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Efficacy and Safety of Burosumab (KRN23) Versus Oral Phosphate and Active Vitamin D Treatment in Pediatric Patients With X Linked Hypophosphatemia (XLH)

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ClinicalTrials.gov Identifier: NCT02915705
Recruitment Status : Completed
First Posted : September 27, 2016
Results First Posted : April 11, 2019
Last Update Posted : January 23, 2020
Sponsor:
Collaborator:
Kyowa Kirin Co., Ltd.
Information provided by (Responsible Party):
Ultragenyx Pharmaceutical Inc

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition X-Linked Hypophosphatemia
Interventions Biological: burosumab
Drug: Oral Phosphate Supplement
Drug: active vitamin D
Enrollment 61
Recruitment Details  
Pre-assignment Details 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.
Arm/Group Title Active Control Burosumab
Hide Arm/Group Description 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 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.
Period Title: Treatment Period
Started 32 29
Completed Week 40 32 29
Completed Week 64 32 29
Completed 32 29
Not Completed 0 0
Period Title: Long Term Extension Period
Started 26 [1] 25 [2]
Completed 26 25
Not Completed 0 0
[1]
6 participants did not enter the extension period
[2]
4 participants did not enter the extension period
Arm/Group Title Active Control Burosumab Total
Hide Arm/Group Description 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 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 of all reporting groups
Overall Number of Baseline Participants 32 29 61
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 32 participants 29 participants 61 participants
6.50  (3.250) 6.01  (3.408) 6.27  (3.307)
[1]
Measure Description: age at first dose
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 32 participants 29 participants 61 participants
Female
18
  56.3%
16
  55.2%
34
  55.7%
Male
14
  43.8%
13
  44.8%
27
  44.3%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 32 participants 29 participants 61 participants
Hispanic or Latino
3
   9.4%
3
  10.3%
6
   9.8%
Not Hispanic or Latino
29
  90.6%
26
  89.7%
55
  90.2%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Asian Number Analyzed 32 participants 29 participants 61 participants
6
  18.8%
2
   6.9%
8
  13.1%
White Number Analyzed 32 participants 29 participants 61 participants
25
  78.1%
25
  86.2%
50
  82.0%
Other (Not Specified) Number Analyzed 32 participants 29 participants 61 participants
1
   3.1%
2
   6.9%
3
   4.9%
Rickets Severity Score (RSS) Total Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Score on a scale
Number Analyzed 32 participants 29 participants 61 participants
3.19  (1.141) 3.17  (0.975) 3.18  (1.057)
[1]
Measure Description: The RSS system is a 10-point radiographic scoring method. 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.
Height-For-Age Z-Score   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Z score
Number Analyzed 32 participants 28 participants 60 participants
-2.05  (0.868) -2.32  (1.167) -2.17  (1.018)
[1]
Measure Description: 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.
[2]
Measure Analysis Population Description: 1 participant in the burosumab group did not have a baseline measurement
Growth Velocity Z Score From Pre-Treatment   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Z score
Number Analyzed 22 participants 22 participants 44 participants
-2.14  (5.571) -1.37  (1.334) -1.75  (4.022)
[1]
Measure Description: 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. Children with a mid-point age under 2.25 years were excluded, because younger ages are not available in Tanner's standard. 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.
[2]
Measure Analysis Population Description: participants with a baseline measurement
Serum Phosphorus  
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 32 participants 29 participants 61 participants
2.30  (0.257) 2.42  (0.244) 2.36  (0.256)
Serum 1,25(OH)D   [1] 
Mean (Standard Deviation)
Unit of measure:  pg/mL
Number Analyzed 30 participants 28 participants 58 participants
40.18  (14.886) 46.00  (20.060) 42.99  (17.663)
[1]
Measure Analysis Population Description: participants with a baseline measurement
Ratio of Renal Tubular Maximum Reabsorption Rate of Phosphate to Glomerular Filtration Rate(TmP/GFR)   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 30 participants 24 participants 54 participants
2.008  (0.3300) 2.193  (0.3733) 2.091  (0.3587)
[1]
Measure Description: Data for urinary phosphorus and tubular reabsorption of phosphate (TRP) were used in the calculation of TmP/GFR.
[2]
Measure Analysis Population Description: participants with a baseline measurement
Serum Alkaline Phosphatase (ALP) Concentration  
Mean (Standard Deviation)
Unit of measure:  U/L
Number Analyzed 32 participants 29 participants 61 participants
523.44  (154.419) 510.76  (124.903) 517.4  (140.15)
Patient-Reported Outcomes Measurement Information System (PROMIS) Pediatric Pain Interference Domain   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  T-score
Number Analyzed 20 participants 15 participants 35 participants
49.9  (12.05) 53.1  (10.95) 51.3  (11.54)
[1]
Measure Description: 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.
[2]
Measure Analysis Population Description: participants with a baseline assessment
PROMIS Physical Function Mobility Domain   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  T-score
Number Analyzed 20 participants 15 participants 35 participants
45.5  (9.86) 45.2  (9.05) 45.3  (9.39)
[1]
Measure Description: 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 Physical Function Mobility Domain, increases indicate greater mobility.
[2]
Measure Analysis Population Description: participants with a baseline assessment
PROMIS Fatigue Domain   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  T-score
Number Analyzed 20 participants 15 participants 35 participants
47.0  (13.70) 48.8  (9.60) 47.8  (11.98)
[1]
Measure Description: 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 Fatigue Domain, decreases indicate less fatigue.
[2]
Measure Analysis Population Description: participants with a baseline assessment
Faces Pain Scale-Revised (FPS-R)   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Score on a scale
Number Analyzed 20 participants 15 participants 35 participants
0.7  (1.17) 0.4  (1.12) 0.6  (1.14)
[1]
Measure Description: 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.
[2]
Measure Analysis Population Description: participants with a baseline assessment
Six Minute Walk Test (6MWT) Total Distance   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Meters
Number Analyzed 20 participants 15 participants 35 participants
450.50  (106.432) 365.93  (118.083) 414.26  (117.790)
[1]
Measure Description: The total distance walked (meters) in a 6-minute period was measured, and the percent predicted distance based on normative data for age and gender was estimated.
[2]
Measure Analysis Population Description: participants with a baseline measurement
Percent of Predicted Normal in the 6MWT Total Distance   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Perecent of predicted meters
Number Analyzed 20 participants 15 participants 35 participants
76.20  (14.838) 62.13  (18.629) 70.17  (17.771)
[1]
Measure Description: The total distance walked (meters) in a 6-minute period was measured, and the percent predicted distance based on normative data for age and gender was estimated.
[2]
Measure Analysis Population Description: participants with a baseline measurement
1.Primary Outcome
Title Radiographic Global Impression of Change (RGI-C) Global Score at Week 40
Hide Description 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).
Time Frame Week 40
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all randomized participants who received at least one dose of assigned medication and had at least one post-baseline assessment.
Arm/Group Title Active Control Burosumab
Hide Arm/Group Description:
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 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.
Overall Number of Participants Analyzed 32 29
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
0.77  (0.107) 1.92  (0.110)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Active Control, Burosumab
Comments Least squares (LS) mean, standard error (SE), confidence interval (CI), and 2-sided p value per ANCOVA model, which included RGI-C as the dependent variable, treatment group and baseline age stratification factor as independent variables and baseline RSS score as a continuous covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 1.14
Confidence Interval (2-Sided) 95%
0.83 to 1.45
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Percentage of Participants With a Mean RGI-C Global Score ≥ +2.0 (Responders) at Week 40
Hide Description 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).
