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Trial record 6 of 9 for:    "Hereditary Hypophosphatemic Rickets" | "Calcium"

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 : July 30, 2019
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
Drug: active vitamin D
Enrollment 61
Recruitment Details Results present data as of the cutoff date of 30 July 2018 (date at which all participants completed at least 64 weeks of the study); the study is ongoing with participants in Europe, the US, Canada, and Australia.
Pre-assignment Details  
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).

Participants not in Japan or Korea crossover to burosumab receive 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection in the Treatment Extension Period (up to 140 weeks total study duration).

Burosumab 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection during the Treatment Period (up to Week 64) and the Treatment Extension Period (up to 140 weeks total study duration).
Period Title: Overall Study
Started 32 29
Completed Week 40 32 29
Completed Week 64 32 29
Completed [1] 6 4
Not Completed 26 25
Reason Not Completed
Entered Extension Treatment Period             26             25
[1]
Completed Treatment Period and did not enter Treatment 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).

Participants not in Japan or Korea crossover to burosumab receive 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection in the Treatment Extension Period (up to 140 weeks total study duration).

Burosumab 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection during the Treatment Period (up to Week 64) and the Treatment Extension Period (up to 140 weeks total study duration). 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).

Participants not in Japan or Korea crossover to burosumab receive 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection in the Treatment Extension Period (up to 140 weeks total study duration).

Burosumab 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection during the Treatment Period (up to Week 64) and the Treatment Extension Period (up to 140 weeks total study duration).
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)
Show Statistical Analysis 1 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).

Participants not in Japan or Korea crossover to burosumab receive 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection in the Treatment Extension Period (up to 140 weeks total study duration).

Burosumab 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection during the Treatment Period (up to Week 64) and the Treatment Extension Period (up to 140 weeks total study duration).
Overall Number of Participants Analyzed 32 29
Measure Type: Number
Unit of Measure: percentage of participants
6.3 72.4
Show Statistical Analysis 1 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).

Participants not in Japan or Korea crossover to burosumab receive 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection in the Treatment Extension Period (up to 140 weeks total study duration).

Burosumab 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection during the Treatment Period (up to Week 64) and the Treatment Extension Period (up to 140 weeks total study duration).
Overall Number of Participants Analyzed 32 29
Measure Type: Number
Unit of Measure: percentage of participants
18.8 86.2
Show Statistical Analysis 1 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).

Participants not in Japan or Korea crossover to burosumab receive 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection in the Treatment Extension Period (up to 140 weeks total study duration).

Burosumab 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection during the Treatment Period (up to Week 64) and the Treatment Extension Period (up to 140 weeks total study duration).
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)
Show Statistical Analysis 1 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).

Participants not in Japan or Korea crossover to burosumab receive 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection in the Treatment Extension Period (up to 140 weeks total study duration).

Burosumab 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection during the Treatment Period (up to Week 64) and the Treatment Extension Period (up to 140 weeks total study duration).
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)
Show Statistical Analysis 1 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).

Participants not in Japan or Korea crossover to burosumab receive 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection in the Treatment Extension Period (up to 140 weeks total study duration).

Burosumab 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection during the Treatment Period (up to Week 64) and the Treatment Extension Period (up to 140 weeks total study duration).
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)
Show Statistical Analysis 1 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).

Participants not in Japan or Korea crossover to burosumab receive 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection in the Treatment Extension Period (up to 140 weeks total study duration).

Burosumab 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection during the Treatment Period (up to Week 64) and the Treatment Extension Period (up to 140 weeks total study duration).
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)
Show Statistical Analysis 1 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).

Participants not in Japan or Korea crossover to burosumab receive 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection in the Treatment Extension Period (up to 140 weeks total study duration).

Burosumab 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection during the Treatment Period (up to Week 64) and the Treatment Extension Period (up to 140 weeks total study duration).
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)
Show Statistical Analysis 1 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).

Participants not in Japan or Korea crossover to burosumab receive 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection in the Treatment Extension Period (up to 140 weeks total study duration).

