
Interval 16.3 to 24.8
|
7.8 IU/L
Interval 6.3 to 9.4
|
|
Circulating Concentrations of Follicle-stimulating Hormone (FSH)
End-of-stimulation visit
|
24.8 IU/L
Interval 20.2 to 30.3
|
7.1 IU/L
Interval 6.2 to 9.6
|
|
Circulating Concentrations of Follicle-stimulating Hormone (FSH)
Oocyte retrieval visit
|
14.8 IU/L
Interval 12.4 to 17.8
|
20.2 IU/L
Interval 20.2 to 20.2
|
SECONDARY outcome
Timeframe: From screening to the day of oocyte retrieval (up to 22 days after start of stimulation)Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
Blood samples for analysis of circulating concentrations of LH were drawn. The median and IQR of LH levels on stimulation day 1, stimulation day 5, end-of-stimulation visit and oocyte retrieval visit are presented.
Outcome measures
| Measure |
FE 999049 (Follitropin Delta)
n=531 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
n=53 Participants
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Circulating Concentrations of Luteinizing Hormone (LH)
Stimulation day 1
|
4.8 IU/L
Interval 3.7 to 6.3
|
5.0 IU/L
Interval 3.6 to 6.6
|
|
Circulating Concentrations of Luteinizing Hormone (LH)
Stimulation day 5
|
2.4 IU/L
Interval 1.6 to 3.7
|
5.7 IU/L
Interval 4.3 to 7.3
|
|
Circulating Concentrations of Luteinizing Hormone (LH)
End-of-stimulation visit
|
2.0 IU/L
Interval 1.3 to 3.3
|
8.8 IU/L
Interval 6.5 to 14.7
|
|
Circulating Concentrations of Luteinizing Hormone (LH)
Oocyte retrieval visit
|
2.2 IU/L
Interval 1.2 to 3.7
|
28.1 IU/L
Interval 28.1 to 28.1
|
SECONDARY outcome
Timeframe: From screening to the day of oocyte retrieval (up to 22 days after start of stimulation)Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
Blood samples for analysis of circulating concentrations of estradiol were drawn. The median and IQR of estradiol levels on stimulation day 1, stimulation day 5, end-of-stimulation visit and oocyte retrieval visit are presented.
Outcome measures
| Measure |
FE 999049 (Follitropin Delta)
n=528 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
n=54 Participants
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Circulating Concentrations of Estradiol
Stimulation day 1
|
41.2 pg/mL
Interval 33.7 to 52.6
|
40.2 pg/mL
Interval 34.0 to 48.9
|
|
Circulating Concentrations of Estradiol
Stimulation day 5
|
383.6 pg/mL
Interval 235.1 to 599.6
|
59.0 pg/mL
Interval 45.4 to 89.4
|
|
Circulating Concentrations of Estradiol
End-of-stimulation visit
|
1471.0 pg/mL
Interval 891.0 to 2292.5
|
109.6 pg/mL
Interval 52.0 to 174.6
|
|
Circulating Concentrations of Estradiol
Oocyte retrieval visit
|
745.1 pg/mL
Interval 439.4 to 1177.3
|
107.4 pg/mL
Interval 107.4 to 107.4
|
SECONDARY outcome
Timeframe: From screening to the day of oocyte retrieval (up to 22 days after start of stimulation)Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
Blood samples for analysis of circulating concentrations of progesterone were drawn. The median and IQR of progesterone levels on stimulation day 1, stimulation day 5, end-of-stimulation visit and oocyte retrieval visit are presented.
Outcome measures
| Measure |
FE 999049 (Follitropin Delta)
n=531 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
n=53 Participants
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Circulating Concentrations of Progesterone
Stimulation day 1
|
0.5 ng/mL
Interval 0.3 to 0.7
|
0.5 ng/mL
Interval 0.3 to 0.7
|
|
Circulating Concentrations of Progesterone
Stimulation day 5
|
0.6 ng/mL
Interval 0.3 to 0.8
|
0.3 ng/mL
Interval 0.3 to 0.5
|
|
Circulating Concentrations of Progesterone
End-of-stimulation visit
|
1.1 ng/mL
Interval 0.7 to 1.5
|
0.3 ng/mL
Interval 0.3 to 0.6
|
|
Circulating Concentrations of Progesterone
Oocyte retrieval visit
|
6.2 ng/mL
Interval 4.3 to 8.9
|
2.0 ng/mL
Interval 2.0 to 2.0
|
SECONDARY outcome
Timeframe: From screening to the day of oocyte retrieval (up to 22 days after start of stimulation)Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment. No circulating concentrations of Inhibin A were assessed for the oocyte retrieval visit for the placebo arm, because no participants who received placebo became pregnant.
Blood samples for analysis of circulating concentrations of inhibin A were drawn. The median and IQR of inhibin A levels on stimulation day 1, stimulation day 5, end-of-stimulation visit and oocyte retrieval visit are presented.
Outcome measures
| Measure |
FE 999049 (Follitropin Delta)
n=523 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
n=54 Participants
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Circulating Concentrations of Inhibin A
Stimulation day 1
|
5.3 pg/mL
Interval 3.8 to 7.0
|
5.8 pg/mL
Interval 4.3 to 7.0
|
|
Circulating Concentrations of Inhibin A
Stimulation day 5
|
70.3 pg/mL
Interval 42.2 to 103.2
|
8.7 pg/mL
Interval 6.0 to 12.1
|
|
Circulating Concentrations of Inhibin A
End-of-stimulation visit
|
258.7 pg/mL
Interval 159.6 to 379.8
|
19.8 pg/mL
Interval 8.0 to 35.4
|
|
Circulating Concentrations of Inhibin A
Oocyte retrieval visit
|
204.3 pg/mL
Interval 136.9 to 287.1
|
—
|
SECONDARY outcome
Timeframe: From screening to the day of oocyte retrieval (up to 22 days after start of stimulation)Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment. No circulating concentrations of Inhibin B were assessed for the oocyte retrieval visit for the placebo arm, because no participants who received placebo became pregnant.
Blood samples for analysis of circulating concentrations of inhibin B were drawn. The median and IQR of inhibin B levels on stimulation day 1, stimulation day 5, end-of-stimulation visit and oocyte retrieval visit are presented.
Outcome measures
| Measure |
FE 999049 (Follitropin Delta)
n=525 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
n=54 Participants
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Circulating Concentrations of Inhibin B
Stimulation day 1
|
75.0 pg/mL
Interval 52.0 to 99.0
|
79.0 pg/mL
Interval 51.0 to 99.0
|
|
Circulating Concentrations of Inhibin B
Stimulation day 5
|
517.0 pg/mL
Interval 301.0 to 828.0
|
93.5 pg/mL
Interval 77.0 to 112.0
|
|
Circulating Concentrations of Inhibin B
End-of-stimulation visit
|
671.0 pg/mL
Interval 356.0 to 1039.0
|
64.5 pg/mL
Interval 51.0 to 97.0
|
|
Circulating Concentrations of Inhibin B
Oocyte retrieval visit
|
301.5 pg/mL
Interval 173.0 to 463.0
|
—
|
SECONDARY outcome
Timeframe: Up to 20 stimulation daysPopulation: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
Calculated by start dates, end dates and daily dose of IMP.
