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Study of Burosumab (KRN23) in Adults With Tumor-Induced Osteomalacia (TIO) or Epidermal Nevus Syndrome (ENS)

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: NCT02304367
Recruitment Status : Active, not recruiting
First Posted : December 1, 2014
Results First Posted : July 30, 2020
Last Update Posted : July 30, 2020
Sponsor:
Information provided by (Responsible Party):
Ultragenyx Pharmaceutical Inc

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Tumor Induced Osteomalacia (TIO)
Epidermal Nevus Syndrome (ENS)
Intervention Biological: Burosumab
Enrollment 17
Recruitment Details

This study is being conducted at 8 centers in the United States. Results are reported through 11 January 2019, through 144 weeks of treatment.

The study enrolled adults with tumor-induced osteomalacia (TIO) or epidermal nevus syndrome (ENS)-associated osteomalacia.

Pre-assignment Details  
Arm/Group Title Burosumab
Hide Arm/Group Description Participants received burosumab at a starting dose of 0.3 mg/kg administered subcutaneously (SC) every 4 weeks (Q4W). Doses may have been titrated up to a maximum of 2.0 mg/kg every 2 weeks (Q2W) in order to achieve fasting peak serum phosphorus levels within the target range of 2.5 to 4.0 mg/dL.
Period Title: Overall Study
Started 17
Completed 48 Weeks of Study Drug 16
Completed 144 Weeks of Study Drug 11
Completed 0
Not Completed 17
Reason Not Completed
Lack of Phosphorus Increase             1
Sponsor Decision             3
Death             1
Ongoing in Study             12
Arm/Group Title Burosumab
Hide Arm/Group Description Participants received burosumab at a starting dose of 0.3 mg/kg administered subcutaneously (SC) every 4 weeks (Q4W). Doses may have been titrated up to a maximum of 2.0 mg/kg every 2 weeks (Q2W) in order to achieve fasting peak serum phosphorus levels within the target range of 2.5 to 4.0 mg/dL.
Overall Number of Baseline Participants 17
Hide Baseline Analysis Population Description
All enrolled participants
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 17 participants
53.1  (13.86)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 17 participants
Female
8
  47.1%
Male
9
  52.9%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 17 participants
Hispanic or Latino
0
   0.0%
Not Hispanic or Latino
17
 100.0%
Unknown or Not Reported
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 17 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Black or African American
2
  11.8%
Native Hawaiian or Other Pacific Islander
0
   0.0%
White
15
  88.2%
Other
0
   0.0%
Diagnosis   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 17 participants
Tumor-Induced osteomalacia (TIO)
14
  82.4%
Epidermal nevus syndrome-associated osteomalacia
1
   5.9%
X-linked hypophosphatemia (XLH)
2
  11.8%
[1]
Measure Description: Two participants who were enrolled in the study with a clinical diagnosis of TIO were later found to have X-linked hypophosphatemia (XLH) based on genetic testing.
Serum Total Fibroblast Growth Factor 23 (FGF23)   [1] 
Mean (Standard Deviation)
Unit of measure:  pg/mL
Number Analyzed 14 participants
770.06  (797.654)
[1]
Measure Analysis Population Description: Tumor-induced osteomalacia (TIO) analysis set includes the 14 participants with TIO who received at least 1 dose of study drug.
Serum Phosphorus   [1] 
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 14 participants
1.60  (0.474)
[1]
Measure Analysis Population Description: TIO analysis set
Osteoid Volume/Bone Volume (OB/BV)   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Percentage of bone volume
Number Analyzed 11 participants
17.61  (19.485)
[1]
Measure Description: The percentage of a given volume of bone tissue that consists of unmineralized bone (osteoid).
[2]
Measure Analysis Population Description: TIO biopsy analysis set includes 11 participants with TIO who received at least 1 dose of study drug and who had paired bone biopsies at Baseline and Week 48.
Osteoid Surface/Bone Surface (OS/BS)   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Percentage of bone surface
Number Analyzed 11 participants
56.82  (31.003)
[1]
Measure Description: The percentage of bone surface covered in osteoid.
[2]
Measure Analysis Population Description: TIO biopsy analysis set
Osteoid Thickness (O.Th)   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  μm
Number Analyzed 11 participants
16.45  (12.044)
[1]
Measure Description: Mean thickness, given in micrometers, for osteoid seams
[2]
Measure Analysis Population Description: TIO biopsy analysis set
Mineralization Lag Time (Mlt)   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Days
Number Analyzed 10 participants
1597.73  (1326.832)
[1]
Measure Description:

Mineralization lag time is the average time interval between osteoid formation and its subsequent mineralization, calculated by dividing the osteoid width by the mineralizing apposition rate (MAR; the average rate at which new bone mineral is being added on any actively forming surface).

If Mlt could not be calculated directly due to low tetracycline uptake, Mlt was imputed according to the following:

Mlt = O.Th/(MAR*MS/OS), where O.Th = osteoid thickness, MAR is imputed as 0.3 μm/day, MS/OS=Mineralizing Surface/Osteoid Surface, each measured at the same visit.

[2]
Measure Analysis Population Description: TIO biopsy analysis set for whom Mlt could be calculated or imputed
1.Primary Outcome
Title Percentage of Participants Achieving Mean Serum Phosphorus Levels Above 2.5 mg/dL at the Mid-Point of the Dose Intervals Between Baseline and Week 24
Hide Description The percentage of participants achieving mean serum phosphorus levels above the lower limit of normal (LLN; 2.5 mg/dL [0.81 mmol/L]) at the mid-point of the dose interval (2 weeks after dosing), as averaged across dose cycles between Baseline and Week 24 (i.e. the average of serum phosphorus levels at Weeks 2, 6, 10, 14 and 22).
Time Frame Mid-point of each dose interval from Baseline to Week 24 (Weeks 2, 6, 10, 14 and 22 [there was no study visit at Week 18])
Hide Outcome Measure Data
Hide Analysis Population Description
TIO analysis set
Arm/Group Title Burosumab
Hide Arm/Group Description:
Participants received burosumab at a starting dose of 0.3 mg/kg administered subcutaneously (SC) every 4 weeks (Q4W). Doses may have been titrated up to a maximum of 2.0 mg/kg every 2 weeks (Q2W) in order to achieve fasting peak serum phosphorus levels within the target range of 2.5 to 4.0 mg/dL.
Overall Number of Participants Analyzed 14
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
50.0
(26.80 to 73.20)
2.Primary Outcome
Title Change From Baseline to Week 48 in Osteoid Thickness
Hide Description

Histomorphometry of trans-iliac crest bone biopsies was assessed by a blinded, central reader.

Osteoid thickness is the mean thickness of osteoid seams.

Time Frame Baseline, Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
TIO bone biopsy analysis set
Arm/Group Title Burosumab
Hide Arm/Group Description:
Participants received burosumab at a starting dose of 0.3 mg/kg administered subcutaneously (SC) every 4 weeks (Q4W). Doses may have been titrated up to a maximum of 2.0 mg/kg every 2 weeks (Q2W) in order to achieve fasting peak serum phosphorus levels within the target range of 2.5 to 4.0 mg/dL.
Overall Number of Participants Analyzed 11
Mean (95% Confidence Interval)
Unit of Measure: µm
-5.12
(-10.04 to -0.20)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments The null hypothesis that the mean change from Baseline to Week 48 in osteoid thickness is zero was tested using a t-test.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0428
Comments [Not Specified]
Method t-test
Comments [Not Specified]
3.Primary Outcome
Title Change From Baseline to Week 48 in Osteoid Surface/Bone Surface (OS/BS)
Hide Description

Histomorphometry of trans-iliac crest bone biopsies was assessed by a blinded, central reader.

Osteoid surface/bone surface is expressed as the percentage of bone surface covered in osteoid.