Burosumab 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection during the Treatment Period (up to Week 64) and the Treatment Extension Period (up to 140 weeks total study duration).
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)
Show Statistical Analysis 1 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).

Participants not in Japan or Korea crossover to burosumab receive 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection in the Treatment Extension Period (up to 140 weeks total study duration).

Burosumab 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection during the Treatment Period (up to Week 64) and the Treatment Extension Period (up to 140 weeks total study duration).
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)
Show Statistical Analysis 1 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).

Participants not in Japan or Korea crossover to burosumab receive 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection in the Treatment Extension Period (up to 140 weeks total study duration).

Burosumab 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection during the Treatment Period (up to Week 64) and the Treatment Extension Period (up to 140 weeks total study duration).
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)
Show Statistical Analysis 1 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).

Participants not in Japan or Korea crossover to burosumab receive 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection in the Treatment Extension Period (up to 140 weeks total study duration).

Burosumab 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection during the Treatment Period (up to Week 64) and the Treatment Extension Period (up to 140 weeks total study duration).
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)
Show Statistical Analysis 1 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 in Serum Phosphorus Concentration at Week 40
Hide Description [Not Specified]
Time Frame Baseline, Week 40
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.
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).

Participants not in Japan or Korea crossover to burosumab receive 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection in the Treatment Extension Period (up to 140 weeks total study duration).

Burosumab 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection during the Treatment Period (up to Week 64) and the Treatment Extension Period (up to 140 weeks total study duration).
Overall Number of Participants Analyzed 32 29
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
0.20  (0.061) 0.92  (0.080)
Show Statistical Analysis 1 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 < 0.0001
Comments [Not Specified]
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in LS means
Estimated Value 0.71
Confidence Interval (2-Sided) 95%
0.52 to 0.91
Estimation Comments [Not Specified]
14.Secondary Outcome
Title Change From Baseline in Serum Phosphorus Concentration at Week 64
Hide Description [Not Specified]
Time Frame Baseline, Week 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).

Participants not in Japan or Korea crossover to burosumab receive 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection in the Treatment Extension Period (up to 140 weeks total study duration).

Burosumab 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection during the Treatment Period (up to Week 64) and the Treatment Extension Period (up to 140 weeks total study duration).
Overall Number of Participants Analyzed 32 29
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
0.21  (0.062) 0.91  (0.078)
Show Statistical Analysis 1 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 < 0.0001
Comments [Not Specified]
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in LS means
Estimated Value 0.69
Confidence Interval (2-Sided) 95%
0.49 to 0.90
Estimation Comments [Not Specified]
15.Secondary Outcome
Title Change From Baseline in Mean Post-Baseline Serum Phosphorus Level to Week 40
Hide Description [Not Specified]
Time Frame Baseline, Week 1, 4, 8, 16, 24, 32, and 40
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).

Participants not in Japan or Korea crossover to burosumab receive 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection in the Treatment Extension Period (up to 140 weeks total study duration).

Burosumab 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection during the Treatment Period (up to Week 64) and the Treatment Extension Period (up to 140 weeks total study duration).
Overall Number of Participants Analyzed 32 29
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
0.23  (0.058) 1.00  (0.062)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Active Control, Burosumab
Comments 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. The LS Mean, SE, 95% CI and 2-sided p-value are from the ANCOVA model.
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 0.77
Confidence Interval (2-Sided) 95%
0.60 to 0.94
Estimation Comments [Not Specified]
16.Secondary Outcome
Title Change From Baseline in Mean Post-Baseline Serum Phosphorus Level to Week 64
Hide Description [Not Specified]
Time Frame Baseline, Week 1, 4, 8, 16, 24, 32, 40, 52 and 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).

Participants not in Japan or Korea crossover to burosumab receive 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection in the Treatment Extension Period (up to 140 weeks total study duration).

Burosumab 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection during the Treatment Period (up to Week 64) and the Treatment Extension Period (up to 140 weeks total study duration).
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)
Show Statistical Analysis 1 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 [Not Specified]
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 Baseline, up to Week 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).

