Trial Outcomes & Findings for Single-Arm Study To Evaluate The Efficacy and Safety of Valoctocogene Roxaparvovec in Hemophilia A Patients (BMN 270-301) (NCT NCT03370913)
NCT ID: NCT03370913
Last Updated: 2025-03-25
Results Overview
All bleeds comprises both treated and non-treated bleeds. In this definition, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. All bleeds are any reported bleeding events regardless of the use of FVIII or other treatments. ABR for all bleeds= Number of bleeding episodes for all bleeds during the calculation period / total number of days during the calculation period \* 365.25. Baseline: prior to BMN 270 infusion while receiving FVIII prophylaxis. EEP: From Week 5 post-BMN 270 infusion (Study Day 33) or the end of FVIII prophylaxis plus the washout period (3 days for products of standard half-life or plasma-derived and 5 days for products of extended half-life), whichever is later, to last visit by the data cut-off for the 2-year analysis, hereafter referred to as "Post FVIII Prophylaxis to Last Visit").
COMPLETED
PHASE3
144 participants
Baseline to efficacy evaluation period (EEP)
2025-03-25
Participant Flow
This study was conducted at 48 sites worldwide (United States, Australia, Belgium, Brazil, France, Germany, Israel, Italy, South Korea, South Africa, Spain, Taiwan, and United Kingdom).
Total of 181 subjects were screened. Of these, 41 subjects were screened without prior participation in 270-902,140 subjects were screened after participating in 270-902. 37 subjects failed screening. Of the remaining 144 enrolled subjects in 270-301,134 were treated with BMN 270. 10 subjects enrolled but were not dosed \[5 subjects who did not previously participate in 270-902(direct enrolled population and 5 subjects dosed in 270-301 who previously participated in 270-902(Rollover population)\].
Participant milestones
| Measure |
BMN 270 (Valoctocogene Roxaparvovec)
Single administration of valoctocogene roxaparvovec at a dose of 6E13 vg/kg
valoctocogene roxaparvovec: Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A subjects
|
|---|---|
|
Overall Study
STARTED
|
134
|
|
Overall Study
COMPLETED
|
132
|
|
Overall Study
NOT COMPLETED
|
2
|
Reasons for withdrawal
| Measure |
BMN 270 (Valoctocogene Roxaparvovec)
Single administration of valoctocogene roxaparvovec at a dose of 6E13 vg/kg
valoctocogene roxaparvovec: Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A subjects
|
|---|---|
|
Overall Study
Death
|
1
|
|
Overall Study
Lost to Follow-up
|
1
|
Baseline Characteristics
Single-Arm Study To Evaluate The Efficacy and Safety of Valoctocogene Roxaparvovec in Hemophilia A Patients (BMN 270-301)
Baseline characteristics by cohort
| Measure |
BMN 270 (Valoctocogene Roxaparvovec)
n=134 Participants
Single administration of valoctocogene roxaparvovec at a dose of 6E13 vg/kg
valoctocogene roxaparvovec: Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A subjects
|
|---|---|
|
Age, Continuous
|
31.7 years
STANDARD_DEVIATION 10.3 • n=99 Participants
|
|
Age, Customized
18 to < 30 years
|
65 Participants
n=99 Participants
|
|
Age, Customized
30 to < 50 years
|
56 Participants
n=99 Participants
|
|
Age, Customized
>= 50 years
|
13 Participants
n=99 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
134 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
7 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
127 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
Asian
|
19 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
Black or African-American
|
15 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian or other Pacific Islander
|
1 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
White
|
96 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
Not provided due to patient privacy
|
3 Participants
n=99 Participants
|
|
Baseline annualized FVIII usage
|
4113.69 IU/kg/year
STANDARD_DEVIATION 1738.92 • n=99 Participants
|
|
Baseline annualized number of FVIII infusions
|
137.55 Infusions/year
STANDARD_DEVIATION 57.04 • n=99 Participants
|
|
Baseline ABR (all bleeds)
|
5.97 bleeds/year
STANDARD_DEVIATION 11.06 • n=99 Participants
|
|
Baseline ABR (all bleeds)
0 bleeds/year
|
41 Participants
n=99 Participants
|
|
Baseline ABR (all bleeds)
> 0 to 4
|
40 Participants
