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Study of KRN23 (Burosumab), a Recombinant Fully Human Monoclonal Antibody Against Fibroblast Growth Factor 23 (FGF23), in Pediatric Subjects With X-linked Hypophosphatemia (XLH)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02163577
Recruitment Status : Completed
First Posted : June 13, 2014
Results First Posted : May 22, 2019
Last Update Posted : July 18, 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
Intervention Biological: burosumab
Enrollment 52
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Burosumab Q2W Burosumab Q4W Then Q2W
Hide Arm/Group Description Burosumab subcutaneous (SC) injections every 2 weeks (Q2W). Dose was determined by the participant's weight and prescribed dose by their study doctor. Burosumab SC injections every 4 weeks (Q4W). Dose was determined by the participant's weight and prescribed dose by their study doctor. Participants in Q4W were to switch to Q2W beginning with Week 64 dosing.
Period Title: Overall Study
Started 26 26
Completed 26 26
Not Completed 0 0
Arm/Group Title Burosumab Q2W Burosumab Q4W Then Q2W Total
Hide Arm/Group Description Burosumab SC injections every 2 weeks (Q2W). Dose is determined by the participant's weight and prescribed dose by their study doctor. Burosumab subcutaneous (SC) injections every 4 weeks (Q4W). Dose is determined by the participant's weight and prescribed dose by their study doctor. Participants in Q4W were to switch to Q2W beginning with Week 64 dosing. Total of all reporting groups
Overall Number of Baseline Participants 26 26 52
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 26 participants 26 participants 52 participants
8.7  (1.72) 8.3  (2.04) 8.5  (1.87)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 26 participants 26 participants 52 participants
Female
14
  53.8%
14
  53.8%
28
  53.8%
Male
12
  46.2%
12
  46.2%
24
  46.2%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Black or African American Number Analyzed 26 participants 26 participants 52 participants
2
   7.7%
0
   0.0%
2
   3.8%
White Number Analyzed 26 participants 26 participants 52 participants
23
  88.5%
23
  88.5%
46
  88.5%
Other, Not Specified Number Analyzed 26 participants 26 participants 52 participants
1
   3.8%
3
  11.5%
4
   7.7%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Hispanic or Latino Number Analyzed 26 participants 26 participants 52 participants
0
   0.0%
2
   7.7%
2
   3.8%
Not Hispanic or Latino Number Analyzed 26 participants 26 participants 52 participants
26
 100.0%
24
  92.3%
50
  96.2%
Rickets Severity Score (RSS) Total Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Score on a scale
Number Analyzed 26 participants 26 participants 52 participants
1.92  (1.172) 1.67  (0.999) 1.80  (1.086)
[1]
Measure 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.
Serum Phosphorus  
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 26 participants 26 participants 52 participants
2.38  (0.405) 2.28  (0.299) 2.33  (0.356)
Serum 1, 25-Dihydroxyvitamin D  
Mean (Standard Deviation)
Unit of measure:  pg/mL
Number Analyzed 26 participants 26 participants 52 participants
41.28  (21.967) 41.37  (15.293) 41.33  (18.740)
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 25 participants 25 participants 50 participants
2.176  (0.4925) 1.978  (0.3474) 2.077  (0.4335)
[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
RSS Knee and Wrist Scores   [1] 
Mean (Standard Deviation)
Unit of measure:  Score on a scale
Knee Score Number Analyzed 26 participants 26 participants 52 participants
1.21  (0.681) 1.19  (0.601) 1.20  (0.636)
Wrist Score Number Analyzed 26 participants 26 participants 52 participants
0.71  (0.619) 0.48  (0.519) 0.60  (0.578)
[1]
Measure 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.
Growth Velocity   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Cm/year
Number Analyzed 25 participants 24 participants 49 participants
5.45  (1.171) 5.24  (1.402) 5.35  (1.280)
[1]
Measure Description: Baseline growth velocity was calculated based on the standing height measured within 2 years prior to Baseline.
[2]
Measure Analysis Population Description: Data presented for participants with evaluable growth velocity data at Baseline. Growth velocity could not be calculated for 3 participants for whom pretreatment height data were not available within 2 years prior to Baseline.
Standing Height Z-Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Z score
Number Analyzed 26 participants 26 participants 52 participants
-1.72  (1.026) -2.05  (0.957) -1.89  (0.996)
[1]
Measure Description: 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
Growth (Standing Height, Sitting Height, Arm Length, Leg Length)  
Mean (Standard Deviation)
Unit of measure:  Cm
Standing Height Number Analyzed 26 participants 26 participants 52 participants
123.28  (10.326) 119.42  (12.623) 121.35  (11.584)
Sitting Height Number Analyzed 26 participants 26 participants 52 participants
70.10  (5.632) 67.04  (5.691) 68.57  (5.815)
Arm Length Number Analyzed 26 participants 26 participants 52 participants
54.80  (4.930) 52.59  (6.129) 53.70  (5.619)
Leg Length Number Analyzed 26 participants 26 participants 52 participants
66.06  (7.027) 63.71  (8.322) 64.89  (7.718)
6-Minute Walk Test (6MWT) Distance (Predicted Percent of Normal)   [1] 
Mean (Standard Deviation)
Unit of measure:  Percentage of predicted distance
Number Analyzed 26 participants 26 participants 52 participants
79.32  (13.257) 81.42  (15.101) 80.37  (14.109)
[1]
Measure Description: The total distance walked (meters) in a 6-minute period was measured. The percent of predicted values were calculated using published normative data based on age, gender, and height (Geiger et al. 2007).
POSNA-PODCI Normative Scores   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  T-score
Upper Extremity Scale Number Analyzed 26 participants 25 participants 51 participants
52.1  (6.77) 48.5  (13.04) 50.3  (10.39)
Transfer and Basic Mobility Scale Number Analyzed 26 participants 25 participants 51 participants
45.7  (10.88) 46.0  (10.53) 45.8  (10.61)
Sports/Physical Functioning Scale Number Analyzed 26 participants 25 participants 51 participants
34.6  (15.70) 32.2  (19.29) 33.4  (17.42)
Pain/Comfort Scale Number Analyzed 26 participants 25 participants 51 participants
35.2  (15.26) 34.8  (16.76) 35.0  (15.85)
Happiness Scale Number Analyzed 26 participants 25 participants 51 participants
43.6  (13.75) 43.4  (13.69) 43.5  (13.58)
Global Functioning Scale Number Analyzed 26 participants 25 participants 51 participants
37.5  (13.96) 35.6  (17.24) 36.6  (15.52)
[1]
Measure Description: The Pediatric Orthopedic Society of North America Pediatric Outcomes Data Collection Instrument (POSNA-PODCI) yields 4 functional assessment scores: Upper Extremity Function,Transfers and Basic Mobility, Sports/Physical Function, and Comfort/Pain. Also a Global Function score, an average of the 4 functional assessments, and a Happiness score are calculated. Normative scores are calculated so that higher scores indicate better functioning. All scores are referenced to the general, healthy population with a normative mean score of 50 and a standard deviation of 10.
[2]
Measure Analysis Population Description: one participant in the "Burosumab Q4W then Q2W" group did not have a Baseline assessment
Fractional Excretion of Phosphorus (FEP)   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Percentage of phosphorus excreted
Number Analyzed 25 participants 26 participants 51 participants
13.91  (6.775) 15.42  (7.373) 14.68  (7.056)
[1]
Measure Description: FEP is defined as 100% × (urine phosphorus × serum creatinine)/(urine creatinine × serum phosphorus), where the 2-hour urine sample was used for urine phosphorus and urine creatinine.