Participants not in Japan or Korea crossover to burosumab receive 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection in the Treatment Extension Period (up to 140 weeks total study duration).

Burosumab 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection during the Treatment Period (up to Week 64) and the Treatment Extension Period (up to 140 weeks total study duration).
Overall Number of Participants Analyzed 32 29
Measure Type: Number
Unit of Measure: percentage of participants
25 97
18.Secondary Outcome
Title Change From Baseline in 1,25-Dihydroxyvitamin D at Week 40
Hide Description [Not Specified]
Time Frame Baseline, Week 40
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).

Participants not in Japan or Korea crossover to burosumab receive 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection in the Treatment Extension Period (up to 140 weeks total study duration).

Burosumab 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection during the Treatment Period (up to Week 64) and the Treatment Extension Period (up to 140 weeks total study duration).
Overall Number of Participants Analyzed 32 29
Least Squares Mean (Standard Error)
Unit of Measure: pg/mL
18.6  (3.70) 29.5  (3.78)
Show Statistical Analysis 1 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 0.0408
Comments [Not Specified]
Method GEE model
Comments [Not Specified]
19.Secondary Outcome
Title Change From Baseline in 1,25-Dihydroxyvitamin D at Week 64
Hide Description [Not Specified]
Time Frame Baseline, Week 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).

Participants not in Japan or Korea crossover to burosumab receive 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection in the Treatment Extension Period (up to 140 weeks total study duration).

Burosumab 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection during the Treatment Period (up to Week 64) and the Treatment Extension Period (up to 140 weeks total study duration).
Overall Number of Participants Analyzed 32 29
Least Squares Mean (Standard Error)
Unit of Measure: pg/mL
1.19  (2.785) 9.89  (2.235)
Show Statistical Analysis 1 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 0.0145
Comments [Not Specified]
Method GEE model
Comments [Not Specified]
20.Secondary Outcome
Title Change From Baseline in TmP/GFR to Week 40
Hide Description Urinary phosphorus and TRP measurements were used in the calculation of TmP/GFR.
Time Frame Baseline, Week 40
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).

Participants not in Japan or Korea crossover to burosumab receive 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection in the Treatment Extension Period (up to 140 weeks total study duration).

Burosumab 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection during the Treatment Period (up to Week 64) and the Treatment Extension Period (up to 140 weeks total study duration).
Overall Number of Participants Analyzed 28 23
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
-0.16  (0.054) 1.19  (0.114)
Show Statistical Analysis 1 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 < 0.0001
Comments [Not Specified]
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in LS means
Estimated Value 1.35
Confidence Interval (2-Sided) 95%
1.10 to 1.61
Estimation Comments [Not Specified]
21.Secondary Outcome
Title Change From Baseline in TmP/GFR to Week 64
Hide Description Urinary phosphorus and TRP measurements were used in the calculation of TmP/GFR.
Time Frame Baseline, Week 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).

Participants not in Japan or Korea crossover to burosumab receive 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection in the Treatment Extension Period (up to 140 weeks total study duration).

Burosumab 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection during the Treatment Period (up to Week 64) and the Treatment Extension Period (up to 140 weeks total study duration).
Overall Number of Participants Analyzed 30 23
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
-0.09  (0.070) 1.16  (0.127)
Show Statistical Analysis 1 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 < 0.0001
Comments [Not Specified]
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in LS means
Estimated Value 1.25
Confidence Interval (2-Sided) 95%
0.96 to 1.54
Estimation Comments [Not Specified]
22.Secondary Outcome
Title Change From Baseline in Serum ALP at Week 40
Hide Description [Not Specified]
Time Frame Baseline, Week 40
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).

Participants not in Japan or Korea crossover to burosumab receive 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection in the Treatment Extension Period (up to 140 weeks total study duration).