n=99 Participants
|
|
Baseline ABR (all bleeds)
> 4 to 10
|
31 Participants
n=99 Participants
|
|
Baseline ABR (all bleeds)
> 10
|
22 Participants
n=99 Participants
|
|
Baseline ABR (treated bleeds)
|
5.42 bleeds/year
STANDARD_DEVIATION 9.96 • n=99 Participants
|
|
Baseline ABR (treated bleeds)
0 bleeds/year
|
43 Participants
n=99 Participants
|
|
Baseline ABR (treated bleeds)
> 0 to 4
|
42 Participants
n=99 Participants
|
|
Baseline ABR (treated bleeds)
> 4 to 10
|
29 Participants
n=99 Participants
|
|
Baseline ABR (treated bleeds)
> 10
|
20 Participants
n=99 Participants
|
|
History of previous diseases
Hepatitis B
|
20 Participants
n=99 Participants
|
|
History of previous diseases
Hepatitis C
|
41 Participants
n=99 Participants
|
|
History of previous diseases
HIV
|
2 Participants
n=99 Participants
|
|
Number of target joints
0
|
97 Participants
n=99 Participants
|
|
Number of target joints
1
|
17 Participants
n=99 Participants
|
|
Number of target joints
2
|
9 Participants
n=99 Participants
|
|
Number of target joints
3
|
8 Participants
n=99 Participants
|
|
Number of target joints
> 3
|
3 Participants
n=99 Participants
|
PRIMARY outcome
Timeframe: Baseline to efficacy evaluation period (EEP)Population: Rollover Population (n=112): Subjects who completed approximately 6 months participation in the non-interventional study 270-902 before enrolling in 270-301, were HIV-negative at study screening, and received BMN 270 infusion in 270-301.
All bleeds comprises both treated and non-treated bleeds. In this definition, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. All bleeds are any reported bleeding events regardless of the use of FVIII or other treatments. ABR for all bleeds= Number of bleeding episodes for all bleeds during the calculation period / total number of days during the calculation period \* 365.25. Baseline: prior to BMN 270 infusion while receiving FVIII prophylaxis. EEP: From Week 5 post-BMN 270 infusion (Study Day 33) or the end of FVIII prophylaxis plus the washout period (3 days for products of standard half-life or plasma-derived and 5 days for products of extended half-life), whichever is later, to last visit by the data cut-off for the 2-year analysis, hereafter referred to as "Post FVIII Prophylaxis to Last Visit").
Outcome measures
| Measure |
BMN 270 (Valoctocogene Roxaparvovec)
n=112 Participants
Single administration of valoctocogene roxaparvovec at a dose of 6E13 vg/kg
valoctocogene roxaparvovec: Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A subjects
|
|---|---|
|
Change From Baseline in Annualized Number of Bleeding Episodes Irrespective of Exogenous FVIII Replacement Treatment [Annualized Bleeding Rate (ABR) for All Bleeds] in EEP.
|
-4.13 bleeds/year
Standard Deviation 6.93
|
SECONDARY outcome
Timeframe: Baseline to EEPPopulation: Rollover Population
ABR for treated bleeds=Number of bleeding episodes for treated bleeds during the calculation period/total number of days during the calculation period \* 365.25 Bleeds that were treated with FVIII replacement therapy (recorded as "treatment for bleed") within 72 hours and were not associated with surgery or a procedure were included. Baseline: prior to BMN 270 infusion while receiving FVIII prophylaxis. EEP: From Week 5 post-BMN 270 infusion (Study Day 33) or the end of FVIII prophylaxis plus the washout period (3 days for products of standard half-life or plasma-derived and 5 days for products of extended half-life), whichever is later, to last visit by the data cut-off for the 2-year analysis, hereafter referred to as "Post FVIII Prophylaxis to Last Visit").
Outcome measures
| Measure |
BMN 270 (Valoctocogene Roxaparvovec)
n=112 Participants
Single administration of valoctocogene roxaparvovec at a dose of 6E13 vg/kg
valoctocogene roxaparvovec: Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A subjects
|
|---|---|
|
Change From Baseline in the Annualized Number of Bleeding Episodes Requiring Exogenous FVIII Replacement Therapy (ABR for Treated Bleeds) in the EEP.
|
-4.08 bleeds/year
Standard Deviation 6.57
|
SECONDARY outcome
Timeframe: Baseline to Week 104Population: Modified Intent-to-Treat (mITT) Population (n=132): All HIV-negative subjects at study screening who were dosed in 270-301.
