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Study of KRN23 in Adults 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: NCT02526160
Recruitment Status : Completed
First Posted : August 18, 2015
Results First Posted : February 5, 2021
Last Update Posted : February 5, 2021
Sponsor:
Collaborator:
Kyowa Kirin Co., Ltd.
Information provided by (Responsible Party):
Ultragenyx Pharmaceutical Inc

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition X-linked Hypophosphatemia
Interventions Biological: burosumab
Other: Placebo
Enrollment 134
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Placebo Burosumab 1 mg/kg
Hide Arm/Group Description Subcutaneous (SC) injection of placebo every 4 weeks (Q4W) for 24 weeks (Double-blind Placebo-controlled Treatment Period), SC injection of burosumab 1 mg/kg Q4W for 24 weeks (Open-label Treatment Continuation Period), SC injection of burosumab 1 mg/kg Q4W for 48 weeks (Open-label Treatment Extension Period I), and SC injection of burosumab 1 mg/kg Q4W up to 53 weeks (Open-label Treatment Extension Period II). SC injection of 1.0 mg/kg burosumab Q4W for 24 weeks (double-blind placebo-controlled Treatment Period), SC injection of burosumab 1 mg/kg Q4W for 24 weeks (open-label Treatment Continuation Period), SC injection of burosumab 1 mg/kg Q4W for 48 weeks (open-label Treatment Extension Period I), and SC injection of burosumab 1 mg/kg Q4W up to 53 weeks (open-label Treatment Extension Period II).
Period Title: Double-Blind (Placebo-Controlled) Period
Started 66 68
Completed 66 67
Not Completed 0 1
Reason Not Completed
Withdrawal by Subject             0             1
Period Title: Open-label Treatment Continuation Period
Started 66 67
Completed 63 63
Not Completed 3 4
Reason Not Completed
Withdrawal by Subject             0             1
Other, Not Specified             3             3
Period Title: Open-Label Treatment Extension Period I
Started 63 63
Completed 60 59
Not Completed 3 4
Reason Not Completed
Death             0             1
Other, Not Specified             3             1
Withdrawal by Subject             0             1
Lost to Follow-up             0             1
Period Title: Open-Label Treatment Extension Period II
Started 52 49
Completed 51 49
Not Completed 1 0
Reason Not Completed
Other, Not Specified             1             0
Arm/Group Title Placebo Burosumab Total
Hide Arm/Group Description Placebo SC Q4W through Week 24 Burosumab 1 mg/kg SC Q4W Total of all reporting groups
Overall Number of Baseline Participants 66 68 134
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 66 participants 68 participants 134 participants
38.65  (12.756) 41.29  (11.582) 39.99  (12.201)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 66 participants 68 participants 134 participants
Female
43
  65.2%
44
  64.7%
87
  64.9%
Male
23
  34.8%
24
  35.3%
47
  35.1%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 66 participants 68 participants 134 participants
Hispanic or Latino
5
   7.6%
7
  10.3%
12
   9.0%
Not Hispanic or Latino
61
  92.4%
61
  89.7%
122
  91.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 66 participants 68 participants 134 participants
Asian
9
  13.6%
12
  17.6%
21
  15.7%
Black or African American
3
   4.5%
0
   0.0%
3
   2.2%
White
53
  80.3%
55
  80.9%
108
  80.6%
Other, Not Specified
1
   1.5%
1
   1.5%
2
   1.5%
Brief Pain Inventory (BPI) Worst Pain Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Score on a scale
Number Analyzed 66 participants 68 participants 134 participants
6.54  (1.433) 6.81  (1.308) 6.68  (1.372)
[1]
Measure Description: The BPI evaluates the condition of all pain over the previous 24 hours. Question 3 of the short-form BPI (BPI-Q3) asks participants to rate their pain at its worst in the last 24 hours on a scale of 0 (no pain) to 10 (pain as bad as you can imagine). The baseline BPI Worst Pain is defined as the mean of the BPI Worst Pain for 8 days including the 7 days of diary scores prior to baseline visit and the baseline visit score.
BPI Pain Severity Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Score on a scale
Number Analyzed 66 participants 68 participants 134 participants
4.92  (1.547) 5.18  (1.531) 5.05  (1.539)
[1]
Measure Description: The BPI evaluates the condition of all pain over the previous 24 hours. Two dimensions are measured: pain severity (worst, least, average, and now) and the impact of pain on functioning (pain interference with general activity, walking, work, mood, enjoyment of life, relations with others, and sleep). The severity of pain in the last 24 hours is rated on a scale of 0 (no pain) to 10 (pain as bad as you can imagine).
BPI Pain Interference Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Score on a scale
Number Analyzed 66 participants 68 participants 134 participants
4.76  (2.174) 5.23  (2.237) 5.00  (2.210)
[1]
Measure Description: The BPI evaluates the condition of all pain over the previous 24 hours. Two dimensions are measured: pain severity (worst, least, average, and now) and the impact of pain on functioning (pain interference with general activity, walking, work, mood, enjoyment of life, relations with others, and sleep). Pain interference in the last 24 hours is rated on a scale of 0 (does not interfere) to 10 (completely interferes).
Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Score on a scale
Number Analyzed 66 participants 68 participants 134 participants
61.36  (20.770) 64.71  (20.253) 63.06  (20.500)
[1]
Measure Description: The WOMAC is a 24-item participant-reported questionnaire with two domains, Stiffness (2 questions) and Physical Function (17 questions) over the previous 48 hours. The WOMAC is administered in a 5-point Likert-scale format using descriptors of none, mild, moderate, severe, and extreme corresponding to an ordinal scale of 0-4. Higher scores on the WOMAC indicate worse stiffness and functional limitations. Scores are normalized to a 0-100 metric where 0 was the best health state and 100 the worst.
WOMAC Physical Function Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Score on a scale
Number Analyzed 66 participants 68 participants 134 participants
43.89  (19.938) 50.79  (19.660) 47.40  (20.024)
[1]
Measure Description: The WOMAC is a 24-item participant-reported questionnaire with two domains, Stiffness (2 questions) and Physical Function (17 questions) over the previous 48 hours. The WOMAC is administered in a 5-point Likert-scale format using descriptors of none, mild, moderate, severe, and extreme corresponding to an ordinal scale of 0-4. Higher scores on the WOMAC indicate worse stiffness and functional limitations. Scores are normalized to a 0-100 metric where 0 was the best health state and 100 the worst.
Brief Fatigue Inventory (BFI) Worst Fatigue Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Score on a scale
Number Analyzed 66 participants 68 participants 134 participants
6.74  (1.526) 6.94  (1.657) 6.84  (1.591)
[1]
Measure Description: The BFI is a self-reported questionnaire consisting of 9 items related to fatigue rated on a 0 to 10 numerical scale with a recall period of 24 hours. Two dimensions are measured: fatigue severity and the interference of fatigue on daily life (activity, mood, walking ability, work, relations with others, and enjoyment of life). Participants are asked to rate their worst fatigue over the past 24 hours from 0 (no fatigue) to 10 (as bad a you can imagine).
BFI Global Fatigue Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Score on a scale
Number Analyzed 66 participants 68 participants 134 participants
4.86  (1.932) 5.37  (2.044) 5.12  (1.999)
[1]
Measure Description: The BFI is a self-reported questionnaire consisting of 9 items related to fatigue that are rated on a numerical scale with a recall period of 24 hours. Two dimensions are measured: fatigue severity and the interference of fatigue on daily life (activity, mood, walking ability, work, relations with others, and enjoyment of life). BFI Global Fatigue score was calculated by averaging all 9 items on the BFI. Global scores range from 0 to 10, with higher score indicating worse fatigue severity and interference.
Serum Procollagen Type 1 N- Propeptide (P1NP)   [1] 
Mean (Standard Deviation)
Unit of measure:  ng/mL
Number Analyzed 66 participants 67 participants 133 participants
87.6  (53.41) 87.5  (53.60) 87.6  (53.30)
[1]
Measure Analysis Population Description: participants with a baseline assessment
Serum Carboxy-Terminal Cross-Linked Telopeptide of Type I Collagen (CTx)   [1] 
Mean (Standard Deviation)
Unit of measure:  pg/mL
Number Analyzed 66 participants 67 participants 133 participants
719.2  (419.24) 718.4  (413.71) 718.8  (414.89)
[1]
Measure Analysis Population Description: participants with a baseline assessment
Serum Bone-Specific Alkaline Phosphatase (BALP)   [1] 
Mean (Standard Deviation)
Unit of measure:  μg/L
Number Analyzed 66 participants 66 participants 132 participants
24.6  (17.30) 25.1  (21.55) 24.9  (19.47)
[1]
Measure Analysis Population Description: participants with a baseline assessment
Serum Phosphorus  
Mean (Standard Deviation)
Unit of measure:  mmol/L
Number Analyzed 66 participants 68 participants 134 participants
0.617  (0.1001) 0.653  (0.1072) 0.635  (0.1050)
Serum 1, 25 (OH)2 D   [1] 
Mean (Standard Deviation)
Unit of measure:  pg/mL
Number Analyzed 64 participants 66 participants 130 participants
33.5  (15.61) 32.4  (12.96) 33.0  (14.28)
[1]
Measure Analysis Population Description: participants with a baseline assessment
24-Hour Urinary Phosphorus   [1] 
Mean (Standard Deviation)
Unit of measure:  G/24 hour
Number Analyzed 65 participants 68 participants 133 participants
0.81  (0.262) 0.72  (0.241) 0.77  (0.255)
[1]
Measure Analysis Population Description: participants with a baseline assessment
Ratio of Renal Tubular Maximum Reabsorption Rate of Phosphate to Glomerular Filtration Rate(TmP/GFR)   [1] 
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 64 participants 66 participants 130 participants
1.598  (0.3693) 1.678  (0.4004) 1.639  (0.3860)
[1]
Measure Analysis Population Description: participants with a baseline assessment
Tubular Reabsorption of Phosphate (TRP)   [1] 
Mean (Standard Deviation)
Unit of measure:  Fraction of phosphate reabsorbed
Number Analyzed 64 participants 67 participants 131 participants
0.812  (0.0842) 0.807  (0.0832) 0.810  (0.0834)
[1]
Measure Analysis Population Description: participants with a baseline assessment
1.Primary Outcome
Title Percentage of Participants Achieving Mean Serum Phosphorus Levels Above the LLN (2.5 mg/dL [0.81 mmol/L]) at the Mid-Point of the Dose Interval, as Averaged Across Dose Cycles Between Baseline and Week 24
Hide Description [Not Specified]
Time Frame Baseline through Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period.
Arm/Group Title Placebo Burosumab
Hide Arm/Group Description:
Placebo SC Q4W through Week 24
Burosumab 1 mg/kg SC Q4W
Overall Number of Participants Analyzed 66 68
Mean (95% Confidence Interval)
Unit of Measure: percentage of participants
7.6
(3.3 to 16.5)
92.6
(83.9 to 96.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Burosumab
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments From Cochran-Mantel-Haenszel (CMH) testing for association between achieving mean serum phosphorus levels above lower limit of normal (LLN) and treatment group, adjusting for stratification of Brief Pain Inventory (BPI) Average Pain and region.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline to Week 24 in Brief Pain Inventory (BPI) Question 3 (Q3; Worst Pain in Past 24 Hours) Score
Hide Description

The BPI evaluates the condition of all pain over the previous 24 hours. Two dimensions are measured: pain severity (worst, least, average, and now) and the impact of pain on functioning (pain interference with general activity, walking, work, mood, enjoyment of life, relations with others, and sleep). Question 3 of the short-form BPI (BPI-Q3) asks subjects to rate their pain at its worst in the last 24 hours on a scale of 0 (no pain) to 10 (pain as bad as you can imagine).

From the generalized estimating equation (GEE) model, which includes the change from Baseline for the endpoint of interest as the dependent variable; region, visit, treatment, actual randomization stratification (not included for analysis of BPI Worst Pain), and visit by treatment as fixed factors; and Baseline value for the endpoint of interest as a covariate, with compound symmetry covariance structure.

Time Frame Baseline, 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period.
Arm/Group Title Placebo Burosumab
Hide Arm/Group Description:
Placebo SC Q4W through Week 24
Burosumab 1 mg/kg SC Q4W
Overall Number of Participants Analyzed 66 68
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
-0.32  (0.222) -0.79  (0.211)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Burosumab
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0919
Comments Prespecified significance level for test after Hochberg adjustment: 0.05
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares (LS) mean difference
Estimated Value -0.46
Confidence Interval (2-Sided) 95%
-1.00 to 0.08
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.275
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline to Week 24 in the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) Stiffness Score
Hide Description

The WOMAC is a 24-item participant-reported questionnaire with two domains, Stiffness (2 questions) and Physical Function (17 questions) over the previous 48 hours. The WOMAC is administered in a 5-point Likert-scale format using descriptors of none, mild, moderate, severe, and extreme corresponding to an ordinal scale of 0-4. Higher scores on the WOMAC indicate worse stiffness and functional limitations. Scores are normalized to a 0-100 metric where 0 was the best health state and 100 the worst.