[2]
Measure Analysis Population Description: participants with a Baseline assessment
Procollagen Type 1 N Propeptide (P1NP)   [1] 
Mean (Standard Deviation)
Unit of measure:  ng/mL
Number Analyzed 24 participants 26 participants 50 participants
843.11  (214.367) 742.35  (209.727) 790.72  (215.864)
[1]
Measure Analysis Population Description: participants with a Baseline assessment
Carboxy-Terminal Crosslinked Telopeptide of Type I Collagen (CTx)  
Mean (Standard Deviation)
Unit of measure:  ng/mL
Number Analyzed 26 participants 26 participants 52 participants
2.23  (0.642) 2.10  (0.679) 2.16  (0.658)
Alkaline Phosphatase (ALP)  
Mean (Standard Deviation)
Unit of measure:  U/L
Number Analyzed 26 participants 26 participants 52 participants
461.92  (110.209) 456.08  (101.157) 459.00  (104.779)
Bone Specific Alkaline Phosphatase (BALP)   [1] 
Mean (Standard Deviation)
Unit of measure:  mcg/L
Number Analyzed 20 participants 20 participants 40 participants
163.54  (58.610) 165.62  (45.534) 164.58  (51.814)
[1]
Measure Analysis Population Description: participants with a baseline assessment
Burosumab Concentration   [1] 
Mean (Standard Deviation)
Unit of measure:  ng/mL
Number Analyzed 26 participants 26 participants 52 participants
25.00  (0.000) 25.00  (0.000) 25.00  (0.000)
[1]
Measure Description: For the lower limit of quantitation (< 50), the value 25 was used.
1.Primary Outcome
Title Change From Baseline in RSS Total Score Over Time
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 40, 64, 160
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (ITT) Analysis Set: all participants who received at least 1 dose of study therapy and had at least 1 post-dose measurement at given time point.
Arm/Group Title Burosumab Q2W Burosumab Q4W Then Q2W
Hide Arm/Group Description:
Burosumab SC injections Q2W. Dose was determined by the participant's weight and prescribed dose by their study doctor.
Burosumab SC injections Q4W. Dose was determined by the participant's weight and prescribed dose by their study doctor. Participants in Q4W were to switch to Q2W beginning with Week 64 dosing.
Overall Number of Participants Analyzed 26 26
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
Change to Week 40 Number Analyzed 26 participants 26 participants
-1.06  (0.100) -0.73  (0.100)
Change to Week 64 Number Analyzed 26 participants 26 participants
-1.00  (0.110) -0.84  (0.098)
Change to Week 160 Number Analyzed 19 participants 22 participants
-0.98  (0.129) -0.83  (0.122)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Burosumab Q2W
Comments Week 40
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments Per generalized estimating equations (GEE) model, which included visit, regimen, visit by regimen as factors, and RSS total score at baseline as a covariate, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Burosumab Q4W Then Q2W
Comments Week 40
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments Per GEE model, which included visit, regimen, visit by regimen as factors, and RSS total score at baseline as a covariate, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Burosumab Q2W, Burosumab Q4W Then Q2W
Comments Difference in change to Week 40
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value -0.33
Confidence Interval (2-Sided) 95%
-0.63 to -0.04
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Burosumab Q2W
Comments Week 64
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments Per GEE model, which included visit, regimen, visit by regimen as factors, and RSS total score at baseline as a covariate, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Burosumab Q4W Then Q2W
Comments Week 64
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments Per GEE model, which included visit, regimen, visit by regimen as factors, and RSS total score at baseline as a covariate, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Burosumab Q2W, Burosumab Q4W Then Q2W
Comments Difference in change to Week 64
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value -0.16
Confidence Interval (2-Sided) 95%
-0.45 to 0.13
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Burosumab Q2W
Comments Week 160
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments Per GEE model, which included visit, regimen, visit by regimen as factors, and RSS total score at baseline as a covariate, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Burosumab Q4W Then Q2W
Comments Week 160
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments Per GEE model, which included visit, regimen, visit by regimen as factors, and RSS total score at baseline as a covariate, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
2.Primary Outcome
Title Change From Baseline in Serum Phosphorus Over Time
Hide Description [Not Specified]
Time Frame Baseline, Week 40, 64, 160
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic/Pharamcodynamic (PK/PD) Analysis Set: all participants who received at least 1 dose of therapy and had evaluable serum data at given time point.
Arm/Group Title Burosumab Q2W Burosumab Q4W Then Q2W
Hide Arm/Group Description:
Burosumab SC injections Q2W. Dose was determined by the participant's weight and prescribed dose by their study doctor.
Burosumab SC injections Q4W. Dose was determined by the participant's weight and prescribed dose by their study doctor. Participants in Q4W were to switch to Q2W beginning with Week 64 dosing.
Overall Number of Participants Analyzed 26 26
Mean (Standard Deviation)
Unit of Measure: mg/dL
Change at Week 40 Number Analyzed 26 participants 26 participants
0.92  (0.480) 0.57  (0.265)
Change at Week 64 Number Analyzed 24 participants 23 participants
0.99  (0.502) 0.69  (0.370)
Change at Week 160 Number Analyzed 26 participants 26 participants
0.97  (0.338) 1.08  (0.377)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Burosumab Q2W
Comments Week 40
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method one sample t test
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Burosumab Q4W Then Q2W
Comments Week 40
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method one sample t test
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Burosumab Q2W
Comments Week 64
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method one sample t test
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Burosumab Q4W Then Q2W
Comments Week 64
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method one sample t test
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Burosumab Q2W
Comments Week 160
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method one sample t test
Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Burosumab Q4W Then Q2W
Comments Week 160
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method one sample t test
Comments [Not Specified]
3.Primary Outcome
Title Change From Baseline in Serum 1,25(OH)2D Over Time
Hide Description [Not Specified]
Time Frame Baseline, Week 40, 64, 160
Hide Outcome Measure Data
Hide Analysis Population Description
PK/PD Analysis Set: all participants who received at least 1 dose of therapy and had evaluable serum data at given time point.
Arm/Group Title Burosumab Q2W Burosumab Q4W Then Q2W
Hide Arm/Group Description:
Burosumab SC injections Q2W. Dose was determined by the participant's weight and prescribed dose by their study doctor.
Burosumab SC injections Q4W. Dose was determined by the participant's weight and prescribed dose by their study doctor. Participants in Q4W were to switch to Q2W beginning with Week 64 dosing.
Overall Number of Participants Analyzed 26 26
Mean (Standard Deviation)
Unit of Measure: pg/mL
Change at Week 40 Number Analyzed 26 participants 26 participants
28.27  (29.312) 17.62  (18.802)
Change at Week 64 Number Analyzed 26 participants 24 participants
23.58  (24.502) 11.50  (16.522)
Change at Week 160 Number Analyzed 26 participants 26 participants
17.03  (24.889) 19.64  (22.857)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Burosumab Q2W
Comments Week 40
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method one sample t test
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Burosumab Q4W Then Q2W
Comments Week 40
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method one sample t test
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Burosumab Q2W
Comments Week 64
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method one sample t test
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Burosumab Q4W Then Q2W
Comments Week 64
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0024
Comments [Not Specified]
Method one sample t test
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Burosumab Q2W
Comments Week 160
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0018
Comments [Not Specified]
Method one sample t test
Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Burosumab Q4W Then Q2W
Comments Week 160
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments [Not Specified]
Method one sample t test
Comments [Not Specified]
4.Primary Outcome
Title Change From Baseline in TmP/GFR Over Time
Hide Description Data for urinary phosphorus and TRP were used in calculation TmP/GFR.
Time Frame Baseline, Week 40, 64, 160
Hide Outcome Measure Data
Hide Analysis Population Description
PK/PD Analysis Set: all participants who received at least 1 dose of therapy and had evaluable serum data at given time point.
Arm/Group Title Burosumab Q2W Burosumab Q4W Then Q2W
Hide Arm/Group Description:
Burosumab SC injections Q2W. Dose was determined by the participant's weight and prescribed dose by their study doctor.