Burosumab 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection during the Treatment Period (up to Week 64) and the Treatment Extension Period (up to 140 weeks total study duration).
Overall Number of Participants Analyzed 32 29
Least Squares Mean (Standard Error)
Unit of Measure: U/L
-34.52  (18.729) -131.49  (12.515)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Active Control, Burosumab
Comments 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 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 < 0.0001
Comments [Not Specified]
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in LS means
Estimated Value -96.97
Confidence Interval (2-Sided) 95%
-138.10 to -55.85
Estimation Comments [Not Specified]
23.Secondary Outcome
Title Change From Baseline in Serum ALP at Week 64
Hide Description [Not Specified]
Time Frame Baseline, Week 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).

Participants not in Japan or Korea crossover to burosumab receive 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection in the Treatment Extension Period (up to 140 weeks total study duration).

Burosumab 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection during the Treatment Period (up to Week 64) and the Treatment Extension Period (up to 140 weeks total study duration).
Overall Number of Participants Analyzed 32 29
Least Squares Mean (Standard Error)
Unit of Measure: U/L
-28.06  (19.980) -174.62  (13.427)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Active Control, Burosumab
Comments 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 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 < 0.0001
Comments [Not Specified]
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in LS means
Estimated Value -146.56
Confidence Interval (2-Sided) 95%
-191.61 to -101.52
Estimation Comments [Not Specified]
24.Secondary Outcome
Title Percent Mean Change From Baseline in Serum ALP at Week 40
Hide Description Decreases indicate improvement.
Time Frame Baseline, Week 40
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).

Participants not in Japan or Korea crossover to burosumab receive 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection in the Treatment Extension Period (up to 140 weeks total study duration).

Burosumab 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection during the Treatment Period (up to Week 64) and the Treatment Extension Period (up to 140 weeks total study duration).
Overall Number of Participants Analyzed 32 29
Measure Type: Number
Unit of Measure: percent mean change in U/L
-7 -24
25.Secondary Outcome
Title Percent Mean Change From Baseline in Serum ALP at Week 64
Hide Description Decreases indicate improvement.
Time Frame Baseline, Week 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).

Participants not in Japan or Korea crossover to burosumab receive 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection in the Treatment Extension Period (up to 140 weeks total study duration).

Burosumab 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection during the Treatment Period (up to Week 64) and the Treatment Extension Period (up to 140 weeks total study duration).
Overall Number of Participants Analyzed 32 29
Measure Type: Number
Unit of Measure: percent mean change in U/L
-5 -33
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 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).

Participants not in Japan or Korea crossover to burosumab receive 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection in the Treatment Extension Period (up to 140 weeks total study duration).

Burosumab 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection during the Treatment Period (up to Week 64) and the Treatment Extension Period (up to 140 weeks total study duration).
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)
Show Statistical Analysis 1 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]
Show Statistical Analysis 2 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]
Show Statistical Analysis 3 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]
27.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).

Participants not in Japan or Korea crossover to burosumab receive 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection in the Treatment Extension Period (up to 140 weeks total study duration).

Burosumab 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection during the Treatment Period (up to Week 64) and the Treatment Extension Period (up to 140 weeks total study duration).
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)
Show Statistical Analysis 1 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]
Show Statistical Analysis 2 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]
Show Statistical Analysis 3 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]
28.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).

Participants not in Japan or Korea crossover to burosumab receive 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection in the Treatment Extension Period (up to 140 weeks total study duration).

Burosumab 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection during the Treatment Period (up to Week 64) and the Treatment Extension Period (up to 140 weeks total study duration).
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)
Show Statistical Analysis 1 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]
29.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).

Participants not in Japan or Korea crossover to burosumab receive 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection in the Treatment Extension Period (up to 140 weeks total study duration).

Burosumab 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection during the Treatment Period (up to Week 64) and the Treatment Extension Period (up to 140 weeks total study duration).
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)
Show Statistical Analysis 1 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]
30.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).

Participants not in Japan or Korea crossover to burosumab receive 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection in the Treatment Extension Period (up to 140 weeks total study duration).