The GEE estimates are from the GEE model which includes the change from baseline for WOMAC Stiffness as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of WOMAC Stiffness as a covariate, with compound symmetry covariance structure.

Time Frame Baseline, 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period.
Arm/Group Title Placebo Burosumab
Hide Arm/Group Description:
Placebo SC Q4W through Week 24
Burosumab 1 mg/kg SC Q4W
Overall Number of Participants Analyzed 66 68
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
0.46  (3.139) -7.85  (3.034)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Burosumab
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0106
Comments Prespecified significance level for test after Hochberg adjustment: 0.0167
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -8.31
Confidence Interval (2-Sided) 95%
-14.68 to -1.94
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.251
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline to Week 24 in the WOMAC Physical Function Score
Hide Description

The WOMAC is a 24-item participant-reported questionnaire with two domains, Stiffness (2 questions) and Physical Function (17 questions) over the previous 48 hours. The WOMAC is administered in a 5-point Likert-scale format using descriptors of none, mild, moderate, severe, and extreme corresponding to an ordinal scale of 0-4. Higher scores on the WOMAC indicate worse stiffness and functional limitations. Scores are normalized to a 0-100 metric where 0 was the best health state and 100 the worst.

The GEE Estimates are from the GEE model which includes the change from baseline for WOMAC Physical Function as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of WOMAC Physical Function as a covariate, with compound symmetry covariance structure.

Time Frame Baseline, 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period.
Arm/Group Title Placebo Burosumab
Hide Arm/Group Description:
Placebo SC Q4W through Week 24
Burosumab 1 mg/kg SC Q4W
Overall Number of Participants Analyzed 66 68
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
1.79  (2.722) -3.11  (2.553)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Burosumab
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0478
Comments Prespecified significance level for test after Hochberg adjustment: 0.025
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -4.9
Confidence Interval (2-Sided) 95%
-9.76 to -0.05
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.479
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline Over Time in BPI Worst Pain Score
Hide Description

Change from baseline to post-baseline visits in BPI-Q3 (Worst Pain) score as averaged from daily diary scores recorded over 1 week and the study visit score. The BPI evaluates the condition of all pain over the previous 24 hours. Two dimensions are measured: pain severity (worst, least, average, and now) and the impact of pain on functioning (pain interference with general activity, walking, work, mood, enjoyment of life, relations with others, and sleep). Question 3 of the short-form BPI (BPI-Q3) asks subjects to rate their pain at its worst in the last 24 hours on a scale of 0 (no pain) to 10 (pain as bad as you can imagine).

The GEE Estimates are from the GEE model which includes the change from baseline for BPI worst pain as the dependent variable, region, visit, treatment and visit by treatment as fixed factors, and baseline of BPI Worst Pain as a covariate, with compound symmetry covariance structure.

Time Frame Baseline, Weeks 12, 24, 36, 48, 72, 96
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period. Participants with an assessment at given time point.
Arm/Group Title Placebo Burosumab 1 mg/kg
Hide Arm/Group Description:
Subcutaneous (SC) injection of placebo every 4 weeks (Q4W) for 24 weeks (Double-blind Placebo-controlled Treatment Period), SC injection of burosumab 1 mg/kg Q4W for 24 weeks (Open-label Treatment Continuation Period), SC injection of burosumab 1 mg/kg Q4W for 48 weeks (Open-label Treatment Extension Period I), and SC injection of burosumab 1 mg/kg Q4W up to 53 weeks (Open-label Treatment Extension Period II).
SC injection of 1.0 mg/kg burosumab Q4W for 24 weeks (double-blind placebo-controlled Treatment Period), SC injection of burosumab 1 mg/kg Q4W for 24 weeks (open-label Treatment Continuation Period), SC injection of burosumab 1 mg/kg Q4W for 48 weeks (open-label Treatment Extension Period I), and SC injection of burosumab 1 mg/kg Q4W up to 53 weeks (open-label Treatment Extension Period II).
Overall Number of Participants Analyzed 66 68
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
Change at Week 12 Number Analyzed 66 participants 68 participants
-0.37  (0.216) -0.62  (0.208)
Change at Week 24 Number Analyzed 65 participants 67 participants
-0.31  (0.242) -0.77  (0.228)
Change at Week 36 Number Analyzed 65 participants 65 participants
-1.25  (0.234) -0.95  (0.228)
Change at Week 48 Number Analyzed 66 participants 66 participants
-1.49  (0.243) -1.05  (0.230)
Change at Week 72 Number Analyzed 60 participants 59 participants
-1.28  (0.283) -1.21  (0.316)
Change at Week 96 Number Analyzed 59 participants 59 participants
-0.99  (0.265) -1.48  (0.299)
6.Secondary Outcome
Title Change From Baseline Over Time in BPI Pain Severity Score
Hide Description

Change from baseline to post-baseline visits in BPI pain severity score as averaged from daily diary scores recorded over 1 week and the study visit score. The BPI evaluates the condition of all pain over the previous 24 hours. Two dimensions are measured: pain severity (worst, least, average, and now) and the impact of pain on functioning (pain interference with general activity, walking, work, mood, enjoyment of life, relations with others, and sleep). The severity of pain in the last 24 hours is rated on a scale of 0 (no pain) to 10 (pain as bad as you can imagine).

The GEE Estimates are from the GEE model which includes the change from baseline for each BPI endpoint as the dependent variable, region, visit, treatment, and visit by treatment as fixed factors, and baseline of each BPI endpoint as a covariate, with compound symmetry covariance structure.

Time Frame Baseline, Weeks 12, 24, 36, 48, 72, 96
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period. Participants with an assessment at given time point.
Arm/Group Title Placebo Burosumab 1 mg/kg
Hide Arm/Group Description:
Subcutaneous (SC) injection of placebo every 4 weeks (Q4W) for 24 weeks (Double-blind Placebo-controlled Treatment Period), SC injection of burosumab 1 mg/kg Q4W for 24 weeks (Open-label Treatment Continuation Period), SC injection of burosumab 1 mg/kg Q4W for 48 weeks (Open-label Treatment Extension Period I), and SC injection of burosumab 1 mg/kg Q4W up to 53 weeks (Open-label Treatment Extension Period II).
SC injection of 1.0 mg/kg burosumab Q4W for 24 weeks (double-blind placebo-controlled Treatment Period), SC injection of burosumab 1 mg/kg Q4W for 24 weeks (open-label Treatment Continuation Period), SC injection of burosumab 1 mg/kg Q4W for 48 weeks (open-label Treatment Extension Period I), and SC injection of burosumab 1 mg/kg Q4W up to 53 weeks (open-label Treatment Extension Period II).
Overall Number of Participants Analyzed 66 68
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
Change at Week 12 Number Analyzed 66 participants 68 participants
-0.32  (0.166) -0.43  (0.163)
Change at Week 24 Number Analyzed 65 participants 67 participants
-0.10  (0.211) -0.53  (0.172)
Change at Week 36 Number Analyzed 65 participants 65 participants
-0.97  (0.214) -0.62  (0.184)
Change at Week 48 Number Analyzed 66 participants 66 participants
-1.13  (0.205) -0.79  (0.162)
Change at Week 72 Number Analyzed 60 participants 59 participants
-1.36  (0.216) -1.24  (0.231)
Change at Week 96 Number Analyzed 59 participants 59 participants
-1.18  (0.195) -1.42  (0.229)
7.Secondary Outcome
Title Change From Baseline Over Time in BPI Pain Interference Score
Hide Description

Change from baseline to post-baseline visits in BPI pain interference score as recorded on the day of the study visit. The BPI evaluates the condition of all pain over the previous 24 hours. Two dimensions are measured: pain severity (worst, least, average, and now) and the impact of pain on functioning (pain interference with general activity, walking, work, mood, enjoyment of life, relations with others, and sleep). Pain interference in the last 24 hours is rated on a scale of 0 (does not interfere) to 10 (completely interferes).

The GEE Estimates are from the GEE model which includes the change from baseline for each BPI endpoint as the dependent variable, region, visit, treatment, and visit by treatment as fixed factors, and baseline of each BPI endpoint as a covariate, with compound symmetry covariance structure.

Time Frame Baseline, Weeks 12, 24, 36, 48, 72, 96
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period. Participants with an assessment at given time point.
Arm/Group Title Placebo Burosumab 1 mg/kg
Hide Arm/Group Description:
Subcutaneous (SC) injection of placebo every 4 weeks (Q4W) for 24 weeks (Double-blind Placebo-controlled Treatment Period), SC injection of burosumab 1 mg/kg Q4W for 24 weeks (Open-label Treatment Continuation Period), SC injection of burosumab 1 mg/kg Q4W for 48 weeks (Open-label Treatment Extension Period I), and SC injection of burosumab 1 mg/kg Q4W up to 53 weeks (Open-label Treatment Extension Period II).
SC injection of 1.0 mg/kg burosumab Q4W for 24 weeks (double-blind placebo-controlled Treatment Period), SC injection of burosumab 1 mg/kg Q4W for 24 weeks (open-label Treatment Continuation Period), SC injection of burosumab 1 mg/kg Q4W for 48 weeks (open-label Treatment Extension Period I), and SC injection of burosumab 1 mg/kg Q4W up to 53 weeks (open-label Treatment Extension Period II).
Overall Number of Participants Analyzed 66 68
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
Change at Week 12 Number Analyzed 66 participants 68 participants
-0.29  (0.215) -0.51  (0.207)
Change at Week 24 Number Analyzed 65 participants 67 participants
-0.28  (0.242) -0.41  (0.207)
Change at Week 36 Number Analyzed 65 participants 65 participants
-1.30  (0.260) -0.79  (0.221)
Change at Week 48 Number Analyzed 66 participants 66 participants
-1.28  (0.251) -1.04  (0.235)
Change at Week 72 Number Analyzed 60 participants 60 participants
-1.22  (0.247) -1.24  (0.263)
Change at Week 96 Number Analyzed 59 participants 59 participants
-1.08  (0.260) -1.43  (0.234)
8.Secondary Outcome
Title Change From Baseline Over Time in WOMAC Stiffness Score
Hide Description

The WOMAC is a 24-item participant-reported questionnaire with two domains, Stiffness (2 questions) and Physical Function (17 questions) over the previous 48 hours. The WOMAC is administered in a 5-point Likert-scale format using descriptors of none, mild, moderate, severe, and extreme corresponding to an ordinal scale of 0-4. Higher scores on the WOMAC indicate worse stiffness and functional limitations. Scores are normalized to a 0-100 metric where 0 was the best health state and 100 the worst.

The GEE Estimates are from the GEE model which includes the change from baseline for WOMAC Stiffness as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of WOMAC Stiffness as a covariate, with compound symmetry covariance structure.

Time Frame Baseline, Weeks 12, 24, 36, 48, 72, 96, 120, 144
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period. Participants with an assessment at given time point.
Arm/Group Title Placebo Burosumab 1 mg/kg
Hide Arm/Group Description:
Subcutaneous (SC) injection of placebo every 4 weeks (Q4W) for 24 weeks (Double-blind Placebo-controlled Treatment Period), SC injection of burosumab 1 mg/kg Q4W for 24 weeks (Open-label Treatment Continuation Period), SC injection of burosumab 1 mg/kg Q4W for 48 weeks (Open-label Treatment Extension Period I), and SC injection of burosumab 1 mg/kg Q4W up to 53 weeks (Open-label Treatment Extension Period II).
SC injection of 1.0 mg/kg burosumab Q4W for 24 weeks (double-blind placebo-controlled Treatment Period), SC injection of burosumab 1 mg/kg Q4W for 24 weeks (open-label Treatment Continuation Period), SC injection of burosumab 1 mg/kg Q4W for 48 weeks (open-label Treatment Extension Period I), and SC injection of burosumab 1 mg/kg Q4W up to 53 weeks (open-label Treatment Extension Period II).
Overall Number of Participants Analyzed 66 68
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
Change at Week 12 Number Analyzed 66 participants 68 participants
-1.24  (2.929) -7.86  (3.622)
Change at Week 24 Number Analyzed 65 participants 67 participants
0.20  (3.289) -8.01  (2.968)
Change at Week 36 Number Analyzed 65 participants 65 participants
-13.50  (3.422) -12.58  (3.411)
Change at Week 48 Number Analyzed 66 participants 66 participants
-15.83  (3.488) -16.63  (3.302)
Change at Week 72 Number Analyzed 61 participants 60 participants
-18.02  (3.613) -15.47  (3.111)
Change at Week 96 Number Analyzed 59 participants 59 participants
-17.67  (3.737) -15.32  (3.577)
Change at Week 120 Number Analyzed 49 participants 46 participants
-19.23  (3.404) -20.57  (3.371)
Change at Week 144 Number Analyzed 9 participants 12 participants
-30.64  (4.407) -25.88  (4.501)
9.Secondary Outcome
Title Change From Baseline Over Time in WOMAC Physical Function Score
Hide Description

The WOMAC is a 24-item participant-reported questionnaire with two domains, Stiffness (2 questions) and Physical Function (17 questions) over the previous 48 hours. The WOMAC is administered in a 5-point Likert-scale format using descriptors of none, mild, moderate, severe, and extreme corresponding to an ordinal scale of 0-4. Higher scores on the WOMAC indicate worse stiffness and functional limitations. Scores are normalized to a 0-100 metric where 0 was the best health state and 100 the worst.