Burosumab SC injections Q4W. Dose was determined by the participant's weight and prescribed dose by their study doctor. Participants in Q4W were to switch to Q2W beginning with Week 64 dosing.
Overall Number of Participants Analyzed 26 26
Mean (Standard Deviation)
Unit of Measure: mg/dL
Change at Week 40 Number Analyzed 24 participants 23 participants
1.14  (0.686) 0.80  (0.506)
Change at Week 64 Number Analyzed 20 participants 19 participants
1.11  (0.626) 0.90  (0.632)
Change at Week 160 Number Analyzed 23 participants 24 participants
1.24  (0.548) 1.45  (0.653)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Burosumab Q2W
Comments Week 40
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method one sample t test
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Burosumab Q4W Then Q2W
Comments Week 40
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method one sample t test
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Burosumab Q2W
Comments Week 64
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method one sample t test
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Burosumab Q4W Then Q2W
Comments Week 64
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method one sample t test
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Burosumab Q2W
Comments Week 160
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method one sample t test
Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Burosumab Q4W Then Q2W
Comments Week 160
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method one sample t test
Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline in RSS Knee Scores Over Time
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 40, 64, 160
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Analysis Set: all participants who received at least 1 dose of study therapy and had at least 1 post-dose measurement at given time point.
Arm/Group Title Burosumab Q2W Burosumab Q4W Then Q2W
Hide Arm/Group Description:
Burosumab SC injections Q2W. Dose was determined by the participant's weight and prescribed dose by their study doctor.
Burosumab SC injections Q4W. Dose was determined by the participant's weight and prescribed dose by their study doctor. Participants in Q4W were to switch to Q2W beginning with Week 64 dosing.
Overall Number of Participants Analyzed 26 26
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
Change at Week 40 Number Analyzed 26 participants 26 participants
-0.62  (0.08) -0.55  (0.08)
Change at Week 64 Number Analyzed 26 participants 26 participants
-0.70  (0.087) -0.61  (0.072)
Change at Week 160 Number Analyzed 19 participants 22 participants
-0.70  (0.105) -0.62  (0.093)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Burosumab Q2W
Comments Week 40
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments ANCOVA model includes the change from baseline in RSS as the dependent variable, regimen group as factor, and RSS at baseline as covariate.
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Burosumab Q4W Then Q2W
Comments Week 40
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments ANCOVA model includes the change from baseline in RSS as the dependent variable, regimen group as factor, and RSS at baseline as covariate.
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Burosumab Q2W
Comments Week 64
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments GEE model includes the change from baseline in RSS as the dependent variable, visit, regimen, visit by regimen as factors, and RSS at baseline as a covariate, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Burosumab Q4W Then Q2W
Comments Week 64
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments GEE model includes the change from baseline in RSS as the dependent variable, visit, regimen, visit by regimen as factors, and RSS at baseline as a covariate, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Burosumab Q2W
Comments Week 160
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments GEE model includes the change from baseline in RSS as the dependent variable, visit, regimen, visit by regimen as factors, and RSS at baseline as a covariate, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Burosumab Q4W Then Q2W
Comments Week 160
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments GEE model includes the change from baseline in RSS as the dependent variable, visit, regimen, visit by regimen as factors, and RSS at baseline as a covariate, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
6.Secondary Outcome
Title Change From Baseline in RSS Wrist Scores Over Time
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 40, 64, 160
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Analysis Set: all participants who received at least 1 dose of study therapy and had at least 1 post-dose measurement at given time point.
Arm/Group Title Burosumab Q2W Burosumab Q4W Then Q2W
Hide Arm/Group Description:
Burosumab SC injections Q2W. Dose was determined by the participant's weight and prescribed dose by their study doctor.
Burosumab SC injections Q4W. Dose was determined by the participant's weight and prescribed dose by their study doctor. Participants in Q4W were to switch to Q2W beginning with Week 64 dosing.
Overall Number of Participants Analyzed 26 26
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
Change at Week 40 Number Analyzed 26 participants 26 participants
-0.44  (0.05) -0.18  (0.05)
Change at Week 64 Number Analyzed 26 participants 26 participants
-0.30  (0.057) -0.24  (0.051)
Change at Week 160 Number Analyzed 19 participants 21 participants
-0.27  (0.065) -0.20  (0.047)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Burosumab Q2W
Comments Week 40
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments ANCOVA model includes the change from baseline in RSS as the dependent variable, regimen group as factor, and RSS at baseline as covariate.
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Burosumab Q4W Then Q2W
Comments Week 40
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0015
Comments ANCOVA model includes the change from baseline in RSS as the dependent variable, regimen group as factor, and RSS at baseline as covariate.
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Burosumab Q2W
Comments Week 64
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments GEE model includes the change from baseline in RSS as the dependent variable, visit, regimen, visit by regimen as factors, and RSS at baseline as a covariate, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Burosumab Q4W Then Q2W
Comments Week 64
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments GEE model includes the change from baseline in RSS as the dependent variable, visit, regimen, visit by regimen as factors, and RSS at baseline as a covariate, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Burosumab Q2W
Comments Week 160
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments GEE model includes the change from baseline in RSS as the dependent variable, visit, regimen, visit by regimen as factors, and RSS at baseline as a covariate, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Burosumab Q4W Then Q2W
Comments Week 160
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments GEE model includes the change from baseline in RSS as the dependent variable, visit, regimen, visit by regimen as factors, and RSS at baseline as a covariate, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
7.Secondary Outcome
Title Radiographic Global Impression of Change (RGI-C) Global Scores Over Time
Hide Description Changes in the severity of rickets and bowing were assessed centrally by three independent pediatric radiologists contracted by a central imaging facility using a disease specific qualitative RGI-C scoring system. The RGI-C is a seven 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 Baseline, Week 40, 64, 160
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Analysis Set: all participants who received at least 1 dose of study therapy and had at least 1 post-dose measurement at given time point.
Arm/Group Title Burosumab Q2W Burosumab Q4W Then Q2W
Hide Arm/Group Description:
Burosumab SC injections Q2W. Dose was determined by the participant's weight and prescribed dose by their study doctor.
Burosumab SC injections Q4W. Dose was determined by the participant's weight and prescribed dose by their study doctor. Participants in Q4W were to switch to Q2W beginning with Week 64 dosing.
Overall Number of Participants Analyzed 26 26
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
Change at Week 40 1.67  (0.12) 1.46  (0.12)
Change at Week 64 1.56  (0.112) 1.58  (0.112)
Change at Week 160 1.92  (0.111) 1.86  (0.119)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Burosumab Q2W
Comments Week 40
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments ANCOVA model includes RGI-C as the dependent variable, regimen group as factor, and RSS at baseline as covariate.
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Burosumab Q4W Then Q2W
Comments Week 40
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments ANCOVA model includes RGI-C as the dependent variable, regimen group as factor, and RSS at baseline as covariate.
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Burosumab Q2W, Burosumab Q4W Then Q2W
Comments Difference in change to Week 40
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value 0.21
Confidence Interval (2-Sided) 95%
-0.12 to 0.54
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Burosumab Q2W
Comments Week 64
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments Per GEE model, which included visit, regimen, visit by regimen as factors, and RSS total score at baseline as a covariate, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Burosumab Q4W Then Q2W
Comments Week 64
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments Per GEE model, which included visit, regimen, visit by regimen as factors, and RSS total score at baseline as a covariate, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Burosumab Q2W, Burosumab Q4W Then Q2W
Comments Difference in change to Week 64
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value -0.02
Confidence Interval (2-Sided) 95%
-0.34 to 0.29
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Burosumab Q2W
Comments Week 160
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments Per GEE model, which included visit, regimen, visit by regimen as factors, and RSS total score at baseline as a covariate, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Burosumab Q4W Then Q2W
Comments Week 160
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments Per GEE model, which included visit, regimen, visit by regimen as factors, and RSS total score at baseline as a covariate, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
8.Secondary Outcome
Title RGI-C Knee Scores Over Time
Hide Description Changes in the severity of rickets and bowing were assessed centrally by three independent pediatric radiologists contracted by a central imaging facility using a disease specific qualitative RGI-C scoring system. The RGI-C is a seven 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 Baseline, Week 40, 64, 160
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Analysis Set: all participants who received at least 1 dose of study therapy and had at least 1 post-dose measurement at given time point.