Time Frame Baseline, Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
TIO biopsy analysis set
Arm/Group Title Burosumab
Hide Arm/Group Description:
Participants received burosumab at a starting dose of 0.3 mg/kg administered subcutaneously (SC) every 4 weeks (Q4W). Doses may have been titrated up to a maximum of 2.0 mg/kg every 2 weeks (Q2W) in order to achieve fasting peak serum phosphorus levels within the target range of 2.5 to 4.0 mg/dL.
Overall Number of Participants Analyzed 11
Mean (95% Confidence Interval)
Unit of Measure: percentage of bone surface
-0.18
(-13.86 to 13.50)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments The null hypothesis that the mean change from Baseline to Week 48 in OS/BS is zero was tested using a t-test.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9770
Comments [Not Specified]
Method t-test
Comments [Not Specified]
4.Primary Outcome
Title Change From Baseline to Week 48 in Osteoid Volume/Bone Volume (OV/BV)
Hide Description Histomorphometry of trans-iliac crest bone biopsies was assessed by a blinded, central reader. Osteoid volume/bone volume is expressed as the percentage of a given volume of bone tissue that consists of unmineralized bone (osteoid).
Time Frame Baseline, Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
TIO bone biopsy analysis set
Arm/Group Title Burosumab
Hide Arm/Group Description:
Participants received burosumab at a starting dose of 0.3 mg/kg administered subcutaneously (SC) every 4 weeks (Q4W). Doses may have been titrated up to a maximum of 2.0 mg/kg every 2 weeks (Q2W) in order to achieve fasting peak serum phosphorus levels within the target range of 2.5 to 4.0 mg/dL.
Overall Number of Participants Analyzed 11
Mean (95% Confidence Interval)
Unit of Measure: percentage of bone volume
-5.47
(-11.87 to 0.93)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments The null hypothesis that the mean change from Baseline to Week 48 in OV/BV is zero was tested using a t-test.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0858
Comments [Not Specified]
Method t-test
Comments [Not Specified]
5.Primary Outcome
Title Change From Baseline to Week 48 in Mineralization Lag Time (MLt)
Hide Description

Mineralization lag time is a dynamic modeling parameter representing the mean time interval between the formation of osteoid and its subsequent mineralization which can be measured using histomorphometry with double tetracycline labeling.

Mlt was calculated by dividing the osteoid width by the mineralizing apposition rate (MAR; the average rate at which new bone mineral is being added on any actively forming surface).

If Mlt could not be calculated directly due to low tetracycline uptake, Mlt was imputed according to the following:

Mlt = O.Th/(MAR*MS/OS), where O.Th = osteoid thickness, MAR is imputed as 0.3 μm/day, MS/OS=mineralizing surface/osteoid surface, each measured at the same visit.