The GEE Estimates are from the GEE model which includes the change from baseline for WOMAC Stiffness as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of WOMAC Stiffness as a covariate, with compound symmetry covariance structure.

Time Frame Baseline, Weeks 12, 24, 36, 48, 72, 96, 120, 144
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period. Participants with an assessment at given time point.
Arm/Group Title Placebo Burosumab 1 mg/kg
Hide Arm/Group Description:
Subcutaneous (SC) injection of placebo every 4 weeks (Q4W) for 24 weeks (Double-blind Placebo-controlled Treatment Period), SC injection of burosumab 1 mg/kg Q4W for 24 weeks (Open-label Treatment Continuation Period), SC injection of burosumab 1 mg/kg Q4W for 48 weeks (Open-label Treatment Extension Period I), and SC injection of burosumab 1 mg/kg Q4W up to 53 weeks (Open-label Treatment Extension Period II).
SC injection of 1.0 mg/kg burosumab Q4W for 24 weeks (double-blind placebo-controlled Treatment Period), SC injection of burosumab 1 mg/kg Q4W for 24 weeks (open-label Treatment Continuation Period), SC injection of burosumab 1 mg/kg Q4W for 48 weeks (open-label Treatment Extension Period I), and SC injection of burosumab 1 mg/kg Q4W up to 53 weeks (open-label Treatment Extension Period II).
Overall Number of Participants Analyzed 66 68
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
Change at Week 12 Number Analyzed 66 participants 68 participants
-1.40  (2.418) -3.96  (1.787)
Change at Week 24 Number Analyzed 65 participants 66 participants
1.14  (2.531) -3.45  (2.193)
Change at Week 36 Number Analyzed 63 participants 65 participants
-5.47  (2.694) -7.14  (2.133)
Change at Week 48 Number Analyzed 66 participants 66 participants
-7.15  (2.801) -8.42  (2.057)
Change at Week 72 Number Analyzed 61 participants 60 participants
-8.68  (2.835) -8.66  (2.523)
Change at Week 96 Number Analyzed 59 participants 59 participants
-8.41  (2.752) -9.02  (2.270)
Change at Week 120 Number Analyzed 49 participants 46 participants
-11.93  (2.685) -11.98  (2.291)
Change at Week 144 Number Analyzed 9 participants 11 participants
-19.49  (3.892) -17.67  (4.061)
10.Secondary Outcome
Title Change From Baseline Over Time in BFI Worst Fatigue Score
Hide Description

Change from baseline to post-baseline visits in Brief Fatigue Inventory Question 3 (Worst Fatigue in Past 24 Hours; BFI-Q3) as averaged from daily diary scores recorded over 1 week and the study visit score. The BFI is a self-reported questionnaire consisting of 9 items related to fatigue rated on a 0 to 10 numerical scale with a recall period of 24 hours. Two dimensions are measured: fatigue severity and the interference of fatigue on daily life (activity, mood, walking ability, work, relations with others, and enjoyment of life). Participants are asked to rate their worst fatigue over the past 24 hours from 0 (no fatigue) to 10 (as bad a you can imagine).

The GEE Estimates are from the GEE model which includes the change from baseline for each BFI endpoint as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of each BFI endpoint as a covariate, with compound symmetry covariance structure.

Time Frame Baseline, Weeks 12, 24, 36, 48, 72, 96
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period. Participants with an assessment at given time point.
Arm/Group Title Placebo Burosumab 1 mg/kg
Hide Arm/Group Description:
Subcutaneous (SC) injection of placebo every 4 weeks (Q4W) for 24 weeks (Double-blind Placebo-controlled Treatment Period), SC injection of burosumab 1 mg/kg Q4W for 24 weeks (Open-label Treatment Continuation Period), SC injection of burosumab 1 mg/kg Q4W for 48 weeks (Open-label Treatment Extension Period I), and SC injection of burosumab 1 mg/kg Q4W up to 53 weeks (Open-label Treatment Extension Period II).
SC injection of 1.0 mg/kg burosumab Q4W for 24 weeks (double-blind placebo-controlled Treatment Period), SC injection of burosumab 1 mg/kg Q4W for 24 weeks (open-label Treatment Continuation Period), SC injection of burosumab 1 mg/kg Q4W for 48 weeks (open-label Treatment Extension Period I), and SC injection of burosumab 1 mg/kg Q4W up to 53 weeks (open-label Treatment Extension Period II).
Overall Number of Participants Analyzed 66 68
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
Change at Week 12 Number Analyzed 66 participants 68 participants
-0.53  (0.266) -0.44  (0.261)
Change at Week 24 Number Analyzed 65 participants 67 participants
-0.45  (0.298) -0.65  (0.280)
Change at Week 36 Number Analyzed 65 participants 65 participants
-1.23  (0.305) -0.90  (0.271)
Change at Week 48 Number Analyzed 66 participants 66 participants
-1.21  (0.317) -0.99  (0.295)
Change at Week 72 Number Analyzed 60 participants 60 participants
-0.79  (0.352) -0.58  (0.309)
Change at Week 96 Number Analyzed 59 participants 58 participants
-0.82  (0.362) -0.75  (0.306)
11.Secondary Outcome
Title Change From Baseline Over Time in BFI Global Fatigue Score
Hide Description

Change from baseline to post-baseline visits in BFI global fatigue score, calculated by averaging all 9 BFI items as recorded on the day of the study visit. The BFI is a self-reported questionnaire consisting of 9 items related to fatigue that are rated on a numerical scale with a recall period of 24 hours. Two dimensions are measured: fatigue severity and the interference of fatigue on daily life (activity, mood, walking ability, work, relations with others, and enjoyment of life). BFI Global Fatigue score was calculated by averaging all 9 items on the BFI. Global scores range from 0 to 10, with higher score indicating worse fatigue severity and interference.

The GEE Estimates are from the GEE model which includes the change from baseline for each BFI endpoint as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of each BFI endpoint as a covariate, with compound symmetry covariance structure.