Arm/Group Title Burosumab Q2W Burosumab Q4W Then Q2W
Hide Arm/Group Description:
Burosumab SC injections Q2W. Dose was determined by the participant's weight and prescribed dose by their study doctor.
Burosumab SC injections Q4W. Dose was determined by the participant's weight and prescribed dose by their study doctor. Participants in Q4W were to switch to Q2W beginning with Week 64 dosing.
Overall Number of Participants Analyzed 26 26
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
Change at Week 40 1.60  (0.13) 1.34  (0.13)
Change at Week 64 1.57  (0.104) 1.53  (0.099)
Change at Week 160 2.01  (0.106) 1.85  (0.118)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Burosumab Q2W
Comments Week 40
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments ANCOVA model includes RGI-C as the dependent variable, regimen group as factor, and RSS at baseline as covariate.
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Burosumab Q4W Then Q2W
Comments Week 40
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments ANCOVA model includes RGI-C as the dependent variable, regimen group as factor, and RSS at baseline as covariate.
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Burosumab Q2W
Comments Week 64
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments GEE model includes RGI-C as the dependent variable, visit, regimen, visit by regimen as factors, and RSS total score at baseline as a covariate, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Burosumab Q4W Then Q2W
Comments Week 64
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments GEE model includes RGI-C as the dependent variable, visit, regimen, visit by regimen as factors, and RSS total score at baseline as a covariate, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Burosumab Q2W
Comments Week 160
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments GEE model includes RGI-C as the dependent variable, visit, regimen, visit by regimen as factors, and RSS total score at baseline as a covariate, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Burosumab Q4W Then Q2W
Comments Week 160
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments GEE model includes RGI-C as the dependent variable, visit, regimen, visit by regimen as factors, and RSS total score at baseline as a covariate, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
9.Secondary Outcome
Title RGI-C Wrist Scores Over Time
Hide Description Changes in the severity of rickets and bowing were assessed centrally by three independent pediatric radiologists contracted by a central imaging facility using a disease specific qualitative RGI-C scoring system. The RGI-C is a seven 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 Baseline, Week 40, 64, 160
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Analysis Set: all participants who received at least 1 dose of study therapy and had at least 1 post-dose measurement at given time point.
Arm/Group Title Burosumab Q2W Burosumab Q4W Then Q2W
Hide Arm/Group Description:
Burosumab SC injections Q2W. Dose was determined by the participant's weight and prescribed dose by their study doctor.
Burosumab SC injections Q4W. Dose was determined by the participant's weight and prescribed dose by their study doctor. Participants in Q4W were to switch to Q2W beginning with Week 64 dosing.
Overall Number of Participants Analyzed 26 26
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
Change at Week 40 Number Analyzed 26 participants 26 participants
1.64  (0.14) 1.45  (0.14)
Change at Week 64 Number Analyzed 26 participants 26 participants
1.65  (0.153) 1.55  (0.124)
Change at Week 160 Number Analyzed 26 participants 25 participants
1.78  (0.133) 1.83  (0.132)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Burosumab Q2W
Comments Week 40
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments ANCOVA model includes RGI-C as the dependent variable, regimen group as factor, and RSS at baseline as covariate.
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Burosumab Q4W Then Q2W
Comments Week 40
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments ANCOVA model includes RGI-C as the dependent variable, regimen group as factor, and RSS at baseline as covariate.
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Burosumab Q2W
Comments Week 64
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments GEE model includes RGI-C as the dependent variable, visit, regimen, visit by regimen as factors, and RSS total score at baseline as a covariate, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Burosumab Q4W Then Q2W
Comments Week 64
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments GEE model includes RGI-C as the dependent variable, visit, regimen, visit by regimen as factors, and RSS total score at baseline as a covariate, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Burosumab Q2W
Comments Week 160
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments GEE model includes RGI-C as the dependent variable, visit, regimen, visit by regimen as factors, and RSS total score at baseline as a covariate, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Burosumab Q4W Then Q2W
Comments Week 160
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments GEE model includes RGI-C as the dependent variable, visit, regimen, visit by regimen as factors, and RSS total score at baseline as a covariate, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
10.Secondary Outcome
Title Change From Baseline in Growth Velocity Over Time
Hide Description [Not Specified]
Time Frame Baseline, Week 40, 64, 160
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Analysis Set: all participants who received at least 1 dose of study therapy and had at least 1 post-dose measurement at given time point.
Arm/Group Title Burosumab Q2W Burosumab Q4W Then Q2W
Hide Arm/Group Description:
Burosumab SC injections Q2W. Dose was determined by the participant's weight and prescribed dose by their study doctor.
Burosumab SC injections Q4W. Dose was determined by the participant's weight and prescribed dose by their study doctor. Participants in Q4W were to switch to Q2W beginning with Week 64 dosing.
Overall Number of Participants Analyzed 25 24
Mean (Standard Deviation)
Unit of Measure: cm/year
Week 0 to Week 40: Change from Baseline 0.96  (1.677) 0.39  (2.559)
Week 0 to Week 64: Change from Baseline 0.73  (1.399) 0.37  (2.164)
Week 64 to Week 112: Change from Baseline 0.29  (2.284) 0.09  (2.523)
Week 112 to Week 160: Change from Baseline 0.67  (2.318) 0.54  (3.158)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Burosumab Q2W
Comments Week 0 to Week 40
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0088
Comments [Not Specified]
Method one sample t-test
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Burosumab Q4W Then Q2W
Comments Week 0 to Week 40
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4650
Comments [Not Specified]
Method one sample t-test
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Burosumab Q2W
Comments Week 0 to Week 64
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0160
Comments [Not Specified]
Method one sample t test
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Burosumab Q4W Then Q2W
Comments Week 0 to Week 64
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4114
Comments [Not Specified]
Method one sample t test
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Burosumab Q2W
Comments Week 64 to Week 112
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5335
Comments [Not Specified]
Method one sample t test
Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Burosumab Q4W Then Q2W
Comments Week 64 to Week 112
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8606
Comments [Not Specified]
Method one sample t test
Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Burosumab Q2W
Comments Week 112 to Week 160
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1627
Comments [Not Specified]
Method one sample t test
Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Burosumab Q4W Then Q2W
Comments Week 112 to Week 160
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4096
Comments [Not Specified]
Method one sample t test
Comments [Not Specified]
11.Secondary Outcome
Title Change From Baseline in Standing Height Z Score Over Time
Hide Description 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 40, 64, 160
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Analysis Set: all participants who received at least 1 dose of study therapy and had at least 1 post-dose measurement at given time point.
Arm/Group Title Burosumab Q2W Burosumab Q4W Then Q2W
Hide Arm/Group Description:
Burosumab SC injections Q2W. Dose was determined by the participant's weight and prescribed dose by their study doctor.
Burosumab SC injections Q4W. Dose was determined by the participant's weight and prescribed dose by their study doctor. Participants in Q4W were to switch to Q2W beginning with Week 64 dosing.