Time Frame Week 40
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all randomized participants who received at least one dose of assigned medication and had at least one post-baseline assessment.
Arm/Group Title Active Control Burosumab
Hide Arm/Group Description:
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 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.
Overall Number of Participants Analyzed 32 29
Measure Type: Number
Unit of Measure: percentage of participants
6.3 72.4
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Active Control, Burosumab
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments Odds ratio, CI, and 2-sided p-value were per logistic regression model, which included treatment group and baseline age stratification factor as independent variables and baseline RSS score as a continuous covariate.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 39.1
Confidence Interval (2-Sided) 95%
7.2 to 211.7
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percentage of Participants With a Mean RGI-C Global Score ≥ +2.0 (Responders) at Week 64
Hide Description 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).
Time Frame Week 64
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all randomized participants who received at least one dose of assigned medication and had at least one post-baseline assessment.
Arm/Group Title Active Control Burosumab
Hide Arm/Group Description:
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 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.
Overall Number of Participants Analyzed 32 29
Measure Type: Number
Unit of Measure: percentage of participants
18.8 86.2
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Active Control, Burosumab
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments Odds ratio, CI, and 2-sided p-value were per generalized linear mixed model, which includes treatment, visit, treatment by visit interaction and baseline age stratification factor as factors, baseline RSS total score as a continuous covariate.
Method generalized linear mixed model
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 34.1
Confidence Interval (2-Sided) 95%
5.6 to 206.3
Estimation Comments [Not Specified]
4.Secondary Outcome
Title RGI-C Global Score at Week 64
Hide Description 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).
Time Frame Week 64
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all randomized participants who received at least one dose of assigned medication and had at least one post-baseline assessment.
Arm/Group Title Active Control Burosumab
Hide Arm/Group Description:
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 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.
Overall Number of Participants Analyzed 32 29
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
1.03  (0.136) 2.06  (0.072)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Active Control, Burosumab
Comments Per generalized estimating equation (GEE) model, which included RGI-C as the dependent variable, treatment, visit, treatment by visit interaction and baseline age stratification factor as factors, baseline RSS score as a continuous covariate, with exchangeable covariate structure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in LS means
Estimated Value 1.02
Confidence Interval (2-Sided) 95%
0.72 to 1.33
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline in RSS Total Score at Week 40
Hide Description 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.
Time Frame Baseline, Week 40
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Active Control Burosumab
Hide Arm/Group Description:
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 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.
Overall Number of Participants Analyzed 32 28
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
-0.71  (0.138) -2.04  (0.145)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Active Control, Burosumab
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments LS mean, SE, CI, and 2-sided p value per ANCOVA model, which included treatment group and baseline age stratification factor as independent variables and baseline RSS score as a continuous covariate.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -1.34
Confidence Interval (2-Sided) 95%
-1.74 to -0.94
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Change From Baseline in RSS Total Score at Week 64
Hide Description 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.
Time Frame Baseline, Week 64
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Active Control Burosumab
Hide Arm/Group Description:
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 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.
Overall Number of Participants Analyzed 32 29
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
-1.01  (0.151) -2.23  (0.117)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Active Control, Burosumab
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments LS mean, SE, CI, and 2-sided p value per GEE model, which included treatment, visit, treatment by visit interaction and baseline age stratification factor as factors, baseline RSS score as a continuous covariate.
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in LS means
Estimated Value -1.21
Confidence Interval (2-Sided) 95%
-1.59 to -0.83
Estimation Comments [Not Specified]
7.Secondary Outcome
Title RGI-C Long Leg Score at Week 40
Hide Description 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).
Time Frame Week 40
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all randomized participants who received at least one dose of assigned medication and had at least one post-baseline assessment.
Arm/Group Title Active Control Burosumab
Hide Arm/Group Description:
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 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.
Overall Number of Participants Analyzed 32 29
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
0.22  (0.080) 0.62  (0.153)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Active Control, Burosumab
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0162
Comments LS mean, SE, CI, and 2-sided p value per GEE model, which included treatment, visit, treatment by visit interaction, and baseline age stratification factor as factors; and baseline RSS score as a continuous covariate.
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.40
Confidence Interval (2-Sided) 95%
0.07 to 0.72
Estimation Comments [Not Specified]
8.Secondary Outcome
Title RGI-C Long Leg Score at Week 64
Hide Description 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).
Time Frame Week 64
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all randomized participants who received at least one dose of assigned medication and had at least one post-baseline assessment.
Arm/Group Title Active Control Burosumab
Hide Arm/Group Description:
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 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.
Overall Number of Participants Analyzed 32 29
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
0.29  (0.119) 1.25  (0.170)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Active Control, Burosumab
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments LS mean, SE, CI, and 2-sided p value per GEE model, which included treatment, visit, treatment by visit interaction, and baseline age stratification factor as factors; and baseline RSS score as a continuous covariate.
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in LS means
Estimated Value 0.97
Confidence Interval (2-Sided) 95%
0.57 to 1.37
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Change From Baseline in Height-For-Age Z-Scores to Week 40
Hide Description 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.
Time Frame Baseline, Week 40
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Active Control Burosumab
Hide Arm/Group Description:
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 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.
Overall Number of Participants Analyzed 32 28
Least Squares Mean (Standard Error)
Unit of Measure: Z score
0.03  (0.031) 0.16  (0.052)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Active Control, Burosumab
Comments LS mean, SE, CI, and 2-sided p value per GEE model, which included change from baseline for recumbent length/standing height Z score as the dependent variable, treatment group, visit, interaction between treatment group by visit and baseline RSS stratification as factors, age and baseline recumbent length/standing height Z score as continuous covariates, with exchangeable covariance structure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0408
Comments [Not Specified]
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.12
Confidence Interval (2-Sided) 95%
0.01 to 0.24
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Change From Baseline in Height-For-Age Z-Scores to Week 64
Hide Description 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.
Time Frame Baseline, Week 64
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Active Control Burosumab
Hide Arm/Group Description:
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 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.
Overall Number of Participants Analyzed 32 28
Least Squares Mean (Standard Error)
Unit of Measure: Z score
0.02  (0.035) 0.17  (0.066)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Active Control, Burosumab
Comments LS mean, SE, CI, and 2-sided p value per GEE model, which included change from baseline for recumbent length/standing height Z score as the dependent variable, treatment group, visit, interaction between treatment group by visit and baseline RSS stratification as factors, age and baseline recumbent length/standing height Z score as continuous covariates, with exchangeable covariance structure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0490
Comments [Not Specified]
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in LS means
Estimated Value 0.14
Confidence Interval (2-Sided) 95%
0.00 to 0.29
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Change in Growth Velocity Z Score From Baseline to Week 40
Hide Description 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.
Time Frame Baseline, Week 40
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Active Control Burosumab
Hide Arm/Group Description:
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 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.
Overall Number of Participants Analyzed 22 22
Least Squares Mean (Standard Error)
Unit of Measure: Z score
0.73  (0.339) 1.76  (0.337)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Active Control, Burosumab
Comments LS mean, SE, CI, and 2-sided p value per ANCOVA model, which included change from baseline for growth velocity Z score as the dependent variable, treatment group and baseline RSS total score stratification as factors, baseline Z score and age as continuous covariates.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0386
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in LS means
Estimated Value 1.02
Confidence Interval (2-Sided) 95%
0.06 to 1.99
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Change in Growth Velocity Z Score From Baseline to Week 64
Hide Description 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.
Time Frame Baseline, Week 64
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Active Control Burosumab
Hide Arm/Group Description:
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 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.