Time Frame Baseline, Weeks 12, 24, 36, 48, 72, 96
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period. Participants with an assessment at given time point.
Arm/Group Title Placebo Burosumab 1 mg/kg
Hide Arm/Group Description:
SC injection of placebo Q4W for 24 weeks (Double-blind Placebo-controlled Treatment Period), SC injection of burosumab 1 mg/kg Q4W for 24 weeks (Open-label Treatment Continuation Period), SC injection of burosumab 1 mg/kg Q4W for 48 weeks (Open-label Treatment Extension Period I), and SC injection of burosumab 1 mg/kg Q4W up to 53 weeks (Open-label Treatment Extension Period II).
SC injection of 1.0 mg/kg burosumab Q4W for 24 weeks (double-blind placebo-controlled Treatment Period), SC injection of burosumab 1 mg/kg Q4W for 24 weeks (open-label Treatment Continuation Period), SC injection of burosumab 1 mg/kg Q4W for 48 weeks (open-label Treatment Extension Period I), and SC injection of burosumab 1 mg/kg Q4W up to 53 weeks (open-label Treatment Extension Period II).
Overall Number of Participants Analyzed 66 68
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
Change at Week 12 Number Analyzed 66 participants 68 participants
-0.14  (0.262) -0.18  (0.261)
Change at Week 24 Number Analyzed 65 participants 67 participants
-0.08  (0.292) 0.05  (0.261)
Change at Week 36 Number Analyzed 65 participants 65 participants
-0.69  (0.315) -0.54  (0.283)
Change at Week 48 Number Analyzed 66 participants 66 participants
-0.75  (0.303) -0.45  (0.275)
Change at Week 72 Number Analyzed 60 participants 60 participants
-0.72  (0.304) -0.78  (0.266)
Change at Week 96 Number Analyzed 59 participants 58 participants
-0.86  (0.291) -0.80  (0.285)
12.Secondary Outcome
Title Change From Baseline Over Time in Biochemical Marker of Bone Remodeling Procollagen Type 1 N-Propeptide (P1NP)
Hide Description [Not Specified]
Time Frame Baseline, Weeks 12, 24, 36, 48, 72, 96
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period. Participants with an assessment at given time point.
Arm/Group Title Placebo Burosumab 1 mg/kg
Hide Arm/Group Description:
SC injection of placebo Q4W for 24 weeks (Double-blind Placebo-controlled Treatment Period), SC injection of burosumab 1 mg/kg Q4W for 24 weeks (Open-label Treatment Continuation Period), SC injection of burosumab 1 mg/kg Q4W for 48 weeks (Open-label Treatment Extension Period I), and SC injection of burosumab 1 mg/kg Q4W up to 53 weeks (Open-label Treatment Extension Period II).
SC injection of 1.0 mg/kg burosumab Q4W for 24 weeks (double-blind placebo-controlled Treatment Period), SC injection of burosumab 1 mg/kg Q4W for 24 weeks (open-label Treatment Continuation Period), SC injection of burosumab 1 mg/kg Q4W for 48 weeks (open-label Treatment Extension Period I), and SC injection of burosumab 1 mg/kg Q4W up to 53 weeks (open-label Treatment Extension Period II).
Overall Number of Participants Analyzed 66 67
Least Squares Mean (Standard Error)
Unit of Measure: ng/mL
Change at Week 12 Number Analyzed 66 participants 67 participants
-1.86  (5.958) 96.22  (14.264)
Change at Week 24 Number Analyzed 65 participants 66 participants
2.95  (6.423) 63.50  (7.239)
Change at Week 36 Number Analyzed 65 participants 64 participants
100.00  (10.562) 49.71  (6.786)
Change at Week 48 Number Analyzed 66 participants 63 participants
85.12  (11.037) 40.07  (7.292)
Change at Week 72 Number Analyzed 60 participants 59 participants
48.98  (7.286) 18.04  (9.186)
Change at Week 96 Number Analyzed 59 participants 59 participants
22.98  (7.075) 12.48  (8.661)
13.Secondary Outcome
Title Percent Change From Baseline Over Time in Biochemical Marker of Bone Remodeling P1NP
Hide Description [Not Specified]
Time Frame Baseline, Weeks 12, 24, 36, 48, 72, 96
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period. Participants with an assessment at given time point.
Arm/Group Title Placebo Burosumab 1 mg/kg
Hide Arm/Group Description:
SC injection of placebo Q4W for 24 weeks (Double-blind Placebo-controlled Treatment Period), SC injection of burosumab 1 mg/kg Q4W for 24 weeks (Open-label Treatment Continuation Period), SC injection of burosumab 1 mg/kg Q4W for 48 weeks (Open-label Treatment Extension Period I), and SC injection of burosumab 1 mg/kg Q4W up to 53 weeks (Open-label Treatment Extension Period II).
SC injection of 1.0 mg/kg burosumab Q4W for 24 weeks (double-blind placebo-controlled Treatment Period), SC injection of burosumab 1 mg/kg Q4W for 24 weeks (open-label Treatment Continuation Period), SC injection of burosumab 1 mg/kg Q4W for 48 weeks (open-label Treatment Extension Period I), and SC injection of burosumab 1 mg/kg Q4W up to 53 weeks (open-label Treatment Extension Period II).
Overall Number of Participants Analyzed 66 67
Least Squares Mean (Standard Error)
Unit of Measure: percentage change
Change at Week 12 Number Analyzed 66 participants 67 participants
2.30  (6.318) 91.78  (10.787)
Change at Week 24 Number Analyzed 65 participants 66 participants
7.83  (7.076) 72.43  (8.519)
Change at Week 36 Number Analyzed 65 participants 64 participants
116.39  (9.726) 63.58  (8.562)
Change a Week 48 Number Analyzed 66 participants 63 participants
99.10  (11.442) 56.51  (8.771)
Change at Week 72 Number Analyzed 60 participants 59 participants
72.56  (10.055) 38.82  (10.225)
Change at Week 96 Number Analyzed 59 participants 59 participants
41.62  (8.163) 31.04  (8.126)
14.Secondary Outcome
Title Change From Baseline Over Time in Biochemical Marker of Bone Remodeling Carboxy-Terminal Cross-Linked Telopeptide of Type I Collagen (CTx)
Hide Description The GEE Estimates are from the GEE model which includes the change from baseline for CTx as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of CTx as a covariate, with compound symmetry covariance structure.
Time Frame Baseline, Weeks 12, 24, 36, 48, 72, 96
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period. Participants with an assessment at given time point.
Arm/Group Title Placebo Burosumab 1 mg/kg
Hide Arm/Group Description:
SC injection of placebo Q4W for 24 weeks (Double-blind Placebo-controlled Treatment Period), SC injection of burosumab 1 mg/kg Q4W for 24 weeks (Open-label Treatment Continuation Period), SC injection of burosumab 1 mg/kg Q4W for 48 weeks (Open-label Treatment Extension Period I), and SC injection of burosumab 1 mg/kg Q4W up to 53 weeks (Open-label Treatment Extension Period II).
SC injection of 1.0 mg/kg burosumab Q4W for 24 weeks (double-blind placebo-controlled Treatment Period), SC injection of burosumab 1 mg/kg Q4W for 24 weeks (open-label Treatment Continuation Period), SC injection of burosumab 1 mg/kg Q4W for 48 weeks (open-label Treatment Extension Period I), and SC injection of burosumab 1 mg/kg Q4W up to 53 weeks (open-label Treatment Extension Period II).
Overall Number of Participants Analyzed 66 67
Least Squares Mean (Standard Error)
Unit of Measure: pg/mL
Change at Week 12 Number Analyzed 66 participants 67 participants
26.96  (35.689) 322.09  (56.924)
Change at Week 24 Number Analyzed 64 participants 66 participants
-4.20  (34.835) 184.56  (39.213)
Change at Week 36 Number Analyzed 65 participants 63 participants
350.89  (53.131) 193.50  (39.461)
Change at Week 48 Number Analyzed 66 participants 63 participants
310.67  (45.003) 138.61  (37.886)
Change at Week 72 Number Analyzed 60 participants 59 participants
178.03  (42.702) 51.59  (42.863)
Change at Week 96 Number Analyzed 59 participants 59 participants
79.04  (45.622) 10.84  (40.761)
15.Secondary Outcome
Title Percent Change From Baseline Over Time in Biochemical Marker of Bone Remodeling CTx
Hide Description The GEE Estimates are from the GEE model which includes the percent change from baseline for CTx as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of CTx as a covariate, with compound symmetry covariance structure.
Time Frame Baseline, Weeks 12, 24, 36, 48, 72, 96
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period. Participants with an assessment at given time point.
Arm/Group Title Placebo Burosumab 1 mg/kg
Hide Arm/Group Description:
SC injection of placebo Q4W for 24 weeks (Double-blind Placebo-controlled Treatment Period), SC injection of burosumab 1 mg/kg Q4W for 24 weeks (Open-label Treatment Continuation Period), SC injection of burosumab 1 mg/kg Q4W for 48 weeks (Open-label Treatment Extension Period I), and SC injection of burosumab 1 mg/kg Q4W up to 53 weeks (Open-label Treatment Extension Period II).
SC injection of 1.0 mg/kg burosumab Q4W for 24 weeks (double-blind placebo-controlled Treatment Period), SC injection of burosumab 1 mg/kg Q4W for 24 weeks (open-label Treatment Continuation Period), SC injection of burosumab 1 mg/kg Q4W for 48 weeks (open-label Treatment Extension Period I), and SC injection of burosumab 1 mg/kg Q4W up to 53 weeks (open-label Treatment Extension Period II).
Overall Number of Participants Analyzed 66 67
Least Squares Mean (Standard Error)
Unit of Measure: percentage change
Change at Week 12 Number Analyzed 66 participants 67 participants
9.64  (5.671) 45.40  (7.267)
Change at Week 24 Number Analyzed 64 participants 66 participants
4.75  (5.280) 32.48  (6.414)
Change at Week 36 Number Analyzed 65 participants 63 participants
61.31  (10.653) 34.07  (6.250)
Change at Week 48 Number Analyzed 66 participants 63 participants
50.35  (6.464) 28.33  (5.354)
Change at Week 72 Number Analyzed 60 participants 59 participants
34.78  (7.007) 17.09  (5.957)
Change at Week 96 Number Analyzed 59 participants 59 participants
27.38  (7.783) 13.47  (5.952)
16.Secondary Outcome
Title Change From Baseline Over Time in Biochemical Marker of Bone Remodeling Bone-Specific Alkaline Phosphatase (BALP)
Hide Description The GEE Estimates are from the GEE model which includes the change from baseline for BALP as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of BALP as a covariate, with compound symmetry covariance structure.
Time Frame Baseline, Weeks 12, 24, 36, 48, 72, 96
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period. Participants with an assessment at given time point.
Arm/Group Title Placebo Burosumab 1 mg/kg
Hide Arm/Group Description:
SC injection of placebo Q4W for 24 weeks (Double-blind Placebo-controlled Treatment Period), SC injection of burosumab 1 mg/kg Q4W for 24 weeks (Open-label Treatment Continuation Period), SC injection of burosumab 1 mg/kg Q4W for 48 weeks (Open-label Treatment Extension Period I), and SC injection of burosumab 1 mg/kg Q4W up to 53 weeks (Open-label Treatment Extension Period II).
SC injection of 1.0 mg/kg burosumab Q4W for 24 weeks (double-blind placebo-controlled Treatment Period), SC injection of burosumab 1 mg/kg Q4W for 24 weeks (open-label Treatment Continuation Period), SC injection of burosumab 1 mg/kg Q4W for 48 weeks (open-label Treatment Extension Period I), and SC injection of burosumab 1 mg/kg Q4W up to 53 weeks (open-label Treatment Extension Period II).
Overall Number of Participants Analyzed 66 66
Least Squares Mean (Standard Error)
Unit of Measure: μg/L
Change at Week 12 Number Analyzed 66 participants 66 participants
-2.11  (1.529) 6.52  (2.832)
Change at Week 24 Number Analyzed 64 participants 65 participants
1.03  (1.801) 5.70  (2.038)
Change at Week 36 Number Analyzed 65 participants 63 participants
10.42  (2.017) 4.46  (1.607)
Change at Week 48 Number Analyzed 66 participants 61 participants
6.69  (1.929) 0.23  (1.830)
Change at Week 72 Number Analyzed 61 participants 58 participants
-0.92  (1.779) -3.39  (1.739)