Overall Number of Participants Analyzed 26 26
Least Squares Mean (Standard Error)
Unit of Measure: Z score
Change to Week 40 Number Analyzed 24 participants 23 participants
0.17  (0.042) 0.10  (0.051)
Change to Week 64 Number Analyzed 26 participants 26 participants
0.19  (0.051) 0.12  (0.061)
Change to Week 160 Number Analyzed 26 participants 26 participants
0.35  (0.084) 0.19  (0.089)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Burosumab Q2W
Comments Week 40
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments GEE model included change from baseline for standing height Z score as dependent variable; visit, regimen, visit by regimen, and gender as factors; and age and standing height Z score at baseline as covariates, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Burosumab Q4W Then Q2W
Comments Week 40
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0569
Comments GEE model included change from baseline for standing height Z score as dependent variable; visit, regimen, visit by regimen, and gender as factors; and age and standing height Z score at baseline as covariates, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Burosumab Q2W
Comments Week 64
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments GEE model included change from baseline for standing height Z score as dependent variable; visit, regimen, visit by regimen, and gender as factors; and age and standing height Z score at baseline as covariates, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Burosumab Q4W Then Q2W
Comments Week 64
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0456
Comments GEE model included change from baseline for standing height Z score as dependent variable; visit, regimen, visit by regimen, and gender as factors; and age and standing height Z score at baseline as covariates, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Burosumab Q2W
Comments Week 160
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments GEE model included change from baseline for standing height Z score as dependent variable; visit, regimen, visit by regimen, and gender as factors; and age and standing height Z score at baseline as covariates, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Burosumab Q4W Then Q2W
Comments Week 160
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0343
Comments GEE model included change from baseline for standing height Z score as dependent variable; visit, regimen, visit by regimen, and gender as factors; and age and standing height Z score at baseline as covariates, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
12.Secondary Outcome
Title Change From Baseline in Growth (Standing Height) Over Time
Hide Description [Not Specified]
Time Frame Baseline, Week 40, 64, 160
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Analysis Set: all participants who received at least 1 dose of study therapy and had at least 1 post-dose measurement at given time point.
Arm/Group Title Burosumab Q2W Burosumab Q4W Then Q2W
Hide Arm/Group Description:
Burosumab SC injections Q2W. Dose was determined by the participant's weight and prescribed dose by their study doctor.
Burosumab SC injections Q4W. Dose was determined by the participant's weight and prescribed dose by their study doctor. Participants in Q4W were to switch to Q2W beginning with Week 64 dosing.
Overall Number of Participants Analyzed 26 26
Mean (Standard Deviation)
Unit of Measure: cm
Change at Week 40 Number Analyzed 24 participants 23 participants
5.03  (1.232) 4.49  (1.455)
Change at Week 64 Number Analyzed 26 participants 26 participants
7.48  (1.934) 6.98  (1.594)
Change at Week 160 Number Analyzed 26 participants 26 participants
18.38  (2.958) 17.22  (2.653)
13.Secondary Outcome
Title Change From Baseline in Growth (Sitting Height) Over Time
Hide Description [Not Specified]
Time Frame Baseline, Week 40, 64, 160
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Analysis Set: all participants who received at least 1 dose of study therapy and had at least 1 post-dose measurement at given time point.
Arm/Group Title Burosumab Q2W Burosumab Q4W Then Q2W
Hide Arm/Group Description:
Burosumab SC injections Q2W. Dose was determined by the participant's weight and prescribed dose by their study doctor.
Burosumab SC injections Q4W. Dose was determined by the participant's weight and prescribed dose by their study doctor. Participants in Q4W were to switch to Q2W beginning with Week 64 dosing.
Overall Number of Participants Analyzed 26 26
Mean (Standard Deviation)
Unit of Measure: cm
Change at Week 40 Number Analyzed 23 participants 23 participants
2.66  (5.496) 2.39  (1.486)
Change at Week 64 Number Analyzed 26 participants 26 participants
3.08  (2.405) 3.45  (1.390)
Change at Week 160 Number Analyzed 26 participants 26 participants
8.29  (2.928) 8.62  (2.163)
14.Secondary Outcome
Title Change From Baseline in Growth (Arm Length) Over Time
Hide Description [Not Specified]
Time Frame Baseline, Week 40, 64, 160
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Analysis Set: all participants who received at least 1 dose of study therapy and had at least 1 post-dose measurement at given time point.
Arm/Group Title Burosumab Q2W Burosumab Q4W Then Q2W
Hide Arm/Group Description:
Burosumab SC injections Q2W. Dose was determined by the participant's weight and prescribed dose by their study doctor.
Burosumab SC injections Q4W. Dose was determined by the participant's weight and prescribed dose by their study doctor. Participants in Q4W were to switch to Q2W beginning with Week 64 dosing.
Overall Number of Participants Analyzed 26 26
Mean (Standard Deviation)
Unit of Measure: cm
Change at Week 40 Number Analyzed 24 participants 23 participants
2.36  (1.058) 2.08  (0.905)
Change at Week 64 Number Analyzed 26 participants 26 participants
3.99  (1.556) 4.77  (7.382)
Change at Week 160 Number Analyzed 26 participants 26 participants
8.50  (1.537) 8.32  (1.798)
15.Secondary Outcome
Title Change From Baseline in Growth (Leg Length) Over Time
Hide Description [Not Specified]
Time Frame Baseline, Week 40, 64, 160
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Analysis Set: all participants who received at least 1 dose of study therapy and had at least 1 post-dose measurement at given time point.
Arm/Group Title Burosumab Q2W Burosumab Q4W Then Q2W
Hide Arm/Group Description:
Burosumab SC injections Q2W. Dose was determined by the participant's weight and prescribed dose by their study doctor.
Burosumab SC injections Q4W. Dose was determined by the participant's weight and prescribed dose by their study doctor. Participants in Q4W were to switch to Q2W beginning with Week 64 dosing.
Overall Number of Participants Analyzed 26 26
Mean (Standard Deviation)
Unit of Measure: cm
Change to Week 40 Number Analyzed 24 participants 23 participants
2.90  (1.365) 2.82  (1.270)
Change at Week 64 Number Analyzed 26 participants 26 participants
5.03  (1.879) 5.16  (1.283)
Change at Week 160 Number Analyzed 26 participants 26 participants
11.78  (3.040) 11.67  (2.338)
16.Secondary Outcome
Title 6MWT Distance (Predicted Percent of Normal) Change From Baseline Over Time
Hide Description The total distance walked (meters) in a 6-minute period was measured. The percent of predicted values were calculated using published normative data based on age, gender, and height (Geiger et al. 2007).
Time Frame Baseline, Week 40, 64, 160
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Analysis Set: all participants who received at least 1 dose of study therapy and had at least 1 post-dose measurement at given time point.
Arm/Group Title Burosumab Q2W Burosumab Q4W Then Q2W
Hide Arm/Group Description:
Burosumab SC injections Q2W. Dose was determined by the participant's weight and prescribed dose by their study doctor.
Burosumab SC injections Q4W. Dose was determined by the participant's weight and prescribed dose by their study doctor. Participants in Q4W were to switch to Q2W beginning with Week 64 dosing.