Time Frame Baseline, Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
TIO biopsy analysis set for whom Mlt could be calculated or imputed
Arm/Group Title Burosumab
Hide Arm/Group Description:
Participants received burosumab at a starting dose of 0.3 mg/kg administered subcutaneously (SC) every 4 weeks (Q4W). Doses may have been titrated up to a maximum of 2.0 mg/kg every 2 weeks (Q2W) in order to achieve fasting peak serum phosphorus levels within the target range of 2.5 to 4.0 mg/dL.
Overall Number of Participants Analyzed 10
Mean (95% Confidence Interval)
Unit of Measure: days
-565.20
(-2037.42 to 907.02)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments The null hypothesis that the mean change from Baseline to Week 48 in Mlt is zero was tested using a t-test.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4077
Comments [Not Specified]
Method t-test
Comments [Not Specified]
6.Secondary Outcome
Title Percentage of Participants Achieving Mean Serum Phosphorus Levels Above 2.5 mg/dL at the End of the Dose Intervals Between Baseline and Week 24
Hide Description The percentage of participants achieving mean serum phosphorus levels above the lower limit of normal (2.5 mg/dL [0.81 mmol/L]) at the end of the dose interval (4 weeks post-dose, prior to the next dose), as averaged across dose cycles between Baseline and Week 24 (i.e. the average of serum phosphorus levels at Weeks 4, 8, 12, 16, 20, and 24).
Time Frame End of each dose interval from Baseline to Week 24 (Weeks 4, 8, 12, 16, 20, and 24)
Hide Outcome Measure Data
Hide Analysis Population Description
TIO analysis set
Arm/Group Title Burosumab
Hide Arm/Group Description:
Participants received burosumab at a starting dose of 0.3 mg/kg administered subcutaneously (SC) every 4 weeks (Q4W). Doses may have been titrated up to a maximum of 2.0 mg/kg every 2 weeks (Q2W) in order to achieve fasting peak serum phosphorus levels within the target range of 2.5 to 4.0 mg/dL.
Overall Number of Participants Analyzed 14
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
21.4
(7.57 to 47.59)
7.Secondary Outcome
Title Mean Change From Baseline in Serum Phosphorus Levels at the Mid-Point of the Dose Interval, as Averaged Across Dose Cycles Between Baseline and Week 24
Hide Description Mean change from Baseline to the mid-point of the dose interval (2 weeks after dosing) averaged across dose cycles between Baseline and Week 24 (i.e. the average of serum phosphorus levels at Weeks 2, 6, 10, 14 and 22).
Time Frame Baseline and the mid-point of each dose interval from Baseline to Week 24 (Weeks 2, 6, 10, 14 and 22)
Hide Outcome Measure Data
Hide Analysis Population Description
TIO analysis set
Arm/Group Title Burosumab
Hide Arm/Group Description:
Participants received burosumab at a starting dose of 0.3 mg/kg administered subcutaneously (SC) every 4 weeks (Q4W). Doses may have been titrated up to a maximum of 2.0 mg/kg every 2 weeks (Q2W) in order to achieve fasting peak serum phosphorus levels within the target range of 2.5 to 4.0 mg/dL.
Overall Number of Participants Analyzed 14
Mean (Standard Deviation)
Unit of Measure: mg/dL
1.039  (0.5622)
8.Secondary Outcome
Title Percent Change From Baseline in Serum Phosphorus Levels at the Mid-Point of the Dose Interval, as Averaged Across Dose Cycles Between Baseline and Week 24
Hide Description Mean percent change from Baseline to the mid-point of the dose interval (2 weeks after dosing) averaged across dose cycles between Baseline and Week 24 (i.e. the average of serum phosphorus levels at Weeks 2, 6, 10, 14 and 22).
Time Frame Baseline and the mid-point of each dose interval from Baseline to Week 24 (Weeks 2, 6, 10, 14 and 22)
Hide Outcome Measure Data
Hide Analysis Population Description
TIO analysis set
Arm/Group Title Burosumab
Hide Arm/Group Description:
Participants received burosumab at a starting dose of 0.3 mg/kg administered subcutaneously (SC) every 4 weeks (Q4W). Doses may have been titrated up to a maximum of 2.0 mg/kg every 2 weeks (Q2W) in order to achieve fasting peak serum phosphorus levels within the target range of 2.5 to 4.0 mg/dL.
Overall Number of Participants Analyzed 14
Mean (Standard Deviation)
Unit of Measure: percent change
69.77  (43.743)
9.Secondary Outcome
Title Mean Change From Baseline in Serum Phosphorus Levels at the End of the Dosing Cycle, as Averaged Across Dose Cycles Between Baseline and Week 24
Hide Description Mean change from Baseline at the end of the dose interval (4 weeks post-dose, prior to the next dose) averaged across dose cycles between Baseline and Week 24 (i.e. the average of serum phosphorus levels at Weeks 4, 8, 12, 16, 20, and 24).
Time Frame Baseline and Weeks 4, 8, 12, 16, 20, and 24
Hide Outcome Measure Data
Hide Analysis Population Description
TIO analysis set
Arm/Group Title Burosumab
Hide Arm/Group Description:
Participants received burosumab at a starting dose of 0.3 mg/kg administered subcutaneously (SC) every 4 weeks (Q4W). Doses may have been titrated up to a maximum of 2.0 mg/kg every 2 weeks (Q2W) in order to achieve fasting peak serum phosphorus levels within the target range of 2.5 to 4.0 mg/dL.
Overall Number of Participants Analyzed 14
Mean (Standard Deviation)
Unit of Measure: mg/dL
0.550  (0.4260)
10.Secondary Outcome
Title Percent Mean Change From Baseline in Serum Phosphorus Levels at the End of the Dosing Cycle, as Averaged Across Dose Cycles Between Baseline and Week 24
Hide Description Mean percent change from Baseline at the end of the dose interval (4 weeks post-dose, prior to the next dose) averaged across dose cycles between Baseline and Week 24 (i.e. the average of serum phosphorus levels at Weeks 4, 8, 12, 16, 20, and 24).
Time Frame Baseline and Weeks 4, 8, 12, 16, 20, and 24
Hide Outcome Measure Data
Hide Analysis Population Description
TIO analysis set
Arm/Group Title Burosumab
Hide Arm/Group Description:
Participants received burosumab at a starting dose of 0.3 mg/kg administered subcutaneously (SC) every 4 weeks (Q4W). Doses may have been titrated up to a maximum of 2.0 mg/kg every 2 weeks (Q2W) in order to achieve fasting peak serum phosphorus levels within the target range of 2.5 to 4.0 mg/dL.
Overall Number of Participants Analyzed 14
Mean (Standard Deviation)
Unit of Measure: percent change
38.56  (33.027)
11.Secondary Outcome
Title Time-Adjusted Area Under the Curve (AUC) of Serum Phosphorus Levels Between Baseline and Week 24
Hide Description Serum phosphorus level versus time AUC was calculated using the trapezoidal rule. Time-adjusted AUC was calculated by dividing the AUC by duration of time included in AUC calculation.
Time Frame Pre-dose on Day 1 and at Weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 21, 22, and 24
Hide Outcome Measure Data
Hide Analysis Population Description
TIO analysis set
Arm/Group Title Burosumab
Hide Arm/Group Description:
Participants received burosumab at a starting dose of 0.3 mg/kg administered subcutaneously (SC) every 4 weeks (Q4W). Doses may have been titrated up to a maximum of 2.0 mg/kg every 2 weeks (Q2W) in order to achieve fasting peak serum phosphorus levels within the target range of 2.5 to 4.0 mg/dL.
Overall Number of Participants Analyzed 14
Mean (Standard Deviation)
Unit of Measure: mg/dL
2.36  (0.632)
12.Secondary Outcome
Title Change From Baseline Over Time in Serum 1,25-dihydroxyvitamin D (1,25(OH)2D) Concentration
Hide Description Least squares (LS) means and standard errors (SE) were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline 1,25(OH)2D, with compound symmetry covariance structure.
Time Frame Baseline and Weeks 24, 48, 96, and 144
Hide Outcome Measure Data
Hide Analysis Population Description
TIO analysis set participants with available data at Baseline and each time point.
Arm/Group Title Burosumab
Hide Arm/Group Description:
Participants received burosumab at a starting dose of 0.3 mg/kg administered subcutaneously (SC) every 4 weeks (Q4W). Doses may have been titrated up to a maximum of 2.0 mg/kg every 2 weeks (Q2W) in order to achieve fasting peak serum phosphorus levels within the target range of 2.5 to 4.0 mg/dL.
Overall Number of Participants Analyzed 11
Least Squares Mean (Standard Error)
Unit of Measure: pg/mL
Week 24 Number Analyzed 11 participants
9.86  (4.126)
Week 48 Number Analyzed 10 participants
10.45  (4.850)
Week 96 Number Analyzed 9 participants
4.23  (3.824)
Week 144 Number Analyzed 8 participants
0.97  (2.585)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 24
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0169
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline 1,25(OH)2D.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 48
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0312
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline 1,25(OH)2D.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 96
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2689
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline 1,25(OH)2D.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 144
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7084
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline 1,25(OH)2D.
13.Secondary Outcome
Title Change From Baseline Over Time in Total Serum Fibroblast Growth Factor 23 (FGF23) Concentration
Hide Description Total FGF23 included free FGF23 and FGF23 bound to burosumab. Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline total FGF23, with compound symmetry covariance structure.
Time Frame Baseline and Weeks 24, 48, 96, and 144
Hide Outcome Measure Data
Hide Analysis Population Description
TIO analysis set with available data at each time point
Arm/Group Title Burosumab
Hide Arm/Group Description:
Participants received burosumab at a starting dose of 0.3 mg/kg administered subcutaneously (SC) every 4 weeks (Q4W). Doses may have been titrated up to a maximum of 2.0 mg/kg every 2 weeks (Q2W) in order to achieve fasting peak serum phosphorus levels within the target range of 2.5 to 4.0 mg/dL.
Overall Number of Participants Analyzed 14
Least Squares Mean (Standard Error)
Unit of Measure: pg/mL
Week 24 Number Analyzed 14 participants
248086.96  (58338.009)
Week 48 Number Analyzed 10 participants
196992.07  (36253.944)
Week 96 Number Analyzed 11 participants
333176.47  (102161.579)
Week 144 Number Analyzed 10 participants
282623.86  (108373.968)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 24
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline total FGF23.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 48
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline total FGF23.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 96
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0011
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline total FGF23.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 144
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0091
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline total FGF23.
14.Secondary Outcome
Title Change From Baseline Over Time in Free Serum Fibroblast Growth Factor 23 (FGF23) Concentration
Hide Description Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline free FGF23, with compound symmetry covariance structure.
Time Frame Baseline and Weeks 24, 48, 96, and 144
Hide Outcome Measure Data
Hide Analysis Population Description
TIO analysis set with available data at each time point
Arm/Group Title Burosumab
Hide Arm/Group Description:
Participants received burosumab at a starting dose of 0.3 mg/kg administered subcutaneously (SC) every 4 weeks (Q4W). Doses may have been titrated up to a maximum of 2.0 mg/kg every 2 weeks (Q2W) in order to achieve fasting peak serum phosphorus levels within the target range of 2.5 to 4.0 mg/dL.
Overall Number of Participants Analyzed 14
Least Squares Mean (Standard Error)
Unit of Measure: pg/mL
Week 24 Number Analyzed 14 participants
615.00  (100.053)
Week 48 Number Analyzed 11 participants
568.16  (94.011)
Week 96 Number Analyzed 12 participants
726.66  (138.531)
Week 144 Number Analyzed 10 participants
808.12  (109.907)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 24
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline free FGF23.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 48
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline free FGF23.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 96
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline free FGF23.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 144
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline free FGF23.
15.Secondary Outcome
Title Change From Baseline Over Time in Serum Alkaline Phosphatase (ALP)
Hide Description Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline ALP, with compound symmetry covariance structure.
Time Frame Baseline and Weeks 24, 48, 96, and 144
Hide Outcome Measure Data
Hide Analysis Population Description
TIO analysis set participants with available data at each time point.
Arm/Group Title Burosumab
Hide Arm/Group Description:
Participants received burosumab at a starting dose of 0.3 mg/kg administered subcutaneously (SC) every 4 weeks (Q4W). Doses may have been titrated up to a maximum of 2.0 mg/kg every 2 weeks (Q2W) in order to achieve fasting peak serum phosphorus levels within the target range of 2.5 to 4.0 mg/dL.
Overall Number of Participants Analyzed 14
Least Squares Mean (Standard Error)
Unit of Measure: U/L
Week 24 Number Analyzed 14 participants
-1.59  (10.911)
Week 48 Number Analyzed 13 participants
-20.16  (11.685)
Week 96 Number Analyzed 12 participants
-37.94  (12.007)
Week 144 Number Analyzed 10 participants
-60.17  (11.752)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 24
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8840
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline ALP.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 48
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0844
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline ALP.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 96
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0016
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline ALP.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 144
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline ALP.
16.Secondary Outcome
Title Change From Baseline Over Time in 24-hour Urinary Phosphorus
Hide Description Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline 24-hour urinary phosphorus, with compound symmetry covariance structure.
Time Frame Baseline and Weeks 24, 48, 96, and 144
Hide Outcome Measure Data
Hide Analysis Population Description
TIO analysis set participants with available data at each time point.
Arm/Group Title Burosumab
Hide Arm/Group Description:
Participants received burosumab at a starting dose of 0.3 mg/kg administered subcutaneously (SC) every 4 weeks (Q4W). Doses may have been titrated up to a maximum of 2.0 mg/kg every 2 weeks (Q2W) in order to achieve fasting peak serum phosphorus levels within the target range of 2.5 to 4.0 mg/dL.
Overall Number of Participants Analyzed 14
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
Week 24 Number Analyzed 11 participants
-4.45  (8.018)
Week 48 Number Analyzed 13 participants
-2.67  (6.426)
Week 96 Number Analyzed 10 participants
2.40  (6.597)
Week 144 Number Analyzed 8 participants
3.25  (6.971)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 24
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5788
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline 24-hour urinary phosphorus.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 48
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6778
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline 24-hour urinary phosphorus.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 96
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7161
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline 24-hour urinary phosphorus.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 144
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6407
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline 24-hour urinary phosphorus.
17.Secondary Outcome
Title Change From Baseline Over Time in Tubular Reabsorption of Phosphate (TRP)
Hide Description