Change at Week 96 Number Analyzed 59 participants 58 participants
-2.49  (1.887) -2.76  (1.640)
17.Secondary Outcome
Title Percent Change From Baseline Over Time in Biochemical Marker of Bone Remodeling BALP
Hide Description The GEE Estimates are from the GEE model which includes the percent change from baseline for BALP as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of Bone ALP as a covariate, with compound symmetry covariance structure.
Time Frame Baseline, Weeks 12, 24, 36, 48, 72, 96
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period. Participants with an assessment at given time point.
Arm/Group Title Placebo Burosumab 1 mg/kg
Hide Arm/Group Description:
SC injection of placebo Q4W for 24 weeks (Double-blind Placebo-controlled Treatment Period), SC injection of burosumab 1 mg/kg Q4W for 24 weeks (Open-label Treatment Continuation Period), SC injection of burosumab 1 mg/kg Q4W for 48 weeks (Open-label Treatment Extension Period I), and SC injection of burosumab 1 mg/kg Q4W up to 53 weeks (Open-label Treatment Extension Period II).
SC injection of 1.0 mg/kg burosumab Q4W for 24 weeks (double-blind placebo-controlled Treatment Period), SC injection of burosumab 1 mg/kg Q4W for 24 weeks (open-label Treatment Continuation Period), SC injection of burosumab 1 mg/kg Q4W for 48 weeks (open-label Treatment Extension Period I), and SC injection of burosumab 1 mg/kg Q4W up to 53 weeks (open-label Treatment Extension Period II).
Overall Number of Participants Analyzed 66 66
Least Squares Mean (Standard Error)
Unit of Measure: percentage change
Change at Week 12 Number Analyzed 66 participants 66 participants
7.85  (9.867) 30.29  (13.476)
Change at Week 24 Number Analyzed 64 participants 65 participants
27.56  (10.339) 39.13  (10.902)
Change at Week 36 Number Analyzed 65 participants 63 participants
64.41  (11.669) 43.13  (11.473)
Change at Week 48 Number Analyzed 66 participants 61 participants
50.65  (11.317) 23.46  (10.041)
Change at Week 72 Number Analyzed 61 participants 58 participants
19.79  (11.755) 14.40  (11.618)
Change at Week 96 Number Analyzed 59 participants 58 participants
16.46  (11.027) 21.21  (9.688)
18.Secondary Outcome
Title Change From Baseline Over Time in Serum Phosphorus
Hide Description The GEE Estimates are from the GEE model which includes the change from baseline for serum phosphorus as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of serum phosphorus as a covariate, with compound symmetry covariance structure.
Time Frame Baseline, Weeks 1, 2, 4, 6, 10, 12, 14, 18, 20, 21, 22, 24, 26, 28, 34, 36, 46, 48, 60, 70, 72, 84, 94, 96, 108, 120, 132, 144
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period. Participants with an assessment at given time point.
Arm/Group Title Placebo Burosumab 1 mg/kg
Hide Arm/Group Description:
SC injection of placebo Q4W for 24 weeks (Double-blind Placebo-controlled Treatment Period), SC injection of burosumab 1 mg/kg Q4W for 24 weeks (Open-label Treatment Continuation Period), SC injection of burosumab 1 mg/kg Q4W for 48 weeks (Open-label Treatment Extension Period I), and SC injection of burosumab 1 mg/kg Q4W up to 53 weeks (Open-label Treatment Extension Period II).
SC injection of 1.0 mg/kg burosumab Q4W for 24 weeks (double-blind placebo-controlled Treatment Period), SC injection of burosumab 1 mg/kg Q4W for 24 weeks (open-label Treatment Continuation Period), SC injection of burosumab 1 mg/kg Q4W for 48 weeks (open-label Treatment Extension Period I), and SC injection of burosumab 1 mg/kg Q4W up to 53 weeks (open-label Treatment Extension Period II).
Overall Number of Participants Analyzed 66 68
Least Squares Mean (Standard Error)
Unit of Measure: mmol/L
Change at Week 1 Number Analyzed 60 participants 61 participants
-0.01  (0.024) 0.44  (0.031)
Change at Week 2 Number Analyzed 64 participants 64 participants
-0.03  (0.023) 0.43  (0.032)
Change at Week 4 Number Analyzed 65 participants 67 participants
-0.03  (0.022) 0.27  (0.034)
Change at Week 6 Number Analyzed 65 participants 65 participants
-0.00  (0.023) 0.45  (0.036)
Change at Week 10 Number Analyzed 64 participants 64 participants
0.01  (0.022) 0.37  (0.033)
Change at Week 12 Number Analyzed 64 participants 68 participants
-0.01  (0.023) 0.17  (0.032)
Change at Week 14 Number Analyzed 66 participants 65 participants
0.02  (0.022) 0.32  (0.032)
Change at Week 18 Number Analyzed 62 participants 68 participants
0.02  (0.023) 0.32  (0.031)
Change at Week 20 Number Analyzed 65 participants 65 participants
-0.01  (0.023) 0.18  (0.028)
Change at Week 21 Number Analyzed 61 participants 65 participants
-0.00  (0.024) 0.31  (0.033)
Change at Week 22 Number Analyzed 65 participants 64 participants
-0.02  (0.022) 0.25  (0.033)
Change at Week 24 Number Analyzed 66 participants 68 participants
-0.00  (0.023) 0.13  (0.028)
Change at Week 26 Number Analyzed 62 participants 66 participants
0.47  (0.035) 0.31  (0.032)
Change at Week 28 Number Analyzed 66 participants 67 participants
0.28  (0.028) 0.18  (0.028)
Change at Week 34 Number Analyzed 65 participants 62 participants
0.36  (0.029) 0.28  (0.031)
Change at Week 36 Number Analyzed 66 participants 64 participants
0.17  (0.026) 0.13  (0.027)
Change at Week 46 Number Analyzed 66 participants 65 participants
0.31  (0.026) 0.27  (0.030)
Change at Week 48 Number Analyzed 66 participants 64 participants
0.13  (0.027) 0.11  (0.027)
Change at Week 60 Number Analyzed 62 participants 61 participants
0.14  (0.028) 0.11  (0.028)
Change at Week 70 Number Analyzed 55 participants 57 participants
0.30  (0.029) 0.30  (0.030)
Change at Week 72 Number Analyzed 61 participants 60 participants
0.13  (0.025) 0.11  (0.027)
Change at Week 84 Number Analyzed 60 participants 59 participants
0.12  (0.025) 0.14  (0.027)
Change at Week 94 Number Analyzed 59 participants 58 participants
0.25  (0.029) 0.30  (0.029)
Change at Week 96 Number Analyzed 60 participants 59 participants
0.07  (0.026) 0.13  (0.025)
Change at Week 108 Number Analyzed 49 participants 48 participants
0.11  (0.028) 0.13  (0.031)
Change at Week 120 Number Analyzed 44 participants 41 participants
0.09  (0.027) 0.13  (0.033)
Change at Week 132 Number Analyzed 19 participants 19 participants
0.12  (0.033) 0.15  (0.036)
Change at Week 144 Number Analyzed 2 participants 0 participants
0.05  (0.064)
19.Secondary Outcome
Title Percent Change From Baseline Over Time in Serum Phosphorus
Hide Description The GEE Estimates are from the GEE model which includes the percent change from baseline for serum phosphorus as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of serum phosphorus as a covariate, with compound symmetry covariance structure.
Time Frame Baseline, Weeks 1, 2, 4, 6, 10, 12, 14, 18, 20, 21, 22, 24, 26, 28, 34, 36, 46, 48, 60, 70, 72, 84, 94, 96, 108, 120, 132, 144
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period. Participants with an assessment at given time point.
Arm/Group Title Placebo Burosumab 1 mg/kg
Hide Arm/Group Description:
SC injection of placebo Q4W for 24 weeks (Double-blind Placebo-controlled Treatment Period), SC injection of burosumab 1 mg/kg Q4W for 24 weeks (Open-label Treatment Continuation Period), SC injection of burosumab 1 mg/kg Q4W for 48 weeks (Open-label Treatment Extension Period I), and SC injection of burosumab 1 mg/kg Q4W up to 53 weeks (Open-label Treatment Extension Period II).
SC injection of 1.0 mg/kg burosumab Q4W for 24 weeks (double-blind placebo-controlled Treatment Period), SC injection of burosumab 1 mg/kg Q4W for 24 weeks (open-label Treatment Continuation Period), SC injection of burosumab 1 mg/kg Q4W for 48 weeks (open-label Treatment Extension Period I), and SC injection of burosumab 1 mg/kg Q4W up to 53 weeks (open-label Treatment Extension Period II).
Overall Number of Participants Analyzed 66 68
Least Squares Mean (Standard Error)
Unit of Measure: percentage change
Change at Week 1 Number Analyzed 60 participants 61 participants
-1.11  (3.936) 69.24  (4.762)
Change at Week 2 Number Analyzed 64 participants 64 participants
-5.91  (3.969) 69.39  (4.881)
Change at Week 4 Number Analyzed 65 participants 67 participants
-4.84  (3.792) 42.89  (5.325)
Change at Week 6 Number Analyzed 65 participants 65 participants
-0.41  (3.951) 72.96  (5.944)
Change at Week 10 Number Analyzed 64 participants 64 participants
2.40  (3.680) 59.96  (5.356)
Change at Week 12 Number Analyzed 64 participants 68 participants
-2.14  (3.798) 29.50  (5.087)
Change at Week 14 Number Analyzed 66 participants 65 participants
3.58  (3.691) 52.14  (5.194)
Change at Week 18 Number Analyzed 62 participants 68 participants
3.93  (3.857) 53.22  (5.106)
Change at Week 20 Number Analyzed 65 participants 65 participants
-1.81  (3.759) 31.28  (4.472)
Change at Week 21 Number Analyzed 61 participants 65 participants
0.21  (4.011) 50.59  (5.123)
Change at Week 22 Number Analyzed 65 participants 64 participants
-3.42  (3.709) 40.98  (5.196)
Change at Week 24 Number Analyzed 66 participants 68 participants
-0.61  (3.802) 22.01  (4.523)
Change at Week 26 Number Analyzed 62 participants 66 participants
78.30  (5.993) 51.51  (5.204)
Change at Week 28 Number Analyzed 66 participants 67 participants
46.07  (4.766) 31.32  (4.415)
Change at Week 34 Number Analyzed 65 participants 62 participants
59.18  (4.959) 45.83  (4.871)
Change at Week 36 Number Analyzed 66 participants 64 participants
28.03  (4.424) 22.34  (4.256)
Change at Week 46 Number Analyzed 66 participants 65 participants
51.49  (4.380) 45.39  (5.018)
Change at Week 48 Number Analyzed 66 participants 64 participants
21.58  (4.365) 19.12  (4.190)
Change at Week 60 Number Analyzed 62 participants 61 participants
22.90  (4.338) 19.60  (4.436)
Change at Week 70 Number Analyzed 55 participants 57 participants
50.22  (4.916) 47.81  (4.768)
Change at Week 72 Number Analyzed 61 participants 60 participants
21.59  (4.155) 19.45  (4.344)
Change at Week 84 Number Analyzed 60 participants 59 participants
21.47  (4.089) 23.58  (4.200)
Change at Week 94 Number Analyzed 59 participants 58 participants
43.67  (4.834) 49.36  (4.501)
Change at Week 96 Number Analyzed 60 participants 59 participants
12.97  (4.216) 21.65  (3.854)
Change at Week 108 Number Analyzed 49 participants 48 participants
19.21  (4.665) 23.39  (4.749)
Change at Week 120 Number Analyzed 44 participants 41 participants
15.13  (4.365) 21.50  (5.268)
Change at Week 132 Number Analyzed 19 participants 19 participants
20.43  (5.362) 25.34  (5.847)
Change at Week 144 Number Analyzed 2 participants 0 participants
5.49  (12.212)
20.Secondary Outcome
Title Change From Baseline Over Time in Serum 1,25(OH)2D
Hide Description The GEE Estimates are from the GEE model which includes the change from baseline for 1,25(OH)2D as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of 1, 25 (OH)2 D as a covariate, with compound symmetry covariance structure.
Time Frame Baseline, Weeks 1, 2, 4, 20, 21, 22, 46, 48, 60, 70, 72, 84, 94, 96, 108, 120, 132, 144
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period. Participants with an assessment at given time point.
Arm/Group Title Placebo Burosumab 1 mg/kg
Hide Arm/Group Description:
SC injection of placebo Q4W for 24 weeks (Double-blind Placebo-controlled Treatment Period), SC injection of burosumab 1 mg/kg Q4W for 24 weeks (Open-label Treatment Continuation Period), SC injection of burosumab 1 mg/kg Q4W for 48 weeks (Open-label Treatment Extension Period I), and SC injection of burosumab 1 mg/kg Q4W up to 53 weeks (Open-label Treatment Extension Period II).