Overall Number of Participants Analyzed 22 22
Least Squares Mean (Standard Error)
Unit of Measure: Z score
0.41  (0.265) 1.53  (0.264)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Active Control, Burosumab
Comments LS mean, SE, CI, and 2-sided p value per ANCOVA model, which included change from baseline for growth velocity Z score as the dependent variable, treatment group and baseline RSS total score stratification as factors, baseline Z score and age as continuous covariates.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0047
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in LS means
Estimated Value 1.12
Confidence Interval (2-Sided) 95%
0.37 to 1.88
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Change From Baseline Over Time in Serum Phosphorus Concentration, up to Week 64
Hide Description 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.
Time Frame Baseline, Weeks 1, 2, 4, 8, 12, 16, 24, 32, 33, 40, 52, 64
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Active Control Burosumab
Hide Arm/Group Description:
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 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.
Overall Number of Participants Analyzed 32 29
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
Week 1 Number Analyzed 31 participants 28 participants
0.22  (0.072) 1.26  (0.094)
Week 2 Number Analyzed 0 participants 26 participants
1.14  (0.098)
Week 4 Number Analyzed 32 participants 29 participants
0.18  (0.061) 1.21  (0.102)
Week 8 Number Analyzed 32 participants 29 participants
0.21  (0.064) 0.99  (0.074)
Week 12 Number Analyzed 0 participants 26 participants
1.01  (0.072)
Week 16 Number Analyzed 29 participants 29 participants
0.24  (0.063) 0.87  (0.072)
Week 24 Number Analyzed 32 participants 29 participants
0.27  (0.073) 0.78  (0.077)
Week 32 Number Analyzed 32 participants 29 participants
0.23  (0.063) 0.93  (0.073)
Week 33 Number Analyzed 0 participants 27 participants
1.23  (0.106)
Week 40 Number Analyzed 32 participants 29 participants
0.20  (0.062) 0.92  (0.080)
Week 52 Number Analyzed 32 participants 29 participants
0.30  (0.082) 0.91  (0.075)
Week 64 Number Analyzed 32 participants 29 participants
0.21  (0.062) 0.91  (0.078)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Active Control, Burosumab
Comments Week 1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference
Estimated Value 1.04
Confidence Interval (2-Sided) 95%
0.81 to 1.27
Estimation Comments Difference (Burosumab - Oral Phosphate/Active Vitamin D)
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Active Control, Burosumab
Comments Week 4
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference
Estimated Value 1.03
Confidence Interval (2-Sided) 95%
0.79 to 1.27
Estimation Comments Difference (Burosumab - Oral Phosphate/Active Vitamin D)
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Active Control, Burosumab
Comments Week 8
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference
Estimated Value 0.78
Confidence Interval (2-Sided) 95%
0.58 to 0.97
Estimation Comments Difference (Burosumab - Oral Phosphate/Active Vitamin D)
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Active Control, Burosumab
Comments Week 16
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference
Estimated Value 0.63
Confidence Interval (2-Sided) 95%
0.44 to 0.81
Estimation Comments Difference (Burosumab - Oral Phosphate/Active Vitamin D)
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Active Control, Burosumab
Comments Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference
Estimated Value 0.51
Confidence Interval (2-Sided) 95%
0.30 to 0.72
Estimation Comments Difference (Burosumab - Oral Phosphate/Active Vitamin D)
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Active Control, Burosumab
Comments Week 32
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference
Estimated Value 0.70
Confidence Interval (2-Sided) 95%
0.51 to 0.89
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Active Control, Burosumab
Comments Week 40
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference
Estimated Value 0.71
Confidence Interval (2-Sided) 95%
0.51 to 0.91
Estimation Comments Difference (burosumab - Oral Phosphate/Active Vitamin D)
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Active Control, Burosumab
Comments Week 52
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference
Estimated Value 0.61
Confidence Interval (2-Sided) 95%
0.39 to 0.82
Estimation Comments [Not Specified]
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Active Control, Burosumab
Comments Week 64
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference
Estimated Value 0.69
Confidence Interval (2-Sided) 95%
0.49 to 0.90
Estimation Comments [Not Specified]
14.Secondary Outcome
Title Change From Baseline Over Time in Serum Phosphorus Concentration, Weeks 66-112
Hide Description [Not Specified]
Time Frame Baseline, Weeks 66, 68, 76, 88, 100, 112
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Active Control Burosumab
Hide Arm/Group Description:
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 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.
Overall Number of Participants Analyzed 26 22
Mean (Standard Deviation)
Unit of Measure: mg/dL
Week 66 Number Analyzed 26 participants 0 participants
0.05  (0.235)
Week 68 Number Analyzed 26 participants 1 participants
1.17  (0.472) 1.10 [1]   (NA)
Week 76 Number Analyzed 22 participants 22 participants
0.90  (0.324) 0.92  (0.324)
Week 88 Number Analyzed 16 participants 11 participants
0.98  (0.433) 1.00  (0.576)
Week 100 Number Analyzed 7 participants 2 participants
0.99  (0.445) 1.00  (0.424)
Week 112 Number Analyzed 5 participants 2 participants
1.26  (0.508) 1.10  (0.283)
[1]
1 participant analyzed
15.Secondary Outcome
Title Change From Baseline in Mean Post-Baseline Serum Phosphorus Level to Week 64
Hide Description 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.
Time Frame Baseline, Weeks 1, 4, 8, 16, 24, 32, 40, 52, 64
Hide Outcome Measure Data
Hide Analysis Population Description
PD Analysis Set: all participants who received at least one dose of study therapy and had evaluable serum data.
Arm/Group Title Active Control Burosumab
Hide Arm/Group Description:
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 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.
Overall Number of Participants Analyzed 32 29
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
0.24  (0.058) 0.98  (0.061)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Active Control, Burosumab
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in LS means
Estimated Value 0.74
Confidence Interval (2-Sided) 95%
0.58 to 0.91
Estimation Comments Difference (KRN23 - Oral Phosphate/Active Vitamin D)
16.Secondary Outcome
Title Change From Baseline in Mean Post-Baseline Serum Phosphorus Level to Week 140 (During Treatment With Burosumab)
Hide Description [Not Specified]
Time Frame 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, 140
Hide Outcome Measure Data
Hide Analysis Population Description
PD Analysis Set: all participants who received at least one dose of study therapy and had evaluable serum data.
Arm/Group Title Active Control Burosumab
Hide Arm/Group Description:
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 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.
Overall Number of Participants Analyzed 26 29
Mean (Standard Deviation)
Unit of Measure: mg/dL
1.05  (0.310) 0.93  (0.336)
17.Secondary Outcome
Title Percentage of Participants Reaching the Normal Range of Serum Phosphorus Concentration (3.2 - 6.1 mg/dL)
Hide Description [Not Specified]
Time Frame Burosumab arm: Baseline, up to Week 140; Active Control arm: Baseline, Week 68 up to Week 140
Hide Outcome Measure Data
Hide Analysis Population Description
PD Analysis Set: all participants who received at least one dose of study therapy and had evaluable serum data.
Arm/Group Title Active Control Burosumab
Hide Arm/Group Description:
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 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.
Overall Number of Participants Analyzed 32 29
Measure Type: Number
Unit of Measure: percentage of participants
75.0 96.6
18.Secondary Outcome
Title Change From Baseline Over Time in 1,25-Dihydroxyvitamin D, up to Week 64
Hide Description 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.
Time Frame Baseline, Weeks 1, 2, 4, 8, 12, 16, 24, 32, 33, 40, 52, 64
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Active Control Burosumab
Hide Arm/Group Description:
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 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.