Outcome measures
| Measure |
FE 999049 (Follitropin Delta)
n=533 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
n=54 Participants
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Total Gonadotropin Dose
|
131.2 microgram of dose
Standard Deviation 30.8
|
146.5 microgram of dose
Standard Deviation 20.4
|
SECONDARY outcome
Timeframe: Up to 20 stimulation daysPopulation: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
Calculated by start dates and end dates.
Outcome measures
| Measure |
FE 999049 (Follitropin Delta)
n=533 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
n=54 Participants
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Number of Stimulation Days
|
8.2 days
Standard Deviation 1.4
|
8.5 days
Standard Deviation 0.9
|
SECONDARY outcome
Timeframe: Stimulation Day 5Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
Investigator-requested decreases and increases of the gonadotropin dose.
Outcome measures
| Measure |
FE 999049 (Follitropin Delta)
n=533 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
n=54 Participants
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Proportion of Participants With Investigator-requested Gonadotropin Dose Adjustments
Decrease
|
6.2 percentage of participants
|
0 percentage of participants
|
|
Proportion of Participants With Investigator-requested Gonadotropin Dose Adjustments
No change
|
50.7 percentage of participants
|
13.0 percentage of participants
|
|
Proportion of Participants With Investigator-requested Gonadotropin Dose Adjustments
Increase
|
43.2 percentage of participants
|
87.0 percentage of participants
|
SECONDARY outcome
Timeframe: From time of signing informed consent until the end-of-cycle visit in the fresh cycle (approximately 6 months)Any AE occurring after start of IMP and before the end-of-trial visit, or a pre-treatment AE or pre-existing medical condition that worsens in intensity after start of IMP and before the end-of-trial visit was considered treatment-emergent, and is presented for this endpoint. Data in this endpoint are presented for the fresh cycle.
Outcome measures
| Measure |
FE 999049 (Follitropin Delta)
n=533 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
n=54 Participants
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Percentage of Participants With Adverse Events (AEs)
|
49.9 percentage of participants
|
13.0 percentage of participants
|
SECONDARY outcome
Timeframe: From time of signing informed consent until the end-of-cycle visit in the fresh cycle (up to approximately 6 months)Population: The safety analysis set comprised all randomized and exposed participants. Participants were analyzed according to actual treatment received.
The intensity of AE was classified using the following 3-point scale: mild = awareness of signs or symptoms, but no disruption of usual activity; moderate = event sufficient to affect usual activity (disturbing); or severe = inability to work or perform usual activities (unacceptable). Data in this endpoint are presented for the fresh cycle.
Outcome measures
| Measure |
FE 999049 (Follitropin Delta)
n=533 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
n=54 Participants
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Intensity of AEs
Mild AEs
|
44.5 percentage of participants
|
11.1 percentage of participants
|
|
Intensity of AEs
Moderate AEs
|
15.4 percentage of participants
|
5.6 percentage of participants
|
|
Intensity of AEs
Severe AEs
|
0.9 percentage of participants
|
0 percentage of participants
|
SECONDARY outcome
Timeframe: From screening (baseline) to the end-of-cycle visit in the fresh cycle (approximately 6 months)Population: The safety analysis set comprised all randomized and exposed participants. Participants were analyzed according to actual treatment received.
Blood samples were collected for the analysis of clinical chemistry parameters including: Albumin and protein. Data in this endpoint are presented for the fresh cycle.
Outcome measures
| Measure |
FE 999049 (Follitropin Delta)
n=519 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
n=54 Participants
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Albumin, Protein
Albumin (End-of-stimulation visit)
|
-1.53 g/L
Standard Deviation 2.45
|
0.18 g/L
Standard Deviation 2.12
|
|
Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Albumin, Protein
Albumin (End-of-cycle visit)
|
-1.90 g/L
Standard Deviation 2.75
|
-0.65 g/L
Standard Deviation 2.29
|
|
Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Albumin, Protein
Protein (End-of-stimulation visit)
|
-2.76 g/L
Standard Deviation 3.98
|
-0.17 g/L
Standard Deviation 3.45
|
|
Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Albumin, Protein
Protein (End-of-cycle visit)
|
-1.92 g/L
Standard Deviation 4.12
|
-0.96 g/L
Standard Deviation 3.55
|
SECONDARY outcome
Timeframe: From screening (baseline) to the end-of-cycle visit in the fresh cycle (approximately 6 months)Population: The safety analysis set comprised all randomized and exposed participants. Participants were analyzed according to actual treatment received.
Blood samples were collected for the analysis of clinical chemistry parameters including: Alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase and gamma glutamyl transferase. Data in this endpoint are presented for the fresh cycle.
Outcome measures
| Measure |
FE 999049 (Follitropin Delta)
n=518 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
n=52 Participants
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase and Gamma Glutamyl Transferase
Alanine aminotransferase (End-of-stimulation visit)
|
0.3 IU/L
Standard Deviation 10.4
|
2.3 IU/L
Standard Deviation 18.9
|
|
Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase and Gamma Glutamyl Transferase
Alanine aminotransferase (End-of-cycle visit)
|
-0.7 IU/L
Standard Deviation 9.0
|
-2.3 IU/L
Standard Deviation 18.0
|
|
Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase and Gamma Glutamyl Transferase
Alkaline phosphatase (End-of-stimulation visit)
|
-1.3 IU/L
Standard Deviation 7.2
|
1.6 IU/L
Standard Deviation 6.2
|
|
Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase and Gamma Glutamyl Transferase
Alkaline phosphatase (End-of-cycle visit)
|
-0.6 IU/L
Standard Deviation 9.6
|
-0.9 IU/L
Standard Deviation 6.7
|
|
Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase and Gamma Glutamyl Transferase
Aspartate aminotransferase (Endof-stimulation visit)
|
0.2 IU/L
Standard Deviation 8.6
|
2.0 IU/L
Standard Deviation 8.6
|
|
Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase and Gamma Glutamyl Transferase
Aspartate aminotransferase (End-of- cycle visit)
|
-0.9 IU/L
Standard Deviation 6.2
|
-0.5 IU/L
Standard Deviation 6.4
|
|
Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase and Gamma Glutamyl Transferase
Gamma glutamy transferase (End-of-stimulation visit)
|
-1.5 IU/L
Standard Deviation 8.3
|
-0.6 IU/L
Standard Deviation 6.5
|
|
Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase and Gamma Glutamyl Transferase
Gamma glutamyl transferase (End-of-cycle visit)
|
-1.0 IU/L
Standard Deviation 11.8
|
-1.0 IU/L
Standard Deviation 8.2
|
SECONDARY outcome
Timeframe: From screening (baseline) to the end-of-cycle visit in the fresh cycle (approximately 6 months)Population: The safety analysis set comprised all randomized and exposed participants. Participants were analyzed according to actual treatment received.
Blood samples were collected for the analysis of clinical chemistry parameters including: Bicarbonate, blood urea nitrogen, calcium, chloride, cholesterol, glucose, Phosphate, Potassium and Sodium. Data in this endpoint are presented for the fresh cycle.