Burosumab 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection during the Treatment Period (up to Week 64) and the Treatment Extension Period (up to 140 weeks total study duration).
Overall Number of Participants Analyzed 20 13
Least Squares Mean (Standard Error)
Unit of Measure: meters
3.65  (14.060) 47.10  (15.768)
Show Statistical Analysis 1 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]
31.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).

Participants not in Japan or Korea crossover to burosumab receive 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection in the Treatment Extension Period (up to 140 weeks total study duration).

Burosumab 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection during the Treatment Period (up to Week 64) and the Treatment Extension Period (up to 140 weeks total study duration).
Overall Number of Participants Analyzed 20 13
Least Squares Mean (Standard Error)
Unit of Measure: meters
29.28  (16.834) 74.83  (12.513)
Show Statistical Analysis 1 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]
32.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).

Participants not in Japan or Korea crossover to burosumab receive 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection in the Treatment Extension Period (up to 140 weeks total study duration).

Burosumab 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection during the Treatment Period (up to Week 64) and the Treatment Extension Period (up to 140 weeks total study duration).
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)
Show Statistical Analysis 1 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]
33.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 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).

Participants not in Japan or Korea crossover to burosumab receive 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection in the Treatment Extension Period (up to 140 weeks total study duration).

Burosumab 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection during the Treatment Period (up to Week 64) and the Treatment Extension Period (up to 140 weeks total study duration).
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)
Show Statistical Analysis 1 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
Adverse Event Reporting Description [Not Specified]
 
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).

Participants not in Japan or Korea crossover to burosumab receive 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection in the Treatment Extension Period (up to 140 weeks total study duration).