Tubular reabsorption of phosphate (TRP) is the fraction of filtered phosphorus that is reabsorbed by renal tubules.

Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline TRP, with compound symmetry covariance structure.

Time Frame Baseline and Weeks 24, 48, 96, and 144
Hide Outcome Measure Data
Hide Analysis Population Description
TIO analysis set participants with available data at Baseline and each time point.
Arm/Group Title Burosumab
Hide Arm/Group Description:
Participants received burosumab at a starting dose of 0.3 mg/kg administered subcutaneously (SC) every 4 weeks (Q4W). Doses may have been titrated up to a maximum of 2.0 mg/kg every 2 weeks (Q2W) in order to achieve fasting peak serum phosphorus levels within the target range of 2.5 to 4.0 mg/dL.
Overall Number of Participants Analyzed 13
Least Squares Mean (Standard Error)
Unit of Measure: fraction of phosphorus reabsorbed
Week 24 Number Analyzed 12 participants
0.13  (0.017)
Week 48 Number Analyzed 12 participants
0.13  (0.023)
Week 96 Number Analyzed 11 participants
0.09  (0.030)
Week 144 Number Analyzed 8 participants
0.14  (0.023)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 24
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline TRP.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 48
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline TRP.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 96
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0017
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline TRP.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 144
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline TRP.
18.Secondary Outcome
Title Change From Baseline Over Time in Ratio of Renal Tubular Maximum Phosphate Reabsorption Rate to Glomerular Filtration Rate (TmP/GFR)
Hide Description

TmP/GFR measures renal phosphate reabsorption (the primary mechanism by which FGF23 regulates phosphate homeostasis) by comparing the fractional absorption of phosphate relative to the estimated rate of glomerular filtration.

Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline TmP/GFR, with compound symmetry covariance structure.

Time Frame Baseline and Weeks 24, 48, 96, and 144
Hide Outcome Measure Data
Hide Analysis Population Description
TIO analysis set participants with available data at Baseline and each time point.
Arm/Group Title Burosumab
Hide Arm/Group Description:
Participants received burosumab at a starting dose of 0.3 mg/kg administered subcutaneously (SC) every 4 weeks (Q4W). Doses may have been titrated up to a maximum of 2.0 mg/kg every 2 weeks (Q2W) in order to achieve fasting peak serum phosphorus levels within the target range of 2.5 to 4.0 mg/dL.
Overall Number of Participants Analyzed 13
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
Week 24 Number Analyzed 12 participants
0.79  (0.131)
Week 48 Number Analyzed 12 participants
0.87  (0.136)
Week 96 Number Analyzed 11 participants
0.72  (0.232)
Week 144 Number Analyzed 8 participants
1.05  (0.225)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 24
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline TmP/GFR
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 48
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline TmP/GFR
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 96
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0019
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline TmP/GFR
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 144
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline TmP/GFR
19.Secondary Outcome
Title Change From Baseline Over Time in Fractional Excretion of Phosphorus (FEP)
Hide Description

Fractional excretion of phosphorus (FEP) is the percentage of phosphorus filtered by the kidney that is excreted into urine, calculated as 100% * (2-hour urine phosphorus*serum creatinine)/(2-hour urine creatinine * serum phosphorus).

Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline FEP, with compound symmetry covariance structure.