Outcome measures
| Measure |
FE 999049 (Follitropin Delta)
n=520 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
n=54 Participants
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium
Bicarbonate (End-of-stimulation visit)
|
-0.05 mmol/L
Standard Deviation 2.24
|
0.56 mmol/L
Standard Deviation 2.22
|
|
Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium
Bicarbonate (End-of-cycle visit)
|
-0.91 mmol/L
Standard Deviation 2.42
|
-0.47 mmol/L
Standard Deviation 2.38
|
|
Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium
Blood urea nitrogen (End-of-stimulation visit)
|
-0.2 mmol/L
Standard Deviation 1.1
|
-0.1 mmol/L
Standard Deviation 1.1
|
|
Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium
Blood urea nitrogen (End-of-cycle visit)
|
-0.3 mmol/L
Standard Deviation 1.1
|
0.0 mmol/L
Standard Deviation 1.1
|
|
Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium
Calcium (End-of-stimulation visit)
|
-0.02 mmol/L
Standard Deviation 0.08
|
0.02 mmol/L
Standard Deviation 0.09
|
|
Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium
Calcium (End-of-cycle visit)
|
-0.02 mmol/L
Standard Deviation 0.09
|
-0.01 mmol/L
Standard Deviation 0.09
|
|
Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium
Chloride (End-of-stimulation visit)
|
-0.6 mmol/L
Standard Deviation 2.3
|
0.3 mmol/L
Standard Deviation 2.1
|
|
Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium
Chloride (End-of-cycle visit)
|
0.4 mmol/L
Standard Deviation 2.4
|
0.9 mmol/L
Standard Deviation 2.3
|
|
Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium
Cholesterol (End-of-stimulation visit)
|
-0.4 mmol/L
Standard Deviation 0.5
|
0.0 mmol/L
Standard Deviation 0.5
|
|
Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium
Cholesterol (End-of-cycle visit)
|
0.1 mmol/L
Standard Deviation 0.6
|
-0.1 mmol/L
Standard Deviation 0.6
|
|
Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium
Glucose (End-of-stimulation visit)
|
-0.1 mmol/L
Standard Deviation 0.9
|
0.2 mmol/L
Standard Deviation 0.9
|
|
Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium
Glucose (End-of-cycle visit)
|
0.0 mmol/L
Standard Deviation 0.9
|
0.2 mmol/L
Standard Deviation 1.1
|
|
Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium
Phosphate (End-of stimulation visit)
|
-0.04 mmol/L
Standard Deviation 0.16
|
0.03 mmol/L
Standard Deviation 0.13
|
|
Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium
Phosphate (End-of-cycle visit)
|
0.01 mmol/L
Standard Deviation 0.18
|
0.00 mmol/L
Standard Deviation 0.18
|
|
Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium
Potassium (End-of-stimulation visit)
|
0.00 mmol/L
Standard Deviation 0.44
|
0.19 mmol/L
Standard Deviation 0.40
|
|
Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium
Potassium (End-of-cycle visit)
|
0.09 mmol/L
Standard Deviation 0.47
|
0.25 mmol/L
Standard Deviation 0.46
|
|
Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium
Sodium (End-of-stimulation visit)
|
-0.6 mmol/L
Standard Deviation 2.4
|
0.9 mmol/L
Standard Deviation 2.5
|
|
Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium
Sodium (End-of-cycle visit)
|
-0.4 mmol/L
Standard Deviation 2.8
|
0.5 mmol/L
Standard Deviation 2.5
|
SECONDARY outcome
Timeframe: From screening (baseline) to the end-of-cycle visit in the fresh cycle (approximately 6 months)Population: The safety analysis set comprised all randomized and exposed participants. Participants were analyzed according to actual treatment received.
Blood samples were collected for the analysis of clinical chemistry parameters including: Direct bilirubin, total bilirubin, creatinine, urate. Data in this endpoint are presented for the fresh cycle.
Outcome measures
| Measure |
FE 999049 (Follitropin Delta)
n=518 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
n=52 Participants
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Direct Bilirubin, Total Bilirubin, Creatinine, Urate
Direct bilirubin (End-of-stimulation visit)
|
-0.09 umol/L
Standard Deviation 0.94
|
-0.26 umol/L
Standard Deviation 0.82
|
|
Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Direct Bilirubin, Total Bilirubin, Creatinine, Urate
Direct bilirubin (End-of-cycle visit)
|
-0.28 umol/L
Standard Deviation 0.96
|
-0.08 umol/L
Standard Deviation 0.92
|
|
Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Direct Bilirubin, Total Bilirubin, Creatinine, Urate
Total bilirubin (End-of-stimulation visit)
|
-0.58 umol/L
Standard Deviation 3.50
|
-0.56 umol/L
Standard Deviation 3.92
|
|
Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Direct Bilirubin, Total Bilirubin, Creatinine, Urate
Total bilirubin (End-of-cycle visit)
|
-0.99 umol/L
Standard Deviation 3.64
|
0.23 umol/L
Standard Deviation 3.82
|
|
Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Direct Bilirubin, Total Bilirubin, Creatinine, Urate
Creatinine (End-of-stimulation visit)
|
-3.99 umol/L
Standard Deviation 7.48
|
-0.18 umol/L
Standard Deviation 8.65
|
|
Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Direct Bilirubin, Total Bilirubin, Creatinine, Urate
Creatinine (End-of-cycle visit)
|
-3.47 umol/L
Standard Deviation 9.55
|
0.85 umol/L
Standard Deviation 7.27
|
|
Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Direct Bilirubin, Total Bilirubin, Creatinine, Urate
Urate (End-of-stimulation visit)
|
-1.13 umol/L
Standard Deviation 36.24
|
-5.08 umol/L
Standard Deviation 36.99
|
|
Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Direct Bilirubin, Total Bilirubin, Creatinine, Urate
Urate (End-of-cycle visit)
|
-10.53 umol/L
Standard Deviation 48.58
|
6.06 umol/L
Standard Deviation 42.05
|
SECONDARY outcome
Timeframe: From screening (baseline) to the end-of-cycle visit in the fresh cycle (approximately 6 months)Population: The safety analysis set comprised all randomized and exposed participants. Participants were analyzed according to actual treatment received.
Blood samples were collected for the analysis of clinical chemistry parameters including: Lactate dehydrogenase. Data in this endpoint are presented for the fresh cycle.
Outcome measures
| Measure |
FE 999049 (Follitropin Delta)
n=477 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
n=48 Participants
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Lactate Dehydrogenase
End-of-stimulation visit
|
-12.0 U/L
Standard Deviation 18.5
|
-3.8 U/L
Standard Deviation 14.3
|
|
Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Lactate Dehydrogenase
End-of-cycle visit
|
-0.4 U/L
Standard Deviation 20.7
|
-0.8 U/L
Standard Deviation 16.8
|
SECONDARY outcome
Timeframe: From screening to the end-of-cycle visit in the fresh cycle (approximately 6 months)Population: The safety analysis set comprised all randomized and exposed participants. Participants were analyzed according to actual treatment received.
Blood samples were collected for the analysis of haematology parameter including: Erythrocytes. Data in this endpoint are presented for the fresh cycle.
Outcome measures
| Measure |
FE 999049 (Follitropin Delta)
n=489 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
n=50 Participants
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Changes in Haematology Parameters Compared to Baseline: Erythrocytes
End-of-stimulation visit
|
-0.13 10^12 cells/L
Standard Deviation 0.23
|
-0.03 10^12 cells/L
Standard Deviation 0.23
|
|
Changes in Haematology Parameters Compared to Baseline: Erythrocytes
End-of-cycle visit
|
-0.15 10^12 cells/L
Standard Deviation 0.26
|
-0.07 10^12 cells/L
Standard Deviation 0.23
|
SECONDARY outcome
Timeframe: From screening (baseline) to the end-of-cycle visit in the fresh cycle (approximately 6 months)Population: The safety analysis set comprised all randomized and exposed participants. Participants were analyzed according to actual treatment received.