The change from baseline (assuming no treatment for severe hemophilia A) in FVIII activity, as measured by chromogenic substrate assay, at Weeks 104 post-BMN 270 infusion. Each subject's FVIII activity level at Week 104 is defined as the median of the values obtained at Week 104 with the analysis window defined. The baseline value is imputed as 1 IU/dL for each subject. Note: One of the subject's wk104 duplicate data issue was corrected in the 3 year analysis per which the mean (standard deviation) values are reported in outcome measure table. Baseline: prior to BMN 270 infusion while receiving FVIII prophylaxis.
Outcome measures
| Measure |
BMN 270 (Valoctocogene Roxaparvovec)
n=132 Participants
Single administration of valoctocogene roxaparvovec at a dose of 6E13 vg/kg
valoctocogene roxaparvovec: Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A subjects
|
|---|---|
|
Change From Baseline in FVIII Activity at Week 104
|
21.94 IU/dL
Standard Deviation 33.04
|
SECONDARY outcome
Timeframe: Baseline to EEPPopulation: Rollover population
The change from baseline in the annualized utilization (IU/kg/year) of exogenous FVIII replacement therapy in the Post FVIII Prophylaxis to Last Visit in the EEP. The annualized utilization (IU/kg/year) of exogenous FVIII replacement therapy is defined as Sum of FVIII use (IU/kg) during calculation period/Total number of days during the calculation period ×365.25. Baseline: prior to BMN 270 infusion while receiving FVIII prophylaxis. EEP: From Week 5 post-BMN 270 infusion (Study Day 33) or the end of FVIII prophylaxis plus the washout period (3 days for products of standard half-life or plasma-derived and 5 days for products of extended half-life), whichever is later, to last visit by the data cut-off for the 2-year analysis, hereafter referred to as "Post FVIII Prophylaxis to Last Visit").
Outcome measures
| Measure |
BMN 270 (Valoctocogene Roxaparvovec)
n=112 Participants
Single administration of valoctocogene roxaparvovec at a dose of 6E13 vg/kg
valoctocogene roxaparvovec: Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A subjects
|
|---|---|
|
Change From Baseline in Annualized FVIII Utilization in EEP.
|
-3891.27 IU/kg/yr
Standard Deviation 1761.16
|
SECONDARY outcome
Timeframe: Baseline to Week 104Population: mITT Population: Modified Intent-to-Treat Population - all HIV-negative subjects dosed in 270-301. Change from baseline was based on the subjects with available measurements at both time points.
The change from baseline(assuming no treatment for severe hemophilia A) in Haemo-Qol-A score, at wk104 post-BMN 270 infusion.The Haemo-Qol-A questionnaire is a fit for purpose hemophilia-specific health related quality of life(HRQoL)questionnaire for adults consisting of 41 items covering 6 domains(Physical Functioning,Role Functioning,Worry,Consequences of Bleeding,Emotional Impact \&Treatment Concerns). The Haemo-Qol-A items are answered on a 6-point Likert scale ranging from 0(none of the time)to 5 (all of the time).The recall period for the Haemo-Qol-A is one month (4-weeks). The Haemo-QoL-A domain(physical functioning, role functioning, worry, consequences of bleeding, emotional impact, treatment concern) scores range from 0 to 5 and the total score is derived by summing each domain score (range, 0 to 30). Domain and total scores are transformed to a 0 (minimum) to 100 (maximum) scale with higher scores indicating a better or less impaired haemophilia related quality of life.
Outcome measures
| Measure |
BMN 270 (Valoctocogene Roxaparvovec)
n=126 Participants
Single administration of valoctocogene roxaparvovec at a dose of 6E13 vg/kg
valoctocogene roxaparvovec: Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A subjects
|
|---|---|
|
Change From Baseline in Haemo-QoL-A Quality of Life: Total Score at Week 104
|
7.01 score on a scale
Standard Deviation 12.55
|
SECONDARY outcome
Timeframe: Baseline to Week 104Population: mITT population Change from baseline was based on the subjects with available measurements at both time points.
