Trial Outcomes & Findings for Efficacy and Safety of Burosumab Versus Oral Phosphate and Active Vitamin D Treatment in Pediatric Patients With XLH (NCT NCT02915705)
NCT ID: NCT02915705
Last Updated: 2024-08-29
Results Overview
Changes in the severity of rickets and bowing were assessed using a disease specific qualitative RGI-C scoring system. The RGI-C is a 7-point ordinal scale with possible values: +3 = very much better (complete or near complete healing of rickets), +2 = much better (substantial healing of rickets), +1 = minimally better (i.e., minimal healing of rickets), 0 = unchanged, -1 = minimally worse (minimal worsening of rickets), -2 = much worse (moderate worsening of rickets), -3 = very much worse (severe worsening of rickets).
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
61 participants
Primary outcome timeframe
Week 40
Results posted on
2024-08-29
Participant Flow
Eligible participants discontinued oral phosphate and active vitamin D therapy for 7 days prior to randomization. Participants were then randomized 1:1 to receive either open label burosumab administered by subcutaneous (SC) injection every 2 weeks (Q2W) or phosphate and active vitamin D therapy administered orally daily for a total of 64 weeks.
Participant milestones
| Measure |
Active Control
Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
Burosumab
Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants continued to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
|---|---|---|
|
Treatment Period
STARTED
|
32
|
29
|
|
Treatment Period
Completed Week 40
|
32
|
29
|
|
Treatment Period
Completed Week 64
|
32
|
29
|
|
Treatment Period
COMPLETED
|
32
|
29
|
|
Treatment Period
NOT COMPLETED
|
0
|
0
|
|
Long Term Extension Period
STARTED
|
26
|
25
|
|
Long Term Extension Period
COMPLETED
|
26
|
25
|
|
Long Term Extension Period
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
1 participant in the burosumab group did not have a baseline measurement
Baseline characteristics by cohort
| Measure |
Active Control
n=32 Participants
Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
Burosumab
n=29 Participants
Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants continued to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
Total
n=61 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
6.50 years
STANDARD_DEVIATION 3.250 • n=32 Participants
|
6.01 years
STANDARD_DEVIATION 3.408 • n=29 Participants
|
6.27 years
STANDARD_DEVIATION 3.307 • n=61 Participants
|
|
Sex: Female, Male
Female
|
18 Participants
n=32 Participants
|
16 Participants
n=29 Participants
|
34 Participants
n=61 Participants
|
|
Sex: Female, Male
Male
|
14 Participants
n=32 Participants
|
13 Participants
n=29 Participants
|
27 Participants
n=61 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
3 Participants
n=32 Participants
|
3 Participants
n=29 Participants
|
6 Participants
n=61 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
29 Participants
n=32 Participants
|
26 Participants
n=29 Participants
|
55 Participants
n=61 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=32 Participants
|
0 Participants
n=29 Participants
|
0 Participants
n=61 Participants
|
|
Race/Ethnicity, Customized
Asian
|
6 Participants
n=32 Participants
|
2 Participants
n=29 Participants
|
8 Participants
n=61 Participants
|
|
Race/Ethnicity, Customized
White
|
25 Participants
n=32 Participants
|
25 Participants
n=29 Participants
|
50 Participants
n=61 Participants
|
|
Race/Ethnicity, Customized
Other (Not Specified)
|
1 Participants
n=32 Participants
|
2 Participants
n=29 Participants
|
3 Participants
n=61 Participants
|
|
Rickets Severity Score (RSS) Total Score
|
3.19 score on a scale
STANDARD_DEVIATION 1.141 • n=32 Participants
|
3.17 score on a scale
STANDARD_DEVIATION 0.975 • n=29 Participants
|
3.18 score on a scale
STANDARD_DEVIATION 1.057 • n=61 Participants
|
|
Height-For-Age Z-Score
|
-2.05 Z score
STANDARD_DEVIATION 0.868 • n=32 Participants • 1 participant in the burosumab group did not have a baseline measurement
|
-2.32 Z score
STANDARD_DEVIATION 1.167 • n=28 Participants • 1 participant in the burosumab group did not have a baseline measurement
|
-2.17 Z score
STANDARD_DEVIATION 1.018 • n=60 Participants • 1 participant in the burosumab group did not have a baseline measurement
|
|
Growth Velocity Z Score From Pre-Treatment
|
-2.14 Z score
STANDARD_DEVIATION 5.571 • n=22 Participants • participants with a baseline measurement
|
-1.37 Z score
STANDARD_DEVIATION 1.334 • n=22 Participants • participants with a baseline measurement
|
-1.75 Z score
STANDARD_DEVIATION 4.022 • n=44 Participants • participants with a baseline measurement
|
|
Serum Phosphorus
|
2.30 mg/dL
STANDARD_DEVIATION 0.257 • n=32 Participants
|
2.42 mg/dL
STANDARD_DEVIATION 0.244 • n=29 Participants
|
2.36 mg/dL
STANDARD_DEVIATION 0.256 • n=61 Participants
|
|
Serum 1,25(OH)D
|
40.18 pg/mL
STANDARD_DEVIATION 14.886 • n=30 Participants • participants with a baseline measurement
|
46.00 pg/mL
STANDARD_DEVIATION 20.060 • n=28 Participants • participants with a baseline measurement
|
42.99 pg/mL
STANDARD_DEVIATION 17.663 • n=58 Participants • participants with a baseline measurement
|
|
Ratio of Renal Tubular Maximum Reabsorption Rate of Phosphate to Glomerular Filtration Rate(TmP/GFR)
|
2.008 mg/dL
STANDARD_DEVIATION 0.3300 • n=30 Participants • participants with a baseline measurement
|
2.193 mg/dL
STANDARD_DEVIATION 0.3733 • n=24 Participants • participants with a baseline measurement
|
2.091 mg/dL
STANDARD_DEVIATION 0.3587 • n=54 Participants • participants with a baseline measurement
|
|
Serum Alkaline Phosphatase (ALP) Concentration
|
523.44 U/L
STANDARD_DEVIATION 154.419 • n=32 Participants
|
510.76 U/L
STANDARD_DEVIATION 124.903 • n=29 Participants
|
517.4 U/L
STANDARD_DEVIATION 140.15 • n=61 Participants
|
|
Patient-Reported Outcomes Measurement Information System (PROMIS) Pediatric Pain Interference Domain
|
49.9 T-score
STANDARD_DEVIATION 12.05 • n=20 Participants • participants with a baseline assessment
|
53.1 T-score
STANDARD_DEVIATION 10.95 • n=15 Participants • participants with a baseline assessment
|
51.3 T-score
STANDARD_DEVIATION 11.54 • n=35 Participants • participants with a baseline assessment
|
|
PROMIS Physical Function Mobility Domain
|
45.5 T-score
STANDARD_DEVIATION 9.86 • n=20 Participants • participants with a baseline assessment
|
45.2 T-score
STANDARD_DEVIATION 9.05 • n=15 Participants • participants with a baseline assessment
|
45.3 T-score
STANDARD_DEVIATION 9.39 • n=35 Participants • participants with a baseline assessment
|
|
PROMIS Fatigue Domain
|
47.0 T-score
STANDARD_DEVIATION 13.70 • n=20 Participants • participants with a baseline assessment
|
48.8 T-score
STANDARD_DEVIATION 9.60 • n=15 Participants • participants with a baseline assessment
|
47.8 T-score
STANDARD_DEVIATION 11.98 • n=35 Participants • participants with a baseline assessment
|
|
Faces Pain Scale-Revised (FPS-R)
|
0.7 score on a scale
STANDARD_DEVIATION 1.17 • n=20 Participants • participants with a baseline assessment
|
0.4 score on a scale
STANDARD_DEVIATION 1.12 • n=15 Participants • participants with a baseline assessment
|
0.6 score on a scale
STANDARD_DEVIATION 1.14 • n=35 Participants • participants with a baseline assessment
|
|
Six Minute Walk Test (6MWT) Total Distance
|
450.50 meters
STANDARD_DEVIATION 106.432 • n=20 Participants • participants with a baseline measurement
|
365.93 meters
STANDARD_DEVIATION 118.083 • n=15 Participants • participants with a baseline measurement
|
414.26 meters
STANDARD_DEVIATION 117.790 • n=35 Participants • participants with a baseline measurement
|
|
Percent of Predicted Normal in the 6MWT Total Distance
|
76.20 perecent of predicted meters
STANDARD_DEVIATION 14.838 • n=20 Participants • participants with a baseline measurement
|
62.13 perecent of predicted meters
STANDARD_DEVIATION 18.629 • n=15 Participants • participants with a baseline measurement
|
70.17 perecent of predicted meters
STANDARD_DEVIATION 17.771 • n=35 Participants • participants with a baseline measurement
|
PRIMARY outcome
Timeframe: Week 40Population: Full Analysis Set: all randomized participants who received at least one dose of assigned medication and had at least one post-baseline assessment.