Blood samples were collected for the analysis of haematology parameters including: Haemoglobin. Data in this endpoint are presented for the fresh cycle.
Outcome measures
| Measure |
FE 999049 (Follitropin Delta)
n=489 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
n=50 Participants
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Changes in Haematology Parameters Compared to Baseline: Haemoglobin
End-of-stimulation visit
|
-3.75 g/L
Standard Deviation 6.60
|
-0.20 g/L
Standard Deviation 6.86
|
|
Changes in Haematology Parameters Compared to Baseline: Haemoglobin
End-of-cycle visit
|
-3.94 g/L
Standard Deviation 7.64
|
-1.76 g/L
Standard Deviation 6.86
|
SECONDARY outcome
Timeframe: From screening (baseline) to the end-of-cycle visit in the fresh cycle (approximately 6 months)Population: The safety analysis set comprised all randomized and exposed participants. Participants were analyzed according to actual treatment received.
Blood samples were collected for the analysis of haematology parameter including: Haematocrit. Data in this endpoint are presented for the fresh cycle.
Outcome measures
| Measure |
FE 999049 (Follitropin Delta)
n=484 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
n=50 Participants
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Changes in Haematology Parameters Compared to Baseline: Haematocrit
End-of-stimulation visit
|
0.0 ratio
Standard Deviation 0.0
|
0.0 ratio
Standard Deviation 0.0
|
|
Changes in Haematology Parameters Compared to Baseline: Haematocrit
End-of-cycle visit
|
0.0 ratio
Standard Deviation 0.0
|
0.0 ratio
Standard Deviation 0.0
|
SECONDARY outcome
Timeframe: From screening (baseline) to the end-of-cycle visit in the fresh cycle (approximately 6 months)Population: The safety analysis set comprised all randomized and exposed participants. Participants were analyzed according to actual treatment received.
Blood samples were collected for the analysis of haematology parameter including: Erythrocyte mean corpuscular volume. Data in this endpoint are presented for the fresh cycle.
Outcome measures
| Measure |
FE 999049 (Follitropin Delta)
n=484 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
n=50 Participants
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Changes in Haematology Parameters Compared to Baseline: Erythrocyte Mean Corpuscular Volume
End-of-stimulation visit
|
1.4 fL
Standard Deviation 3.0
|
1.2 fL
Standard Deviation 3.2
|
|
Changes in Haematology Parameters Compared to Baseline: Erythrocyte Mean Corpuscular Volume
End-of-cycle visit
|
1.1 fL
Standard Deviation 3.1
|
1.4 fL
Standard Deviation 3.0
|
SECONDARY outcome
Timeframe: From screening (baseline) to the end-of-cycle visit in the fresh cycle (approximately 6 months)Population: The safety analysis set comprised all randomized and exposed participants. Participants were analyzed according to actual treatment received.
Blood samples were collected for the analysis of haematology parameters including: Leukocytes and platelets. Data in this endpoint are presented for the fresh cycle.
Outcome measures
| Measure |
FE 999049 (Follitropin Delta)
n=489 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
n=50 Participants
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Changes in Haematology Parameters Compared to Baseline: Leukocytes and Platelets
Leukocytes (End-of-stimulation visit)
|
0.904 10^9 cells/L
Standard Deviation 1.913
|
-0.822 10^9 cells/L
Standard Deviation 1.508
|
|
Changes in Haematology Parameters Compared to Baseline: Leukocytes and Platelets
Leukocytes (End-of-cycle visit)
|
0.357 10^9 cells/L
Standard Deviation 2.174
|
-0.534 10^9 cells/L
Standard Deviation 1.636
|
|
Changes in Haematology Parameters Compared to Baseline: Leukocytes and Platelets
Platelets (End-of-stimulation visit)
|
-3.0 10^9 cells/L
Standard Deviation 41.0
|
-2.0 10^9 cells/L
Standard Deviation 35.1
|
|
Changes in Haematology Parameters Compared to Baseline: Leukocytes and Platelets
Platelets (End-of-cycle visit)
|
9.5 10^9 cells/L
Standard Deviation 50.2
|
-16.1 10^9 cells/L
Standard Deviation 42.1
|
SECONDARY outcome
Timeframe: From screening (baseline) to the end-of-cycle visit in the fresh cycle (approximately 6 months)Population: The safety analysis set comprised all randomized and exposed participants. Participants were analyzed according to actual treatment received.
Blood samples were collected for the analysis of haematology parameter including: Erythrocyte mean corpuscular haemoglobin. Data in this endpoint are presented for the fresh cycle.
Outcome measures
| Measure |
FE 999049 (Follitropin Delta)
n=489 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
n=50 Participants
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Changes in Haematology Parameters Compared to Baseline: Erythrocyte Mean Corpuscular Hemoglobin
End-of-stimulation visit
|
0.1 picogram
Standard Deviation 0.8
|
0.1 picogram
Standard Deviation 1.0
|
|
Changes in Haematology Parameters Compared to Baseline: Erythrocyte Mean Corpuscular Hemoglobin
End-of-cycle visit
|
0.1 picogram
Standard Deviation 0.9
|
0.1 picogram
Standard Deviation 0.8
|
SECONDARY outcome
Timeframe: From screening (baseline) to the end-of-cycle visit in the fresh cycle (approximately 6 months)Population: The safety analysis set comprised all randomized and exposed participants. Participants were analyzed according to actual treatment received.
Blood samples were collected for the analysis of haematology parameter including: Erythrocyte mean corpuscular haemoglobin concentration. Data in this endpoint are presented for the fresh cycle.
Outcome measures
| Measure |
FE 999049 (Follitropin Delta)
n=484 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
n=50 Participants
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Changes in Haematology Parameters Compared to Baseline: Erythrocyte Mean Corpuscular Haemoglobin Concentration
End-of-stimulation visit
|
-0.3 mmol/L
Standard Deviation 0.8
|
-0.2 mmol/L
Standard Deviation 0.8
|
|
Changes in Haematology Parameters Compared to Baseline: Erythrocyte Mean Corpuscular Haemoglobin Concentration
End-of-cycle visit
|
-0.2 mmol/L
Standard Deviation 0.8
|
-0.3 mmol/L
Standard Deviation 0.7
|
SECONDARY outcome
Timeframe: From screening (baseline) to the end-of-cycle visit in the fresh cycle (approximately 6 months)Population: The safety analysis set comprised all randomized and exposed participants. Participants were analyzed according to actual treatment received.
Blood samples were collected for the analysis of haematology parameters including: Basophils/leukocytes, eosinophils/ leukocytes, lymphocytes/leukocytes, monocytes/leukocytes and neutrophils/leukocytes. Data in this endpoint are presented for the fresh cycle.