SC injection of 1.0 mg/kg burosumab Q4W for 24 weeks (double-blind placebo-controlled Treatment Period), SC injection of burosumab 1 mg/kg Q4W for 24 weeks (open-label Treatment Continuation Period), SC injection of burosumab 1 mg/kg Q4W for 48 weeks (open-label Treatment Extension Period I), and SC injection of burosumab 1 mg/kg Q4W up to 53 weeks (open-label Treatment Extension Period II).
Overall Number of Participants Analyzed 64 66
Least Squares Mean (Standard Error)
Unit of Measure: pg/mL
Change at Week 1 Number Analyzed 58 participants 59 participants
2.04  (2.251) 87.23  (5.500)
Change at Week 2 Number Analyzed 63 participants 65 participants
1.40  (2.113) 58.20  (3.931)
Change at Week 4 Number Analyzed 63 participants 66 participants
2.61  (2.300) 20.55  (2.828)
Change at Week 20 Number Analyzed 64 participants 63 participants
2.88  (2.163) 8.11  (2.294)
Change at Week 21 Number Analyzed 59 participants 64 participants
3.09  (2.177) 33.95  (3.019)
Change at Week 22 Number Analyzed 64 participants 65 participants
3.45  (2.289) 26.10  (2.952)
Change at Week 46 Number Analyzed 64 participants 64 participants
25.23  (2.576) 23.08  (3.243)
Change at Week 48 Number Analyzed 64 participants 63 participants
10.50  (2.418) 7.24  (2.449)
Change at Week 60 Number Analyzed 59 participants 60 participants
9.29  (2.336) 5.69  (2.583)
Change at Week 70 Number Analyzed 54 participants 60 participants
24.20  (2.529) 18.82  (2.486)
Change at Week 72 Number Analyzed 59 participants 58 participants
7.12  (2.424) 5.52  (2.607)
Change at Week 84 Number Analyzed 58 participants 57 participants
5.13  (2.388) 1.16  (2.549)
Change at Week 94 Number Analyzed 57 participants 58 participants
18.96  (2.655) 15.26  (2.502)
Change at Week 96 Number Analyzed 56 participants 58 participants
3.43  (2.348) 1.95  (2.356)
Change at Week 108 Number Analyzed 48 participants 48 participants
4.76  (2.349) 4.29  (2.672)
Change at Week 120 Number Analyzed 43 participants 42 participants
4.64  (2.496) 5.37  (2.935)
Change at Week 132 Number Analyzed 18 participants 19 participants
4.08  (3.142) 8.05  (4.227)
Change at Week 144 Number Analyzed 2 participants 0 participants
-0.38  (4.677)
21.Secondary Outcome
Title Percent Change From Baseline Over Time in Serum 1,25(OH)2D
Hide Description The GEE Estimates are from the GEE model which includes the percent change from baseline for 1,25(OH)2D as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of 1, 25 (OH)2 D as a covariate, with compound symmetry covariance structure.
Time Frame Baseline, Weeks 1, 2, 4, 20, 21, 22, 46, 48, 60, 70, 72, 84, 94, 96, 108, 120, 132, 144
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period. Participants with an assessment at given time point.
Arm/Group Title Placebo Burosumab 1 mg/kg
Hide Arm/Group Description:
SC injection of placebo Q4W for 24 weeks (Double-blind Placebo-controlled Treatment Period), SC injection of burosumab 1 mg/kg Q4W for 24 weeks (Open-label Treatment Continuation Period), SC injection of burosumab 1 mg/kg Q4W for 48 weeks (Open-label Treatment Extension Period I), and SC injection of burosumab 1 mg/kg Q4W up to 53 weeks (Open-label Treatment Extension Period II).
SC injection of 1.0 mg/kg burosumab Q4W for 24 weeks (double-blind placebo-controlled Treatment Period), SC injection of burosumab 1 mg/kg Q4W for 24 weeks (open-label Treatment Continuation Period), SC injection of burosumab 1 mg/kg Q4W for 48 weeks (open-label Treatment Extension Period I), and SC injection of burosumab 1 mg/kg Q4W up to 53 weeks (open-label Treatment Extension Period II).
Overall Number of Participants Analyzed 64 66
Least Squares Mean (Standard Error)
Unit of Measure: percentage change
Change at Week 1 Number Analyzed 58 participants 59 participants
10.45  (13.041) 310.72  (23.225)
Change at Week 2 Number Analyzed 63 participants 65 participants
10.53  (12.760) 207.90  (16.728)
Change at Week 4 Number Analyzed 63 participants 66 participants
16.07  (12.810) 76.22  (12.147)
Change at Week 20 Number Analyzed 64 participants 63 participants
21.36  (12.424) 41.08  (11.943)
Change at Week 21 Number Analyzed 59 participants 64 participants
21.51  (12.825) 131.76  (14.862)
Change at Week 22 Number Analyzed 64 participants 65 participants
21.07  (12.725) 102.81  (14.619)
Change at Week 46 Number Analyzed 64 participants 64 participants
130.29  (22.718) 96.63  (16.909)
Change at Week 48 Number Analyzed 64 participants 63 participants
70.09  (17.114) 34.47  (12.903)
Change at Week 60 Number Analyzed 59 participants 60 participants
65.46  (13.083) 32.32  (12.230)
Change at Week 70 Number Analyzed 54 participants 60 participants
123.58  (17.315) 82.03  (12.604)
Change at Week 72 Number Analyzed 59 participants 58 participants
58.45  (13.957) 31.14  (13.070)
Change at Week 84 Number Analyzed 58 participants 57 participants
55.67  (15.323) 18.83  (12.801)
Change at Week 94 Number Analyzed 57 participants 58 participants
111.25  (21.970) 71.30  (12.280)
Change at Week 96 Number Analyzed 56 participants 58 participants
50.17  (18.857) 22.15  (10.487)
Change at Week 108 Number Analyzed 48 participants 48 participants
44.78  (14.219) 29.16  (13.326)
Change at Week 120 Number Analyzed 43 participants 42 participants
58.37  (19.621) 36.09  (13.089)
Change at Week 132 Number Analyzed 18 participants 19 participants
67.59  (35.770) 42.55  (15.925)
Change at Week 144 Number Analyzed 2 participants 0 participants
22.65  (19.297)
22.Secondary Outcome
Title Change From Baseline Over Time in 24-Hour Urinary Phosphorus
Hide Description The GEE Estimates are from the GEE model which includes the change from baseline for 24-Hour urinary phosphorus as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of urinary phosphorus as a covariate, with compound symmetry covariance structure.
Time Frame Baseline, Week 12, 24, 36, 48, 72, 96
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period. Participants with an assessment at given time point.
Arm/Group Title Placebo Burosumab 1 mg/kg
Hide Arm/Group Description:
SC injection of placebo Q4W for 24 weeks (Double-blind Placebo-controlled Treatment Period), SC injection of burosumab 1 mg/kg Q4W for 24 weeks (Open-label Treatment Continuation Period), SC injection of burosumab 1 mg/kg Q4W for 48 weeks (Open-label Treatment Extension Period I), and SC injection of burosumab 1 mg/kg Q4W up to 53 weeks (Open-label Treatment Extension Period II).
SC injection of 1.0 mg/kg burosumab Q4W for 24 weeks (double-blind placebo-controlled Treatment Period), SC injection of burosumab 1 mg/kg Q4W for 24 weeks (open-label Treatment Continuation Period), SC injection of burosumab 1 mg/kg Q4W for 48 weeks (open-label Treatment Extension Period I), and SC injection of burosumab 1 mg/kg Q4W up to 53 weeks (open-label Treatment Extension Period II).
Overall Number of Participants Analyzed 65 67
Least Squares Mean (Standard Error)
Unit of Measure: g/24 hour
Change at Week 12 Number Analyzed 63 participants 63 participants
0.06  (0.052) 0.05  (0.046)
Change at Week 24 Number Analyzed 65 participants 67 participants
0.07  (0.065) 0.05  (0.046)
Change at Week 36 Number Analyzed 64 participants 64 participants
0.04  (0.054) 0.07  (0.045)
Change at Week 48 Number Analyzed 63 participants 63 participants
0.07  (0.060) 0.13  (0.067)
Change at Week 72 Number Analyzed 57 participants 57 participants
0.08  (0.065) 0.05  (0.052)
Change at Week 96 Number Analyzed 58 participants 59 participants
0.10  (0.075) 0.10  (0.054)
23.Secondary Outcome
Title Percent Change From Baseline Over Time in 24-Hour Urinary Phosphorus
Hide Description The GEE Estimates are from the GEE model which includes the percent change from baseline for 24-hour urinary phosphorus as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of urinary phosphorus as a covariate, with compound symmetry covariance structure.
Time Frame Baseline, Week 12, 24, 36, 48, 72, 96
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period. Participants with an assessment at given time point.
Arm/Group Title Placebo Burosumab 1 mg/kg
Hide Arm/Group Description:
SC injection of placebo Q4W for 24 weeks (Double-blind Placebo-controlled Treatment Period), SC injection of burosumab 1 mg/kg Q4W for 24 weeks (Open-label Treatment Continuation Period), SC injection of burosumab 1 mg/kg Q4W for 48 weeks (Open-label Treatment Extension Period I), and SC injection of burosumab 1 mg/kg Q4W up to 53 weeks (Open-label Treatment Extension Period II).
SC injection of 1.0 mg/kg burosumab Q4W for 24 weeks (double-blind placebo-controlled Treatment Period), SC injection of burosumab 1 mg/kg Q4W for 24 weeks (open-label Treatment Continuation Period), SC injection of burosumab 1 mg/kg Q4W for 48 weeks (open-label Treatment Extension Period I), and SC injection of burosumab 1 mg/kg Q4W up to 53 weeks (open-label Treatment Extension Period II).
Overall Number of Participants Analyzed 65 67
Least Squares Mean (Standard Error)
Unit of Measure: percentage change
Change at Week 12 Number Analyzed 63 participants 63 participants
21.91  (11.844) 21.40  (11.453)
Change at Week 24 Number Analyzed 65 participants 67 participants
28.45  (15.518) 20.35  (11.567)
Change at Week 36 Number Analyzed 64 participants 64 participants
18.19  (11.784) 28.31  (12.173)
Change at Week 48 Number Analyzed 63 participants 63 participants
27.32  (14.328) 37.50  (14.687)
Change at Week 72 Number Analyzed 57 participants 57 participants
29.53  (14.485) 25.80  (15.476)
Change at Week 96 Number Analyzed 58 participants 59 participants
31.17  (17.248) 30.64  (10.420)
24.Secondary Outcome
Title Change From Baseline Over Time in Ratio of Renal Tubular Maximum Reabsorption Rate of Phosphate to Glomerular Filtration Rate (TmP/GFR)
Hide Description The GEE Estimates are from the GEE model which includes the change from baseline for TmP/GFR as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of TmP/GFR as a covariate, with compound symmetry covariance structure.
Time Frame Baseline, Weeks 2, 4, 12, 22, 24, 48, 60, 72, 84, 96
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period. Participants with an assessment at given time point.
Arm/Group Title Placebo Burosumab 1 mg/kg
Hide Arm/Group Description:
SC injection of placebo Q4W for 24 weeks (Double-blind Placebo-controlled Treatment Period), SC injection of burosumab 1 mg/kg Q4W for 24 weeks (Open-label Treatment Continuation Period), SC injection of burosumab 1 mg/kg Q4W for 48 weeks (Open-label Treatment Extension Period I), and SC injection of burosumab 1 mg/kg Q4W up to 53 weeks (Open-label Treatment Extension Period II).
SC injection of 1.0 mg/kg burosumab Q4W for 24 weeks (double-blind placebo-controlled Treatment Period), SC injection of burosumab 1 mg/kg Q4W for 24 weeks (open-label Treatment Continuation Period), SC injection of burosumab 1 mg/kg Q4W for 48 weeks (open-label Treatment Extension Period I), and SC injection of burosumab 1 mg/kg Q4W up to 53 weeks (open-label Treatment Extension Period II).
Overall Number of Participants Analyzed 63 66
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
Change at Week 2 Number Analyzed 60 participants 60 participants
-0.02  (0.072) 1.60  (0.121)
Change at Week 4 Number Analyzed 61 participants 63 participants
-0.03  (0.070) 0.91  (0.117)
Change at Week 12 Number Analyzed 61 participants 64 participants
0.11  (0.082) 0.70  (0.107)
Change at Week 22 Number Analyzed 63 participants 62 participants
0.02  (0.069) 1.01  (0.123)