The change from baseline (assuming no treatment for severe hemophilia A) in Haemo-Qol-A score, at week 104 post-BMN 270 infusion. The Haemo-Qol-A questionnaire is a fit for purpose hemophilia-specific health related quality of life (HRQoL) questionnaire for adults consisting of 41 items covering six domains (Physical Functioning, Role Functioning, Worry, Consequences of Bleeding, Emotional Impact and Treatment Concerns).The Haemo-Qol-A items are answered on a 6-point Likert scale ranging from 0 (none of the time) to 5 (all of the time).The recall period for the Haemo-Qol-A is one month (4-weeks). The Haemo-Qol-A physical functioning domain score is an average of each item value within a domain.The range of domain scores is 0 to 5; higher scores mean better HRQoL or less impairment for the domain. The physical functioning domain score is transformed to a 0 (minimum) to 100 (maximum) scale with higher scores indicating a better or less impaired haemophilia-related physical functioning
Outcome measures
| Measure |
BMN 270 (Valoctocogene Roxaparvovec)
n=129 Participants
Single administration of valoctocogene roxaparvovec at a dose of 6E13 vg/kg
valoctocogene roxaparvovec: Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A subjects
|
|---|---|
|
Change From Baseline in Haemo-QoL-A Quality of Life: Physical Functioning Domain Score, at Week 104
|
4.90 score on a scale
Standard Deviation 13.78
|
SECONDARY outcome
Timeframe: Baseline to Week 104Population: mITT population. Change from baseline was based on the subjects with available measurements at both time points.
The change from baseline(assuming no treatment for severe hemophilia A)in Haemo-Qol-A score, at week 104 post-BMN 270 infusion. The Haemo-Qol-A questionnaire is a fit for purpose hemophilia-specific health related quality of life(HRQoL)questionnaire for adults consisting of 41 items covering 6 domains(Physical Functioning,Role Functioning,Worry,Consequences of Bleeding,Emotional Impact and Treatment Concerns). The Haemo-Qol-A items are answered on a 6-point Likert scale ranging from 0(none of the time) to 5(all of the time). The recall period for the Haemo-Qol-A is one month (4-wks). The Haemo-Qol-A consequences of bleeding domain score is an average of each item value within a domain. The range of domain scores is 0 to 5; higher scores mean better HRQoL or less impairment for the domain. The consequences of bleeding domain score is transformed to a 0 (minimum) to 100 (maximum) scale with higher scores indicating a better or less impaired haemophilia-related consequences of bleeding
Outcome measures
| Measure |
BMN 270 (Valoctocogene Roxaparvovec)
n=129 Participants
Single administration of valoctocogene roxaparvovec at a dose of 6E13 vg/kg
valoctocogene roxaparvovec: Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A subjects
|
|---|---|
|
Change From Baseline in Haemo-QoL-A Quality of Life: Consequences of Bleeding Domain Score, at Week 104
|
10.29 score on a scale
Standard Deviation 17.65
|
SECONDARY outcome
Timeframe: Baseline to Week 104Population: mITT population Change from baseline was based on the subjects with available measurements at both time points.
The change from baseline (assuming no treatment for severe hemophilia A) in Haemo-Qol-A score, at week 104 post-BMN 270 infusion. The Haemo-Qol-A questionnaire is a fit for purpose hemophilia-specific health related quality of life (HRQoL) questionnaire for adults consisting of 41 items covering six domains (Physical Functioning, Role Functioning, Worry, Consequences of Bleeding, Emotional Impact and Treatment Concerns).The Haemo-Qol-A items are answered on a 6-point Likert scale ranging from 0 (none of the time) to 5 (all of the time). The recall period for the Haemo-Qol-A is one month (4-weeks). The Haemo-Qol-A role functioning domain score is an average of each item value within a domain. The range of domain scores is 0 to 5; higher scores mean better HRQoL or less impairment for the domain. The role functioning domain score is transformed to a 0 (minimum) to 100 (maximum) scale with higher scores indicating a better or less impaired haemophilia-related role functioning.