Outcome measures
| Measure |
FE 999049 (Follitropin Delta)
n=489 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
n=50 Participants
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Changes in Haematology Parameters Compared to Baseline: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes and Neutrophils/Leukocytes
Monocytes/leukocytes (End-of-cycle visit)
|
0.14 percentage
Standard Deviation 1.73
|
0.66 percentage
Standard Deviation 1.80
|
|
Changes in Haematology Parameters Compared to Baseline: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes and Neutrophils/Leukocytes
Basophils/leukocytes (End-of-stimulation visit)
|
0.11 percentage
Standard Deviation 0.52
|
0.10 percentage
Standard Deviation 0.62
|
|
Changes in Haematology Parameters Compared to Baseline: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes and Neutrophils/Leukocytes
Basophils/leukocytes (End-of-cycle visit)
|
0.07 percentage
Standard Deviation 0.43
|
0.01 percentage
Standard Deviation 0.55
|
|
Changes in Haematology Parameters Compared to Baseline: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes and Neutrophils/Leukocytes
Eosinophils/leukocytes (End-of-stimulation visit)
|
-0.36 percentage
Standard Deviation 1.25
|
0.03 percentage
Standard Deviation 1.16
|
|
Changes in Haematology Parameters Compared to Baseline: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes and Neutrophils/Leukocytes
Eosinophils/leukocytes (End-of-cycle visit)
|
-0.16 percentage
Standard Deviation 1.35
|
0.04 percentage
Standard Deviation 0.99
|
|
Changes in Haematology Parameters Compared to Baseline: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes and Neutrophils/Leukocytes
Lymphocytes/leukocytes (End-of-stimulation visit)
|
-5.46 percentage
Standard Deviation 6.73
|
0.59 percentage
Standard Deviation 6.34
|
|
Changes in Haematology Parameters Compared to Baseline: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes and Neutrophils/Leukocytes
Lymphocytes/leukocytes (End-of-cycle visit)
|
-1.27 percentage
Standard Deviation 8.24
|
0.80 percentage
Standard Deviation 5.39
|
|
Changes in Haematology Parameters Compared to Baseline: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes and Neutrophils/Leukocytes
Monocytes/leukocytes (End-of-stimulation visit)
|
-0.44 percentage
Standard Deviation 1.73
|
0.00 percentage
Standard Deviation 1.74
|
|
Changes in Haematology Parameters Compared to Baseline: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes and Neutrophils/Leukocytes
Neutrophils/leukocytes (End-of-stimulation visit)
|
6.14 percentage
Standard Deviation 7.67
|
-0.73 percentage
Standard Deviation 7.40
|
|
Changes in Haematology Parameters Compared to Baseline: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes and Neutrophils/Leukocytes
Neutrophils/leukocytes (End-of-cycle visit)
|
1.22 percentage
Standard Deviation 9.09
|
-1.51 percentage
Standard Deviation 6.27
|
SECONDARY outcome
Timeframe: From screening (baseline) to the end-of-cycle visit in the fresh cycle (approximately 6 months)Population: The safety analysis set comprised all randomized and exposed participants. Participants were analyzed according to actual treatment received.
The table represents the percentage of participants in each group with normal baseline values and markedly abnormal end-of-stimulation or end-of-cycle visit values for alanine aminotransferase, aspartate aminotransferase, bicarbonate, calcium, potassium. Data in this endpoint are presented for the fresh cycle.
Outcome measures
| Measure |
FE 999049 (Follitropin Delta)
n=515 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
n=52 Participants
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Proportion of Subjects With Markedly Abnormal Changes of Clinical Chemistry Parameters: Alanine Aminotransferase, Aspartate Aminotransferase, Bicarbonate, Calcium, Potassium
Alanine aminotransferase (End-of-stimulation visit)
|
0.2 percentage of participants
|
0.0 percentage of participants
|
|
Proportion of Subjects With Markedly Abnormal Changes of Clinical Chemistry Parameters: Alanine Aminotransferase, Aspartate Aminotransferase, Bicarbonate, Calcium, Potassium
Aspartate aminotransferase (End-of-stimulation visit)
|
0.2 percentage of participants
|
0.0 percentage of participants
|
|
Proportion of Subjects With Markedly Abnormal Changes of Clinical Chemistry Parameters: Alanine Aminotransferase, Aspartate Aminotransferase, Bicarbonate, Calcium, Potassium
Bicarbonate (End-of-stimulation visit)
|
0.2 percentage of participants
|
0.0 percentage of participants
|
|
Proportion of Subjects With Markedly Abnormal Changes of Clinical Chemistry Parameters: Alanine Aminotransferase, Aspartate Aminotransferase, Bicarbonate, Calcium, Potassium
Calcium (End-of-stimulation visit)
|
0.0 percentage of participants
|
2.1 percentage of participants
|
|
Proportion of Subjects With Markedly Abnormal Changes of Clinical Chemistry Parameters: Alanine Aminotransferase, Aspartate Aminotransferase, Bicarbonate, Calcium, Potassium
Glucose (End-of-stimulation visit)
|
0.3 percentage of participants
|
0.0 percentage of participants
|
|
Proportion of Subjects With Markedly Abnormal Changes of Clinical Chemistry Parameters: Alanine Aminotransferase, Aspartate Aminotransferase, Bicarbonate, Calcium, Potassium
Potassium (End-of-stimulation visit)
|
0.2 percentage of participants
|
0.0 percentage of participants
|
|
Proportion of Subjects With Markedly Abnormal Changes of Clinical Chemistry Parameters: Alanine Aminotransferase, Aspartate Aminotransferase, Bicarbonate, Calcium, Potassium
Alanine aminotransferase (End-of-cycle visit)
|
0.2 percentage of participants
|
0.0 percentage of participants
|
|
Proportion of Subjects With Markedly Abnormal Changes of Clinical Chemistry Parameters: Alanine Aminotransferase, Aspartate Aminotransferase, Bicarbonate, Calcium, Potassium
Bicarbonate (End-of-cycle visit)
|
0.2 percentage of participants
|
0.0 percentage of participants
|
SECONDARY outcome
Timeframe: From screening (baseline) to the end-of-stimulation visit and end-of-cycle visit in the fresh cycle (approximately 6 months)Population: The safety analysis set comprised all randomized and exposed participants. Participants were analyzed according to actual treatment received.
The table represents the percentage of participants in each group with normal baseline values and markedly abnormal end-of-stimulation or end-of-cycle visit values for Leukocytes, eosinophils/leukocytes, lymphocytes/leukocytes and neutrophils/leukocytes. Data in this endpoint are presented for the fresh cycle.
Outcome measures
| Measure |
FE 999049 (Follitropin Delta)
n=479 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
n=50 Participants
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Proportion of Subjects With Markedly Abnormal Changes of Haematology Parameters: Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Neutrophils/Leukocytes
Leukocytes (End-of-stimulation visit)
|
0.2 percentage of participants
|
0.0 percentage of participants
|
|
Proportion of Subjects With Markedly Abnormal Changes of Haematology Parameters: Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Neutrophils/Leukocytes
Eosinophils/leukocytes (End-of-stimulation visit)
|
0.2 percentage of participants
|
0.0 percentage of participants
|
|
Proportion of Subjects With Markedly Abnormal Changes of Haematology Parameters: Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Neutrophils/Leukocytes
Lymphocytes/leukocytes (End-of-stimulation visit)
|
0.4 percentage of participants
|
0.0 percentage of participants
|
|
Proportion of Subjects With Markedly Abnormal Changes of Haematology Parameters: Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Neutrophils/Leukocytes
Neutrophils/leukocytes (End-of-stimulation visit)
|
0.2 percentage of participants
|
0.0 percentage of participants
|
|
Proportion of Subjects With Markedly Abnormal Changes of Haematology Parameters: Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Neutrophils/Leukocytes
Leukocytes (End-of-cycle visit)
|
0.6 percentage of participants
|
0.0 percentage of participants
|
|
Proportion of Subjects With Markedly Abnormal Changes of Haematology Parameters: Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Neutrophils/Leukocytes
Eosinophils/leukocytes (End-of-cycle visit)
|
0.2 percentage of participants
|
0.0 percentage of participants
|
SECONDARY outcome
Timeframe: End-of-stimulation (up to 20 stimulation days)Population: The safety analysis set comprised all randomized and exposed participants. Participants were analyzed according to actual treatment received.