Overall Number of Participants Analyzed 26 26
Least Squares Mean (Standard Error)
Unit of Measure: percentage of predicted distance
Change to Week 40 3.25  (1.841) 0.24  (2.153)
Change to Week 64 5.29  (1.568) 3.70  (1.731)
Change to Week 160 1.96  (1.483) 2.15  (1.932)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Burosumab Q2W
Comments Week 40
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0771
Comments GEE model included change in 6MWT score as the dependent variable; visit, regimen, visit by regimen as factors; and 6MWT at baseline as a covariate, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Burosumab Q4W Then Q2W
Comments Week 40
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9098
Comments GEE model included change in 6MWT score as the dependent variable; visit, regimen, visit by regimen as factors; and 6MWT at baseline as a covariate, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Burosumab Q2W
Comments Week 64
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0007
Comments GEE model included change in percent of predicted 6MWT score as the dependent variable; visit, regimen, visit by regimen as factors; and 6MWT at baseline as a covariate, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Burosumab Q4W Then Q2W
Comments Week 64
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0327
Comments GEE model included change in percent of predicted 6MWT score as the dependent variable; visit, regimen, visit by regimen as factors; and 6MWT at baseline as a covariate, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Burosumab Q2W
Comments Week 160
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1865
Comments GEE model included change in percent of predicted 6MWT score as the dependent variable; visit, regimen, visit by regimen as factors; and 6MWT at baseline as a covariate, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Burosumab Q4W Then Q2W
Comments Week 160
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2654
Comments GEE model included change in percent of predicted 6MWT score as the dependent variable; visit, regimen, visit by regimen as factors; and 6MWT at baseline as a covariate, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
17.Secondary Outcome
Title Change From Baseline in POSNA-PODCI (Normative Score) Upper Extremity Scale Scores Over Time
Hide Description The POSNA-PODCI yields 4 functional assessment scores: Upper Extremity Function,Transfers and Basic Mobility, Sports and Physical Function, and Comfort/Pain. In addition, a Global Function score, which is an average of the 4 functional assessments, and a Happiness score are calculated. Raw, mean, standardized, and normative scores are calculated for each scale. Normative scores are calculated so that higher scores indicate better functioning. All scores are referenced to the general, healthy population with a normative mean score of 50 and a standard deviation of 10.
Time Frame Baseline, Week 40, 64, 160
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Analysis Set: all participants who received at least 1 dose of study therapy and had at least 1 post-dose measurement at given time point.
Arm/Group Title Burosumab Q2W Burosumab Q4W Then Q2W
Hide Arm/Group Description:
Burosumab SC injections Q2W. Dose was determined by the participant's weight and prescribed dose by their study doctor.
Burosumab SC injections Q4W. Dose was determined by the participant's weight and prescribed dose by their study doctor. Participants in Q4W were to switch to Q2W beginning with Week 64 dosing.
Overall Number of Participants Analyzed 26 25
Least Squares Mean (Standard Error)
Unit of Measure: T-score
Change at Week 40 Number Analyzed 25 participants 24 participants
2.97  (0.710) 2.97  (1.212)
Change at Week 64 Number Analyzed 26 participants 25 participants
1.89  (0.914) 3.20  (0.911)
Change at Week 160 Number Analyzed 26 participants 25 participants
-0.02  (0.740) 1.82  (1.449)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Burosumab Q2W
Comments Week 40
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Burosumab Q4W Then Q2W
Comments Week 40
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0144
Comments GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Burosumab Q2W
Comments Week 64
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0384
Comments GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Burosumab Q4W Then Q2W
Comments Week 64
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0004
Comments GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Burosumab Q2W
Comments Week 160
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9795
Comments GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Burosumab Q4W Then Q2W
Comments Week 160
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2082
Comments GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
18.Secondary Outcome
Title Change From Baseline in POSNA-PODCI (Normative Score) Transfer and Basic Mobility Scale Scores Over Time
Hide Description The POSNA-PODCI yields 4 functional assessment scores: Upper Extremity Function,Transfers and Basic Mobility, Sports and Physical Function, and Comfort/Pain. In addition, a Global Function score, which is an average of the 4 functional assessments, and a Happiness score are calculated. Raw, mean, standardized, and normative scores are calculated for each scale. Normative scores are calculated so that higher scores indicate better functioning. All scores are referenced to the general, healthy population with a normative mean score of 50 and a standard deviation of 10.
Time Frame Baseline, Week 40, 64, 160
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Analysis Set: all participants who received at least 1 dose of study therapy and had at least 1 post-dose measurement at given time point.
Arm/Group Title Burosumab Q2W Burosumab Q4W Then Q2W
Hide Arm/Group Description:
Burosumab SC injections Q2W. Dose was determined by the participant's weight and prescribed dose by their study doctor.
Burosumab SC injections Q4W. Dose was determined by the participant's weight and prescribed dose by their study doctor. Participants in Q4W were to switch to Q2W beginning with Week 64 dosing.
Overall Number of Participants Analyzed 26 25
Least Squares Mean (Standard Error)
Unit of Measure: T-score
Change at Week 40 Number Analyzed 25 participants 24 participants
4.04  (0.827) 3.69  (1.648)
Change at Week 64 Number Analyzed 26 participants 25 participants
-0.34  (3.123) 4.32  (1.364)
Change at Week 160 Number Analyzed 26 participants 25 participants
1.88  (3.285) 5.44  (1.113)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Burosumab Q2W
Comments Week 40
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Burosumab Q4W Then Q2W
Comments Week 40
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0251
Comments GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Burosumab Q2W
Comments Week 64
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9124
Comments GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Burosumab Q4W Then Q2W
Comments Week 64
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0016
Comments GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Burosumab Q2W
Comments Week 160
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5677
Comments GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Burosumab Q4W Then Q2W
Comments Week 160
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
19.Secondary Outcome
Title Change From Baseline in POSNA-PODCI (Normative Score) Sports/Physical Functioning Scale Scores Over Time
Hide Description The POSNA-PODCI yields 4 functional assessment scores: Upper Extremity Function,Transfers and Basic Mobility, Sports and Physical Function, and Comfort/Pain. In addition, a Global Function score, which is an average of the 4 functional assessments, and a Happiness score are calculated. Raw, mean, standardized, and normative scores are calculated for each scale. Normative scores are calculated so that higher scores indicate better functioning. All scores are referenced to the general, healthy population with a normative mean score of 50 and a standard deviation of 10.
Time Frame Baseline, Week 40, 64, 160
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Analysis Set: all participants who received at least 1 dose of study therapy and had at least 1 post-dose measurement at given time point.
Arm/Group Title Burosumab Q2W Burosumab Q4W Then Q2W
Hide Arm/Group Description:
Burosumab SC injections Q2W. Dose was determined by the participant's weight and prescribed dose by their study doctor.
Burosumab SC injections Q4W. Dose was determined by the participant's weight and prescribed dose by their study doctor. Participants in Q4W were to switch to Q2W beginning with Week 64 dosing.
Overall Number of Participants Analyzed 26 25
Least Squares Mean (Standard Error)
Unit of Measure: T-score
Change at Week 40 Number Analyzed 25 participants 24 participants
9.78  (1.679) 9.15  (2.249)
Change at Week 64 Number Analyzed 26 participants 25 participants
7.74  (2.636) 9.84  (2.534)
Change at Week 160 Number Analyzed 25 participants 25 participants
12.04  (2.102) 14.33  (1.834)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Burosumab Q2W
Comments Week 40
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Burosumab Q4W Then Q2W
Comments Week 40
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Burosumab Q2W
Comments Week 64
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0033
Comments GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Burosumab Q4W Then Q2W
Comments Week 64
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Burosumab Q2W
Comments Week 160
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Burosumab Q4W Then Q2W
Comments Week 160
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
20.Secondary Outcome
Title Change From Baseline in POSNA-PODCI (Normative Score) Pain/Comfort Scale Scores Over Time
Hide Description The POSNA-PODCI yields 4 functional assessment scores: Upper Extremity Function,Transfers and Basic Mobility, Sports and Physical Function, and Comfort/Pain. In addition, a Global Function score, which is an average of the 4 functional assessments, and a Happiness score are calculated. Raw, mean, standardized, and normative scores are calculated for each scale. Normative scores are calculated so that higher scores indicate better functioning. All scores are referenced to the general, healthy population with a normative mean score of 50 and a standard deviation of 10.
Time Frame Baseline, Week 40, 64, 160
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Analysis Set: all participants who received at least 1 dose of study therapy and had at least 1 post-dose measurement at given time point.
Arm/Group Title Burosumab Q2W Burosumab Q4W Then Q2W
Hide Arm/Group Description:
Burosumab SC injections Q2W. Dose was determined by the participant's weight and prescribed dose by their study doctor.