Time Frame Baseline and Weeks 24, 48, 96, and 144
Hide Outcome Measure Data
Hide Analysis Population Description
TIO analysis set participants with available data at each time point.
Arm/Group Title Burosumab
Hide Arm/Group Description:
Participants received burosumab at a starting dose of 0.3 mg/kg administered subcutaneously (SC) every 4 weeks (Q4W). Doses may have been titrated up to a maximum of 2.0 mg/kg every 2 weeks (Q2W) in order to achieve fasting peak serum phosphorus levels within the target range of 2.5 to 4.0 mg/dL.
Overall Number of Participants Analyzed 14
Least Squares Mean (Standard Error)
Unit of Measure: percentage of phosphorus
Week 24 Number Analyzed 14 participants
-0.13  (0.016)
Week 48 Number Analyzed 13 participants
-0.14  (0.022)
Week 96 Number Analyzed 12 participants
-0.10  (0.027)
Week 144 Number Analyzed 9 participants
-0.15  (0.022)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 24
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline FEP.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 48
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline FEP.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 96
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0004
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline FEP.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 144
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline FEP.
20.Secondary Outcome
Title Change From Baseline Over Time in Bone-Specific Alkaline Phosphatase (BALP)
Hide Description Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline BALP, with compound symmetry covariance structure.
Time Frame Baseline and Weeks 24, 48, 96, and 144
Hide Outcome Measure Data
Hide Analysis Population Description
TIO analysis set participants with available data at each time point.
Arm/Group Title Burosumab
Hide Arm/Group Description:
Participants received burosumab at a starting dose of 0.3 mg/kg administered subcutaneously (SC) every 4 weeks (Q4W). Doses may have been titrated up to a maximum of 2.0 mg/kg every 2 weeks (Q2W) in order to achieve fasting peak serum phosphorus levels within the target range of 2.5 to 4.0 mg/dL.
Overall Number of Participants Analyzed 14
Least Squares Mean (Standard Error)
Unit of Measure: μg/L
Week 24 Number Analyzed 14 participants
-0.84  (4.807)
Week 48 Number Analyzed 12 participants
-9.42  (4.670)
Week 96 Number Analyzed 12 participants
-15.50  (4.245)
Week 144 Number Analyzed 10 participants
-20.31  (4.716)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 24
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8617
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline BALP.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 48
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0436
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline BALP.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 96
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0003
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline BALP.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 144
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline BALP.
21.Secondary Outcome
Title Percent Change From Baseline Over Time in BALP
Hide Description Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline BALP, with compound symmetry covariance structure.
Time Frame Baseline and Weeks 24, 48, 96, and 144
Hide Outcome Measure Data
Hide Analysis Population Description
TIO analysis set participants with available data at each time point.
Arm/Group Title Burosumab
Hide Arm/Group Description:
Participants received burosumab at a starting dose of 0.3 mg/kg administered subcutaneously (SC) every 4 weeks (Q4W). Doses may have been titrated up to a maximum of 2.0 mg/kg every 2 weeks (Q2W) in order to achieve fasting peak serum phosphorus levels within the target range of 2.5 to 4.0 mg/dL.
Overall Number of Participants Analyzed 14
Least Squares Mean (Standard Error)
Unit of Measure: percent change
Week 24 Number Analyzed 14 participants
5.46  (13.088)
Week 48 Number Analyzed 12 participants
-16.12  (8.277)
Week 96 Number Analyzed 12 participants
-30.02  (8.608)
Week 144 Number Analyzed 10 participants
-36.49  (10.296)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 24
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6764
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline BALP.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 48
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0514
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline BALP.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 96
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0005
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline BALP.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 144
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0004
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline BALP.
22.Secondary Outcome
Title Change From Baseline Over Time in Carboxy Terminal Cross-Linked Telopeptide of Type 1 Collagen (CTx)
Hide Description Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline CTx, with compound symmetry covariance structure.
Time Frame Baseline and Weeks 24, 48, 96, and 144
Hide Outcome Measure Data
Hide Analysis Population Description
TIO analysis set participants with available data at each time point
Arm/Group Title Burosumab
Hide Arm/Group Description:
Participants received burosumab at a starting dose of 0.3 mg/kg administered subcutaneously (SC) every 4 weeks (Q4W). Doses may have been titrated up to a maximum of 2.0 mg/kg every 2 weeks (Q2W) in order to achieve fasting peak serum phosphorus levels within the target range of 2.5 to 4.0 mg/dL.
Overall Number of Participants Analyzed 14
Least Squares Mean (Standard Error)
Unit of Measure: pg/mL
Week 24 Number Analyzed 14 participants
219.42  (113.720)
Week 48 Number Analyzed 13 participants
101.10  (80.308)
Week 96 Number Analyzed 12 participants
12.89  (68.593)
Week 144 Number Analyzed 10 participants
-34.01  (52.812)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 24
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0537
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline CTx.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 48
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2081
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline CTx.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 96
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8509
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline CTx.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 144
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5195
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline CTx.
23.Secondary Outcome
Title Percent Change From Baseline Over Time in CTx
Hide Description Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline CTx, with compound symmetry covariance structure.
Time Frame Baseline and Weeks 24, 48, 96, and 144
Hide Outcome Measure Data
Hide Analysis Population Description
TIO analysis set participants with available data at each time point.
Arm/Group Title Burosumab
Hide Arm/Group Description:
Participants received burosumab at a starting dose of 0.3 mg/kg administered subcutaneously (SC) every 4 weeks (Q4W). Doses may have been titrated up to a maximum of 2.0 mg/kg every 2 weeks (Q2W) in order to achieve fasting peak serum phosphorus levels within the target range of 2.5 to 4.0 mg/dL.
Overall Number of Participants Analyzed 14
Least Squares Mean (Standard Error)
Unit of Measure: percent change
Week 24 Number Analyzed 14 participants
34.80  (14.377)
Week 48 Number Analyzed 13 participants
31.05  (20.220)
Week 96 Number Analyzed 12 participants
12.87  (12.020)
Week 144 Number Analyzed 10 participants
8.55  (10.213)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 24
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0155
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline CTx.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 48
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1246
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline CTx.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 96
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2844
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline CTx.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 144
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4028
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline CTx.
24.Secondary Outcome
Title Change From Baseline Over Time in Procollagen Type 1 N-Propeptide (P1NP)
Hide Description Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline P1NP, with compound symmetry covariance structure.
Time Frame Baseline and Weeks 24, 48, 96, and 144
Hide Outcome Measure Data
Hide Analysis Population Description
TIO analysis set participants with available data at each time point.
Arm/Group Title Burosumab
Hide Arm/Group Description:
Participants received burosumab at a starting dose of 0.3 mg/kg administered subcutaneously (SC) every 4 weeks (Q4W). Doses may have been titrated up to a maximum of 2.0 mg/kg every 2 weeks (Q2W) in order to achieve fasting peak serum phosphorus levels within the target range of 2.5 to 4.0 mg/dL.
Overall Number of Participants Analyzed 14
Least Squares Mean (Standard Error)
Unit of Measure: ng/mL
Week 24 Number Analyzed 14 participants
33.63  (10.674)
Week 48 Number Analyzed 13 participants
7.15  (6.891)
Week 96 Number Analyzed 12 participants
10.92  (15.528)
Week 144 Number Analyzed 10 participants
-1.63  (6.758)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 24
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0016
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline P1NP.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 48
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2994
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline P1NP.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 96
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4818
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline P1NP.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 144
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8090
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline P1NP.
25.Secondary Outcome
Title Percent Change From Baseline Over Time in P1NP
Hide Description Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline P1NP, with compound symmetry covariance structure.
Time Frame Baseline and Weeks 24, 48, 96, and 144
Hide Outcome Measure Data
Hide Analysis Population Description
TIO analysis set participants with available data at each time point.
Arm/Group Title Burosumab
Hide Arm/Group Description:
Participants received burosumab at a starting dose of 0.3 mg/kg administered subcutaneously (SC) every 4 weeks (Q4W). Doses may have been titrated up to a maximum of 2.0 mg/kg every 2 weeks (Q2W) in order to achieve fasting peak serum phosphorus levels within the target range of 2.5 to 4.0 mg/dL.
Overall Number of Participants Analyzed 14
Least Squares Mean (Standard Error)
Unit of Measure: percent change
Week 24 Number Analyzed 14 participants
53.04  (16.318)
Week 48 Number Analyzed 13 participants
15.23  (10.551)
Week 96 Number Analyzed 12 participants
17.87  (20.052)
Week 144 Number Analyzed 10 participants
10.56  (10.029)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 24
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0012
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline P1NP.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 48
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1488
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline P1NP.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 96
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3727
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline P1NP.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 144
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2924
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline P1NP.
26.Secondary Outcome
Title Change From Baseline Over Time in Osteocalcin
Hide Description Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline osteocalcin, with compound symmetry covariance structure.
Time Frame Baseline and Weeks 24, 48, 96, and 144
Hide Outcome Measure Data
Hide Analysis Population Description
TIO analysis set with available data at each time point
Arm/Group Title Burosumab
Hide Arm/Group Description:
Participants received burosumab at a starting dose of 0.3 mg/kg administered subcutaneously (SC) every 4 weeks (Q4W). Doses may have been titrated up to a maximum of 2.0 mg/kg every 2 weeks (Q2W) in order to achieve fasting peak serum phosphorus levels within the target range of 2.5 to 4.0 mg/dL.
Overall Number of Participants Analyzed 14
Least Squares Mean (Standard Error)
Unit of Measure: ng/mL
Week 24 Number Analyzed 14 participants
9.59  (4.251)
Week 48 Number Analyzed 11 participants
2.30  (3.147)
Week 96 Number Analyzed 12 participants
-0.51  (3.276)
Week 144 Number Analyzed 9 participants
-1.24  (2.847)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 24
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0241
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline osteocalcin.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 48
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4653
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline osteocalcin.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 96
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8755
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline osteocalcin.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 144
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6633
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline osteocalcin.
27.Secondary Outcome
Title Percent Change From Baseline Over Time in Osteocalcin
Hide Description Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline osteocalcin, with compound symmetry covariance structure.
Time Frame Baseline and Weeks 24, 48, 96, and 144
Hide Outcome Measure Data
Hide Analysis Population Description
TIO analysis set with available data at each time point
Arm/Group Title Burosumab
Hide Arm/Group Description:
Participants received burosumab at a starting dose of 0.3 mg/kg administered subcutaneously (SC) every 4 weeks (Q4W). Doses may have been titrated up to a maximum of 2.0 mg/kg every 2 weeks (Q2W) in order to achieve fasting peak serum phosphorus levels within the target range of 2.5 to 4.0 mg/dL.
Overall Number of Participants Analyzed 14
Least Squares Mean (Standard Error)
Unit of Measure: percent change
Week 24 Number Analyzed 14 participants
41.60  (12.178)
Week 48 Number Analyzed 11 participants
17.87  (14.357)
Week 96 Number Analyzed 12 participants
14.89  (14.034)
Week 144 Number Analyzed 9 participants
12.57  (8.647)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 24
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0006
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline osteocalcin.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 48
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2133
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline osteocalcin.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 96
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2888
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline osteocalcin.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 144
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1459
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline osteocalcin.
28.Secondary Outcome
Title Change From Baseline Over Time in Hand-Held Dynamometry (HHD) Elbow Measurements
Hide Description

To assess muscle strength, hand-held dynamometry was conducted using a standardized technique. Bilateral strength (defined as the average of the left and the right scores, measured in kilograms) of the elbow flexors and extensors was measured by the maximum voluntary isometric contraction against a dynamometer.

Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline strength measurements, with compound symmetry covariance structure.

Time Frame Baseline and Weeks 24 and 48
Hide Outcome Measure Data
Hide Analysis Population Description
TIO analysis set with available elbow dynamometry measurements at Baseline and each time point.
Arm/Group Title Elbow Flexion Elbow Extension
Hide Arm/Group Description:
Elbow flexor (biceps brachii, brachioradialis, and brachialis) muscle strength was measured in participants who received burosumab at a starting dose of 0.3 mg/kg administered subcutaneously Q4W. Doses may have been titrated up to a maximum of 2.0 mg/kg Q2W.
Elbow extensor (triceps brachii and anconeus) muscle strength was measured in participants who received burosumab at a starting dose of 0.3 mg/kg administered subcutaneously Q4W. Doses may have been titrated up to a maximum of 2.0 mg/kg Q2W.
Overall Number of Participants Analyzed 9 9
Least Squares Mean (Standard Error)
Unit of Measure: kg
Week 24 Number Analyzed 8 participants 8 participants
0.12  (0.512) 0.75  (0.704)
Week 48 Number Analyzed 8 participants 8 participants
0.32  (0.753) 1.06  (0.760)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Elbow Flexion
Comments Week 24
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8209
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline measurement.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Elbow Extension
Comments Week 24
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2851
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline measurement.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Elbow Flexion
Comments Week 48
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6689
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline measurement.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Elbow Extension
Comments Week 48
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1612
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline measurement.
29.Secondary Outcome
Title Change From Baseline Over Time in Hand-Held Dynamometry (HHD) Knee Measurements
Hide Description

To assess muscle strength, hand-held dynamometry was conducted using a standardized technique. Bilateral strength (defined as the average of the left and the right scores, measured in kilograms) of the knee flexors and extensors was measured by the maximum voluntary isometric contraction against a dynamometer.

Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline strength measurements, with compound symmetry covariance structure.

Time Frame Baseline and Weeks 24 and 48
Hide Outcome Measure Data
Hide Analysis Population Description
TIO analysis set with available knee dynamometry measurements at Baseline and each time point.
Arm/Group Title Knee Flexion Knee Extension
Hide Arm/Group Description:
Elbow flexor (hamstring) muscle strength was measured in participants who received burosumab at a starting dose of 0.3 mg/kg administered subcutaneously Q4W. Doses may have been titrated up to a maximum of 2.0 mg/kg Q2W.
Knee extensor (quadriceps) muscle strength was measured in participants who received burosumab at a starting dose of 0.3 mg/kg administered subcutaneously Q4W. Doses may have been titrated up to a maximum of 2.0 mg/kg Q2W.
Overall Number of Participants Analyzed 10 10
Least Squares Mean (Standard Error)
Unit of Measure: kg
Week 24 Number Analyzed 9 participants 9 participants
0.94  (1.139) -0.89  (1.573)
Week 48 Number Analyzed 9 participants 9 participants
1.21  (1.297) 0.75  (1.158)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Knee Flexion
Comments Week 24
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4093
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline measurement.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Knee Extension
Comments Week 24
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5720
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline measurement.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Knee Flexion
Comments Week 48
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3501
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline measurement.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Knee Extension
Comments Week 48
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5172
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline measurement.
30.Secondary Outcome
Title Change From Baseline Over Time in Sit-to-Stand (STS) Test
Hide Description

The STS test measures lower extremity strength and mobility as a participant moves repeatedly from a seated position to standing. This study used a modified STS test that allowed participants to use the arms of the chair to help them stand and sit if necessary. The number of sit-to-stand repetitions performed in a 30-second period was recorded.

Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline measurement, with compound symmetry covariance structure.

Time Frame Baseline and Weeks 24 and 48
Hide Outcome Measure Data
Hide Analysis Population Description
TIO analysis set with available STS data at each time point; One participant did not perform the test at Baseline as it was not included in the original protocol, and 2 participants were unable to perform the test due to underlying medical issues.
Arm/Group Title Burosumab
Hide Arm/Group Description:
Participants received burosumab at a starting dose of 0.3 mg/kg administered subcutaneously (SC) every 4 weeks (Q4W). Doses may have been titrated up to a maximum of 2.0 mg/kg every 2 weeks (Q2W) in order to achieve fasting peak serum phosphorus levels within the target range of 2.5 to 4.0 mg/dL.
Overall Number of Participants Analyzed 11
Least Squares Mean (Standard Error)
Unit of Measure: sit-to-stand repetitions
Week 24 Number Analyzed 10 participants
1.5  (0.54)
Week 48 Number Analyzed 10 participants
1.6  (0.50)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 24
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0046
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline STS measurement.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 48
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0012
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline STS measurement.
31.Secondary Outcome
Title Change From Baseline Over Time in Weighted Arm Lift (WAL) Test
Hide Description

The Weighted arm lift (WAL) test assesses upper extremity strength, mobility and reaching ability. The test was administered bilaterally to determine the number of times the participant could raise a 1 kg weight above the head in a 30-second period. The number of repetitions completed with each arm was recorded.

Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline WAL measurements, with compound symmetry covariance structure.

Time Frame Baseline and Weeks 24 and 48
Hide Outcome Measure Data
Hide Analysis Population Description
TIO analysis set with available WAL measurements at Baseline and each time point.
Arm/Group Title Left Upper Extremity Right Upper Extremity
Hide Arm/Group Description:
Left arm lifts in participants who received burosumab at a starting dose of 0.3 mg/kg administered subcutaneously Q4W, titrated up to a maximum of 2.0 mg/kg Q2W.
Right arm lifts in participants who received burosumab at a starting dose of 0.3 mg/kg administered subcutaneously Q4W, titrated up to a maximum of 2.0 mg/kg Q2W.
Overall Number of Participants Analyzed 8 9
Least Squares Mean (Standard Error)
Unit of Measure: arm lifts
Week 24 -0.5  (1.09) 0.6  (0.89)
Week 48 0.1  (1.25) 1.7  (1.17)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Left Upper Extremity
Comments Week 24
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6475
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline measurement.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Right Upper Extremity
Comments Week 24
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5319
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline measurement.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Left Upper Extremity
Comments Week 48
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9206
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline measurement.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Right Upper Extremity
Comments Week 48
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1530
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline measurement.
32.Secondary Outcome
Title Change From Baseline Over Time in Six-Minute Walk Test (6MWT)
Hide Description

The 6MWT is a commonly used measure of mobility and was conducted in accordance with general principles set forth in the American Thoracic Society guidelines (ATS 2002). Participants were instructed to walk the length of a pre-measured course for 6 consecutive minutes (assistive devices could be used). The total distance walked at the end of 6 minutes was recorded in meters.

Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline 6MWT measurement, with compound symmetry covariance structure.