Overall Number of Participants Analyzed 30 28
Least Squares Mean (Standard Error)
Unit of Measure: pg/mL
Week 1 Number Analyzed 29 participants 27 participants
19.81  (2.758) 68.09  (5.251)
Week 2 Number Analyzed 0 participants 24 participants
31.78  (5.130)
Week 4 Number Analyzed 30 participants 27 participants
12.77  (2.998) 33.86  (3.561)
Week 8 Number Analyzed 30 participants 28 participants
15.10  (2.528) 30.85  (3.830)
Week 12 Number Analyzed 0 participants 24 participants
33.43  (3.176)
Week 16 Number Analyzed 27 participants 28 participants
19.41  (3.757) 32.38  (3.032)
Week 24 Number Analyzed 28 participants 27 participants
17.46  (2.905) 28.35  (3.113)
Week 32 Number Analyzed 29 participants 28 participants
17.25  (3.156) 23.49  (2.439)
Week 33 Number Analyzed 0 participants 24 participants
31.50  (3.423)
Week 40 Number Analyzed 27 participants 25 participants
18.42  (3.594) 29.63  (3.721)
Week 52 Number Analyzed 29 participants 27 participants
8.74  (3.866) 13.75  (2.862)
Week 64 Number Analyzed 29 participants 27 participants
1.19  (2.785) 9.89  (2.235)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Active Control, Burosumab
Comments Week 1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference
Estimated Value 48.27
Confidence Interval (2-Sided) 95%
36.53 to 60.02
Estimation Comments Difference (Burosumab - Oral Phosphate/Active Vitamin D)
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Active Control, Burosumab
Comments Week 4
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference
Estimated Value 21.09
Confidence Interval (2-Sided) 95%
12.01 to 30.16
Estimation Comments Difference (Burosumab - Oral Phosphate/Active Vitamin D)
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Active Control, Burosumab
Comments Week 8
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0010
Comments [Not Specified]
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference
Estimated Value 15.75
Confidence Interval (2-Sided) 95%
6.35 to 25.15
Estimation Comments Difference (Burosumab - Oral Phosphate/Active Vitamin D)
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Active Control, Burosumab
Comments Week 16
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0078
Comments [Not Specified]
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference
Estimated Value 12.97
Confidence Interval (2-Sided) 95%
3.41 to 22.53
Estimation Comments Difference (Burosumab - Oral Phosphate/Active Vitamin D)
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Active Control, Burosumab
Comments Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0101
Comments [Not Specified]
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference
Estimated Value 10.89
Confidence Interval (2-Sided) 95%
2.59 to 19.19
Estimation Comments Difference (Burosumab - Oral Phosphate/Active Vitamin D)
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Active Control, Burosumab
Comments Week 32
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1165
Comments [Not Specified]
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference
Estimated Value 6.23
Confidence Interval (2-Sided) 95%
-1.55 to 14.02
Estimation Comments Difference (Burosumab - Oral Phosphate/Active Vitamin D)
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Active Control, Burosumab
Comments Week 40
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0317
Comments [Not Specified]
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference
Estimated Value 11.21
Confidence Interval (2-Sided) 95%
0.98 to 21.44
Estimation Comments Difference (Burosumab - Oral Phosphate/Active Vitamin D)
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Active Control, Burosumab
Comments Week 52
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3044
Comments [Not Specified]
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference
Estimated Value 5.01
Confidence Interval (2-Sided) 95%
-4.55 to 14.56
Estimation Comments Difference (Burosumab - Oral Phosphate/Active Vitamin D)
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Active Control, Burosumab
Comments Week 64
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0145
Comments [Not Specified]
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference
Estimated Value 8.70
Confidence Interval (2-Sided) 95%
1.72 to 15.68
Estimation Comments Difference (Burosumab - Oral Phosphate/Active Vitamin D
19.Secondary Outcome
Title Change From Baseline Over Time in 1,25-Dihydroxyvitamin D, Weeks 68 to 112
Hide Description [Not Specified]
Time Frame Baseline, Weeks 68, 76, 88, 100, 112
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Active Control Burosumab
Hide Arm/Group Description:
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 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.
Overall Number of Participants Analyzed 25 21
Mean (Standard Deviation)
Unit of Measure: pg/mL
Week 68 Number Analyzed 25 participants 1 participants
22.12  (23.950) -9.80 [1]   (NA)
Week 76 Number Analyzed 21 participants 21 participants
19.05  (22.612) 12.80  (20.093)
Week 88 Number Analyzed 14 participants 10 participants
24.58  (17.787) 11.76  (22.874)
Week 100 Number Analyzed 6 participants 2 participants
33.57  (16.591) 13.25  (1.061)
Week 112 Number Analyzed 5 participants 2 participants
29.94  (15.402) 31.05  (33.729)
[1]
1 participant analyzed
20.Secondary Outcome
Title Change From Baseline Over Time in TmP/GFR, up to Week 64
Hide Description

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.

Time Frame Baseline, Weeks 4, 8, 16, 24, 32, 40, 52, 64
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Active Control Burosumab
Hide Arm/Group Description:
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 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.
Overall Number of Participants Analyzed 30 24
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
Week 4 Number Analyzed 28 participants 23 participants
-0.17  (0.065) 1.48  (0.173)
Week 8 Number Analyzed 27 participants 24 participants
-0.20  (0.057) 1.22  (0.101)
Week 16 Number Analyzed 26 participants 24 participants
-0.15  (0.085) 1.00  (0.139)
Week 24 Number Analyzed 29 participants 23 participants
-0.12  (0.072) 0.99  (0.134)
Week 32 Number Analyzed 29 participants 22 participants
-0.10  (0.062) 1.14  (0.115)
Week 40 Number Analyzed 28 participants 23 participants
-0.15  (0.053) 1.20  (0.113)
Week 52 Number Analyzed 28 participants 22 participants
-0.12  (0.069) 1.13  (0.124)
Week 64 Number Analyzed 30 participants 23 participants
-0.09  (0.070) 1.16  (0.127)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Active Control, Burosumab
Comments Week 4
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference
Estimated Value 1.65
Confidence Interval (2-Sided) 95%
1.28 to 2.02
Estimation Comments Difference (Burosumab - Oral Phosphate/Active Vitamin D)
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Active Control, Burosumab
Comments Week 8
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference
Estimated Value 1.42
Confidence Interval (2-Sided) 95%
1.19 to 1.64
Estimation Comments Difference (Burosumab - Oral Phosphate/Active Vitamin D)
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Active Control, Burosumab
Comments Week 16
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference
Estimated Value 1.16
Confidence Interval (2-Sided) 95%
0.84 to 1.48
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Active Control, Burosumab
Comments Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference
Estimated Value 1.11
Confidence Interval (2-Sided) 95%
0.80 to 1.41
Estimation Comments Difference (Burosumab - Oral Phosphate/Active Vitamin D)
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Active Control, Burosumab
Comments Week 32
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference
Estimated Value 1.24
Confidence Interval (2-Sided) 95%
0.98 to 1.51
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Active Control, Burosumab
Comments Week 40
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference
Estimated Value 1.35
Confidence Interval (2-Sided) 95%
1.10 to 1.60
Estimation Comments Difference (Burosumab - Oral Phosphate/Active Vitamin D)
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Active Control, Burosumab
Comments Week 52
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference
Estimated Value 1.26
Confidence Interval (2-Sided) 95%
0.97 to 1.54
Estimation Comments Difference (Burosumab - Oral Phosphate/Active Vitamin D)
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Active Control, Burosumab
Comments Week 64
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference
Estimated Value 1.25
Confidence Interval (2-Sided) 95%
0.96 to 1.54
Estimation Comments Difference (Burosumab - Oral Phosphate/Active Vitamin D)
21.Secondary Outcome
Title Change From Baseline Over Time in TmP/GFR, Week 68 to 112
Hide Description Serum phosphorus and TRP measurements were used in the calculation of TmP/GFR.