Changes in the severity of rickets and bowing were assessed using a disease specific qualitative RGI-C scoring system. The RGI-C is a 7-point ordinal scale with possible values: +3 = very much better (complete or near complete healing of rickets), +2 = much better (substantial healing of rickets), +1 = minimally better (i.e., minimal healing of rickets), 0 = unchanged, -1 = minimally worse (minimal worsening of rickets), -2 = much worse (moderate worsening of rickets), -3 = very much worse (severe worsening of rickets).
Outcome measures
| Measure |
Active Control
n=32 Participants
Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
Burosumab
n=29 Participants
Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants continued to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
|---|---|---|
|
Radiographic Global Impression of Change (RGI-C) Global Score at Week 40
|
0.77 score on a scale
Standard Error 0.107
|
1.92 score on a scale
Standard Error 0.110
|
SECONDARY outcome
Timeframe: Week 40Population: Full Analysis Set: all randomized participants who received at least one dose of assigned medication and had at least one post-baseline assessment.
RGI-C responders are defined as participants with a mean RGI-C global score \>= +2.0. The RGI-C is a 7-point ordinal scale with possible values: +3 = very much better (complete or near complete healing of rickets), +2 = much better (substantial healing of rickets), +1 = minimally better (i.e., minimal healing of rickets), 0 = unchanged, -1 = minimally worse (minimal worsening of rickets), -2 = much worse (moderate worsening of rickets), -3 = very much worse (severe worsening of rickets).
Outcome measures
| Measure |
Active Control
n=32 Participants
Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
Burosumab
n=29 Participants
Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants continued to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
|---|---|---|
|
Percentage of Participants With a Mean RGI-C Global Score ≥ +2.0 (Responders) at Week 40
|
6.3 percentage of participants
|
72.4 percentage of participants
|
SECONDARY outcome
Timeframe: Week 64Population: Full Analysis Set: all randomized participants who received at least one dose of assigned medication and had at least one post-baseline assessment.
RGI-C responders are defined as participants with a mean RGI-C global score \>= +2.0. The RGI-C is a 7-point ordinal scale with possible values: +3 = very much better (complete or near complete healing of rickets), +2 = much better (substantial healing of rickets), +1 = minimally better (i.e., minimal healing of rickets), 0 = unchanged, -1 = minimally worse (minimal worsening of rickets), -2 = much worse (moderate worsening of rickets), -3 = very much worse (severe worsening of rickets).
Outcome measures
| Measure |
Active Control
n=32 Participants
Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
Burosumab
n=29 Participants
Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants continued to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
|---|---|---|
|
Percentage of Participants With a Mean RGI-C Global Score ≥ +2.0 (Responders) at Week 64
|
18.8 percentage of participants
|
86.2 percentage of participants
|
SECONDARY outcome
Timeframe: Week 64Population: Full Analysis Set: all randomized participants who received at least one dose of assigned medication and had at least one post-baseline assessment.
Changes in the severity of rickets and bowing were assessed using a disease specific qualitative RGI-C scoring system. The RGI-C is a 7-point ordinal scale with possible values: +3 = very much better (complete or near complete healing of rickets), +2 = much better (substantial healing of rickets), +1 = minimally better (i.e., minimal healing of rickets), 0 = unchanged, -1 = minimally worse (minimal worsening of rickets), -2 = much worse (moderate worsening of rickets), -3 = very much worse (severe worsening of rickets).
Outcome measures
| Measure |
Active Control
n=32 Participants
Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
Burosumab
n=29 Participants
Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants continued to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
|---|---|---|
|
RGI-C Global Score at Week 64
|
1.03 score on a scale
Standard Error 0.136
|
2.06 score on a scale
Standard Error 0.072
|
SECONDARY outcome
Timeframe: Baseline, Week 40Population: Full Analysis Set: all randomized participants who received at least one dose of assigned medication and had at least one post-baseline RSS Total Score assessment.
The RSS system is a 10-point radiographic scoring method that was developed to assess the severity of nutritional rickets in the wrists and knees based on the degree of metaphyseal fraying, cupping, lucency, separation, and the proportion of the growth plate affected. Scores are assigned for the unilateral wrist and knee X-rays deemed by the rater to be the more severe of the bilateral images. The maximum total score on the RSS is 10 points and the minimum score is 0, with a total possible score of 4 points for the wrists and 6 points for the knees (the total score is the sum of the wrist and knee score). Higher scores indicate greater rickets severity.
Outcome measures
| Measure |
Active Control
n=32 Participants
Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
Burosumab
n=28 Participants
Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants continued to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
|---|---|---|
|
Change From Baseline in RSS Total Score at Week 40
|
-0.71 score on a scale
Standard Error 0.138
|
-2.04 score on a scale
Standard Error 0.145
|
SECONDARY outcome
Timeframe: Baseline, Week 64Population: Full Analysis Set: all randomized participants who received at least one dose of assigned medication and had at least one post-baseline RSS Total Score assessment.
The RSS system is a 10-point radiographic scoring method that was developed to assess the severity of nutritional rickets in the wrists and knees based on the degree of metaphyseal fraying, cupping, and the proportion of the growth plate affected. Scores are assigned for the unilateral wrist and knee X-rays deemed by the rater to be the more severe of the bilateral images. The maximum total score on the RSS is 10 points and the minimum score is 0, with a total possible score of 4 points for the wrists and 6 points for the knees. Higher scores indicate greater rickets severity.
Outcome measures
| Measure |
Active Control
n=32 Participants
Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
Burosumab
n=29 Participants
Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants continued to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
|---|---|---|
|
Change From Baseline in RSS Total Score at Week 64
|
-1.01 score on a scale
Standard Error 0.151
|
-2.23 score on a scale
Standard Error 0.117
|
SECONDARY outcome
Timeframe: Week 40Population: Full Analysis Set: all randomized participants who received at least one dose of assigned medication and had at least one post-baseline assessment.
Changes in the severity of lower extremity skeletal abnormalities, including genu varum and genu valgus, were assessed using a disease specific qualitative RGI-C scoring system. The RGI-C is a 7-point ordinal scale with possible values: +3 = very much better (complete or near complete healing), +2 = much better (substantial healing), +1 = minimally better (i.e., minimal healing), 0 = unchanged, -1 = minimally worse (minimal worsening), -2 = much worse (moderate worsening), -3 = very much worse (severe worsening).
Outcome measures
| Measure |
Active Control
n=32 Participants
Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
Burosumab
n=29 Participants
Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants continued to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
|---|---|---|
|
RGI-C Long Leg Score at Week 40
|
0.22 score on a scale
Standard Error 0.080
|
0.62 score on a scale
Standard Error 0.153
|
SECONDARY outcome
Timeframe: Week 64Population: Full Analysis Set: all randomized participants who received at least one dose of assigned medication and had at least one post-baseline assessment.