Time Frame Baseline and Weeks 24 and 48
Hide Outcome Measure Data
Hide Analysis Population Description
TIO analysis set with available 6MWT measurements at Baseline and each time point. Six participants did not perform the test at Baseline as it was not included in the original protocol, and 2 participants were unable to perform the test due to underlying medical issues.
Arm/Group Title Burosumab
Hide Arm/Group Description:
Participants received burosumab at a starting dose of 0.3 mg/kg administered subcutaneously (SC) every 4 weeks (Q4W). Doses may have been titrated up to a maximum of 2.0 mg/kg every 2 weeks (Q2W) in order to achieve fasting peak serum phosphorus levels within the target range of 2.5 to 4.0 mg/dL.
Overall Number of Participants Analyzed 6
Least Squares Mean (Standard Error)
Unit of Measure: meters
Week 24 19.5  (15.64)
Week 48 25.5  (16.58)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 24
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2125
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline measurement.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 48
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1241
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline measurement.
33.Secondary Outcome
Title Change From Baseline Over Time in Brief Pain Inventory (BPI) Worst Pain Score
Hide Description

The Brief Pain Inventory (BPI) is a self-reported, pain-specific questionnaire with a recall period of 24 hours. Worst pain is defined as the answer to Question 3, in which participants rated their pain at its worst in the last 24 hours on a scale from 0 (no pain) to 10 (pain as bad as you can imagine).

A negative change from Baseline score indicates improvement.

Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline BPI measurement, with compound symmetry covariance structure.

Time Frame Baseline and Weeks 24, 48, 96, and 144
Hide Outcome Measure Data
Hide Analysis Population Description
TIO analysis set participants with available data at each time point
Arm/Group Title Burosumab
Hide Arm/Group Description:
Participants received burosumab at a starting dose of 0.3 mg/kg administered subcutaneously (SC) every 4 weeks (Q4W). Doses may have been titrated up to a maximum of 2.0 mg/kg every 2 weeks (Q2W) in order to achieve fasting peak serum phosphorus levels within the target range of 2.5 to 4.0 mg/dL.
Overall Number of Participants Analyzed 14
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
Week 24 Number Analyzed 14 participants
-0.55  (0.693)
Week 48 Number Analyzed 13 participants
-0.90  (0.734)
Week 96 Number Analyzed 12 participants
-0.70  (0.383)
Week 144 Number Analyzed 10 participants
-0.98  (0.643)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 24
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4284
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline measurement.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 48
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2193
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline measurement.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 96
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0663
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline measurement.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 144
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1268
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline measurement.
34.Secondary Outcome
Title Change From Baseline Over Time in Brief Pain Inventory (BPI) Pain Severity Score
Hide Description

The Brief Pain Inventory (BPI) is a self-reported, pain-specific questionnaire with a recall period of 24 hours.

Pain severity is defined as the average of 4 questions (Questions 3 through 6) assessing worst pain, least pain, average pain, and pain right now, rated on a scale from 0 (no pain) to 10 (pain as bad as you can imagine). Mild pain is defined as a score of 1 to 4, moderate pain is defined as a score of 5 to 6, and severe pain is defined as a score of 7 to 10. A negative change from Baseline score indicates improvement.

Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline BPI measurement, with compound symmetry covariance structure.

Time Frame Baseline and Weeks 24, 48, 96, and 144
Hide Outcome Measure Data
Hide Analysis Population Description
TIO analysis set participants with available data at each time point
Arm/Group Title Burosumab
Hide Arm/Group Description:
Participants received burosumab at a starting dose of 0.3 mg/kg administered subcutaneously (SC) every 4 weeks (Q4W). Doses may have been titrated up to a maximum of 2.0 mg/kg every 2 weeks (Q2W) in order to achieve fasting peak serum phosphorus levels within the target range of 2.5 to 4.0 mg/dL.
Overall Number of Participants Analyzed 14
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
Week 24 Number Analyzed 14 participants
-0.49  (0.622)
Week 48 Number Analyzed 13 participants
-0.85  (0.665)
Week 96 Number Analyzed 12 participants
-0.60  (0.379)
Week 144 Number Analyzed 10 participants
-0.94  (0.410)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 24
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4299
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline measurement.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 48
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2031
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline measurement.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 96
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1151
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline measurement.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 144
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0217
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline measurement.
35.Secondary Outcome
Title Change From Baseline Over Time in Brief Pain Inventory (BPI) Pain Interference Score
Hide Description

The Brief Pain Inventory (BPI) is a self-reported, pain-specific questionnaire with a recall period of 24 hours.

Pain interference is defined as the average of 7 questions (9A through 9G) regarding the extent to which pain interfered with daily activities, including general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life in the last 24 hours, rated on a scale from 0 (does not interfere) to 10 (completely interferes).

A negative change from Baseline score indicates improvement. Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline BPI measurement, with compound symmetry covariance structure.

Time Frame Baseline and Weeks 24, 48, 96, and 144
Hide Outcome Measure Data
Hide Analysis Population Description
TIO analysis set participants with available data at each time point
Arm/Group Title Burosumab
Hide Arm/Group Description:
Participants received burosumab at a starting dose of 0.3 mg/kg administered subcutaneously (SC) every 4 weeks (Q4W). Doses may have been titrated up to a maximum of 2.0 mg/kg every 2 weeks (Q2W) in order to achieve fasting peak serum phosphorus levels within the target range of 2.5 to 4.0 mg/dL.
Overall Number of Participants Analyzed 14
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
Week 24 Number Analyzed 14 participants
-1.09  (0.659)
Week 48 Number Analyzed 13 participants
-1.04  (0.800)
Week 96 Number Analyzed 12 participants
-1.04  (0.538)
Week 144 Number Analyzed 10 participants
-1.54  (0.616)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 24
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0987
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline measurement.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 48
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1942
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline measurement.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 96
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0538
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline measurement.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 144
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0126
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline measurement.
36.Secondary Outcome
Title Change From Baseline Over Time in Brief Fatigue Inventory (BFI) Worst Fatigue Score
Hide Description

The Brief Fatigue Inventory (BFI) is a self-reported questionnaire consisting of 9 items related to fatigue that are rated on a 0 to 10 numerical rating scale with a recall period of 24 hours.

Worst fatigue is defined as the answer to Question 3 in which participants rated their fatigue at its worst in the last 24 hours on a scale from 0 (no fatigue) to 10 (as bad as you can imagine).

A negative change from Baseline score indicates improvement. Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline BFI measurement, with compound symmetry covariance structure.

Time Frame Baseline and Weeks 24, 48, 96, and 144
Hide Outcome Measure Data
Hide Analysis Population Description
TIO analysis set participants with available data at Baseline and each time point.
Arm/Group Title Burosumab
Hide Arm/Group Description:
Participants received burosumab at a starting dose of 0.3 mg/kg administered subcutaneously (SC) every 4 weeks (Q4W). Doses may have been titrated up to a maximum of 2.0 mg/kg every 2 weeks (Q2W) in order to achieve fasting peak serum phosphorus levels within the target range of 2.5 to 4.0 mg/dL.
Overall Number of Participants Analyzed 13
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
Week 24 Number Analyzed 13 participants
-1.24  (0.518)
Week 48 Number Analyzed 12 participants
-0.84  (0.843)
Week 96 Number Analyzed 11 participants
-1.03  (0.492)
Week 144 Number Analyzed 13 participants
-0.83  (0.598)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 24
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0166
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline measurement.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 48
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3177
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline measurement.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 96
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0358
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline measurement.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 144
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1649
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline measurement.
37.Secondary Outcome
Title Change From Baseline Over Time in Brief Fatigue Inventory (BFI) Fatigue Severity Score
Hide Description

The Brief Fatigue Inventory (BFI) is a self-reported questionnaire consisting of 9 items related to fatigue that are rated on a 0 to 10 numerical rating scale with a recall period of 24 hours.

Fatigue severity is defined as the average of 3 questions (Questions 1 through 3) assessing fatigue right now, usual level of fatigue, and worst fatigue, rated on a scale from 0 (no fatigue) to 10 (as bad as you can imagine).

A negative change from Baseline score indicates improvement.

Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline BFI measurement, with compound symmetry covariance structure.