Outcome measures
| Measure |
BMN 270 (Valoctocogene Roxaparvovec)
n=128 Participants
Single administration of valoctocogene roxaparvovec at a dose of 6E13 vg/kg
valoctocogene roxaparvovec: Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A subjects
|
|---|---|
|
Change From Baseline in Haemo-QoL-A Quality of Life: Role Functioning Domain Score, at Week 104
|
7.37 Score on a scale
Standard Deviation 15.17
|
Adverse Events
BMN 270 (Valoctocogene Roxaparvovec)
Serious adverse events
| Measure |
BMN 270 (Valoctocogene Roxaparvovec)
n=134 participants at risk
Single administration of valoctocogene roxaparvovec at a dose of 6E13 vg/kg
valoctocogene roxaparvovec: Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A subjects
|
|---|---|
|
Investigations
Alanine aminotransferase increased
|
1.5%
2/134 • Number of events 2 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Immune system disorders
Anaphylactic reaction
|
1.5%
2/134 • Number of events 2 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Gastrointestinal disorders
Diarrhea
|
1.5%
2/134 • Number of events 2 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Infections and infestations
Gastroenteritis
|
1.5%
2/134 • Number of events 2 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Gastrointestinal disorders
Rectal hemorrhage
|
1.5%
2/134 • Number of events 2 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Injury, poisoning and procedural complications
Acetabulum fracture
|
0.75%
1/134 • Number of events 1 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Respiratory, thoracic and mediastinal disorders
Apnea
|
0.75%
1/134 • Number of events 1 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Musculoskeletal and connective tissue disorders
Arthropathy
|
0.75%
1/134 • Number of events 1 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Eye disorders
Cataract
|
0.75%
1/134 • Number of events 2 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Psychiatric disorders
Completed suicide
|
0.75%
1/134 • Number of events 1 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Cardiac disorders
Coronary artery disease
|
0.75%
1/134 • Number of events 1 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Psychiatric disorders
Depression
|
0.75%
1/134 • Number of events 2 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
0.75%
1/134 • Number of events 1 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Gastrointestinal disorders
Diverticulum
|
0.75%
1/134 • Number of events 1 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Gastrointestinal disorders
Hemoperitoneum
|
0.75%
1/134 • Number of events 1 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Injury, poisoning and procedural complications
Hand fracture
|
0.75%
1/134 • Number of events 1 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Immune system disorders
Hypersensitivity
|
0.75%
1/134 • Number of events 1 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Vascular disorders
Hypertension
|
0.75%
1/134 • Number of events 1 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Infections and infestations
Infection
|
0.75%
1/134 • Number of events 1 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Infections and infestations
Influenza
|
0.75%
1/134 • Number of events 1 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Investigations
Influenza A virus test positive
|
0.75%
1/134 • Number of events 1 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Injury, poisoning and procedural complications
Lower limb fracture
|
0.75%
1/134 • Number of events 1 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Eye disorders
Macular hole
|
0.75%
1/134 • Number of events 1 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Psychiatric disorders
Major depression
|
0.75%
1/134 • Number of events 1 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Renal and urinary disorders
Nephrolithiasis
|
0.75%
1/134 • Number of events 1 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
General disorders
Non-cardiac chest pain
|
0.75%
1/134 • Number of events 1 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
General disorders
Pain
|
0.75%
1/134 • Number of events 1 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
General disorders
Peripheral swelling
|
0.75%
1/134 • Number of events 1 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Injury, poisoning and procedural complications
Periprosthetic fracture
|
0.75%
1/134 • Number of events 1 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Infections and infestations
Pneumonia
|
0.75%
1/134 • Number of events 1 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Infections and infestations
Pneumonia cytomegaloviral
|
0.75%
1/134 • Number of events 1 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Injury, poisoning and procedural complications
Post-procedural hemorrhage
|
0.75%
1/134 • Number of events 1 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Nervous system disorders
Presyncope
|
0.75%
1/134 • Number of events 1 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Skin and subcutaneous tissue disorders
Rash maculopapular
|
0.75%
1/134 • Number of events 1 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Eye disorders
Retinal detachment
|
0.75%
1/134 • Number of events 1 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Injury, poisoning and procedural complications
Skin laceration
|
0.75%
1/134 • Number of events 2 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Metabolism and nutrition disorders
Steroid diabetes
|
0.75%
1/134 • Number of events 1 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Injury, poisoning and procedural complications
Traumatic hematoma
|
0.75%
1/134 • Number of events 1 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Infections and infestations
Upper respiratory tract infection
|
0.75%
1/134 • Number of events 1 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
Other adverse events
| Measure |
BMN 270 (Valoctocogene Roxaparvovec)
n=134 participants at risk
Single administration of valoctocogene roxaparvovec at a dose of 6E13 vg/kg
valoctocogene roxaparvovec: Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A subjects
|
|---|---|
|
Investigations
Alanine aminotransferase increased
|
88.8%
119/134 • Number of events 385 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Investigations
Aspartate aminotransferase increased
|
35.1%
47/134 • Number of events 104 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Investigations
Weight increased
|
16.4%