Changes in the severity of lower extremity skeletal abnormalities, including genu varum and genu valgus, were assessed using a disease specific qualitative RGI-C scoring system. The RGI-C is a 7-point ordinal scale with possible values: +3 = very much better (complete or near complete healing), +2 = much better (substantial healing), +1 = minimally better (i.e., minimal healing), 0 = unchanged, -1 = minimally worse (minimal worsening), -2 = much worse (moderate worsening), -3 = very much worse (severe worsening).
Outcome measures
| Measure |
Active Control
n=32 Participants
Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
Burosumab
n=29 Participants
Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants continued to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
|---|---|---|
|
RGI-C Long Leg Score at Week 64
|
0.29 score on a scale
Standard Error 0.119
|
1.25 score on a scale
Standard Error 0.170
|
SECONDARY outcome
Timeframe: Baseline, Week 40Population: Full Analysis Set: all randomized participants who received at least one dose of assigned medication and had at least one post-baseline assessment. Participants with an assessment at Week 40.
Recumbent length/Standing height z scores are measures of height adjusted for a child's age and sex. The Z-score indicates the number of standard deviations away from a reference population (from the Centers for Disease Control \[CDC\] growth charts) in the same age range and with the same sex. A Z-score of 0 is equal to the mean with negative numbers indicating values lower than the mean and positive values higher. Higher Z-scores indicate a better outcome.
Outcome measures
| Measure |
Active Control
n=32 Participants
Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
Burosumab
n=28 Participants
Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants continued to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
|---|---|---|
|
Change From Baseline in Height-For-Age Z-Scores to Week 40
|
0.03 Z score
Standard Error 0.031
|
0.16 Z score
Standard Error 0.052
|
SECONDARY outcome
Timeframe: Baseline, Week 64Population: Full Analysis Set: all randomized participants who received at least one dose of assigned medication and had at least one post-baseline assessment. Participants with an assessment at Week 64.
Recumbent length/Standing height z scores are measures of height adjusted for a child's age and sex. The Z-score indicates the number of standard deviations away from a reference population (from the CDC growth charts) in the same age range and with the same sex. A Z-score of 0 is equal to the mean with negative numbers indicating values lower than the mean and positive values higher. Higher Z-scores indicate a better outcome.
Outcome measures
| Measure |
Active Control
n=32 Participants
Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
Burosumab
n=28 Participants
Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants continued to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
|---|---|---|
|
Change From Baseline in Height-For-Age Z-Scores to Week 64
|
0.02 Z score
Standard Error 0.035
|
0.17 Z score
Standard Error 0.066
|
SECONDARY outcome
Timeframe: Baseline, Week 40Population: Full Analysis Set: all randomized participants who received at least one dose of assigned medication and had at least one post-baseline assessment. Participants with Baseline growth velocity.
A growth velocity Z score was calculated based on Tanner's standard. The Z score indicates the number of standard deviations away from a reference population (from Tanner's standard) in the same age range and with the same sex. The baseline growth velocity was calculated for participants who had data available from within 1.5 years prior to baseline. The Week 64 growth velocity was calculated using data between baseline and Week 64. The mid-point of the age interval was used to locate the closest reference age provided by Tanner's Standard. Children with a mid-point age under 2.25 years were excluded, because younger ages are not available in Tanner's standard. To smoothly transition from recumbent length to standing height, 0·8 cm was subtracted from recumbent length before pooling with standing height. A Z score of 0 is equal to the mean with negative numbers indicating values lower than the mean and positive values higher. Higher Z scores indicate a better outcome.
Outcome measures
| Measure |
Active Control
n=22 Participants
Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
Burosumab
n=22 Participants
Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants continued to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
|---|---|---|
|
Change in Growth Velocity Z Score From Baseline to Week 40
|
0.73 Z score
Standard Error 0.339
|
1.76 Z score
Standard Error 0.337
|
SECONDARY outcome
Timeframe: Baseline, Week 64Population: Full Analysis Set: all randomized participants who received at least one dose of assigned medication and had at least one post-baseline assessment. Participants with Baseline growth velocity.
A growth velocity Z score was calculated based on Tanner's standard. The Z score indicates the number of standard deviations away from a reference population (from Tanner's standard) in the same age range and with the same sex. The baseline growth velocity was calculated for participants who had data available from within 1.5 years prior to baseline. The Week 64 growth velocity was calculated using data between baseline and Week 64. The mid-point of the age interval was used to locate the closest reference age provided by Tanner's Standard. Children with a mid-point age under 2.25 years were excluded, because younger ages are not available in Tanner's standard. To smoothly transition from recumbent length to standing height, 0·8 cm was subtracted from recumbent length before pooling with standing height. A Z score of 0 is equal to the mean with negative numbers indicating values lower than the mean and positive values higher. Higher Z scores indicate a better outcome.
Outcome measures
| Measure |
Active Control
n=22 Participants
Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
Burosumab
n=22 Participants
Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants continued to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
|---|---|---|
|
Change in Growth Velocity Z Score From Baseline to Week 64
|
0.41 Z score
Standard Error 0.265
|
1.53 Z score
Standard Error 0.264
|
SECONDARY outcome
Timeframe: Baseline, Weeks 1, 2, 4, 8, 12, 16, 24, 32, 33, 40, 52, 64Population: Pharmacodynamic (PD) Analysis Set: all participants who received at least one dose of study therapy and had evaluable serum data. Participants with data at given time point.
The GEE model includes change from baseline for serum phosphorous measurement as the dependent variable, treatment group, visit, interaction between treatment group by visit, baseline age and baseline RSS stratification as factors, baseline phosphorous measure as a covariate, with exchangeable covariance structure. The GEE model included data up to Week 64.
Outcome measures
| Measure |
Active Control
n=32 Participants
Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
Burosumab
n=29 Participants
Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants continued to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
|---|---|---|
|
Change From Baseline Over Time in Serum Phosphorus Concentration, up to Week 64
Week 1
|
0.22 mg/dL
Standard Error 0.072
|
1.26 mg/dL
Standard Error 0.094
|
|
Change From Baseline Over Time in Serum Phosphorus Concentration, up to Week 64
Week 2
|
—
|
1.14 mg/dL
Standard Error 0.098
|
|
Change From Baseline Over Time in Serum Phosphorus Concentration, up to Week 64
Week 4
|
0.18 mg/dL
Standard Error 0.061
|
1.21 mg/dL
Standard Error 0.102
|
|
Change From Baseline Over Time in Serum Phosphorus Concentration, up to Week 64
Week 8
|
0.21 mg/dL
Standard Error 0.064
|
0.99 mg/dL
Standard Error 0.074
|
|
Change From Baseline Over Time in Serum Phosphorus Concentration, up to Week 64
Week 12
|
—
|
1.01 mg/dL
Standard Error 0.072
|
|
Change From Baseline Over Time in Serum Phosphorus Concentration, up to Week 64
Week 16
|
0.24 mg/dL
Standard Error 0.063
|
0.87 mg/dL
Standard Error 0.072
|
|
Change From Baseline Over Time in Serum Phosphorus Concentration, up to Week 64
Week 24
|
0.27 mg/dL
Standard Error 0.073
|
0.78 mg/dL
Standard Error 0.077
|
|
Change From Baseline Over Time in Serum Phosphorus Concentration, up to Week 64
Week 32
|
0.23 mg/dL
Standard Error 0.063
|
0.93 mg/dL
Standard Error 0.073
|
|
Change From Baseline Over Time in Serum Phosphorus Concentration, up to Week 64
Week 33
|
—
|
1.23 mg/dL
Standard Error 0.106
|
|
Change From Baseline Over Time in Serum Phosphorus Concentration, up to Week 64
Week 40
|
0.20 mg/dL
Standard Error 0.062
|
0.92 mg/dL
Standard Error 0.080
|
|
Change From Baseline Over Time in Serum Phosphorus Concentration, up to Week 64
Week 52
|
0.30 mg/dL
Standard Error 0.082
|
0.91 mg/dL
Standard Error 0.075
|
|
Change From Baseline Over Time in Serum Phosphorus Concentration, up to Week 64
Week 64
|
0.21 mg/dL
Standard Error 0.062
|
0.91 mg/dL
Standard Error 0.078
|
SECONDARY outcome
Timeframe: Baseline, Weeks 66, 68, 76, 88, 100, 112Population: PD Analysis Set: all participants who received at least one dose of study therapy and had evaluable serum data. Participants with an assessment at given time point.