Assessed by the participant during the stimulation period. Participants assessed the injection site reactions (redness, pain, itching, swelling and bruising) three times daily: immediately after the injection, 30 minutes after the injection and 24 hours after the injection.
Outcome measures
| Measure |
FE 999049 (Follitropin Delta)
n=64939 Total number of events
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
n=6805 Total number of events
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Frequency and Intensity of Injection Site Reactions (Redness, Pain, Itching, Swelling and Bruising) Assessed by the Subject During the Stimulation Period
|
4.2 percentage of events
|
4.0 percentage of events
|
SECONDARY outcome
Timeframe: End-of-stimulation (up to 20 stimulation days)Population: The safety analysis set comprised all randomized and exposed participants. Participants were analyzed according to actual treatment received.
Assessed by the participant during the stimulation period as mild, moderate or severe.
Outcome measures
| Measure |
FE 999049 (Follitropin Delta)
n=64939 Total number of events
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
n=6805 Total number of events
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Intensity of Injection Site Reactions (Redness, Pain, Itching, Swelling and Bruising) Assessed by the Subject During the Stimulation Period
Mild injection site reaction
|
4.0 percentage of events
|
3.9 percentage of events
|
|
Intensity of Injection Site Reactions (Redness, Pain, Itching, Swelling and Bruising) Assessed by the Subject During the Stimulation Period
Moderate injection site reaction
|
0.1 percentage of events
|
0.1 percentage of events
|
|
Intensity of Injection Site Reactions (Redness, Pain, Itching, Swelling and Bruising) Assessed by the Subject During the Stimulation Period
Severe injection site reaction
|
0.0123 percentage of events
|
0.0147 percentage of events
|
SECONDARY outcome
Timeframe: Up to 28 days after end of the stimulation periodPopulation: The safety analysis set comprised all randomized and exposed participants. Participants were analyzed according to actual treatment received.
Measured by presence of anti-FSH antibodies. 95% Clopper-Pearson confidence interval has been reported in this endpoint.
Outcome measures
| Measure |
FE 999049 (Follitropin Delta)
n=533 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
n=54 Participants
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Proportion of Subjects With Treatment-induced Anti-FSH Antibodies, Overall as Well as With Neutralizing Capacity
Treatment-induced anti-FSH antibodies (Overall)
|
0.75 percentage of participants
Interval 0.2 to 1.91
|
0.00 percentage of participants
Interval 0.0 to 6.6
|
|
Proportion of Subjects With Treatment-induced Anti-FSH Antibodies, Overall as Well as With Neutralizing Capacity
Treatment-induced anti-FSH antibodies with neutralizing capacity
|
0 percentage of participants
For participants with treatment-induced anti-FSH antibodies, none of the antibodies were of neutralizing capacity at any sampling time point.
|
0 percentage of participants
For participants with treatment-induced anti-FSH antibodies, none of the antibodies were of neutralizing capacity at any sampling time point.
|
SECONDARY outcome
Timeframe: From time of signing informed consent for participation in the trial until the end-of-cycle visit in the fresh cycle (approximately 6 months)Population: The safety analysis set comprised all randomized and exposed participants. Participants were analyzed according to actual treatment received.
Standardised Medical Dictionary for Regulatory Activities (MedDRA) Queries (SMQs).
Outcome measures
| Measure |
FE 999049 (Follitropin Delta)
n=533 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
n=54 Participants
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Frequency and Intensity of Immune-related Adverse Events
SMQ = Severe cutaneous adverse reactions
|
3 events
|
0 events
|
|
Frequency and Intensity of Immune-related Adverse Events
SMQ = Anaphylactic reaction
|
7 events
|
1 events
|
|
Frequency and Intensity of Immune-related Adverse Events
SMQ = Angioedema
|
2 events
|
0 events
|
|
Frequency and Intensity of Immune-related Adverse Events
SMQ = Hypersensitivity
|
13 events
|
1 events
|
|
Frequency and Intensity of Immune-related Adverse Events
Any general and local hypersensitivity reactions
|
11 events
|
1 events
|
SECONDARY outcome
Timeframe: Up to 20 stimulation daysPopulation: The safety analysis set comprised all randomized and exposed participants. Participants were analyzed according to actual treatment received.
For each participant the reason for cycle cancellation will be recorded. Data in this endpoint are presented for the fresh cycle.
Outcome measures
| Measure |
FE 999049 (Follitropin Delta)
n=533 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
n=54 Participants
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Proportion of Subjects With Cycle Cancellations Due to an Adverse Event, Including Immune-related Adverse Events, or Due to Technical Malfunctions of the Administration Pen
AE (including immune-related AEs)
|
0 percentage of participants
|
0 percentage of participants
|
|
Proportion of Subjects With Cycle Cancellations Due to an Adverse Event, Including Immune-related Adverse Events, or Due to Technical Malfunctions of the Administration Pen
Technical malfunctions of the administration pen
|
0 percentage of participants
|
0 percentage of participants
|
SECONDARY outcome
Timeframe: ≤9 days after triggering of final follicular maturation (early OHSS), >9 days after triggering of final follicular maturation until 21-28 days after last IMP dose or up to ongoing pregnancy 8-9 weeks after transfer in pregnant participants (late OHSS)Population: The safety analysis set comprised all randomized and exposed participants. Participants were analyzed according to actual treatment received.
Classification of grade was according to Golan's classification system, and all OHSS cases were graded as mild, moderate or severe. Data in this endpoint are presented for the fresh cycle.
Outcome measures
| Measure |
FE 999049 (Follitropin Delta)
n=533 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
n=54 Participants
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Proportion of Subjects With OHSS, Overall and by Grade, and Proportion of Subjects With Moderate/Severe OHSS
OHSS (any grade)
|
2.4 percentage of participants
|
0 percentage of participants
|
|
Proportion of Subjects With OHSS, Overall and by Grade, and Proportion of Subjects With Moderate/Severe OHSS
OHSS (moderate/severe)
|
1.5 percentage of participants
|
0 percentage of participants
|
SECONDARY outcome
Timeframe: ≤9 days after triggering of final follicular maturation (early OHSS), >9 days after triggering of final follicular maturation until 21-28 days after last IMP dose or up to ongoing pregnancy 8-9 weeks after transfer in pregnant participants (late OHSS)Population: The safety analysis set comprised all randomized and exposed participants. Participants were analyzed according to actual treatment received.