Burosumab SC injections Q4W. Dose was determined by the participant's weight and prescribed dose by their study doctor. Participants in Q4W were to switch to Q2W beginning with Week 64 dosing.
Overall Number of Participants Analyzed 26 25
Least Squares Mean (Standard Error)
Unit of Measure: T-score
Change at Week 40 Number Analyzed 25 participants 24 participants
7.67  (2.399) 7.39  (2.477)
Change at Week 64 Number Analyzed 26 participants 25 participants
5.60  (2.904) 7.74  (2.077)
Change at Week 160 Number Analyzed 26 participants 25 participants
13.06  (2.187) 12.38  (2.265)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Burosumab Q2W
Comments Week 40
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0014
Comments GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Burosumab Q4W Then Q2W
Comments Week 40
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0028
Comments GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Burosumab Q2W
Comments Week 64
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0536
Comments GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Burosumab Q4W Then Q2W
Comments Week 64
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Burosumab Q2W
Comments Week 160
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Burosumab Q4W Then Q2W
Comments Week 160
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
21.Secondary Outcome
Title Change From Baseline in POSNA-PODCI (Normative Score) Happiness Scale Scores Over Time
Hide Description The POSNA-PODCI yields 4 functional assessment scores: Upper Extremity Function,Transfers and Basic Mobility, Sports and Physical Function, and Comfort/Pain. In addition, a Global Function score, which is an average of the 4 functional assessments, and a Happiness score are calculated. Raw, mean, standardized, and normative scores are calculated for each scale. Normative scores are calculated so that higher scores indicate better functioning. All scores are referenced to the general, healthy population with a normative mean score of 50 and a standard deviation of 10.
Time Frame Baseline, Week 40, 64, 160
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Analysis Set: all participants who received at least 1 dose of study therapy and had at least 1 post-dose measurement at given time point.
Arm/Group Title Burosumab Q2W Burosumab Q4W Then Q2W
Hide Arm/Group Description:
Burosumab SC injections Q2W. Dose was determined by the participant's weight and prescribed dose by their study doctor.
Burosumab SC injections Q4W. Dose was determined by the participant's weight and prescribed dose by their study doctor. Participants in Q4W were to switch to Q2W beginning with Week 64 dosing.
Overall Number of Participants Analyzed 26 25
Least Squares Mean (Standard Error)
Unit of Measure: T-score
Change at Week 40 Number Analyzed 25 participants 24 participants
2.84  (2.328) 3.01  (1.902)
Change at Week 64 Number Analyzed 26 participants 25 participants
2.18  (1.914) 3.34  (1.914)
Change at Week 160 Number Analyzed 26 participants 25 participants
6.46  (2.486) 9.19  (1.075)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Burosumab Q2W
Comments Week 40
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2230
Comments GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Burosumab Q4W Then Q2W
Comments Week 40
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1132
Comments GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Burosumab Q2W
Comments Week 64
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2558
Comments GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Burosumab Q4W Then Q2W
Comments Week 64
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0814
Comments GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Burosumab Q2W
Comments Week 160
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0093
Comments GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Burosumab Q4W Then Q2W
Comments Week 160
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
22.Secondary Outcome
Title Change From Baseline in POSNA-PODCI (Normative Score) Global Functioning Scale Scores Over Time
Hide Description The POSNA-PODCI yields 4 functional assessment scores: Upper Extremity Function,Transfers and Basic Mobility, Sports and Physical Function, and Comfort/Pain. In addition, a Global Function score, which is an average of the 4 functional assessments, and a Happiness score are calculated. Raw, mean, standardized, and normative scores are calculated for each scale. Normative scores are calculated so that higher scores indicate better functioning. All scores are referenced to the general, healthy population with a normative mean score of 50 and a standard deviation of 10.
Time Frame Baseline, Week 40, 64, 160
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Analysis Set: all participants who received at least 1 dose of study therapy and had at least 1 post-dose measurement at given time point.
Arm/Group Title Burosumab Q2W Burosumab Q4W Then Q2W
Hide Arm/Group Description:
Burosumab SC injections Q2W. Dose was determined by the participant's weight and prescribed dose by their study doctor.
Burosumab SC injections Q4W. Dose was determined by the participant's weight and prescribed dose by their study doctor. Participants in Q4W were to switch to Q2W beginning with Week 64 dosing.
Overall Number of Participants Analyzed 26 25
Least Squares Mean (Standard Error)
Unit of Measure: T-score
Change at Week 40 Number Analyzed 25 participants 24 participants
9.06  (1.560) 8.12  (2.351)
Change at Week 64 Number Analyzed 26 participants 25 participants
6.02  (2.706) 8.72  (2.019)
Change at Week 160 Number Analyzed 25 participants 25 participants
11.37  (1.804) 11.94  (2.024)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Burosumab Q2W
Comments Week 40
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Burosumab Q4W Then Q2W
Comments Week 40
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0006
Comments GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Burosumab Q2W
Comments Week 64
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0260
Comments GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Burosumab Q4W Then Q2W
Comments Week 64
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Burosumab Q2W
Comments Week 160
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Burosumab Q4W Then Q2W
Comments Week 160
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.
Method GEE model
Comments [Not Specified]
23.Secondary Outcome
Title Change From Baseline in FEP Over Time
Hide Description FEP is defined as 100% × (urine phosphorus × serum creatinine)/(urine creatinine × serum phosphorus), where the 2-hour urine sample was used for urine phosphorus and urine creatinine.
Time Frame Baseline, Week 40, 64, 160
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set: All participants who received at least 1 dose of study therapy and had an assessment at given time point.
Arm/Group Title Burosumab Q2W Burosumab Q4W Then Q2W
Hide Arm/Group Description:
Burosumab SC injections Q2W. Dose was determined by the participant's weight and prescribed dose by their study doctor.
Burosumab SC injections Q4W. Dose was determined by the participant's weight and prescribed dose by their study doctor. Participants in Q4W were to switch to Q2W beginning with Week 64 dosing.
Overall Number of Participants Analyzed 25 26
Mean (Standard Deviation)
Unit of Measure: percentage of phosphorus excreted
Change at Week 40 Number Analyzed 25 participants 26 participants
-3.97  (7.161) -4.85  (7.170)
Change at Week 64 Number Analyzed 20 participants 22 participants
-2.63  (4.446) -3.96  (7.522)
Change at Week 160 Number Analyzed 23 participants 26 participants
-5.43  (6.985) -6.47  (8.072)
24.Secondary Outcome
Title Change From Baseline in P1NP Over Time
Hide Description [Not Specified]
Time Frame Baseline, Week 40, 64
Hide Outcome Measure Data
Hide Analysis Population Description
PK/PD Analysis Set: all participants who received at least 1 dose of therapy and had evaluable serum data at given time point.
Arm/Group Title Burosumab Q2W Burosumab Q4W Then Q2W
Hide Arm/Group Description:
Burosumab SC injections Q2W. Dose was determined by the participant's weight and prescribed dose by their study doctor.
Burosumab SC injections Q4W. Dose was determined by the participant's weight and prescribed dose by their study doctor. Participants in Q4W were to switch to Q2W beginning with Week 64 dosing.
Overall Number of Participants Analyzed 24 26
Mean (Standard Deviation)
Unit of Measure: ng/mL
Change at Week 40 Number Analyzed 24 participants 26 participants
275.98  (329.587) 224.91  (161.053)
Change at Week 64 Number Analyzed 22 participants 23 participants
137.35  (354.315) 133.56  (192.306)
25.Secondary Outcome
Title Change From Baseline in CTx Over Time
Hide Description [Not Specified]
Time Frame Baseline, Week 40, 64
Hide Outcome Measure Data
Hide Analysis Population Description
PK/PD Analysis Set: all participants who received at least 1 dose of therapy and had evaluable serum data at given time point.