Time Frame Baseline, Weeks 68, 76, 88, 112
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Active Control Burosumab
Hide Arm/Group Description:
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 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.
Overall Number of Participants Analyzed 24 7
Mean (Standard Deviation)
Unit of Measure: mg/dL
Week 68 Number Analyzed 24 participants 1 participants
1.61  (0.705) 1.65 [1]   (NA)
Week 76 Number Analyzed 4 participants 4 participants
1.18  (0.758) 0.59  (0.429)
Week 88 Number Analyzed 14 participants 7 participants
1.33  (0.480) 0.95  (0.620)
Week 112 Number Analyzed 3 participants 2 participants
1.56  (0.233) 1.32  (0.233)
[1]
1 participant analyzed
22.Secondary Outcome
Title Change From Baseline Over Time in Serum ALP, up to Week 64
Hide Description 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.
Time Frame Baseline, Weeks 16, 24, 40, 52, 64
Hide Outcome Measure Data
Hide Analysis Population Description
PD Analysis Set: all participants who received at least one dose of study therapy and had evaluable serum data.
Arm/Group Title Active Control Burosumab
Hide Arm/Group Description:
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 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.
Overall Number of Participants Analyzed 32 29
Least Squares Mean (Standard Error)
Unit of Measure: U/L
Week 16 -5.43  (17.885) -97.97  (11.281)
Week 24 -22.43  (15.074) -108.00  (16.225)
Week 40 -34.78  (18.132) -130.72  (12.365)
Week 52 -50.03  (18.641) -161.31  (11.674)
Week 64 -28.06  (19.980) -174.62  (13.427)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Active Control, Burosumab
Comments Week 16
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference
Estimated Value -92.53
Confidence Interval (2-Sided) 95%
-131.40 to -53.66
Estimation Comments Difference (Burosumab - Oral Phosphate/Active Vitamin D)
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Active Control, Burosumab
Comments Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference
Estimated Value -85.57
Confidence Interval (2-Sided) 95%
-126.37 to -44.76
Estimation Comments Difference (Burosumab - Oral Phosphate/Active Vitamin D)
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Active Control, Burosumab
Comments Week 40
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference
Estimated Value -95.95
Confidence Interval (2-Sided) 95%
-136.05 to -55.84
Estimation Comments Difference (Burosumab - Oral Phosphate/Active Vitamin D)
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Active Control, Burosumab
Comments Week 52
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference
Estimated Value -111.28
Confidence Interval (2-Sided) 95%
-152.08 to -70.49
Estimation Comments Difference (Burosumab - Oral Phosphate/Active Vitamin D)
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Active Control, Burosumab
Comments Week 64
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference
Estimated Value -146.56
Confidence Interval (2-Sided) 95%
-191.61 to -101.52
Estimation Comments Difference (Burosumab - Oral Phosphate/Active Vitamin D)
23.Secondary Outcome
Title Change From Baseline Over Time in Serum ALP, Week 68 to 112
Hide Description [Not Specified]
Time Frame Baseline, Weeks 68, 76, 88, 100, 112
Hide Outcome Measure Data
Hide Analysis Population Description
PD Analysis Set: all participants who received at least one dose of study therapy and had evaluable serum data.
Arm/Group Title Active Control Burosumab
Hide Arm/Group Description:
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 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.
Overall Number of Participants Analyzed 26 22
Mean (Standard Deviation)
Unit of Measure: U/L
Week 68 Number Analyzed 26 participants 1 participants
-82.73  (83.683) -184.00 [1]   (NA)
Week 76 Number Analyzed 22 participants 22 participants
-106.73  (73.316) -166.73  (87.700)
Week 88 Number Analyzed 16 participants 11 participants
-146.56  (73.120) -154.55  (48.148)
Week 100 Number Analyzed 7 participants 2 participants
-83.14  (104.675) -184.00  (48.083)
Week 112 Number Analyzed 5 participants 2 participants
-104.80  (80.350) -172.00  (26.870)
[1]
1 participant analyzed
24.Secondary Outcome
Title Percent Change From Baseline Over Time in Serum ALP, up to Week 112
Hide Description Decreases indicate improvement.
Time Frame Baseline, Weeks 16, 24, 40, 52, 64, 68, 76, 88, 100, 112
Hide Outcome Measure Data
Hide Analysis Population Description
PD Analysis Set: all participants who received at least one dose of study therapy and had evaluable serum data.
Arm/Group Title Active Control Burosumab
Hide Arm/Group Description:
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 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.
Overall Number of Participants Analyzed 32 29
Mean (Standard Deviation)
Unit of Measure: percent change
Week 16 Number Analyzed 29 participants 29 participants
0.41  (21.021) -18.39  (10.815)
Week 24 Number Analyzed 32 participants 29 participants
-3.21  (15.827) -19.88  (17.642)
Week 40 Number Analyzed 32 participants 29 participants
-6.85  (16.493) -24.38  (13.498)
Week 52 Number Analyzed 32 participants 29 participants
-8.60  (19.027) -30.60  (11.852)
Week 64 Number Analyzed 32 participants 29 participants
-4.60  (20.711) -32.78  (13.095)
Week 68 Number Analyzed 26 participants 1 participants
-14.66  (14.760) -38.02 [1]   (NA)
Week 76 Number Analyzed 22 participants 22 participants
-20.49  (13.926) -31.42  (13.422)
Week 88 Number Analyzed 16 participants 11 participants
-28.77  (12.201) -32.02  (10.610)
Week 100 Number Analyzed 7 participants 2 participants
-16.06  (23.703) -39.29  (11.460)
Week 112 Number Analyzed 5 participants 2 participants
-21.00  (15.053) -36.67  (6.868)
[1]
1 participant analyzed
25.Secondary Outcome
Title 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
Hide Description 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.
Time Frame Baseline, Week 40
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Active Control Burosumab
Hide Arm/Group Description:
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 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.
Overall Number of Participants Analyzed 20 15
Least Squares Mean (Standard Error)
Unit of Measure: T-score
Pain Interference Domain Score -0.29  (1.539) -5.31  (1.705)
Physical Function Mobility Domain Score 0.10  (0.966) 2.78  (1.336)
Fatigue Domain Score -1.05  (1.754) -4.29  (1.709)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Active Control, Burosumab
Comments Pain Interference Domain. 2-sided p value per GEE model, which included change from baseline for the parameter as the dependent variable, treatment group, visit, interaction between treatment group by visit, baseline age and baseline RSS stratification as factors, baseline parameter measure as a covariate, with exchangeable covariance structure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0212
Comments [Not Specified]
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in LS means
Estimated Value -5.02
Confidence Interval (2-Sided) 95%
-9.29 to -0.75
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Active Control, Burosumab
Comments Physical Function Mobility Domain. 2-sided p value per GEE model, which included change from baseline for the parameter as the dependent variable, treatment group, visit, interaction between treatment group by visit, baseline age and baseline RSS stratification as factors, baseline parameter measure as a covariate, with exchangeable covariance structure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1009
Comments [Not Specified]
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in LS means
Estimated Value 2.68
Confidence Interval (2-Sided) 95%
-0.52 to 5.89
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Active Control, Burosumab
Comments Fatigue Domain. 2-sided p value per GEE model, which included change from baseline for the parameter as the dependent variable, treatment group, visit, interaction between treatment group by visit, baseline age and baseline RSS stratification as factors, baseline parameter measure as a covariate, with exchangeable covariance structure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1676
Comments [Not Specified]
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in LS means
Estimated Value -3.25
Confidence Interval (2-Sided) 95%
-7.86 to 1.37
Estimation Comments [Not Specified]
26.Secondary Outcome
Title 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
Hide Description 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.