Percentage of participants hospitalized or undergoing paracentesis due to OHSS are reported
Outcome measures
| Measure |
FE 999049 (Follitropin Delta)
n=533 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
n=54 Participants
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Proportion of Subjects Hospitalized Due to OHSS and Proportion of Subjects Undergoing Paracentesis Due to OHSS
Hospitalization
|
0 percentage of participants
|
0 percentage of participants
|
|
Proportion of Subjects Hospitalized Due to OHSS and Proportion of Subjects Undergoing Paracentesis Due to OHSS
Paracentesis
|
0 percentage of participants
|
0 percentage of participants
|
SECONDARY outcome
Timeframe: Up to 8-9 weeks after transferPopulation: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
Defined as pregnancy with more than one fetus. Among participants with ongoing pregnancy, percentage of participants with twin pregnancies are presented. '%' in the unit of measure refers to 'percentage'.
Outcome measures
| Measure |
FE 999049 (Follitropin Delta)
n=117 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Proportion of Participants With Multi-fetal Gestation in the Fresh Cycle
|
2.6 % of participants with twin pregnancy
|
—
|
SECONDARY outcome
Timeframe: Up to 8-9 weeks after transferPopulation: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
Defined as pregnancy with more than one fetus. Among cryopreserved cycles with ongoing pregnancy, percentage of cycles with twin pregnancies are presented. '%' in the unit of measure refers to 'percentage'.
Outcome measures
| Measure |
FE 999049 (Follitropin Delta)
n=117 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Proportion of Cryopreserved Cycles With Multi-fetal Gestation
|
3.4 % of cycles with twin pregnancy
|
—
|
SECONDARY outcome
Timeframe: Up to 8-9 weeks after transferPopulation: The safety analysis set comprised all randomized and exposed participants. Participants were analyzed according to actual treatment received.
The percentage of participants with biochemical pregnancy, spontaneous abortion, ectopic pregnancy (with and without medical/surgical intervention) and vanishing twins in the fresh cycle are presented. Data represents participants with positive βhCG. Data is not shown for placebo arm because no participants had a positive βhCG. '%' in the unit of measure refers to 'percentage'. Unit: % of participants with early pregnancy loss.
Outcome measures
| Measure |
FE 999049 (Follitropin Delta)
n=171 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Biochemical Pregnancy, Spontaneous Abortion, Ectopic Pregnancy (With and Without Medical/Surgical Intervention) and Vanishing Twins in the Fresh Cycle
Biochemical pregnancy
|
15.8 % of participants
|
—
|
|
Biochemical Pregnancy, Spontaneous Abortion, Ectopic Pregnancy (With and Without Medical/Surgical Intervention) and Vanishing Twins in the Fresh Cycle
Spontaneous abortion
|
15.2 % of participants
|
—
|
|
Biochemical Pregnancy, Spontaneous Abortion, Ectopic Pregnancy (With and Without Medical/Surgical Intervention) and Vanishing Twins in the Fresh Cycle
Induced abortion
|
0.0 % of participants
|
—
|
|
Biochemical Pregnancy, Spontaneous Abortion, Ectopic Pregnancy (With and Without Medical/Surgical Intervention) and Vanishing Twins in the Fresh Cycle
Ectopic pregnancy
|
0.6 % of participants
|
—
|
SECONDARY outcome
Timeframe: Up to 8-9 weeks after transferPopulation: The safety analysis set comprised all randomized and exposed participants. Participants were analyzed according to actual treatment received.
The percentage of cryopreserved cycles with biochemical pregnancy, spontaneous abortion, ectopic pregnancy (with and without medical/surgical intervention) and vanishing twins are presented. Data is not shown for placebo arm because no participants had a positive βhCG. '%' in the unit of measure refers to 'percentage'.
Outcome measures
| Measure |
FE 999049 (Follitropin Delta)
n=185 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Biochemical Pregnancy, Spontaneous Abortion, Ectopic Pregnancy (With and Without Medical/Surgical Intervention) and Vanishing Twins in the Cryopreserved Cycles
Biochemical pregnancy
|
16.8 % of cycles with early pregnancy loss
|
—
|
|
Biochemical Pregnancy, Spontaneous Abortion, Ectopic Pregnancy (With and Without Medical/Surgical Intervention) and Vanishing Twins in the Cryopreserved Cycles
Spontaneous abortion
|
18.9 % of cycles with early pregnancy loss
|
—
|
|
Biochemical Pregnancy, Spontaneous Abortion, Ectopic Pregnancy (With and Without Medical/Surgical Intervention) and Vanishing Twins in the Cryopreserved Cycles
Induced abortion
|
0.0 % of cycles with early pregnancy loss
|
—
|
|
Biochemical Pregnancy, Spontaneous Abortion, Ectopic Pregnancy (With and Without Medical/Surgical Intervention) and Vanishing Twins in the Cryopreserved Cycles
Ectopic pregnancy
|
1.1 % of cycles with early pregnancy loss
|
—
|
SECONDARY outcome
Timeframe: Up to 20 stimulation daysPopulation: The safety analysis set comprised all randomized and exposed participants. Participants were analyzed according to actual treatment received.
Incidences of technical malfunctions of the administration pen were recorded.
Outcome measures
| Measure |
FE 999049 (Follitropin Delta)
n=533 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
n=54 Participants
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Proportion of Participants With Technical Malfunctions of the Administration Pen
|
0 percentage of participants
|
0 percentage of participants
|
Adverse Events
FE 999049 (Follitropin Delta)
Serious events: 2 serious events
Other events: 151 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
FE 999049 (Follitropin Delta)
n=533 participants at risk
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
n=54 participants at risk
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Pregnancy, puerperium and perinatal conditions
Ectopic pregnancy
|
0.19%
1/533 • Number of events 1 • The AEs were recorded from time of signing informed consent to end-of-trial (up to Ongoing pregnancy visit (10-11 weeks after transfer)). Data for the AEs is presented for the fresh cycle and cryopreserved cycle.
Adverse events occurring after start of IMP and before the end-of-trial visit, or a pre-treatment AE or preexisting medical condition that worsens in intensity after start of FE 999049 or placebo treatment and before the end-of-trial visit (treatment-emergent AEs) are presented for the safety analysis set.
|
0.00%
0/54 • The AEs were recorded from time of signing informed consent to end-of-trial (up to Ongoing pregnancy visit (10-11 weeks after transfer)). Data for the AEs is presented for the fresh cycle and cryopreserved cycle.
Adverse events occurring after start of IMP and before the end-of-trial visit, or a pre-treatment AE or preexisting medical condition that worsens in intensity after start of FE 999049 or placebo treatment and before the end-of-trial visit (treatment-emergent AEs) are presented for the safety analysis set.
|
|
Pregnancy, puerperium and perinatal conditions
Hyperemesis gravidarum
|
0.19%
1/533 • Number of events 1 • The AEs were recorded from time of signing informed consent to end-of-trial (up to Ongoing pregnancy visit (10-11 weeks after transfer)). Data for the AEs is presented for the fresh cycle and cryopreserved cycle.
Adverse events occurring after start of IMP and before the end-of-trial visit, or a pre-treatment AE or preexisting medical condition that worsens in intensity after start of FE 999049 or placebo treatment and before the end-of-trial visit (treatment-emergent AEs) are presented for the safety analysis set.
|
0.00%
0/54 • The AEs were recorded from time of signing informed consent to end-of-trial (up to Ongoing pregnancy visit (10-11 weeks after transfer)). Data for the AEs is presented for the fresh cycle and cryopreserved cycle.