Outcome measures
| Measure |
Active Control
n=26 Participants
Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
Burosumab
n=22 Participants
Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants continued to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
|---|---|---|
|
Change From Baseline Over Time in Serum Phosphorus Concentration, Weeks 66-112
Week 112
|
1.26 mg/dL
Standard Deviation 0.508
|
1.10 mg/dL
Standard Deviation 0.283
|
|
Change From Baseline Over Time in Serum Phosphorus Concentration, Weeks 66-112
Week 66
|
0.05 mg/dL
Standard Deviation 0.235
|
—
|
|
Change From Baseline Over Time in Serum Phosphorus Concentration, Weeks 66-112
Week 68
|
1.17 mg/dL
Standard Deviation 0.472
|
1.10 mg/dL
Standard Deviation NA
1 participant analyzed
|
|
Change From Baseline Over Time in Serum Phosphorus Concentration, Weeks 66-112
Week 76
|
0.90 mg/dL
Standard Deviation 0.324
|
0.92 mg/dL
Standard Deviation 0.324
|
|
Change From Baseline Over Time in Serum Phosphorus Concentration, Weeks 66-112
Week 88
|
0.98 mg/dL
Standard Deviation 0.433
|
1.00 mg/dL
Standard Deviation 0.576
|
|
Change From Baseline Over Time in Serum Phosphorus Concentration, Weeks 66-112
Week 100
|
0.99 mg/dL
Standard Deviation 0.445
|
1.00 mg/dL
Standard Deviation 0.424
|
SECONDARY outcome
Timeframe: Baseline, Weeks 1, 4, 8, 16, 24, 32, 40, 52, 64Population: PD Analysis Set: all participants who received at least one dose of study therapy and had evaluable serum data.
The ANCOVA model includes change in serum phosphorus from baseline to mean post-baseline as the dependent variable, treatment group, baseline age and baseline RSS stratification as factors, baseline phosphorous measure as a covariate.
Outcome measures
| Measure |
Active Control
n=32 Participants
Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
Burosumab
n=29 Participants
Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants continued to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
|---|---|---|
|
Change From Baseline in Mean Post-Baseline Serum Phosphorus Level to Week 64
|
0.24 mg/dL
Standard Error 0.058
|
0.98 mg/dL
Standard Error 0.061
|
SECONDARY outcome
Timeframe: Burosumab arm: Baseline, Week 1, 4, 8, 16, 24, 32, 40, 52, 64, 66, 68, 76, 88, 100, 112, 124, 140; Active Control arm: Baseline, Week 68, 76, 88, 100, 112, 124, 140Population: PD Analysis Set: all participants who received at least one dose of study therapy and had evaluable serum data.
Outcome measures
| Measure |
Active Control
n=26 Participants
Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
Burosumab
n=29 Participants
Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants continued to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
|---|---|---|
|
Change From Baseline in Mean Post-Baseline Serum Phosphorus Level to Week 140 (During Treatment With Burosumab)
|
1.05 mg/dL
Standard Deviation 0.310
|
0.93 mg/dL
Standard Deviation 0.336
|
SECONDARY outcome
Timeframe: Burosumab arm: Baseline, up to Week 140; Active Control arm: Baseline, Week 68 up to Week 140Population: PD Analysis Set: all participants who received at least one dose of study therapy and had evaluable serum data.
Outcome measures
| Measure |
Active Control
n=32 Participants
Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
Burosumab
n=29 Participants
Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants continued to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
|---|---|---|
|
Percentage of Participants Reaching the Normal Range of Serum Phosphorus Concentration (3.2 - 6.1 mg/dL)
|
75.0 percentage of participants
|
96.6 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline, Weeks 1, 2, 4, 8, 12, 16, 24, 32, 33, 40, 52, 64Population: PD Analysis Set: all participants who received at least one dose of study therapy and had evaluable serum data. Participants with an assessment at given time point.
The GEE model includes change from baseline for 1, 25-Dihydroxyvitamin D measurement as the dependent variable, treatment group, visit, interaction between treatment group by visit, baseline age and baseline RSS stratification as factors, baseline 1, 25-Dihydroxyvitamin D measure as a covariate, with exchangeable covariance structure. The GEE model included data up to Week 64.
Outcome measures
| Measure |
Active Control
n=30 Participants
Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
Burosumab
n=28 Participants
Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants continued to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
|---|---|---|
|
Change From Baseline Over Time in 1,25-Dihydroxyvitamin D, up to Week 64
Week 1
|
19.81 pg/mL
Standard Error 2.758
|
68.09 pg/mL
Standard Error 5.251
|
|
Change From Baseline Over Time in 1,25-Dihydroxyvitamin D, up to Week 64
Week 2
|
—
|
31.78 pg/mL
Standard Error 5.130
|
|
Change From Baseline Over Time in 1,25-Dihydroxyvitamin D, up to Week 64
Week 4
|
12.77 pg/mL
Standard Error 2.998
|
33.86 pg/mL
Standard Error 3.561
|
|
Change From Baseline Over Time in 1,25-Dihydroxyvitamin D, up to Week 64
Week 8
|
15.10 pg/mL
Standard Error 2.528
|
30.85 pg/mL
Standard Error 3.830
|
|
Change From Baseline Over Time in 1,25-Dihydroxyvitamin D, up to Week 64
Week 12
|
—
|
33.43 pg/mL
Standard Error 3.176
|
|
Change From Baseline Over Time in 1,25-Dihydroxyvitamin D, up to Week 64
Week 16
|
19.41 pg/mL
Standard Error 3.757
|
32.38 pg/mL
Standard Error 3.032
|
|
Change From Baseline Over Time in 1,25-Dihydroxyvitamin D, up to Week 64
Week 24
|
17.46 pg/mL
Standard Error 2.905
|
28.35 pg/mL
Standard Error 3.113
|
|
Change From Baseline Over Time in 1,25-Dihydroxyvitamin D, up to Week 64
Week 32
|
17.25 pg/mL
Standard Error 3.156
|
23.49 pg/mL
Standard Error 2.439
|
|
Change From Baseline Over Time in 1,25-Dihydroxyvitamin D, up to Week 64
Week 33
|
—
|
31.50 pg/mL
Standard Error 3.423
|
|
Change From Baseline Over Time in 1,25-Dihydroxyvitamin D, up to Week 64
Week 40
|
18.42 pg/mL
Standard Error 3.594
|
29.63 pg/mL
Standard Error 3.721
|
|
Change From Baseline Over Time in 1,25-Dihydroxyvitamin D, up to Week 64
Week 52
|
8.74 pg/mL
Standard Error 3.866
|
13.75 pg/mL
Standard Error 2.862
|
|
Change From Baseline Over Time in 1,25-Dihydroxyvitamin D, up to Week 64
Week 64
|
1.19 pg/mL
Standard Error 2.785
|
9.89 pg/mL
Standard Error 2.235
|
SECONDARY outcome
Timeframe: Baseline, Weeks 68, 76, 88, 100, 112Population: PD Analysis Set: all participants who received at least one dose of study therapy and had evaluable serum data. Participants with an assessment at given time point.