Time Frame Baseline and Weeks 24, 48, 96, and 144
Hide Outcome Measure Data
Hide Analysis Population Description
TIO analysis set participants with available data at Baseline and each time point.
Arm/Group Title Burosumab
Hide Arm/Group Description:
Participants received burosumab at a starting dose of 0.3 mg/kg administered subcutaneously (SC) every 4 weeks (Q4W). Doses may have been titrated up to a maximum of 2.0 mg/kg every 2 weeks (Q2W) in order to achieve fasting peak serum phosphorus levels within the target range of 2.5 to 4.0 mg/dL.
Overall Number of Participants Analyzed 13
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
Week 24 Number Analyzed 13 participants
-1.45  (0.524)
Week 48 Number Analyzed 12 participants
-1.31  (0.558)
Week 96 Number Analyzed 11 participants
-1.58  (0.426)
Week 144 Number Analyzed 9 participants
-1.22  (0.614)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 24
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0057
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline measurement.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 48
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0192
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline measurement.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 96
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline measurement.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 144
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0462
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline measurement.
38.Secondary Outcome
Title Change From Baseline Over Time in Brief Fatigue Inventory (BFI) Fatigue Interference Score
Hide Description

The Brief Fatigue Inventory (BFI) is a self-reported questionnaire consisting of 9 items related to fatigue that are rated on a 0 to 10 numerical rating scale with a recall period of 24 hours.

The fatigue interference score is defined as the average of 6 questions (Questions 4A through 4F) regarding the extent to which fatigue interfered with daily activities, including general activity, mood, walking ability, work, relations with others, and enjoyment of life in the last 24 hours, rated on a scale from 0 (does not interfere) to 10 (completely interferes).

A negative change from Baseline score indicates improvement. Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline BFI measurement, with compound symmetry covariance structure.

Time Frame Baseline and Weeks 24, 48, 96, and 144
Hide Outcome Measure Data
Hide Analysis Population Description
TIO analysis set participants with available data at Baseline and each time point.
Arm/Group Title Burosumab
Hide Arm/Group Description:
Participants received burosumab at a starting dose of 0.3 mg/kg administered subcutaneously (SC) every 4 weeks (Q4W). Doses may have been titrated up to a maximum of 2.0 mg/kg every 2 weeks (Q2W) in order to achieve fasting peak serum phosphorus levels within the target range of 2.5 to 4.0 mg/dL.
Overall Number of Participants Analyzed 13
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
Week 24 Number Analyzed 13 participants
-1.56  (0.652)
Week 48 Number Analyzed 12 participants
-1.85  (0.666)
Week 96 Number Analyzed 11 participants
-1.94  (0.470)
Week 144 Number Analyzed 9 participants
-1.85  (0.495)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 24
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0167
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline measurement.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 48
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0055
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline measurement.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 96
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline measurement.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 144
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline measurement.
39.Secondary Outcome
Title Change From Baseline Over Time in Brief Fatigue Inventory (BFI) Global Fatigue Score
Hide Description

The Brief Fatigue Inventory (BFI) is a self-reported questionnaire consisting of 9 items related to fatigue that are rated on a 0 to 10 numerical rating scale with a recall period of 24 hours. The first 3 questions measure fatigue severity and the next 6 questions assess the impact of fatigue on daily activities.

The global fatigue score is defined as the average of all 9 questions on the BFI including severity and interference, and ranges from from 0 to 10, where higher scores correspond to greater levels of fatigue.

A negative change from Baseline score indicates improvement. Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline BFI measurement, with compound symmetry covariance structure.

Time Frame Baseline and Weeks 24, 48, 96, and 144
Hide Outcome Measure Data
Hide Analysis Population Description
TIO analysis set participants with available data at Baseline and each time point.
Arm/Group Title Burosumab
Hide Arm/Group Description:
Participants received burosumab at a starting dose of 0.3 mg/kg administered subcutaneously (SC) every 4 weeks (Q4W). Doses may have been titrated up to a maximum of 2.0 mg/kg every 2 weeks (Q2W) in order to achieve fasting peak serum phosphorus levels within the target range of 2.5 to 4.0 mg/dL.
Overall Number of Participants Analyzed 13
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
Week 24 Number Analyzed 13 participants
-1.53  (0.561)
Week 48 Number Analyzed 12 participants
-1.64  (0.559)
Week 96 Number Analyzed 11 participants
-1.80  (0.439)
Week 144 Number Analyzed 9 participants
-1.62  (0.453)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 24
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0065
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline measurement.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 48
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0034
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline measurement.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 96
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline measurement.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 144
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0003
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline measurement.
40.Secondary Outcome
Title Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Physical Component Summary Score
Hide Description

The SF-36 v2 is a self-administered questionnaire that measures the impact of disease on overall quality of life during the past 4 weeks. The SF-36 consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health).

The physical component summary score (PCS) is a weighted combination of the 8 subscales with positive weighting for physical functioning, role-physical, bodily pain, and general health. The PCS was calculated using norm-based scoring so that 50 is the average score and the standard deviation equals 10. Higher scores are associated with better functioning/quality of life; a positive change from Baseline score indicates an improvement.

LS means and SEs were estimated from a GEE model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline SF-36, with compound symmetry covariance struct

Time Frame Baseline and Weeks 24, 48, 96, and 144
Hide Outcome Measure Data
Hide Analysis Population Description
TIO analysis set participants with available data at each time point
Arm/Group Title Burosumab
Hide Arm/Group Description:
Participants received burosumab at a starting dose of 0.3 mg/kg administered subcutaneously (SC) every 4 weeks (Q4W). Doses may have been titrated up to a maximum of 2.0 mg/kg every 2 weeks (Q2W) in order to achieve fasting peak serum phosphorus levels within the target range of 2.5 to 4.0 mg/dL.
Overall Number of Participants Analyzed 14
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
Week 24 Number Analyzed 14 participants
3.893  (1.4351)
Week 48 Number Analyzed 13 participants
5.576  (2.3694)
Week 96 Number Analyzed 12 participants
2.874  (1.3530)
Week 144 Number Analyzed 9 participants
8.586  (2.6370)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 24
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0067
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline measurement.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 48
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0186
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline measurement.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 96
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0336
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline measurement.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 144
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0011
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline measurement.
41.Secondary Outcome
Title Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Physical Functioning Domain Score
Hide Description

The SF-36 v2 is a self-administered questionnaire that measures the impact of disease on overall quality of life during the past 4 weeks. The SF-36 consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health).

The physical functioning (PF) domain includes 10 questions that assess limitations in physical activities because of health problems. The PF domain score was calculated using norm-based scoring so that 50 is the average score and the standard deviation equals 10. Higher scores are associated with better functioning/quality of life; a positive change from Baseline score indicates an improvement.

LS means and SEs were estimated from a GEE model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline SF-36, with compound symmetry covariance structure.

Time Frame Baseline and Weeks 24, 48, 96, and 144
Hide Outcome Measure Data
Hide Analysis Population Description
TIO analysis set participants with available data at each time point
Arm/Group Title Burosumab
Hide Arm/Group Description:
Participants received burosumab at a starting dose of 0.3 mg/kg administered subcutaneously (SC) every 4 weeks (Q4W). Doses may have been titrated up to a maximum of 2.0 mg/kg every 2 weeks (Q2W) in order to achieve fasting peak serum phosphorus levels within the target range of 2.5 to 4.0 mg/dL.
Overall Number of Participants Analyzed 14
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
Week 24 Number Analyzed 14 participants
2.486  (1.6039)
Week 48 Number Analyzed 13 participants
2.819  (2.5121)
Week 96 Number Analyzed 12 participants
3.960  (1.5919)
Week 144 Number Analyzed 10 participants
8.202  (2.1525)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 24
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1211
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline measurement.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 48
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2618
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline measurement.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 96
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0129
Comments [Not Specified]
Method GEE model
Comments Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline measurement.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Burosumab
Comments Week 144
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]