22/134 • Number of events 36 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Investigations
Blood creatine phosphokinase increased
|
12.7%
17/134 • Number of events 22 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Investigations
Blood lactate dehydrogenase increased
|
6.7%
9/134 • Number of events 14 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Infections and infestations
Upper respiratory tract infection
|
24.6%
33/134 • Number of events 45 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Infections and infestations
Nasopharyngitis
|
21.6%
29/134 • Number of events 52 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Infections and infestations
Rhinitis
|
9.0%
12/134 • Number of events 16 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Infections and infestations
Folliculitis
|
8.2%
11/134 • Number of events 13 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Infections and infestations
Rash pustular
|
8.2%
11/134 • Number of events 12 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Infections and infestations
Gastroenteritis
|
5.2%
7/134 • Number of events 8 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Infections and infestations
Influenza
|
5.2%
7/134 • Number of events 7 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Infections and infestations
Viral infection
|
5.2%
7/134 • Number of events 7 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
39.6%
53/134 • Number of events 105 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
18.7%
25/134 • Number of events 32 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
12.7%
17/134 • Number of events 18 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
11.9%
16/134 • Number of events 19 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Musculoskeletal and connective tissue disorders
Arthropathy
|
6.0%
8/134 • Number of events 8 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
6.0%
8/134 • Number of events 8 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Gastrointestinal disorders
Nausea
|
38.1%
51/134 • Number of events 79 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Gastrointestinal disorders
Diarrhoea
|
20.9%
28/134 • Number of events 43 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Gastrointestinal disorders
Vomiting
|
15.7%
21/134 • Number of events 27 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Gastrointestinal disorders
Dyspepsia
|
8.2%
11/134 • Number of events 13 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Gastrointestinal disorders
Abdominal discomfort
|
7.5%
10/134 • Number of events 10 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
7.5%
10/134 • Number of events 15 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Gastrointestinal disorders
Constipation
|
6.7%
9/134 • Number of events 12 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
6.0%
8/134 • Number of events 9 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
General disorders
Fatigue
|
29.9%
40/134 • Number of events 53 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
General disorders
Pyrexia
|
23.1%
31/134 • Number of events 35 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
General disorders
Pain
|
7.5%
10/134 • Number of events 11 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
General disorders
Chills
|
6.7%
9/134 • Number of events 9 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
General disorders
Influenza like illness
|
5.2%
7/134 • Number of events 8 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
General disorders
Malaise
|
5.2%
7/134 • Number of events 8 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Skin and subcutaneous tissue disorders
Acne
|
26.9%
36/134 • Number of events 45 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Skin and subcutaneous tissue disorders
Rash
|
8.2%
11/134 • Number of events 11 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Nervous system disorders
Headache
|
41.0%
55/134 • Number of events 174 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Nervous system disorders
Dizziness
|
6.7%
9/134 • Number of events 14 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Nervous system disorders
Lethargy
|
6.0%
8/134 • Number of events 9 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Nervous system disorders
Migraine
|
5.2%
7/134 • Number of events 8 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Nervous system disorders
Tremor
|
5.2%
7/134 • Number of events 7 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
17.9%
24/134 • Number of events 33 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
17.9%
24/134 • Number of events 28 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
6.7%
9/134 • Number of events 10 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
6.0%
8/134 • Number of events 8 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Injury, poisoning and procedural complications
Muscle strain
|
9.7%
13/134 • Number of events 19 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Injury, poisoning and procedural complications
Limb injury
|
6.7%
9/134 • Number of events 10 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Injury, poisoning and procedural complications
Contusion
|
6.0%
8/134 • Number of events 11 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Injury, poisoning and procedural complications
Ligament sprain
|
6.0%
8/134 • Number of events 8 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Injury, poisoning and procedural complications
Fall
|
5.2%
7/134 • Number of events 9 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Psychiatric disorders
Insomnia
|
20.1%
27/134 • Number of events 46 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Psychiatric disorders
Anxiety
|
8.2%
11/134 • Number of events 12 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Psychiatric disorders
Irritability
|
5.2%
7/134 • Number of events 8 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Endocrine disorders
Cushingoid
|
11.9%
16/134 • Number of events 16 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Vascular disorders
Hypertension
|
11.9%
16/134 • Number of events 20 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
|
Blood and lymphatic system disorders
Iron deficiency anaemia
|
6.0%
8/134 • Number of events 8 • Up to data cutoff date 15 November 2021 (Two year data analysis).
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study.
|
Additional Information
Tara Robinson, MD, PhD, Senior Medical Director, Clinical Sciences
BioMarin Pharmaceutical Inc.
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60