Outcome measures
| Measure |
Active Control
n=25 Participants
Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
Burosumab
n=21 Participants
Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants continued to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
|---|---|---|
|
Change From Baseline Over Time in 1,25-Dihydroxyvitamin D, Weeks 68 to 112
Week 68
|
22.12 pg/mL
Standard Deviation 23.950
|
-9.80 pg/mL
Standard Deviation NA
1 participant analyzed
|
|
Change From Baseline Over Time in 1,25-Dihydroxyvitamin D, Weeks 68 to 112
Week 76
|
19.05 pg/mL
Standard Deviation 22.612
|
12.80 pg/mL
Standard Deviation 20.093
|
|
Change From Baseline Over Time in 1,25-Dihydroxyvitamin D, Weeks 68 to 112
Week 88
|
24.58 pg/mL
Standard Deviation 17.787
|
11.76 pg/mL
Standard Deviation 22.874
|
|
Change From Baseline Over Time in 1,25-Dihydroxyvitamin D, Weeks 68 to 112
Week 100
|
33.57 pg/mL
Standard Deviation 16.591
|
13.25 pg/mL
Standard Deviation 1.061
|
|
Change From Baseline Over Time in 1,25-Dihydroxyvitamin D, Weeks 68 to 112
Week 112
|
29.94 pg/mL
Standard Deviation 15.402
|
31.05 pg/mL
Standard Deviation 33.729
|
SECONDARY outcome
Timeframe: Baseline, Weeks 4, 8, 16, 24, 32, 40, 52, 64Population: PD Analysis Set: all participants who received at least one dose of study therapy and had evaluable serum data. Participants with an assessment at given time point.
Serum phosphorus and TRP measurements were used in the calculation of TmP/GFR. The GEE model includes change from baseline for TmP/GFR measurement as the dependent variable, treatment group, visit, interaction between treatment group by visit, baseline age and baseline RSS stratification as factors, baseline TmP/GFR measure as a covariate, with exchangeable covariance structure. The GEE model included data up to Week 64.
Outcome measures
| Measure |
Active Control
n=30 Participants
Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
Burosumab
n=24 Participants
Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants continued to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
|---|---|---|
|
Change From Baseline Over Time in TmP/GFR, up to Week 64
Week 4
|
-0.17 mg/dL
Standard Error 0.065
|
1.48 mg/dL
Standard Error 0.173
|
|
Change From Baseline Over Time in TmP/GFR, up to Week 64
Week 8
|
-0.20 mg/dL
Standard Error 0.057
|
1.22 mg/dL
Standard Error 0.101
|
|
Change From Baseline Over Time in TmP/GFR, up to Week 64
Week 16
|
-0.15 mg/dL
Standard Error 0.085
|
1.00 mg/dL
Standard Error 0.139
|
|
Change From Baseline Over Time in TmP/GFR, up to Week 64
Week 24
|
-0.12 mg/dL
Standard Error 0.072
|
0.99 mg/dL
Standard Error 0.134
|
|
Change From Baseline Over Time in TmP/GFR, up to Week 64
Week 32
|
-0.10 mg/dL
Standard Error 0.062
|
1.14 mg/dL
Standard Error 0.115
|
|
Change From Baseline Over Time in TmP/GFR, up to Week 64
Week 40
|
-0.15 mg/dL
Standard Error 0.053
|
1.20 mg/dL
Standard Error 0.113
|
|
Change From Baseline Over Time in TmP/GFR, up to Week 64
Week 52
|
-0.12 mg/dL
Standard Error 0.069
|
1.13 mg/dL
Standard Error 0.124
|
|
Change From Baseline Over Time in TmP/GFR, up to Week 64
Week 64
|
-0.09 mg/dL
Standard Error 0.070
|
1.16 mg/dL
Standard Error 0.127
|
SECONDARY outcome
Timeframe: Baseline, Weeks 68, 76, 88, 112Population: PD Analysis Set: all participants who received at least one dose of study therapy and had evaluable serum data. Participants with data at given time point.
Serum phosphorus and TRP measurements were used in the calculation of TmP/GFR.
Outcome measures
| Measure |
Active Control
n=24 Participants
Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
Burosumab
n=7 Participants
Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants continued to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
|---|---|---|
|
Change From Baseline Over Time in TmP/GFR, Week 68 to 112
Week 88
|
1.33 mg/dL
Standard Deviation 0.480
|
0.95 mg/dL
Standard Deviation 0.620
|
|
Change From Baseline Over Time in TmP/GFR, Week 68 to 112
Week 68
|
1.61 mg/dL
Standard Deviation 0.705
|
1.65 mg/dL
Standard Deviation NA
1 participant analyzed
|
|
Change From Baseline Over Time in TmP/GFR, Week 68 to 112
Week 76
|
1.18 mg/dL
Standard Deviation 0.758
|
0.59 mg/dL
Standard Deviation 0.429
|
|
Change From Baseline Over Time in TmP/GFR, Week 68 to 112
Week 112
|
1.56 mg/dL
Standard Deviation 0.233
|
1.32 mg/dL
Standard Deviation 0.233
|
SECONDARY outcome
Timeframe: Baseline, Weeks 16, 24, 40, 52, 64Population: PD Analysis Set: all participants who received at least one dose of study therapy and had evaluable serum data.
The GEE model includes change from baseline for ALP measurement as the dependent variable, treatment group, visit, interaction between treatment group by visit, baseline age and baseline RSS stratification as factors, baseline ALP measure as a covariate, with exchangeable covariance structure. The GEE model included data up to Week 64.
Outcome measures
| Measure |
Active Control
n=32 Participants
Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
Burosumab
n=29 Participants
Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants continued to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
|---|---|---|
|
Change From Baseline Over Time in Serum ALP, up to Week 64
Week 16
|
-5.43 U/L
Standard Error 17.885
|
-97.97 U/L
Standard Error 11.281
|
|
Change From Baseline Over Time in Serum ALP, up to Week 64
Week 24
|
-22.43 U/L
Standard Error 15.074
|
-108.00 U/L
Standard Error 16.225
|
|
Change From Baseline Over Time in Serum ALP, up to Week 64
Week 40
|
-34.78 U/L
Standard Error 18.132
|
-130.72 U/L
Standard Error 12.365
|
|
Change From Baseline Over Time in Serum ALP, up to Week 64
Week 52
|
-50.03 U/L
Standard Error 18.641
|
-161.31 U/L
Standard Error 11.674
|
|
Change From Baseline Over Time in Serum ALP, up to Week 64
Week 64
|
-28.06 U/L
Standard Error 19.980
|
-174.62 U/L
Standard Error 13.427
|
SECONDARY outcome
Timeframe: Baseline, Weeks 68, 76, 88, 100, 112Population: PD Analysis Set: all participants who received at least one dose of study therapy and had evaluable serum data.
Outcome measures
| Measure |
Active Control
n=26 Participants
Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
Burosumab
n=22 Participants
Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants continued to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
|---|---|---|
|
Change From Baseline Over Time in Serum ALP, Week 68 to 112
Week 68
|
-82.73 U/L
Standard Deviation 83.683
|
-184.00 U/L
Standard Deviation NA
1 participant analyzed
|
|
Change From Baseline Over Time in Serum ALP, Week 68 to 112
Week 76
|
-106.73 U/L
Standard Deviation 73.316
|
-166.73 U/L
Standard Deviation 87.700
|
|
Change From Baseline Over Time in Serum ALP, Week 68 to 112
Week 88
|
-146.56 U/L
Standard Deviation 73.120
|
-154.55 U/L
Standard Deviation 48.148
|
|
Change From Baseline Over Time in Serum ALP, Week 68 to 112
Week 100
|
-83.14 U/L
Standard Deviation 104.675
|
-184.00 U/L
Standard Deviation 48.083
|
|
Change From Baseline Over Time in Serum ALP, Week 68 to 112
Week 112
|
-104.80 U/L
Standard Deviation 80.350
|
-172.00 U/L
Standard Deviation 26.870
|
SECONDARY outcome
Timeframe: Baseline, Weeks 16, 24, 40, 52, 64, 68, 76, 88, 100, 112Population: PD Analysis Set: all participants who received at least one dose of study therapy and had evaluable serum data.
Decreases indicate improvement.