Change at Week 24 Number Analyzed 62 participants 66 participants
0.07  (0.071) 0.51  (0.093)
Change at Week 48 Number Analyzed 62 participants 61 participants
0.55  (0.087) 0.48  (0.091)
Change at Week 60 Number Analyzed 58 participants 58 participants
0.57  (0.097) 0.43  (0.086)
Change at Week 72 Number Analyzed 57 participants 57 participants
0.55  (0.086) 0.43  (0.091)
Change at Week 84 Number Analyzed 57 participants 56 participants
0.49  (0.078) 0.42  (0.092)
Change at Week 96 Number Analyzed 58 participants 57 participants
0.29  (0.086) 0.46  (0.084)
25.Secondary Outcome
Title Percent Change From Baseline Over Time in TmP/GFR
Hide Description The GEE Estimates are from the GEE model which includes the percent change from baseline for TmP/GFR as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of TmP/GFR as a covariate, with compound symmetry covariance structure.
Time Frame Baseline, Weeks 2, 4, 12, 22, 24, 48, 60, 72, 84, 96
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period. Participants with an assessment at given time point.
Arm/Group Title Placebo Burosumab 1 mg/kg
Hide Arm/Group Description:
SC injection of placebo Q4W for 24 weeks (Double-blind Placebo-controlled Treatment Period), SC injection of burosumab 1 mg/kg Q4W for 24 weeks (Open-label Treatment Continuation Period), SC injection of burosumab 1 mg/kg Q4W for 48 weeks (Open-label Treatment Extension Period I), and SC injection of burosumab 1 mg/kg Q4W up to 53 weeks (Open-label Treatment Extension Period II).
SC injection of 1.0 mg/kg burosumab Q4W for 24 weeks (double-blind placebo-controlled Treatment Period), SC injection of burosumab 1 mg/kg Q4W for 24 weeks (open-label Treatment Continuation Period), SC injection of burosumab 1 mg/kg Q4W for 48 weeks (open-label Treatment Extension Period I), and SC injection of burosumab 1 mg/kg Q4W up to 53 weeks (open-label Treatment Extension Period II).
Overall Number of Participants Analyzed 63 66
Least Squares Mean (Standard Error)
Unit of Measure: percentage change
Change at Week 2 Number Analyzed 60 participants 60 participants
-2.15  (4.515) 100.10  (7.222)
Change at Week 4 Number Analyzed 61 participants 63 participants
-2.73  (4.416) 56.53  (6.816)
Change at Week 12 Number Analyzed 61 participants 64 participants
6.28  (4.900) 43.65  (6.206)
Change at Week 22 Number Analyzed 63 participants 62 participants
1.38  (4.252) 62.38  (7.144)
Change at Week 24 Number Analyzed 62 participants 66 participants
3.63  (4.460) 33.02  (5.464)
Change at Week 48 Number Analyzed 62 participants 61 participants
35.52  (5.390) 31.02  (5.489)
Change at Week 60 Number Analyzed 58 participants 58 participants
37.13  (5.855) 27.49  (5.002)
Change at Week 72 Number Analyzed 57 participants 57 participants
35.89  (5.492) 28.98  (5.513)
Change at Week 84 Number Analyzed 57 participants 56 participants
33.15  (4.924) 27.69  (5.527)
Change at Week 96 Number Analyzed 58 participants 57 participants
19.95  (5.417) 29.67  (4.759)
26.Secondary Outcome
Title Change From Baseline Over Time in Tubular Reabsorption of Phosphate (TRP)
Hide Description The GEE Estimates are from the GEE model which includes the change from baseline for TRP as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of TRP as a covariate, with compound symmetry covariance structure.
Time Frame Baseline, Weeks 2, 4, 12, 22, 24, 48, 60, 72, 84, 96
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period. Participants with an assessment at given time point.
Arm/Group Title Placebo Burosumab 1 mg/kg
Hide Arm/Group Description:
SC injection of placebo Q4W for 24 weeks (Double-blind Placebo-controlled Treatment Period), SC injection of burosumab 1 mg/kg Q4W for 24 weeks (Open-label Treatment Continuation Period), SC injection of burosumab 1 mg/kg Q4W for 48 weeks (Open-label Treatment Extension Period I), and SC injection of burosumab 1 mg/kg Q4W up to 53 weeks (Open-label Treatment Extension Period II).
SC injection of 1.0 mg/kg burosumab Q4W for 24 weeks (double-blind placebo-controlled Treatment Period), SC injection of burosumab 1 mg/kg Q4W for 24 weeks (open-label Treatment Continuation Period), SC injection of burosumab 1 mg/kg Q4W for 48 weeks (open-label Treatment Extension Period I), and SC injection of burosumab 1 mg/kg Q4W up to 53 weeks (open-label Treatment Extension Period II).
Overall Number of Participants Analyzed 64 67
Least Squares Mean (Standard Error)
Unit of Measure: fraction of phosphate reabsorbed
Change at Week 2 Number Analyzed 62 participants 63 participants
-0.02  (0.013) 0.07  (0.008)
Change at Week 4 Number Analyzed 63 participants 65 participants
-0.03  (0.012) 0.03  (0.009)
Change at Week 12 Number Analyzed 62 participants 64 participants
-0.00  (0.010) 0.04  (0.008)
Change at Week 22 Number Analyzed 63 participants 64 participants
-0.01  (0.009) 0.05  (0.011)
Change at Week 24 Number Analyzed 63 participants 67 participants
-0.02  (0.012) 0.03  (0.009)
Change at Week 48 Number Analyzed 64 participants 63 participants
0.02  (0.012) 0.03  (0.009)
Change at Week 60 Number Analyzed 60 participants 60 participants
0.03  (0.009) 0.02  (0.009)
Change at Week 72 Number Analyzed 60 participants 59 participants
0.02  (0.011) 0.02  (0.011)
Change at Week 84 Number Analyzed 58 participants 58 participants
0.02  (0.010) 0.01  (0.012)
Change at Week 96 Number Analyzed 59 participants 58 participants
-0.01  (0.014) 0.03  (0.009)
27.Secondary Outcome
Title Percent Change From Baseline Over Time in TRP
Hide Description The GEE Estimates are from the GEE model which includes the percent change from baseline for TRP as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of TRP as a covariate, with compound symmetry covariance structure.
Time Frame Baseline, Weeks 2, 4, 12, 22, 24, 48, 60, 72, 84, 96
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period. Participants with an assessment at given time point.
Arm/Group Title Placebo Burosumab 1 mg/kg
Hide Arm/Group Description:
SC injection of placebo Q4W for 24 weeks (Double-blind Placebo-controlled Treatment Period), SC injection of burosumab 1 mg/kg Q4W for 24 weeks (Open-label Treatment Continuation Period), SC injection of burosumab 1 mg/kg Q4W for 48 weeks (Open-label Treatment Extension Period I), and SC injection of burosumab 1 mg/kg Q4W up to 53 weeks (Open-label Treatment Extension Period II).
SC injection of 1.0 mg/kg burosumab Q4W for 24 weeks (double-blind placebo-controlled Treatment Period), SC injection of burosumab 1 mg/kg Q4W for 24 weeks (open-label Treatment Continuation Period), SC injection of burosumab 1 mg/kg Q4W for 48 weeks (open-label Treatment Extension Period I), and SC injection of burosumab 1 mg/kg Q4W up to 53 weeks (open-label Treatment Extension Period II).
Overall Number of Participants Analyzed 64 67
Least Squares Mean (Standard Error)
Unit of Measure: percentage change
Change at Week 2 Number Analyzed 62 participants 63 participants
-2.00  (1.530) 9.81  (1.111)
Change at Week 4 Number Analyzed 63 participants 65 participants
-3.75  (1.486) 4.86  (1.114)
Change at Week 12 Number Analyzed 62 participants 64 participants
0.56  (1.261) 5.45  (1.079)
Change at Week 22 Number Analyzed 63 participants 64 participants
-0.01  (1.163) 7.03  (1.451)
Change at Week 24 Number Analyzed 63 participants 67 participants
-1.56  (1.579) 4.21  (1.141)
Change at Week 48 Number Analyzed 64 participants 63 participants
3.95  (1.547) 4.70  (1.183)
Change at Week 60 Number Analyzed 60 participants 60 participants
3.99  (1.096) 3.00  (1.123)
Change at Week 72 Number Analyzed 60 participants 59 participants
3.90  (1.427) 3.24  (1.414)
Change at Week 84 Number Analyzed 58 participants 58 participants
3.78  (1.276) 1.97  (1.516)
Change at Week 96 Number Analyzed 59 participants 58 participants
-0.09  (1.582) 4.44  (1.116)
28.Secondary Outcome
Title Percentage of Participants Achieving Mean Serum Phosphorus Levels Above the LLN (2.5 mg/dL [0.81 mmol/L]) at the End of the Dosing Cycle, as Averaged Across Dose Cycles Between Baseline and Week 24
Hide Description [Not Specified]
Time Frame Baseline through Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period.
Arm/Group Title Placebo Burosumab
Hide Arm/Group Description:
Placebo SC Q4W through Week 24
Burosumab 1 mg/kg SC Q4W
Overall Number of Participants Analyzed 66 68
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
6.1
(2.4 to 14.6)
67.6
(55.8 to 77.6)
29.Secondary Outcome
Title Change From Baseline in Serum Phosphorus at Each Mid-Point of Dosing Cycle, as Averaged Across Dose Cycles Between Baseline and Week 24
Hide Description [Not Specified]
Time Frame Baseline through Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period.
Arm/Group Title Placebo Burosumab
Hide Arm/Group Description:
Placebo SC Q4W through Week 24
Burosumab 1 mg/kg SC Q4W
Overall Number of Participants Analyzed 66 68
Mean (Standard Deviation)
Unit of Measure: mg/dL
0.16  (0.272) 1.21  (0.513)
30.Secondary Outcome
Title Percent Change From Baseline in Serum Phosphorus at Each Mid-Point of Dosing Cycle, as Averaged Across Dose Cycles Between Baseline and Week 24
Hide Description [Not Specified]
Time Frame Baseline through Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period.
Arm/Group Title Placebo Burosumab
Hide Arm/Group Description:
Placebo SC Q4W through Week 24
Burosumab 1 mg/kg SC Q4W
Overall Number of Participants Analyzed 66 68
Mean (Standard Deviation)
Unit of Measure: percentage change
9.85  (15.292) 61.44  (28.961)
31.Secondary Outcome
Title Change From Baseline in Serum Phosphorus at Each End of Dosing Cycle, as Averaged Across Dose Cycles Between Baseline and Week 24
Hide Description [Not Specified]
Time Frame Baseline through Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period.
Arm/Group Title Placebo Burosumab
Hide Arm/Group Description:
Placebo SC Q4W through Week 24
Burosumab 1 mg/kg SC Q4W
Overall Number of Participants Analyzed 66 68
Mean (Standard Deviation)
Unit of Measure: mg/dL
0.13  (0.265) 0.69  (0.392)
32.Secondary Outcome
Title Percent Change From Baseline in Serum Phosphorus at Each End of Dosing Cycle, as Averaged Across Dose Cycles Between Baseline and Week 24
Hide Description [Not Specified]
Time Frame Baseline through Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period.
Arm/Group Title Placebo Burosumab
Hide Arm/Group Description:
Placebo SC Q4W through Week 24
Burosumab 1 mg/kg SC Q4W
Overall Number of Participants Analyzed 66 68
Mean (Standard Deviation)
Unit of Measure: percentage change
7.83  (14.755) 35.18  (20.731)
33.Secondary Outcome
Title Time-Adjusted Area Under the Curve (AUC) of Serum Phosphorus Between Baseline and Week 24
Hide Description [Not Specified]
Time Frame Baseline through Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period.
Arm/Group Title Placebo Burosumab
Hide Arm/Group Description:
Placebo SC Q4W through Week 24
Burosumab 1 mg/kg SC Q4W
Overall Number of Participants Analyzed 66 68
Mean (Standard Deviation)
Unit of Measure: mg/dL
2.08  (0.292) 3.08  (0.477)
Time Frame From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo (DB Period) Placebo -> Burosumab (OL Period) Burosumab -> Burosumab (Combined DB and OL Period) Total Burosumab (Combined DB and OL Period)