Arm/Group Title Burosumab Q2W Burosumab Q4W Then Q2W
Hide Arm/Group Description:
Burosumab SC injections Q2W. Dose was determined by the participant's weight and prescribed dose by their study doctor.
Burosumab SC injections Q4W. Dose was determined by the participant's weight and prescribed dose by their study doctor. Participants in Q4W were to switch to Q2W beginning with Week 64 dosing.
Overall Number of Participants Analyzed 26 26
Mean (Standard Deviation)
Unit of Measure: ng/mL
Change at Week 40 Number Analyzed 26 participants 26 participants
1.01  (0.802) 0.64  (0.578)
Change at Week 64 Number Analyzed 25 participants 25 participants
1.08  (0.870) 0.81  (0.706)
26.Secondary Outcome
Title Change From Baseline in ALP Over Time
Hide Description [Not Specified]
Time Frame Baseline, Week 40, 64, 160
Hide Outcome Measure Data
Hide Analysis Population Description
PK/PD Analysis Set: all participants who received at least 1 dose of therapy and had evaluable serum data at given time point.
Arm/Group Title Burosumab Q2W Burosumab Q4W Then Q2W
Hide Arm/Group Description:
Burosumab SC injections Q2W. Dose was determined by the participant's weight and prescribed dose by their study doctor.
Burosumab SC injections Q4W. Dose was determined by the participant's weight and prescribed dose by their study doctor. Participants in Q4W were to switch to Q2W beginning with Week 64 dosing.
Overall Number of Participants Analyzed 26 26
Mean (Standard Deviation)
Unit of Measure: U/L
Change at Week 40 Number Analyzed 26 participants 26 participants
-79.4  (97.40) -47.8  (70.86)
Change at Week 64 Number Analyzed 24 participants 23 participants
-113.9  (81.28) -80.9  (67.11)
Change at Week 160 Number Analyzed 26 participants 26 participants
-153.1  (132.45) -140.0  (115.82)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Burosumab Q2W
Comments Week 40
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0003
Comments [Not Specified]
Method one sample t test
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Burosumab Q4W Then Q2W
Comments Week 40
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0021
Comments [Not Specified]
Method one sample t test
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Burosumab Q2W
Comments Week 64
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method one sample t test
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Burosumab Q4W Then Q2W
Comments Week 64
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method one sample t test
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Burosumab Q2W
Comments Week 160
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method one sample t test
Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Burosumab Q4W Then Q2W
Comments Week 160
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method one sample t test
Comments [Not Specified]
27.Secondary Outcome
Title Change From Baseline in BALP Over Time
Hide Description [Not Specified]
Time Frame Baseline, Week 40, 64, 160
Hide Outcome Measure Data
Hide Analysis Population Description
PK/PD Analysis Set: all participants who received at least 1 dose of therapy and had evaluable serum data at given time point.
Arm/Group Title Burosumab Q2W Burosumab Q4W Then Q2W
Hide Arm/Group Description:
Burosumab SC injections Q2W. Dose was determined by the participant's weight and prescribed dose by their study doctor.
Burosumab SC injections Q4W. Dose was determined by the participant's weight and prescribed dose by their study doctor. Participants in Q4W were to switch to Q2W beginning with Week 64 dosing.
Overall Number of Participants Analyzed 20 20
Mean (Standard Deviation)
Unit of Measure: mcg/L
Change at Week 40 Number Analyzed 20 participants 20 participants
-35.55  (46.738) -27.80  (31.409)
Change at Week 64 Number Analyzed 19 participants 20 participants
-50.40  (36.478) -47.13  (28.822)
Change at Week 160 Number Analyzed 20 participants 20 participants
-67.25  (59.309) -56.73  (52.284)
28.Secondary Outcome
Title Serum Pre-Dose Concentrations of Burosumab
Hide Description [Not Specified]
Time Frame Week 40, 64, 160
Hide Outcome Measure Data
Hide Analysis Population Description
PK/PD Analysis Set: all participants who received at least 1 dose of therapy and had evaluable serum data at given time point.
Arm/Group Title Burosumab Q2W Burosumab Q4W Then Q2W
Hide Arm/Group Description:
Burosumab SC injections Q2W. Dose was determined by the participant's weight and prescribed dose by their study doctor.
Burosumab SC injections Q4W. Dose was determined by the participant's weight and prescribed dose by their study doctor. Participants in Q4W were to switch to Q2W beginning with Week 64 dosing.
Overall Number of Participants Analyzed 26 26
Mean (Standard Deviation)
Unit of Measure: ng/mL
Week 40 Number Analyzed 26 participants 26 participants
13188.81  (7188.588) 6443.08  (3266.215)
Week 64 Number Analyzed 26 participants 24 participants
15846.65  (9385.393) 8525.63  (3968.821)
Week 160 Number Analyzed 26 participants 26 participants
13975.27  (8168.877) 13163.96  (6593.120)
29.Secondary Outcome
Title Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Discontinuations Due to Adverse Events (AEs)
Hide Description An AE is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An SAE is defined as an AE or suspected adverse reaction that at any dose results in any of the following outcomes: death; life-threatening AE; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; a congenital anomaly/birth defect. Severity was graded as 1 (mild), 2 (moderate), 3 (severe), 4 (life-threatening), 5 (death). TEAEs are defined as AEs with onset on or after the time of initiation of study drug administration.
Time Frame Up to 216 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set: All participants who received at least 1 dose of study therapy.
Arm/Group Title Burosumab Q2W Burosumab Q4W Then Q2W
Hide Arm/Group Description:
Burosumab SC injections Q2W. Dose was determined by the participant's weight and prescribed dose by their study doctor.
Burosumab SC injections Q4W. Dose was determined by the participant's weight and prescribed dose by their study doctor. Participants in Q4W were to switch to Q2W beginning with Week 64 dosing.
Overall Number of Participants Analyzed 26 26
Measure Type: Count of Participants
Unit of Measure: Participants
All TEAEs
26
 100.0%
26
 100.0%
Serious TEAE
0
   0.0%
1
   3.8%
Related TEAE
17
  65.4%
21
  80.8%
Serious Related TEAE
0
   0.0%
1
   3.8%
Grade 3 or 4 TEAE
1
   3.8%
1
   3.8%
TEAE Leading to Study Discontinuation
0
   0.0%
0
   0.0%
TEAE Leading to Treatment Discontinuation
0
   0.0%
0
   0.0%
TEAE Leading to Death
0
   0.0%
0
   0.0%
Time Frame Up to 216 weeks
Adverse Event Reporting Description TEAEs, defined as AEs with onset on or after the time of initiation of study drug administration, are presented.
 
Arm/Group Title Burosumab Q2W Burosumab Q4W Then Q2W
Hide Arm/Group Description Burosumab SC injections Q2W. Dose was determined by the participant's weight and prescribed dose by their study doctor. Burosumab SC injections Q4W. Dose was determined by the participant's weight and prescribed dose by their study doctor. Participants in Q4W were to switch to Q2W beginning with Week 64 dosing.
All-Cause Mortality
Burosumab Q2W Burosumab Q4W Then Q2W
Affected / at Risk (%) Affected / at Risk (%)
Total   0/26 (0.00%)   0/26 (0.00%) 
Hide Serious Adverse Events
Burosumab Q2W Burosumab Q4W Then Q2W
Affected / at Risk (%) Affected / at Risk (%)
Total   0/26 (0.00%)   1/26 (3.85%) 
General disorders     
Pyrexia † 1  0/26 (0.00%)  1/26 (3.85%) 
Musculoskeletal and connective tissue disorders     
Myalgia † 1  0/26 (0.00%)  1/26 (3.85%) 
Nervous system disorders     
Headache † 1  0/26 (0.00%)  1/26 (3.85%) 
1
Term from vocabulary, MedDRA 20.0
†
Indicates events were collected by systematic assessment