Outcome measures
| Measure |
Active Control
n=32 Participants
Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
Burosumab
n=29 Participants
Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants continued to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
|---|---|---|
|
Percent Change From Baseline Over Time in Serum ALP, up to Week 112
Week 64
|
-4.60 percent change
Standard Deviation 20.711
|
-32.78 percent change
Standard Deviation 13.095
|
|
Percent Change From Baseline Over Time in Serum ALP, up to Week 112
Week 16
|
0.41 percent change
Standard Deviation 21.021
|
-18.39 percent change
Standard Deviation 10.815
|
|
Percent Change From Baseline Over Time in Serum ALP, up to Week 112
Week 24
|
-3.21 percent change
Standard Deviation 15.827
|
-19.88 percent change
Standard Deviation 17.642
|
|
Percent Change From Baseline Over Time in Serum ALP, up to Week 112
Week 40
|
-6.85 percent change
Standard Deviation 16.493
|
-24.38 percent change
Standard Deviation 13.498
|
|
Percent Change From Baseline Over Time in Serum ALP, up to Week 112
Week 52
|
-8.60 percent change
Standard Deviation 19.027
|
-30.60 percent change
Standard Deviation 11.852
|
|
Percent Change From Baseline Over Time in Serum ALP, up to Week 112
Week 68
|
-14.66 percent change
Standard Deviation 14.760
|
-38.02 percent change
Standard Deviation NA
1 participant analyzed
|
|
Percent Change From Baseline Over Time in Serum ALP, up to Week 112
Week 76
|
-20.49 percent change
Standard Deviation 13.926
|
-31.42 percent change
Standard Deviation 13.422
|
|
Percent Change From Baseline Over Time in Serum ALP, up to Week 112
Week 88
|
-28.77 percent change
Standard Deviation 12.201
|
-32.02 percent change
Standard Deviation 10.610
|
|
Percent Change From Baseline Over Time in Serum ALP, up to Week 112
Week 100
|
-16.06 percent change
Standard Deviation 23.703
|
-39.29 percent change
Standard Deviation 11.460
|
|
Percent Change From Baseline Over Time in Serum ALP, up to Week 112
Week 112
|
-21.00 percent change
Standard Deviation 15.053
|
-36.67 percent change
Standard Deviation 6.868
|
SECONDARY outcome
Timeframe: Baseline, Week 40Population: Full Analysis Set: all randomized participants who received at least one dose of assigned medication and had at least one post-baseline assessment. Participants with an assessment at Week 40.
The PROMIS was developed by the National Institutes of Health and uses domain-specific measures to assess patient well-being (Broderick et al. 2013), (NIH 2015). It uses a T-score metric in which 50 is the mean of a relevant reference population and 10 is the standard deviation (SD) of that population. For the Pain Interference Domain, decreases indicate less pain, for the Physical Function Mobility Domain, increases indicate greater mobility and for the Fatigue Domain, decreases indicate less fatigue.
Outcome measures
| Measure |
Active Control
n=20 Participants
Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
Burosumab
n=15 Participants
Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants continued to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
|---|---|---|
|
Change From Baseline in the PROMIS Pediatric Pain Interference, Physical Function Mobility and Fatigue Domain Scores (For Participants ≥ 5 Years of Age at the Screening Visit) at Week 40
Fatigue Domain Score
|
-1.05 T-score
Standard Error 1.754
|
-4.29 T-score
Standard Error 1.709
|
|
Change From Baseline in the PROMIS Pediatric Pain Interference, Physical Function Mobility and Fatigue Domain Scores (For Participants ≥ 5 Years of Age at the Screening Visit) at Week 40
Pain Interference Domain Score
|
-0.29 T-score
Standard Error 1.539
|
-5.31 T-score
Standard Error 1.705
|
|
Change From Baseline in the PROMIS Pediatric Pain Interference, Physical Function Mobility and Fatigue Domain Scores (For Participants ≥ 5 Years of Age at the Screening Visit) at Week 40
Physical Function Mobility Domain Score
|
0.10 T-score
Standard Error 0.966
|
2.78 T-score
Standard Error 1.336
|
SECONDARY outcome
Timeframe: Baseline, Week 64Population: Full Analysis Set: all randomized participants who received at least one dose of assigned medication and had at least one post-baseline assessment. Participants with an assessment at Week 64.
The PROMIS was developed by the National Institutes of Health and uses domain-specific measures to assess patient well-being (Broderick et al. 2013), (NIH 2015). It uses a T-score metric in which 50 is the mean of a relevant reference population and 10 is the standard deviation (SD) of that population. For the Pain Interference Domain, decreases indicate less pain, for the Physical Function Mobility Domain, increases indicate greater mobility and for the Fatigue Domain, decreases indicate less fatigue.
Outcome measures
| Measure |
Active Control
n=20 Participants
Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
Burosumab
n=15 Participants
Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants continued to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
|---|---|---|
|
Change From Baseline in the PROMIS Pediatric Pain Interference, Physical Function Mobility and Fatigue Domain Scores (For Participants ≥ 5 Years of Age at the Screening Visit) at Week 64
Pain Interference Domain Score
|
-1.29 T-score
Standard Error 1.267
|
-3.55 T-score
Standard Error 1.873
|
|
Change From Baseline in the PROMIS Pediatric Pain Interference, Physical Function Mobility and Fatigue Domain Scores (For Participants ≥ 5 Years of Age at the Screening Visit) at Week 64
Physical Function Mobility Domain Score
|
0.92 T-score
Standard Error 0.962
|
2.82 T-score
Standard Error 1.648
|
|
Change From Baseline in the PROMIS Pediatric Pain Interference, Physical Function Mobility and Fatigue Domain Scores (For Participants ≥ 5 Years of Age at the Screening Visit) at Week 64
Fatigue Domain Score
|
-2.57 T-score
Standard Error 1.547
|
-3.65 T-score
Standard Error 2.119
|
SECONDARY outcome
Timeframe: Baseline, Week 40Population: Full Analysis Set: all randomized participants who received at least one dose of assigned medication and had at least one post-baseline assessment. Participants with an assessment at Week 40.
The FPS-R is a dimensionless 10 point Likert scale used to assess self-reported pain intensity on a scale from 0 (no pain) to 10 (most pain you can imagine). Greater pain scores are indicative of more severe pain.
Outcome measures
| Measure |
Active Control
n=20 Participants
Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
Burosumab
n=15 Participants
Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants continued to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
|---|---|---|
|
Change From Baseline in the FPS-R (For Participants ≥ 5 Years of Age at the Screening Visit) at Week 40
|
0.02 units on a scale
Standard Error 0.323
|
0.03 units on a scale
Standard Error 0.323
|
SECONDARY outcome
Timeframe: Baseline, Week 64Population: Full Analysis Set: all randomized participants who received at least one dose of assigned medication and had at least one post-baseline assessment. Participants with an assessment at Week 64.
The FPS-R is a dimensionless 10 point Likert scale used to assess self-reported pain intensity on a scale from 0 (no pain) to 10 (most pain you can imagine). Greater pain scores are indicative of more severe pain.
Outcome measures
| Measure |
Active Control
n=19 Participants
Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
Burosumab
n=15 Participants
Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants continued to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
|---|---|---|
|
Change From Baseline in the FPS-R (For Participants ≥ 5 Years of Age at the Screening Visit) at Week 64
|
0.04 units on a scale
Standard Error 0.270
|
-0.01 units on a scale
Standard Error 0.234
|
SECONDARY outcome
Timeframe: Baseline, Week 40Population: Full Analysis Set: all randomized participants who received at least one dose of assigned medication and had at least one post-baseline assessment. Participants with an assessment at Week 40 in subjects ≥ 5 years who were able to complete the test.
The total distance walked (meters) in a 6-minute period was measured in participants ≥ 5 years of age at the Screening Visit who were able to complete the test.