Time Frame Baseline, Week 64
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Active Control Burosumab
Hide Arm/Group Description:
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 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.
Overall Number of Participants Analyzed 20 15
Least Squares Mean (Standard Error)
Unit of Measure: T-score
Pain Interference Domain Score -1.29  (1.267) -3.55  (1.873)
Physical Function Mobility Domain Score 0.92  (0.962) 2.82  (1.648)
Fatigue Domain Score -2.57  (1.547) -3.65  (2.119)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Active Control, Burosumab
Comments Pain Interference Domain. 2-sided p value per GEE model, which included change from baseline for the parameter as the dependent variable, treatment group, visit, interaction between treatment group by visit, baseline age and baseline RSS stratification as factors, baseline parameter measure as a covariate, with exchangeable covariance structure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3091
Comments [Not Specified]
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in LS means
Estimated Value -2.26
Confidence Interval (2-Sided) 95%
-6.61 to 2.09
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Active Control, Burosumab
Comments Physical Function Mobility Domain. 2-sided p value per GEE model, which included change from baseline for the parameter as the dependent variable, treatment group, visit, interaction between treatment group by visit, baseline age and baseline RSS stratification as factors, baseline parameter measure as a covariate, with exchangeable covariance structure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3145
Comments [Not Specified]
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in LS means
Estimated Value 1.90
Confidence Interval (2-Sided) 95%
-1.80 to 5.59
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Active Control, Burosumab
Comments Fatigue Domain. 2-sided p value per GEE model, which included change from baseline for the parameter as the dependent variable, treatment group, visit, interaction between treatment group by visit, baseline age and baseline RSS stratification as factors, baseline parameter measure as a covariate, with exchangeable covariance structure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6810
Comments [Not Specified]
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in LS means
Estimated Value -1.08
Confidence Interval (2-Sided) 95%
-6.21 to 4.06
Estimation Comments [Not Specified]
27.Secondary Outcome
Title Change From Baseline in the FPS-R (For Participants ≥ 5 Years of Age at the Screening Visit) at Week 40
Hide Description 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.
Time Frame Baseline, Week 40
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Active Control Burosumab
Hide Arm/Group Description:
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 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.
Overall Number of Participants Analyzed 20 15
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
0.02  (0.323) 0.03  (0.323)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Active Control, Burosumab
Comments GEE model includes change from baseline for FPS-R as the dependent variable, treatment group, visit, interaction between treatment group by visit and baseline RSS stratification as factors, baseline FPS-R as a covariate, with exchangeable covariance structure. The LS Mean, SE, 95% CI and 2-sided p-value are from the GEE model.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9862
Comments [Not Specified]
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value 0.01
Confidence Interval (2-Sided) 95%
-0.79 to 0.80
Estimation Comments [Not Specified]
28.Secondary Outcome
Title Change From Baseline in the FPS-R (For Participants ≥ 5 Years of Age at the Screening Visit) at Week 64
Hide Description 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.
Time Frame Baseline, Week 64
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Active Control Burosumab
Hide Arm/Group Description:
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 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.
Overall Number of Participants Analyzed 19 15
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
0.04  (0.270) -0.01  (0.234)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Active Control, Burosumab
Comments GEE model includes change from baseline for FPS-R as the dependent variable, treatment group, visit, interaction between treatment group by visit and baseline RSS stratification as factors, baseline FPS-R as a covariate, with exchangeable covariance structure. The LS Mean, SE, 95% CI and 2-sided p-value are from the GEE model.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8786
Comments [Not Specified]
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in LS means
Estimated Value 0.05
Confidence Interval (2-Sided) 95%
-0.58 to 0.68
Estimation Comments [Not Specified]
29.Secondary Outcome
Title Change From Baseline in the 6MWT Total Distance at Week 40
Hide Description 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.
Time Frame Baseline, Week 40
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Active Control Burosumab
Hide Arm/Group Description:
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 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.
Overall Number of Participants Analyzed 20 13
Least Squares Mean (Standard Error)
Unit of Measure: meters
3.65  (14.060) 47.10  (15.768)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Active Control, Burosumab
Comments 2-sided p value per GEE model, which included change from baseline for the parameter as the dependent variable, treatment group, visit, interaction between treatment group by visit, baseline age and baseline RSS stratification as factors, baseline parameter measure as a covariate, with exchangeable covariance structure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0514
Comments [Not Specified]
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in LS means
Estimated Value 43.46
Confidence Interval (2-Sided) 95%
-0.26 to 87.17
Estimation Comments [Not Specified]
30.Secondary Outcome
Title Change From Baseline in the 6MWT Total Distance at Week 64
Hide Description 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.
Time Frame Baseline, Week 64
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Active Control Burosumab
Hide Arm/Group Description:
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 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.
Overall Number of Participants Analyzed 20 13
Least Squares Mean (Standard Error)
Unit of Measure: meters
29.28  (16.834) 74.83  (12.513)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Active Control, Burosumab
Comments 2-sided p value per GEE model, which included change from baseline for the parameter as the dependent variable, treatment group, visit, interaction between treatment group by visit, baseline age and baseline RSS stratification as factors, baseline parameter measure as a covariate, with exchangeable covariance structure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0399
Comments [Not Specified]
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in LS means
Estimated Value 45.55
Confidence Interval (2-Sided) 95%
2.09 to 89.02
Estimation Comments [Not Specified]
31.Secondary Outcome
Title Percent of Predicted Normal in the 6MWT Total Distance at Week 40
Hide Description 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.
Time Frame Baseline, Week 40
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Active Control Burosumab
Hide Arm/Group Description:
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 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.
Overall Number of Participants Analyzed 20 13
Least Squares Mean (Standard Error)
Unit of Measure: percent of predicted meters
-1.14  (2.224) 5.59  (2.633)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Active Control, Burosumab
Comments 2-sided p value per GEE model, which included change from baseline for the parameter as the dependent variable, treatment group, visit, interaction between treatment group by visit, baseline age and baseline RSS stratification as factors, baseline parameter measure as a covariate, with exchangeable covariance structure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0633
Comments [Not Specified]
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in LS means
Estimated Value 6.72
Confidence Interval (2-Sided) 95%
-0.37 to 13.82
Estimation Comments [Not Specified]
32.Secondary Outcome
Title Percent of Predicted Normal in the 6MWT Total Distance at Week 64
Hide Description 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.
Time Frame Baseline, Week 64
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Active Control Burosumab
Hide Arm/Group Description:
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 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.