Adverse events occurring after start of IMP and before the end-of-trial visit, or a pre-treatment AE or preexisting medical condition that worsens in intensity after start of FE 999049 or placebo treatment and before the end-of-trial visit (treatment-emergent AEs) are presented for the safety analysis set.
|
Other adverse events
| Measure |
FE 999049 (Follitropin Delta)
n=533 participants at risk
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
Placebo
n=54 participants at risk
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
|
|---|---|---|
|
Injury, poisoning and procedural complications
Procedural pain
|
20.8%
111/533 • Number of events 115 • The AEs were recorded from time of signing informed consent to end-of-trial (up to Ongoing pregnancy visit (10-11 weeks after transfer)). Data for the AEs is presented for the fresh cycle and cryopreserved cycle.
Adverse events occurring after start of IMP and before the end-of-trial visit, or a pre-treatment AE or preexisting medical condition that worsens in intensity after start of FE 999049 or placebo treatment and before the end-of-trial visit (treatment-emergent AEs) are presented for the safety analysis set.
|
0.00%
0/54 • The AEs were recorded from time of signing informed consent to end-of-trial (up to Ongoing pregnancy visit (10-11 weeks after transfer)). Data for the AEs is presented for the fresh cycle and cryopreserved cycle.
Adverse events occurring after start of IMP and before the end-of-trial visit, or a pre-treatment AE or preexisting medical condition that worsens in intensity after start of FE 999049 or placebo treatment and before the end-of-trial visit (treatment-emergent AEs) are presented for the safety analysis set.
|
|
Nervous system disorders
Headache
|
5.4%
29/533 • Number of events 34 • The AEs were recorded from time of signing informed consent to end-of-trial (up to Ongoing pregnancy visit (10-11 weeks after transfer)). Data for the AEs is presented for the fresh cycle and cryopreserved cycle.
Adverse events occurring after start of IMP and before the end-of-trial visit, or a pre-treatment AE or preexisting medical condition that worsens in intensity after start of FE 999049 or placebo treatment and before the end-of-trial visit (treatment-emergent AEs) are presented for the safety analysis set.
|
3.7%
2/54 • Number of events 2 • The AEs were recorded from time of signing informed consent to end-of-trial (up to Ongoing pregnancy visit (10-11 weeks after transfer)). Data for the AEs is presented for the fresh cycle and cryopreserved cycle.
Adverse events occurring after start of IMP and before the end-of-trial visit, or a pre-treatment AE or preexisting medical condition that worsens in intensity after start of FE 999049 or placebo treatment and before the end-of-trial visit (treatment-emergent AEs) are presented for the safety analysis set.
|
|
Pregnancy, puerperium and perinatal conditions
Biochemical pregnancy (Fresh cycle)
|
5.1%
27/533 • Number of events 27 • The AEs were recorded from time of signing informed consent to end-of-trial (up to Ongoing pregnancy visit (10-11 weeks after transfer)). Data for the AEs is presented for the fresh cycle and cryopreserved cycle.
Adverse events occurring after start of IMP and before the end-of-trial visit, or a pre-treatment AE or preexisting medical condition that worsens in intensity after start of FE 999049 or placebo treatment and before the end-of-trial visit (treatment-emergent AEs) are presented for the safety analysis set.
|
0.00%
0/54 • The AEs were recorded from time of signing informed consent to end-of-trial (up to Ongoing pregnancy visit (10-11 weeks after transfer)). Data for the AEs is presented for the fresh cycle and cryopreserved cycle.
Adverse events occurring after start of IMP and before the end-of-trial visit, or a pre-treatment AE or preexisting medical condition that worsens in intensity after start of FE 999049 or placebo treatment and before the end-of-trial visit (treatment-emergent AEs) are presented for the safety analysis set.
|
|
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous
|
13.1%
32/245 • Number of events 35 • The AEs were recorded from time of signing informed consent to end-of-trial (up to Ongoing pregnancy visit (10-11 weeks after transfer)). Data for the AEs is presented for the fresh cycle and cryopreserved cycle.
Adverse events occurring after start of IMP and before the end-of-trial visit, or a pre-treatment AE or preexisting medical condition that worsens in intensity after start of FE 999049 or placebo treatment and before the end-of-trial visit (treatment-emergent AEs) are presented for the safety analysis set.
|
0.00%
0/54 • The AEs were recorded from time of signing informed consent to end-of-trial (up to Ongoing pregnancy visit (10-11 weeks after transfer)). Data for the AEs is presented for the fresh cycle and cryopreserved cycle.
Adverse events occurring after start of IMP and before the end-of-trial visit, or a pre-treatment AE or preexisting medical condition that worsens in intensity after start of FE 999049 or placebo treatment and before the end-of-trial visit (treatment-emergent AEs) are presented for the safety analysis set.
|
|
Pregnancy, puerperium and perinatal conditions
Biochemical pregnancy (Cryopreserved cycle)
|
11.8%
29/245 • Number of events 31 • The AEs were recorded from time of signing informed consent to end-of-trial (up to Ongoing pregnancy visit (10-11 weeks after transfer)). Data for the AEs is presented for the fresh cycle and cryopreserved cycle.
Adverse events occurring after start of IMP and before the end-of-trial visit, or a pre-treatment AE or preexisting medical condition that worsens in intensity after start of FE 999049 or placebo treatment and before the end-of-trial visit (treatment-emergent AEs) are presented for the safety analysis set.
|
0.00%
0/54 • The AEs were recorded from time of signing informed consent to end-of-trial (up to Ongoing pregnancy visit (10-11 weeks after transfer)). Data for the AEs is presented for the fresh cycle and cryopreserved cycle.
Adverse events occurring after start of IMP and before the end-of-trial visit, or a pre-treatment AE or preexisting medical condition that worsens in intensity after start of FE 999049 or placebo treatment and before the end-of-trial visit (treatment-emergent AEs) are presented for the safety analysis set.
|
|
Pregnancy, puerperium and perinatal conditions
Morning sickness
|
11.0%
27/245 • Number of events 34 • The AEs were recorded from time of signing informed consent to end-of-trial (up to Ongoing pregnancy visit (10-11 weeks after transfer)). Data for the AEs is presented for the fresh cycle and cryopreserved cycle.
Adverse events occurring after start of IMP and before the end-of-trial visit, or a pre-treatment AE or preexisting medical condition that worsens in intensity after start of FE 999049 or placebo treatment and before the end-of-trial visit (treatment-emergent AEs) are presented for the safety analysis set.
|
0.00%
0/54 • The AEs were recorded from time of signing informed consent to end-of-trial (up to Ongoing pregnancy visit (10-11 weeks after transfer)). Data for the AEs is presented for the fresh cycle and cryopreserved cycle.
Adverse events occurring after start of IMP and before the end-of-trial visit, or a pre-treatment AE or preexisting medical condition that worsens in intensity after start of FE 999049 or placebo treatment and before the end-of-trial visit (treatment-emergent AEs) are presented for the safety analysis set.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The only disclosure restriction on the PI is that the sponsor can review the draft manuscript prior to publication and can request delay of publication where any contents are deemed patentable by the sponsor or confidential to the sponsor. Comments will be given within four weeks from receipt of the draft manuscript. Additional time may be required to allow Ferring to seek patent protection of the invention.
- Publication restrictions are in place
Restriction type: OTHER