Outcome measures
| Measure |
Active Control
n=20 Participants
Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
Burosumab
n=13 Participants
Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants continued to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
|---|---|---|
|
Change From Baseline in the 6MWT Total Distance at Week 40
|
3.65 meters
Standard Error 14.060
|
47.10 meters
Standard Error 15.768
|
SECONDARY outcome
Timeframe: Baseline, Week 64Population: Full Analysis Set: all randomized participants who received at least one dose of assigned medication and had at least one post-baseline assessment. Participants with an assessment at Week 64.
The total distance walked (meters) in a 6-minute period was measured in participants ≥ 5 years of age at the Screening Visit who were able to complete the test.
Outcome measures
| Measure |
Active Control
n=20 Participants
Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
Burosumab
n=13 Participants
Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants continued to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
|---|---|---|
|
Change From Baseline in the 6MWT Total Distance at Week 64
|
29.28 meters
Standard Error 16.834
|
74.83 meters
Standard Error 12.513
|
SECONDARY outcome
Timeframe: Baseline, Week 40Population: Full Analysis Set: all randomized participants who received at least one dose of assigned medication and had at least one post-baseline assessment. Participants with an assessment at Week 40.
The total distance walked (meters) in a 6-minute period was measured in participants ≥ 5 years of age at the Screening Visit who were able to complete the test, and the percent predicted distance based on normative data for age and gender was estimated.
Outcome measures
| Measure |
Active Control
n=20 Participants
Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
Burosumab
n=13 Participants
Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants continued to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
|---|---|---|
|
Percent of Predicted Normal in the 6MWT Total Distance at Week 40
|
-1.14 percent of predicted meters
Standard Error 2.224
|
5.59 percent of predicted meters
Standard Error 2.633
|
SECONDARY outcome
Timeframe: Baseline, Week 64Population: Full Analysis Set: all randomized participants who received at least one dose of assigned medication and had at least one post-baseline assessment. Participants with an assessment at Week 64.
The total distance walked (meters) in a 6-minute period was measured in participants ≥ 5 years of age at the Screening Visit who were able to complete the test, and the percent predicted distance based on normative data for age and gender was estimated.
Outcome measures
| Measure |
Active Control
n=20 Participants
Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
Burosumab
n=13 Participants
Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants continued to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
|---|---|---|
|
Percent of Predicted Normal in the 6MWT Total Distance at Week 64
|
1.88 percent of predicted meters
Standard Error 2.789
|
9.15 percent of predicted meters
Standard Error 2.056
|
Adverse Events
Oral Phosphate/Active Vitamin D (Treatment Period)
Serious events: 3 serious events
Other events: 23 other events
Deaths: 0 deaths
Burosumab (Treatment Period)
Serious events: 3 serious events
Other events: 21 other events
Deaths: 0 deaths
Oral Phosphate/Active Vitamin D->Burosumab (Extension Period)
Serious events: 0 serious events
Other events: 9 other events
Deaths: 0 deaths
Burosumab->Burosumab (Treatment Period and Extension Period)
Serious events: 4 serious events
Other events: 25 other events
Deaths: 0 deaths
Total Burosumab (Treatment Period and Extension Period)
Serious events: 4 serious events
Other events: 34 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Oral Phosphate/Active Vitamin D (Treatment Period)
n=32 participants at risk
Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64).
|
Burosumab (Treatment Period)
n=29 participants at risk
Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection during the Treatment Period (up to Week 64).
|
Oral Phosphate/Active Vitamin D->Burosumab (Extension Period)
n=26 participants at risk
Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
Burosumab->Burosumab (Treatment Period and Extension Period)
n=29 participants at risk
Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants continued to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
Total Burosumab (Treatment Period and Extension Period)
n=55 participants at risk
Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection at any time during the study.
|
|---|---|---|---|---|---|
|
Congenital, familial and genetic disorders
Craniosynostosis
|
3.1%
1/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
3.4%
1/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
0.00%
0/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
3.4%
1/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
1.8%
1/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
|
Eye disorders
Papilloedema
|
0.00%
0/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
0.00%
0/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
0.00%
0/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
3.4%
1/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
1.8%
1/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
|
Infections and infestations
Viral Infection
|
0.00%
0/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
3.4%
1/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
0.00%
0/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
3.4%
1/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
1.8%
1/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
|
Musculoskeletal and connective tissue disorders
Knee Deformity
|
3.1%
1/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
0.00%
0/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
0.00%
0/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
0.00%
0/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
0.00%
0/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
|
Nervous system disorders
Migraine
|
0.00%
0/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
3.4%
1/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
0.00%
0/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
3.4%
1/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
1.8%
1/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
|
Renal and urinary disorders
Haematuria
|
3.1%
1/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
0.00%
0/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
0.00%
0/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
0.00%
0/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
0.00%
0/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
Other adverse events
| Measure |
Oral Phosphate/Active Vitamin D (Treatment Period)
n=32 participants at risk
Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64).
|
Burosumab (Treatment Period)
n=29 participants at risk
Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection during the Treatment Period (up to Week 64).
|
Oral Phosphate/Active Vitamin D->Burosumab (Extension Period)
n=26 participants at risk
Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
Burosumab->Burosumab (Treatment Period and Extension Period)
n=29 participants at risk
Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants continued to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
|
Total Burosumab (Treatment Period and Extension Period)
n=55 participants at risk
Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection at any time during the study.
|
|---|---|---|---|---|---|
|
Congenital, familial and genetic disorders
Tooth Hypoplasia
|
0.00%
0/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
6.9%
2/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
0.00%
0/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
6.9%
2/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
3.6%
2/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
|
Ear and labyrinth disorders
Ear Discomfort
|
0.00%
0/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
3.4%
1/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
0.00%
0/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
6.9%
2/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
3.6%
2/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
|
Ear and labyrinth disorders
Ear Pain
|
3.1%
1/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
13.8%
4/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
7.7%
2/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
13.8%
4/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
10.9%
6/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
|
Gastrointestinal disorders
Abdominal Discomfort
|
6.2%
2/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
6.9%
2/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
3.8%
1/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
6.9%
2/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
5.5%
3/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
|
Gastrointestinal disorders
Abdominal Pain
|
3.1%
1/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
6.9%
2/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
3.8%
1/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
6.9%
2/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
5.5%
3/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
|
Gastrointestinal disorders
Abdominal Pain Upper
|
9.4%
3/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
10.3%
3/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
7.7%
2/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
13.8%
4/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
10.9%
6/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
17.2%
5/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
7.7%
2/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
17.2%
5/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
12.7%
7/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
|
Gastrointestinal disorders
Dental Caries
|
6.2%
2/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
31.0%
9/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
0.00%
0/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
34.5%
10/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
18.2%
10/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
|
Gastrointestinal disorders
Diarrhoea
|
6.2%
2/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
24.1%
7/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
3.8%
1/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
24.1%
7/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
14.5%
8/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
|
Gastrointestinal disorders
Haematochezia
|
0.00%
0/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
3.4%
1/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
0.00%
0/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
6.9%
2/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
3.6%
2/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
|
Gastrointestinal disorders
Nausea
|
3.1%
1/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
10.3%
3/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
7.7%
2/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
17.2%
5/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
12.7%
7/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
|
Gastrointestinal disorders
Teething
|
0.00%
0/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
6.9%
2/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
3.8%
1/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
6.9%
2/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
5.5%
3/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
|
Gastrointestinal disorders
Tooth Loss
|
0.00%
0/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
3.4%
1/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
3.8%
1/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
6.9%
2/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
5.5%
3/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
|
Gastrointestinal disorders
Toothache
|
3.1%
1/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
13.8%
4/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
3.8%
1/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
17.2%
5/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
10.9%
6/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
|
Gastrointestinal disorders
Vomiting
|
25.0%
8/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
41.4%
12/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
19.2%
5/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
48.3%
14/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
34.5%
19/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
|
General disorders
Fatigue
|
6.2%
2/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
3.4%
1/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
3.8%
1/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
6.9%
2/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
5.5%
3/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
|
General disorders
Injection Site Bruising
|
0.00%
0/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
0.00%
0/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
7.7%
2/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
3.4%
1/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
5.5%
3/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
|
General disorders
Injection Site Erosion
|
0.00%
0/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
6.9%
2/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
0.00%
0/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
6.9%
2/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
3.6%
2/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
|
General disorders
Injection Site Erythema
|
0.00%
0/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
31.0%
9/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
23.1%
6/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
31.0%
9/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
27.3%
15/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
|
General disorders
Injection Site Pruritus
|
0.00%
0/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
10.3%
3/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
7.7%
2/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
10.3%
3/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
9.1%
5/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
|
General disorders
Injection Site Rash
|
0.00%
0/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
10.3%
3/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
0.00%
0/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
10.3%
3/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
5.5%
3/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
|
General disorders
Injection Site Reaction
|
0.00%
0/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
24.1%
7/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
7.7%
2/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
27.6%
8/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
18.2%