Overall Number of Participants Analyzed 20 13
Least Squares Mean (Standard Error)
Unit of Measure: percent of predicted meters
1.88  (2.789) 9.15  (2.056)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Active Control, Burosumab
Comments 2-sided p value per GEE model, which included change from baseline for the parameter as the dependent variable, treatment group, visit, interaction between treatment group by visit, baseline age and baseline RSS stratification as factors, baseline parameter measure as a covariate, with exchangeable covariance structure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0496
Comments [Not Specified]
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in LS means
Estimated Value 7.27
Confidence Interval (2-Sided) 95%
0.01 to 14.52
Estimation Comments [Not Specified]
Time Frame Up to Week 64 in the Treatment Period and up to Week 140 in the Long Term Extension Period, plus up to 12 weeks ±1 week after the last dose of study drug.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Oral Phosphate/Active Vitamin D (Treatment Period) Burosumab (Treatment Period) Oral Phosphate/Active Vitamin D->Burosumab (Extension Period) Burosumab->Burosumab (Treatment Period and Extension Period) Total Burosumab (Treatment Period and Extension Period)
Hide Arm/Group Description 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 0.8 mg/kg starting dose, administered Q2W by SC injection during the Treatment Period (up to Week 64). 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 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. Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection at any time during the study.
All-Cause Mortality
Oral Phosphate/Active Vitamin D (Treatment Period) Burosumab (Treatment Period) Oral Phosphate/Active Vitamin D->Burosumab (Extension Period) Burosumab->Burosumab (Treatment Period and Extension Period) Total Burosumab (Treatment Period and Extension Period)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/32 (0.00%)   0/29 (0.00%)   0/26 (0.00%)   0/29 (0.00%)   0/55 (0.00%) 
Hide Serious Adverse Events
Oral Phosphate/Active Vitamin D (Treatment Period) Burosumab (Treatment Period) Oral Phosphate/Active Vitamin D->Burosumab (Extension Period) Burosumab->Burosumab (Treatment Period and Extension Period) Total Burosumab (Treatment Period and Extension Period)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   3/32 (9.38%)   3/29 (10.34%)   0/26 (0.00%)   4/29 (13.79%)   4/55 (7.27%) 
Congenital, familial and genetic disorders           
Craniosynostosis  1  1/32 (3.13%)  1/29 (3.45%)  0/26 (0.00%)  1/29 (3.45%)  1/55 (1.82%) 
Eye disorders           
Papilloedema  1  0/32 (0.00%)  0/29 (0.00%)  0/26 (0.00%)  1/29 (3.45%)  1/55 (1.82%) 
Infections and infestations           
Viral Infection  1  0/32 (0.00%)  1/29 (3.45%)  0/26 (0.00%)  1/29 (3.45%)  1/55 (1.82%) 
Musculoskeletal and connective tissue disorders           
Knee Deformity  1  1/32 (3.13%)  0/29 (0.00%)  0/26 (0.00%)  0/29 (0.00%)  0/55 (0.00%) 
Nervous system disorders           
Migraine  1  0/32 (0.00%)  1/29 (3.45%)  0/26 (0.00%)  1/29 (3.45%)  1/55 (1.82%) 
Renal and urinary disorders           
Haematuria  1  1/32 (3.13%)  0/29 (0.00%)  0/26 (0.00%)  0/29 (0.00%)  0/55 (0.00%) 
1
Term from vocabulary, MedDRA 18.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Oral Phosphate/Active Vitamin D (Treatment Period) Burosumab (Treatment Period) Oral Phosphate/Active Vitamin D->Burosumab (Extension Period) Burosumab->Burosumab (Treatment Period and Extension Period) Total Burosumab (Treatment Period and Extension Period)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   23/32 (71.88%)   21/29 (72.41%)   9/26 (34.62%)   25/29 (86.21%)   34/55 (61.82%) 
Congenital, familial and genetic disorders           
Tooth Hypoplasia  1  0/32 (0.00%)  2/29 (6.90%)  0/26 (0.00%)  2/29 (6.90%)  2/55 (3.64%) 
Ear and labyrinth disorders           
Ear Discomfort  1  0/32 (0.00%)  1/29 (3.45%)  0/26 (0.00%)  2/29 (6.90%)  2/55 (3.64%) 
Ear Pain  1  1/32 (3.13%)  4/29 (13.79%)  2/26 (7.69%)  4/29 (13.79%)  6/55 (10.91%) 
Gastrointestinal disorders           
Abdominal Discomfort  1  2/32 (6.25%)  2/29 (6.90%)  1/26 (3.85%)  2/29 (6.90%)  3/55 (5.45%) 
Abdominal Pain  1  1/32 (3.13%)  2/29 (6.90%)  1/26 (3.85%)  2/29 (6.90%)  3/55 (5.45%) 
Abdominal Pain Upper  1  3/32 (9.38%)  3/29 (10.34%)  2/26 (7.69%)  4/29 (13.79%)  6/55 (10.91%) 
Constipation  1  0/32 (0.00%)  5/29 (17.24%)  2/26 (7.69%)  5/29 (17.24%)  7/55 (12.73%) 
Dental Caries  1  2/32 (6.25%)  9/29 (31.03%)  0/26 (0.00%)  10/29 (34.48%)  10/55 (18.18%) 
Diarrhoea  1  2/32 (6.25%)  7/29 (24.14%)  1/26 (3.85%)  7/29 (24.14%)  8/55 (14.55%) 
Haematochezia  1  0/32 (0.00%)  1/29 (3.45%)  0/26 (0.00%)  2/29 (6.90%)  2/55 (3.64%) 
Nausea  1  1/32 (3.13%)  3/29 (10.34%)  2/26 (7.69%)  5/29 (17.24%)  7/55 (12.73%) 
Teething  1  0/32 (0.00%)  2/29 (6.90%)  1/26 (3.85%)  2/29 (6.90%)  3/55 (5.45%) 
Tooth Loss  1  0/32 (0.00%)  1/29 (3.45%)  1/26 (3.85%)  2/29 (6.90%)  3/55 (5.45%) 
Toothache  1  1/32 (3.13%)  4/29 (13.79%)  1/26 (3.85%)  5/29 (17.24%)  6/55 (10.91%) 
Vomiting  1  8/32 (25.00%)  12/29 (41.38%)  5/26 (19.23%)  14/29 (48.28%)  19/55 (34.55%) 
General disorders           
Fatigue  1  2/32 (6.25%)  1/29 (3.45%)  1/26 (3.85%)  2/29 (6.90%)  3/55 (5.45%) 
Injection Site Bruising  1  0/32 (0.00%)  0/29 (0.00%)  2/26 (7.69%)  1/29 (3.45%)  3/55 (5.45%) 
Injection Site Erosion  1  0/32 (0.00%)  2/29 (6.90%)  0/26 (0.00%)  2/29 (6.90%)  2/55 (3.64%) 