Hide Arm/Group Description SC injection of placebo Q4W for 24 weeks (double-blind placebo-controlled Treatment Period) SC injection of placebo Q4W for 24 weeks (double-blind placebo-controlled Treatment Period), SC injection of burosumab 1 mg/kg Q4W for 24 weeks (open-label Treatment Continuation Period), SC injection of burosumab 1 mg/kg Q4W for 48 weeks (open label Treatment Extension Period I), and SC injection of burosumab 1 mg/kg Q4W up to 53 weeks (open-label Treatment Extension Period II [US only]). SC injection of 1.0 mg/kg burosumab Q4W for 24 weeks (double-blind placebo-controlled Treatment Period), SC injection of burosumab 1 mg/kg Q4W for 24 weeks (open-label Treatment Continuation Period), SC injection of burosumab 1 mg/kg Q4W for 48 weeks (open-label Treatment Extension Period I), and SC injection of burosumab 1 mg/kg Q4W up to 53 weeks (open-label Treatment Extension Period II [US only]). SC injection of 1.0 mg/kg burosumab at any time during the study.
All-Cause Mortality
Placebo (DB Period) Placebo -> Burosumab (OL Period) Burosumab -> Burosumab (Combined DB and OL Period) Total Burosumab (Combined DB and OL Period)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/66 (0.00%)   0/66 (0.00%)   1/68 (1.47%)   1/134 (0.75%) 
Hide Serious Adverse Events
Placebo (DB Period) Placebo -> Burosumab (OL Period) Burosumab -> Burosumab (Combined DB and OL Period) Total Burosumab (Combined DB and OL Period)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/66 (1.52%)   10/66 (15.15%)   12/68 (17.65%)   22/134 (16.42%) 
Cardiac disorders         
Palpitations  1  0/66 (0.00%)  1/66 (1.52%)  0/68 (0.00%)  1/134 (0.75%) 
Gastrointestinal disorders         
Colitis  1  0/66 (0.00%)  0/66 (0.00%)  1/68 (1.47%)  1/134 (0.75%) 
Duodenal Ulcer  1  0/66 (0.00%)  0/66 (0.00%)  1/68 (1.47%)  1/134 (0.75%) 
Ileus  1  0/66 (0.00%)  0/66 (0.00%)  1/68 (1.47%)  1/134 (0.75%) 
Irritable Bowel Syndrome  1  0/66 (0.00%)  0/66 (0.00%)  1/68 (1.47%)  1/134 (0.75%) 
Periodontal Disease  1  0/66 (0.00%)  1/66 (1.52%)  0/68 (0.00%)  1/134 (0.75%) 
Peritoneal Adhesions  1  0/66 (0.00%)  1/66 (1.52%)  0/68 (0.00%)  1/134 (0.75%) 
Hepatobiliary disorders         
Cholelithiasis  1  0/66 (0.00%)  0/66 (0.00%)  1/68 (1.47%)  1/134 (0.75%) 
Infections and infestations         
Gastroenteritis  1  0/66 (0.00%)  0/66 (0.00%)  1/68 (1.47%)  1/134 (0.75%) 
Medical Device Site Infection  1  0/66 (0.00%)  0/66 (0.00%)  1/68 (1.47%)  1/134 (0.75%) 
Injury, poisoning and procedural complications         
Overdose  1  0/66 (0.00%)  0/66 (0.00%)  1/68 (1.47%)  1/134 (0.75%) 
Procedural Nausea  1  0/66 (0.00%)  0/66 (0.00%)  1/68 (1.47%)  1/134 (0.75%) 
Procedural Vomiting  1  0/66 (0.00%)  0/66 (0.00%)  1/68 (1.47%)  1/134 (0.75%) 
Road Traffic Accident  1  0/66 (0.00%)  0/66 (0.00%)  1/68 (1.47%)  1/134 (0.75%) 
Subdural Haematoma  1  0/66 (0.00%)  1/66 (1.52%)  0/68 (0.00%)  1/134 (0.75%) 
Musculoskeletal and connective tissue disorders         
Arthralgia  1  0/66 (0.00%)  1/66 (1.52%)  1/68 (1.47%)  2/134 (1.49%) 
Back Pain  1  0/66 (0.00%)  0/66 (0.00%)  1/68 (1.47%)  1/134 (0.75%) 
Cervical Spinal Stenosis  1  0/66 (0.00%)  1/66 (1.52%)  0/68 (0.00%)  1/134 (0.75%) 
Joint Range Of Motion Decreased  1  0/66 (0.00%)  1/66 (1.52%)  0/68 (0.00%)  1/134 (0.75%) 
Knee Deformity  1  0/66 (0.00%)  0/66 (0.00%)  1/68 (1.47%)  1/134 (0.75%) 
Musculoskeletal Pain  1  0/66 (0.00%)  0/66 (0.00%)  1/68 (1.47%)  1/134 (0.75%) 
Osteoarthritis  1  0/66 (0.00%)  0/66 (0.00%)  1/68 (1.47%)  1/134 (0.75%) 
Pseudarthrosis  1  0/66 (0.00%)  1/66 (1.52%)  0/68 (0.00%)  1/134 (0.75%) 
Spinal Column Stenosis  1  0/66 (0.00%)  0/66 (0.00%)  1/68 (1.47%)  1/134 (0.75%) 
Spondylolisthesis  1  0/66 (0.00%)  0/66 (0.00%)  1/68 (1.47%)  1/134 (0.75%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Invasive Ductal Breast Carcinoma  1  1/66 (1.52%)  0/66 (0.00%)  0/68 (0.00%)  0/134 (0.00%) 
Parathyroid Tumour Benign  1  0/66 (0.00%)  1/66 (1.52%)  0/68 (0.00%)  1/134 (0.75%) 
Nervous system disorders         
Cerebrospinal Fluid Leakage  1  0/66 (0.00%)  0/66 (0.00%)  1/68 (1.47%)  1/134 (0.75%) 
Cervical Radiculopathy  1  0/66 (0.00%)  0/66 (0.00%)  1/68 (1.47%)  1/134 (0.75%) 
Dizziness  1  0/66 (0.00%)  1/66 (1.52%)  0/68 (0.00%)  1/134 (0.75%) 
Myelopathy  1  0/66 (0.00%)  0/66 (0.00%)  2/68 (2.94%)  2/134 (1.49%) 
Neuralgia  1  0/66 (0.00%)  1/66 (1.52%)  0/68 (0.00%)  1/134 (0.75%) 
Paraesthesia  1  0/66 (0.00%)  1/66 (1.52%)  0/68 (0.00%)  1/134 (0.75%) 
Partial Seizures  1  0/66 (0.00%)  1/66 (1.52%)  0/68 (0.00%)  1/134 (0.75%) 
Presyncope  1  0/66 (0.00%)  1/66 (1.52%)  0/68 (0.00%)  1/134 (0.75%) 
1
Term from vocabulary, MedDRA 18.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo (DB Period) Placebo -> Burosumab (OL Period) Burosumab -> Burosumab (Combined DB and OL Period) Total Burosumab (Combined DB and OL Period)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   57/66 (86.36%)   63/66 (95.45%)   68/68 (100.00%)   131/134 (97.76%) 
Ear and labyrinth disorders         
Vertigo  1  1/66 (1.52%)  4/66 (6.06%)  3/68 (4.41%)  7/134 (5.22%) 
Endocrine disorders         
Hyperparathyroidism Secondary  1  0/66 (0.00%)  3/66 (4.55%)  4/68 (5.88%)  7/134 (5.22%) 
Gastrointestinal disorders         
Abdominal Discomfort  1  0/66 (0.00%)  3/66 (4.55%)  4/68 (5.88%)  7/134 (5.22%) 
Abdominal Pain  1  2/66 (3.03%)  2/66 (3.03%)  6/68 (8.82%)  8/134 (5.97%) 
Abdominal Pain Upper  1  0/66 (0.00%)  6/66 (9.09%)  3/68 (4.41%)  9/134 (6.72%) 
Constipation  1  0/66 (0.00%)  4/66 (6.06%)  10/68 (14.71%)  14/134 (10.45%) 
Diarrhoea  1  5/66 (7.58%)  5/66 (7.58%)  13/68 (19.12%)  18/134 (13.43%) 
Nausea  1  6/66 (9.09%)  5/66 (7.58%)  11/68 (16.18%)  16/134 (11.94%) 
Toothache  1  1/66 (1.52%)  10/66 (15.15%)  12/68 (17.65%)  22/134 (16.42%) 
Vomiting  1  2/66 (3.03%)  4/66 (6.06%)  6/68 (8.82%)  10/134 (7.46%) 
General disorders         
Asthenia  1  2/66 (3.03%)  1/66 (1.52%)  5/68 (7.35%)  6/134 (4.48%) 
Fatigue  1  7/66 (10.61%)  14/66 (21.21%)  16/68 (23.53%)  30/134 (22.39%) 
Injection Site Erythema  1  2/66 (3.03%)  6/66 (9.09%)  6/68 (8.82%)  12/134 (8.96%) 
Injection Site Pruritus  1  0/66 (0.00%)  8/66 (12.12%)  3/68 (4.41%)  11/134 (8.21%) 
Injection Site Reaction  1  2/66 (3.03%)  8/66 (12.12%)  7/68 (10.29%)  15/134 (11.19%) 
Pain  1  6/66 (9.09%)  9/66 (13.64%)  12/68 (17.65%)  21/134 (15.67%) 
Pyrexia  1  0/66 (0.00%)  4/66 (6.06%)  5/68 (7.35%)  9/134 (6.72%) 
Immune system disorders         
Seasonal Allergy  1  1/66 (1.52%)  6/66 (9.09%)  5/68 (7.35%)  11/134 (8.21%) 
Infections and infestations         
Bronchitis  1  1/66 (1.52%)  6/66 (9.09%)  4/68 (5.88%)  10/134 (7.46%) 
Gastroenteritis  1  2/66 (3.03%)  4/66 (6.06%)  2/68 (2.94%)  6/134 (4.48%) 
Influenza  1  3/66 (4.55%)  6/66 (9.09%)  9/68 (13.24%)  15/134 (11.19%) 
Nasopharyngitis  1  6/66 (9.09%)  24/66 (36.36%)  28/68 (41.18%)  52/134 (38.81%) 
Oral Herpes  1  0/66 (0.00%)  4/66 (6.06%)  4/68 (5.88%)  8/134 (5.97%) 
Pharyngitis  1  1/66 (1.52%)  0/66 (0.00%)  4/68 (5.88%)  4/134 (2.99%) 
Rhinitis  1  1/66 (1.52%)  4/66 (6.06%)  1/68 (1.47%)  5/134 (3.73%) 
Sinusitis  1  2/66 (3.03%)  2/66 (3.03%)  6/68 (8.82%)  8/134 (5.97%) 
Tooth Abscess  1  6/66 (9.09%)  5/66 (7.58%)  19/68 (27.94%)  24/134 (17.91%) 
Upper Respiratory Tract Infection  1  6/66 (9.09%)  2/66 (3.03%)  12/68 (17.65%)  14/134 (10.45%) 
Urinary Tract Infection  1  4/66 (6.06%)  6/66 (9.09%)  5/68 (7.35%)  11/134 (8.21%) 
Injury, poisoning and procedural complications         
Contusion  1  1/66 (1.52%)  5/66 (7.58%)  4/68 (5.88%)  9/134 (6.72%) 
Fall  1  0/66 (0.00%)  7/66 (10.61%)  6/68 (8.82%)  13/134 (9.70%) 
Ligament Sprain  1  6/66 (9.09%)  2/66 (3.03%)  4/68 (5.88%)  6/134 (4.48%) 
Procedural Pain  1  0/66 (0.00%)  6/66 (9.09%)  9/68 (13.24%)  15/134 (11.19%) 
Investigations         
Blood 25-Hydroxycholecalciferol Decreased  1  1/66 (1.52%)  3/66 (4.55%)  6/68 (8.82%)  9/134 (6.72%) 
Blood Glucose Increased  1  0/66 (0.00%)  1/66 (1.52%)  5/68 (7.35%)  6/134 (4.48%) 
Blood Parathyroid Hormone Increased  1  1/66 (1.52%)  1/66 (1.52%)  5/68 (7.35%)  6/134 (4.48%) 
Blood Pressure Increased  1  1/66 (1.52%)  1/66 (1.52%)  6/68 (8.82%)  7/134 (5.22%) 
Lipase Increased  1  0/66 (0.00%)  0/66 (0.00%)  4/68 (5.88%)  4/134 (2.99%) 
Vitamin D Decreased  1  0/66 (0.00%)  9/66 (13.64%)  8/68 (11.76%)  17/134 (12.69%) 
Metabolism and nutrition disorders         
Decreased Appetite  1  1/66 (1.52%)  0/66 (0.00%)  4/68 (5.88%)  4/134 (2.99%) 
Hyperphosphataemia  1  0/66 (0.00%)  4/66 (6.06%)  1/68 (1.47%)  5/134 (3.73%) 
Vitamin D Deficiency  1  3/66 (4.55%)  7/66 (10.61%)  15/68 (22.06%)  22/134 (16.42%) 
Musculoskeletal and connective tissue disorders         
Arthralgia  1  16/66 (24.24%)  23/66 (34.85%)  27/68 (39.71%)  50/134 (37.31%) 
Back Pain  1  6/66 (9.09%)  17/66 (25.76%)  18/68 (26.47%)  35/134 (26.12%) 
Bone Pain  1  4/66 (6.06%)  6/66 (9.09%)  8/68 (11.76%)  14/134 (10.45%) 
Joint Stiffness  1  0/66 (0.00%)  4/66 (6.06%)  4/68 (5.88%)  8/134 (5.97%) 
Joint Swelling  1  0/66 (0.00%)  7/66 (10.61%)  5/68 (7.35%)  12/134 (8.96%) 
Muscle Spasms  1  2/66 (3.03%)  9/66 (13.64%)  11/68 (16.18%)  20/134 (14.93%) 
Muscular Weakness  1  1/66 (1.52%)  2/66 (3.03%)  6/68 (8.82%)  8/134 (5.97%) 
Musculoskeletal Chest Pain  1  0/66 (0.00%)  4/66 (6.06%)  3/68 (4.41%)  7/134 (5.22%) 
Musculoskeletal Pain  1  4/66 (6.06%)  10/66 (15.15%)  12/68 (17.65%)  22/134 (16.42%) 
Musculoskeletal Stiffness  1  3/66 (4.55%)  4/66 (6.06%)  4/68 (5.88%)  8/134 (5.97%) 
Myalgia  1  1/66 (1.52%)  5/66 (7.58%)  8/68 (11.76%)  13/134 (9.70%) 
Neck Pain  1  1/66 (1.52%)  5/66 (7.58%)  3/68 (4.41%)  8/134 (5.97%) 
Pain In Extremity  1  10/66 (15.15%)  10/66 (15.15%)  18/68 (26.47%)  28/134 (20.90%) 
Nervous system disorders         
Dizziness  1  4/66 (6.06%)  5/66 (7.58%)  11/68 (16.18%)  16/134 (11.94%) 
Headache  1  5/66 (7.58%)  18/66 (27.27%)  22/68 (32.35%)  40/134 (29.85%) 
Hypoaesthesia  1  1/66 (1.52%)  3/66 (4.55%)  7/68 (10.29%)  10/134 (7.46%) 
Migraine  1  1/66 (1.52%)  2/66 (3.03%)  7/68 (10.29%)  9/134 (6.72%) 
Restless Legs Syndrome  1  5/66 (7.58%)  10/66 (15.15%)  11/68 (16.18%)  21/134 (15.67%) 
Psychiatric disorders         
Depression  1  1/66 (1.52%)  3/66 (4.55%)  9/68 (13.24%)  12/134 (8.96%) 
Insomnia  1  1/66 (1.52%)  6/66 (9.09%)  9/68 (13.24%)  15/134 (11.19%) 
Renal and urinary disorders         
Nephrocalcinosis  1  0/66 (0.00%)  4/66 (6.06%)  2/68 (2.94%)  6/134 (4.48%) 
Respiratory, thoracic and mediastinal disorders         
Asthma  1  0/66 (0.00%)  5/66 (7.58%)  2/68 (2.94%)  7/134 (5.22%) 
Cough  1  3/66 (4.55%)  11/66 (16.67%)  10/68 (14.71%)  21/134 (15.67%) 
Nasal Congestion  1  2/66 (3.03%)  5/66 (7.58%)  5/68 (7.35%)  10/134 (7.46%) 
Oropharyngeal Pain  1  7/66 (10.61%)  8/66 (12.12%)  4/68 (5.88%)  12/134 (8.96%) 
Rhinorrhoea  1  3/66 (4.55%)  2/66 (3.03%)  4/68 (5.88%)  6/134 (4.48%) 
Skin and subcutaneous tissue disorders         
Pruritus  1  0/66 (0.00%)  1/66 (1.52%)  5/68 (7.35%)  6/134 (4.48%) 
Rash  1  3/66 (4.55%)  1/66 (1.52%)  4/68 (5.88%)  5/134 (3.73%) 
Vascular disorders         
Hot Flush  1  0/66 (0.00%)  2/66 (3.03%)  6/68 (8.82%)  8/134 (5.97%) 
Hypertension  1  2/66 (3.03%)  5/66 (7.58%)  8/68 (11.76%)  13/134 (9.70%) 
1
Term from vocabulary, MedDRA 18.1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Information
Organization: Ultragenyx Pharmaceutical Inc
Phone: 1-888-756-8657
EMail: medinfo@ultragenyx.com
Layout table for additonal information
Responsible Party: Ultragenyx Pharmaceutical Inc
ClinicalTrials.gov Identifier: NCT02526160    
Other Study ID Numbers: UX023-CL303
2014-005529-11 ( EudraCT Number )
First Submitted: July 17, 2015
First Posted: August 18, 2015
Results First Submitted: December 17, 2020
Results First Posted: February 5, 2021
Last Update Posted: February 5, 2021