Burosumab 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection during the Treatment Period (up to Week 64) and the Treatment Extension Period (up to 140 weeks total study duration).
All-Cause Mortality
Active Control Burosumab
Affected / at Risk (%) Affected / at Risk (%)
Total   0/32 (0.00%)   0/29 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
Active Control Burosumab
Affected / at Risk (%) Affected / at Risk (%)
Total   3/32 (9.38%)   3/29 (10.34%) 
Congenital, familial and genetic disorders     
Craniosynostosis  1  1/32 (3.13%)  1/29 (3.45%) 
Infections and infestations     
Viral Infection  1  0/32 (0.00%)  1/29 (3.45%) 
Musculoskeletal and connective tissue disorders     
Knee Deformity  1  1/32 (3.13%)  0/29 (0.00%) 
Nervous system disorders     
Migraine  1  0/32 (0.00%)  1/29 (3.45%) 
Renal and urinary disorders     
Haematuria  1  1/32 (3.13%)  0/29 (0.00%) 
1
Term from vocabulary, MedDRA 20.0
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Active Control Burosumab
Affected / at Risk (%) Affected / at Risk (%)
Total   24/32 (75.00%)   29/29 (100.00%) 
Congenital, familial and genetic disorders     
Tooth Hypoplasia  1  0/32 (0.00%)  2/29 (6.90%) 
Ear and labyrinth disorders     
Ear Pain  1  1/32 (3.13%)  4/29 (13.79%) 
Gastrointestinal disorders     
Abdominal Discomfort  1  2/32 (6.25%)  2/29 (6.90%) 
Abdominal Pain  1  1/32 (3.13%)  2/29 (6.90%) 
Abdominal Pain Upper  1  3/32 (9.38%)  3/29 (10.34%) 
Constipation  1  0/32 (0.00%)  5/29 (17.24%) 
Dental Caries  1  2/32 (6.25%)  9/29 (31.03%) 
Diarrhoea  1  2/32 (6.25%)  7/29 (24.14%) 
Nausea  1  1/32 (3.13%)  3/29 (10.34%) 
Teething  1  0/32 (0.00%)  2/29 (6.90%) 
Toothache  1  1/32 (3.13%)  4/29 (13.79%) 
Vomiting  1  8/32 (25.00%)  12/29 (41.38%) 
General disorders     
Fatigue  1  2/32 (6.25%)  1/29 (3.45%) 
Injection Site Erosion  1  0/32 (0.00%)  2/29 (6.90%) 
Injection Site Erythema  1  0/32 (0.00%)  9/29 (31.03%) 
Injection Site Pruritus  1  0/32 (0.00%)  3/29 (10.34%) 
Injection Site Rash  1  0/32 (0.00%)  3/29 (10.34%) 
Injection Site Reaction  1  0/32 (0.00%)  7/29 (24.14%) 
Injection Site Swelling  1  0/32 (0.00%)  3/29 (10.34%) 
Injection Site Urticaria  1  0/32 (0.00%)  2/29 (6.90%) 
Pain  1  0/32 (0.00%)  2/29 (6.90%) 
Pyrexia  1  6/32 (18.75%)  16/29 (55.17%) 
Immune system disorders     
Hypersensitivity  1  2/32 (6.25%)  1/29 (3.45%) 
Seasonal Allergy  1  2/32 (6.25%)  4/29 (13.79%) 
Infections and infestations     
Ear Infection  1  3/32 (9.38%)  2/29 (6.90%) 
Gastroenteritis  1  3/32 (9.38%)  2/29 (6.90%) 
Gastroenteritis Viral  1  3/32 (9.38%)  2/29 (6.90%) 
Influenza  1  6/32 (18.75%)  4/29 (13.79%) 
Nasopharyngitis  1  14/32 (43.75%)  11/29 (37.93%) 
Otitis Externa  1  3/32 (9.38%)  0/29 (0.00%) 
Otitis Media  1  3/32 (9.38%)  2/29 (6.90%) 
Pneumonia  1  0/32 (0.00%)  2/29 (6.90%) 
Rhinitis  1  2/32 (6.25%)  2/29 (6.90%) 
Tooth Abscess  1  3/32 (9.38%)  8/29 (27.59%) 
Upper Respiratory Tract Infection  1  3/32 (9.38%)  3/29 (10.34%) 
Varicella  1  0/32 (0.00%)  2/29 (6.90%) 
Viral Upper Respiratory Tract Infection  1  2/32 (6.25%)  0/29 (0.00%) 
Injury, poisoning and procedural complications     
Contusion  1  0/32 (0.00%)  4/29 (13.79%) 
Fall  1  0/32 (0.00%)  3/29 (10.34%) 
Procedural Pain  1  0/32 (0.00%)  2/29 (6.90%) 
Investigations     
Vitamin D Decreased  1  1/32 (3.13%)  6/29 (20.69%) 
Metabolism and nutrition disorders     
Decreased Appetite  1  2/32 (6.25%)  1/29 (3.45%) 
Vitamin D Deficiency  1  1/32 (3.13%)  5/29 (17.24%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  10/32 (31.25%)  13/29 (44.83%) 
Back Pain  1  3/32 (9.38%)  2/29 (6.90%) 
Pain In Extremity  1  10/32 (31.25%)  11/29 (37.93%) 
Nervous system disorders     
Headache  1  6/32 (18.75%)  10/29 (34.48%) 
Migraine  1  2/32 (6.25%)  1/29 (3.45%) 
Renal and urinary disorders     
Dysuria  1  0/32 (0.00%)  2/29 (6.90%) 
Respiratory, thoracic and mediastinal disorders     
Asthma  1  1/32 (3.13%)  4/29 (13.79%) 
Cough  1  6/32 (18.75%)  15/29 (51.72%) 
Nasal Congestion  1  1/32 (3.13%)  5/29 (17.24%) 
Oropharyngeal Pain  1  1/32 (3.13%)  5/29 (17.24%) 
Rhinitis Allergic  1  0/32 (0.00%)  2/29 (6.90%) 
Rhinorrhoea  1  2/32 (6.25%)  7/29 (24.14%) 
Skin and subcutaneous tissue disorders     
Erythema  1  0/32 (0.00%)  2/29 (6.90%) 
Rash  1  2/32 (6.25%)  3/29 (10.34%) 
1
Term from vocabulary, MedDRA 20.0
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
Layout table for additonal information
Responsible Party: Ultragenyx Pharmaceutical Inc
ClinicalTrials.gov Identifier: NCT02915705     History of Changes
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: July 30, 2019