Injection Site Erythema  1  0/32 (0.00%)  9/29 (31.03%)  6/26 (23.08%)  9/29 (31.03%)  15/55 (27.27%) 
Injection Site Pruritus  1  0/32 (0.00%)  3/29 (10.34%)  2/26 (7.69%)  3/29 (10.34%)  5/55 (9.09%) 
Injection Site Rash  1  0/32 (0.00%)  3/29 (10.34%)  0/26 (0.00%)  3/29 (10.34%)  3/55 (5.45%) 
Injection Site Reaction  1  0/32 (0.00%)  7/29 (24.14%)  2/26 (7.69%)  8/29 (27.59%)  10/55 (18.18%) 
Injection Site Swelling  1  0/32 (0.00%)  3/29 (10.34%)  1/26 (3.85%)  3/29 (10.34%)  4/55 (7.27%) 
Injection Site Urticaria  1  0/32 (0.00%)  2/29 (6.90%)  0/26 (0.00%)  2/29 (6.90%)  2/55 (3.64%) 
Pain  1  0/32 (0.00%)  2/29 (6.90%)  0/26 (0.00%)  3/29 (10.34%)  3/55 (5.45%) 
Pyrexia  1  7/32 (21.88%)  16/29 (55.17%)  7/26 (26.92%)  17/29 (58.62%)  24/55 (43.64%) 
Immune system disorders           
Hypersensitivity  1  2/32 (6.25%)  1/29 (3.45%)  0/26 (0.00%)  1/29 (3.45%)  1/55 (1.82%) 
Seasonal Allergy  1  2/32 (6.25%)  4/29 (13.79%)  1/26 (3.85%)  4/29 (13.79%)  5/55 (9.09%) 
Infections and infestations           
Ear Infection  1  3/32 (9.38%)  2/29 (6.90%)  1/26 (3.85%)  3/29 (10.34%)  4/55 (7.27%) 
Gastroenteritis  1  3/32 (9.38%)  2/29 (6.90%)  0/26 (0.00%)  2/29 (6.90%)  2/55 (3.64%) 
Gastroenteritis Viral  1  3/32 (9.38%)  2/29 (6.90%)  0/26 (0.00%)  2/29 (6.90%)  2/55 (3.64%) 
Influenza  1  6/32 (18.75%)  4/29 (13.79%)  0/26 (0.00%)  4/29 (13.79%)  4/55 (7.27%) 
Nasopharyngitis  1  14/32 (43.75%)  11/29 (37.93%)  6/26 (23.08%)  15/29 (51.72%)  21/55 (38.18%) 
Otitis Externa  1  3/32 (9.38%)  0/29 (0.00%)  0/26 (0.00%)  0/29 (0.00%)  0/55 (0.00%) 
Otitis Media  1  4/32 (12.50%)  2/29 (6.90%)  0/26 (0.00%)  3/29 (10.34%)  3/55 (5.45%) 
Pharyngitis Streptococcal  1  1/32 (3.13%)  1/29 (3.45%)  1/26 (3.85%)  2/29 (6.90%)  3/55 (5.45%) 
Pneumonia  1  0/32 (0.00%)  2/29 (6.90%)  0/26 (0.00%)  2/29 (6.90%)  2/55 (3.64%) 
Rhinitis  1  2/32 (6.25%)  2/29 (6.90%)  0/26 (0.00%)  2/29 (6.90%)  2/55 (3.64%) 
Tooth Abscess  1  3/32 (9.38%)  8/29 (27.59%)  2/26 (7.69%)  9/29 (31.03%)  11/55 (20.00%) 
Upper Respiratory Tract Infection  1  3/32 (9.38%)  3/29 (10.34%)  0/26 (0.00%)  3/29 (10.34%)  3/55 (5.45%) 
Varicella  1  0/32 (0.00%)  2/29 (6.90%)  1/26 (3.85%)  2/29 (6.90%)  3/55 (5.45%) 
Viral Upper Respiratory Tract Infection  1  2/32 (6.25%)  0/29 (0.00%)  0/26 (0.00%)  0/29 (0.00%)  0/55 (0.00%) 
Injury, poisoning and procedural complications           
Contusion  1  0/32 (0.00%)  4/29 (13.79%)  0/26 (0.00%)  4/29 (13.79%)  4/55 (7.27%) 
Fall  1  0/32 (0.00%)  3/29 (10.34%)  0/26 (0.00%)  3/29 (10.34%)  3/55 (5.45%) 
Procedural Pain  1  0/32 (0.00%)  2/29 (6.90%)  0/26 (0.00%)  2/29 (6.90%)  2/55 (3.64%) 
Investigations           
Vitamin D Decreased  1  1/32 (3.13%)  6/29 (20.69%)  1/26 (3.85%)  6/29 (20.69%)  7/55 (12.73%) 
Metabolism and nutrition disorders           
Decreased Appetite  1  2/32 (6.25%)  1/29 (3.45%)  0/26 (0.00%)  1/29 (3.45%)  1/55 (1.82%) 
Vitamin D Deficiency  1  1/32 (3.13%)  5/29 (17.24%)  0/26 (0.00%)  5/29 (17.24%)  5/55 (9.09%) 
Musculoskeletal and connective tissue disorders           
Arthralgia  1  10/32 (31.25%)  13/29 (44.83%)  3/26 (11.54%)  13/29 (44.83%)  16/55 (29.09%) 
Back Pain  1  3/32 (9.38%)  2/29 (6.90%)  0/26 (0.00%)  2/29 (6.90%)  2/55 (3.64%) 
Pain In Extremity  1  10/32 (31.25%)  11/29 (37.93%)  3/26 (11.54%)  11/29 (37.93%)  14/55 (25.45%) 
Nervous system disorders           
Headache  1  6/32 (18.75%)  10/29 (34.48%)  3/26 (11.54%)  10/29 (34.48%)  13/55 (23.64%) 
Migraine  1  2/32 (6.25%)  1/29 (3.45%)  1/26 (3.85%)  1/29 (3.45%)  2/55 (3.64%) 
Psychiatric disorders           
Attention Deficit/Hyperactivity Disorder  1  0/32 (0.00%)  0/29 (0.00%)  0/26 (0.00%)  2/29 (6.90%)  2/55 (3.64%) 
Renal and urinary disorders           
Dysuria  1  0/32 (0.00%)  2/29 (6.90%)  0/26 (0.00%)  2/29 (6.90%)  2/55 (3.64%) 
Respiratory, thoracic and mediastinal disorders           
Asthma  1  1/32 (3.13%)  4/29 (13.79%)  0/26 (0.00%)  4/29 (13.79%)  4/55 (7.27%) 
Cough  1  6/32 (18.75%)  15/29 (51.72%)  4/26 (15.38%)  15/29 (51.72%)  19/55 (34.55%) 
Nasal Congestion  1  1/32 (3.13%)  5/29 (17.24%)  1/26 (3.85%)  7/29 (24.14%)  8/55 (14.55%) 
Oropharyngeal Pain  1  1/32 (3.13%)  5/29 (17.24%)  3/26 (11.54%)  6/29 (20.69%)  9/55 (16.36%) 
Rhinitis Allergic  1  0/32 (0.00%)  2/29 (6.90%)  0/26 (0.00%)  2/29 (6.90%)  2/55 (3.64%) 
Rhinorrhoea  1  2/32 (6.25%)  7/29 (24.14%)  3/26 (11.54%)  8/29 (27.59%)  11/55 (20.00%) 
Wheezing  1  0/32 (0.00%)  1/29 (3.45%)  0/26 (0.00%)  2/29 (6.90%)  2/55 (3.64%) 
Skin and subcutaneous tissue disorders           
Erythema  1  0/32 (0.00%)  2/29 (6.90%)  0/26 (0.00%)  2/29 (6.90%)  2/55 (3.64%) 
Rash  1  2/32 (6.25%)  3/29 (10.34%)  0/26 (0.00%)  4/29 (13.79%)  4/55 (7.27%) 
Skin Lesion  1  0/32 (0.00%)  1/29 (3.45%)  0/26 (0.00%)  2/29 (6.90%)  2/55 (3.64%) 
Swelling Face  1  0/32 (0.00%)  1/29 (3.45%)  0/26 (0.00%)  2/29 (6.90%)  2/55 (3.64%) 
1
Term from vocabulary, MedDRA 18.1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Information
Organization: Ultragenyx Pharmaceutical Inc
Phone: 1-888-756-8567
EMail: medinfo@ultragenyx.com
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Responsible Party: Ultragenyx Pharmaceutical Inc
ClinicalTrials.gov Identifier: NCT02915705    
Other Study ID Numbers: UX023-CL301
First Submitted: May 23, 2016
First Posted: September 27, 2016
Results First Submitted: February 28, 2019
Results First Posted: April 11, 2019
Last Update Posted: January 23, 2020