10/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
|
General disorders
Injection Site Swelling
|
0.00%
0/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
10.3%
3/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
3.8%
1/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
10.3%
3/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
7.3%
4/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
|
General disorders
Injection Site Urticaria
|
0.00%
0/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
6.9%
2/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
0.00%
0/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
6.9%
2/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
3.6%
2/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
|
General disorders
Pain
|
0.00%
0/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
6.9%
2/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
0.00%
0/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
10.3%
3/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
5.5%
3/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
|
General disorders
Pyrexia
|
21.9%
7/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
55.2%
16/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
26.9%
7/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
58.6%
17/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
43.6%
24/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
|
Immune system disorders
Hypersensitivity
|
6.2%
2/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
3.4%
1/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
0.00%
0/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
3.4%
1/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
1.8%
1/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
|
Immune system disorders
Seasonal Allergy
|
6.2%
2/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
13.8%
4/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
3.8%
1/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
13.8%
4/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
9.1%
5/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
|
Infections and infestations
Ear Infection
|
9.4%
3/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
6.9%
2/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
3.8%
1/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
10.3%
3/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
7.3%
4/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
|
Infections and infestations
Gastroenteritis
|
9.4%
3/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
6.9%
2/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
0.00%
0/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
6.9%
2/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
3.6%
2/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
|
Infections and infestations
Gastroenteritis Viral
|
9.4%
3/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
6.9%
2/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
0.00%
0/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
6.9%
2/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
3.6%
2/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
|
Infections and infestations
Influenza
|
18.8%
6/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
13.8%
4/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
0.00%
0/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
13.8%
4/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
7.3%
4/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
|
Infections and infestations
Nasopharyngitis
|
43.8%
14/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
37.9%
11/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
23.1%
6/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
51.7%
15/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
38.2%
21/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
|
Infections and infestations
Otitis Externa
|
9.4%
3/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
0.00%
0/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
0.00%
0/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
0.00%
0/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
0.00%
0/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
|
Infections and infestations
Otitis Media
|
12.5%
4/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
6.9%
2/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
0.00%
0/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
10.3%
3/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
5.5%
3/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
|
Infections and infestations
Pharyngitis Streptococcal
|
3.1%
1/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
3.4%
1/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
3.8%
1/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
6.9%
2/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
5.5%
3/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
|
Infections and infestations
Pneumonia
|
0.00%
0/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
6.9%
2/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
0.00%
0/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
6.9%
2/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
3.6%
2/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
|
Infections and infestations
Rhinitis
|
6.2%
2/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
6.9%
2/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
0.00%
0/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
6.9%
2/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
3.6%
2/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
|
Infections and infestations
Tooth Abscess
|
9.4%
3/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
27.6%
8/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
7.7%
2/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
31.0%
9/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
20.0%
11/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
|
Infections and infestations
Upper Respiratory Tract Infection
|
9.4%
3/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
10.3%
3/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
0.00%
0/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
10.3%
3/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
5.5%
3/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
|
Infections and infestations
Varicella
|
0.00%
0/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
6.9%
2/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
3.8%
1/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
6.9%
2/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
5.5%
3/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
|
Infections and infestations
Viral Upper Respiratory Tract Infection
|
6.2%
2/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
0.00%
0/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
0.00%
0/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
0.00%
0/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
0.00%
0/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
|
Injury, poisoning and procedural complications
Contusion
|
0.00%
0/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
13.8%
4/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
0.00%
0/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
13.8%
4/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
7.3%
4/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
10.3%
3/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
0.00%
0/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
10.3%
3/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
5.5%
3/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
|
Injury, poisoning and procedural complications
Procedural Pain
|
0.00%
0/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
6.9%
2/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
0.00%
0/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
6.9%
2/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
3.6%
2/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
|
Investigations
Vitamin D Decreased
|
3.1%
1/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
20.7%
6/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
3.8%
1/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
20.7%
6/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
12.7%
7/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
|
Metabolism and nutrition disorders
Decreased Appetite
|
6.2%
2/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
3.4%
1/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
0.00%
0/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
3.4%
1/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
1.8%
1/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
|
Metabolism and nutrition disorders
Vitamin D Deficiency
|
3.1%
1/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
17.2%
5/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
0.00%
0/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
17.2%
5/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
9.1%
5/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
31.2%
10/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
44.8%
13/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
11.5%
3/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
44.8%
13/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
29.1%
16/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
9.4%
3/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
6.9%
2/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
0.00%
0/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
6.9%
2/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
3.6%
2/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
|
Musculoskeletal and connective tissue disorders
Pain In Extremity
|
31.2%
10/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
37.9%
11/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
11.5%
3/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
37.9%
11/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
25.5%
14/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
|
Nervous system disorders
Headache
|
18.8%
6/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
34.5%
10/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
11.5%
3/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
34.5%
10/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
23.6%
13/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
|
Nervous system disorders
Migraine
|
6.2%
2/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
3.4%
1/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
3.8%
1/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
3.4%
1/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
3.6%
2/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
|
Psychiatric disorders
Attention Deficit/Hyperactivity Disorder
|
0.00%
0/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
0.00%
0/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
0.00%
0/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
6.9%
2/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
3.6%
2/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
|
Renal and urinary disorders
Dysuria
|
0.00%
0/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
6.9%
2/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
0.00%
0/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
6.9%
2/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
3.6%
2/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
3.1%
1/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
13.8%
4/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
0.00%
0/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
13.8%
4/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
7.3%
4/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
18.8%
6/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
51.7%
15/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
15.4%
4/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
51.7%
15/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
34.5%
19/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Nasal Congestion
|
3.1%
1/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
17.2%
5/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
3.8%
1/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
24.1%
7/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
14.5%
8/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal Pain
|
3.1%
1/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
17.2%
5/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
11.5%
3/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
20.7%
6/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
16.4%
9/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Rhinitis Allergic
|
0.00%
0/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
6.9%
2/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
0.00%
0/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
6.9%
2/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
3.6%
2/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
6.2%
2/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
24.1%
7/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
11.5%
3/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
27.6%
8/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
20.0%
11/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
0.00%
0/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
3.4%
1/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
0.00%
0/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
6.9%
2/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
3.6%
2/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
|
Skin and subcutaneous tissue disorders
Erythema
|
0.00%
0/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
6.9%
2/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
0.00%
0/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
6.9%
2/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
3.6%
2/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
|
Skin and subcutaneous tissue disorders
Rash
|
6.2%
2/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
10.3%
3/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
0.00%
0/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
13.8%
4/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
7.3%
4/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
|
Skin and subcutaneous tissue disorders
Skin Lesion
|
0.00%
0/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
3.4%
1/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
0.00%
0/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
6.9%
2/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
3.6%
2/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
|
Skin and subcutaneous tissue disorders
Swelling Face
|
0.00%
0/32 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
3.4%
1/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
0.00%
0/26 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
6.9%
2/29 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
3.6%
2/55 • Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.
- Publication restrictions are in place
Restriction type: OTHER