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

• ClinicalTrials.gov Identifier: NCT02304367
• Recruitment Status: Completed
• First Posted: December 1, 2014
• Results First Posted: July 30, 2020
• Last Update Posted: April 18, 2023
• Sponsor: Kyowa Kirin, Inc.
• Information provided by (Responsible Party): Kyowa Kirin, 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

Participant Flow

Recruitment Details	This study was conducted at 8 centers in the United States, and enrolled adults with tumor-induced osteomalacia (TIO), epidermal nevus syndrome (ENS)-associated osteomalacia, or x-linked hypophosphatemia (XLH).
Pre-assignment Details

Arm/Group Title	Burosumab
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 [1]
Completed 48 Weeks of Study Drug	16
Completed 144 Weeks of Study Drug	12
Completed	9
Not Completed	8
Reason Not Completed
Lack of Response to Bruosumab	1
Sponsor Decision	3
Death	2
Physician Decision	1
Unable to Return Due to Corona Virus Pandemic	1
[1] 14 participants with TIO; 1 participant with ENS; 2 participants with XLH

Baseline Characteristics

Arm/Group Title		Burosumab
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
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

Outcome Measures

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
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])

Outcome Measure Data

Analysis Population Description

TIO analysis set: includes participants with TIO who received at least 1 dose of burosumab during the study.

Arm/Group Title	Burosumab
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
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

Outcome Measure Data

Analysis Population Description

TIO bone biopsy analysis set

Arm/Group Title	Burosumab
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)

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)
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

Outcome Measure Data

Analysis Population Description

TIO biopsy analysis set

Arm/Group Title	Burosumab
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)

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)
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

Outcome Measure Data

Analysis Population Description

TIO bone biopsy analysis set

Arm/Group Title	Burosumab
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)

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)
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

Outcome Measure Data

Analysis Population Description

TIO biopsy analysis set for whom Mlt could be calculated or imputed

Arm/Group Title	Burosumab
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)

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
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)

Outcome Measure Data

Analysis Population Description

TIO analysis set

Arm/Group Title	Burosumab
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
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)

Outcome Measure Data

Analysis Population Description

TIO analysis set

Arm/Group Title	Burosumab
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
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)

Outcome Measure Data

Analysis Population Description

TIO analysis set

Arm/Group Title	Burosumab
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
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

Outcome Measure Data

Analysis Population Description

TIO analysis set

Arm/Group Title	Burosumab
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
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

Outcome Measure Data

Analysis Population Description

TIO analysis set

Arm/Group Title	Burosumab
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
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

Outcome Measure Data

Analysis Population Description

TIO analysis set

Arm/Group Title	Burosumab
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
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, 144, 168, 192, 216, and 240

Outcome Measure Data

Analysis Population Description

TIO analysis set participants with available data at Baseline and each time point.

Arm/Group Title		Burosumab
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
		9.90 (4.10)
Week 48	Number Analyzed	10 participants
		10.49 (4.82)
Week 96	Number Analyzed	9 participants
		4.28 (3.80)
Week 144	Number Analyzed	9 participants
		3.15 (3.34)
Week 168	Number Analyzed	8 participants
		4.91 (3.94)
Week 192	Number Analyzed	8 participants
		0.67 (4.19)
Week 216	Number Analyzed	5 participants
		9.78 (3.04)
Week 240	Number Analyzed	5 participants
		6.56 (3.19)

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	0.016
	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.

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	0.030
	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.

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	0.259
	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.

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	0.346
	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.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Burosumab
	Comments	Week 168
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.213
	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.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Burosumab
	Comments	Week 192
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.873
	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.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Burosumab
	Comments	Week 216
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.001
	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.

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Burosumab
	Comments	Week 240
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.040
	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
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, 144, 168, 192, 216, and 240

Outcome Measure Data

Analysis Population Description

TIO analysis set with available data at each time point

Arm/Group Title		Burosumab
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
		246335.35 (61089.98)
Week 48	Number Analyzed	10 participants
		180511.74 (33529.14)
Week 96	Number Analyzed	11 participants
		331267.40 (103226.37)
Week 144	Number Analyzed	11 participants
		275758.40 (102349.79)
Week 168	Number Analyzed	10 participants
		185769.23 (65423.93)
Week 192	Number Analyzed	9 participants
		234826.20 (82198.24)
Week 216	Number Analyzed	7 participants
		254359.96 (81615.67)
Week 240	Number Analyzed	7 participants
		210119.10 (76610.50)

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.

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.

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	0.001
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline total FGF23.

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	0.007
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline total FGF23.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Burosumab
	Comments	Week 168
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.005
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline total FGF23.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Burosumab
	Comments	Week 192
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.004
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline total FGF23.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Burosumab
	Comments	Week 216
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.002
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline total FGF23.

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Burosumab
	Comments	Week 240
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.006
	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
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, 144, 168, 192, 216, and 240

Outcome Measure Data

Analysis Population Description

TIO analysis set with available data at each time point

Arm/Group Title		Burosumab
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
		624.91 (101.89)
Week 48	Number Analyzed	11 participants
		578.07 (95.37)
Week 96	Number Analyzed	12 participants
		736.59 (139.18)
Week 144	Number Analyzed	11 participants
		801.69 (103.41)
Week 168	Number Analyzed	10 participants
		787.16 (95.52)
Week 192	Number Analyzed	9 participants
		717.71 (115.99)
Week 216	Number Analyzed	7 participants
		704.87 (115.30)
Week 240	Number Analyzed	7 participants
		625.16 (125.93)

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	< 0.001
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline free FGF23.

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	< 0.001
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline free FGF23.

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	<0.001
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline free FGF23.

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	< 0.001
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline free FGF23.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Burosumab
	Comments	Week 168
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline free FGF23.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Burosumab
	Comments	Week 192
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline free FGF23.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Burosumab
	Comments	Week 216
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline free FGF23.

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Burosumab
	Comments	Week 240
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.001
	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 24-hour Urinary Phosphorus
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, 144, 168, 192, 216, and 240

Outcome Measure Data

Analysis Population Description

TIO analysis set participants with available data at each time point.

Arm/Group Title		Burosumab
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
		-3.66 (8.28)
Week 48	Number Analyzed	13 participants
		3.59 (6.73)
Week 96	Number Analyzed	9 participants
		3.22 (6.40)
Week 144	Number Analyzed	8 participants
		3.25 (6.971)
Week 168	Number Analyzed	10 participants
		4.98 (8.18)
Week 192	Number Analyzed	8 participants
		8.31 (4.54)
Week 216	Number Analyzed	7 participants
		13.93 (14.30)
Week 240	Number Analyzed	6 participants
		13.11 (9.35)

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	0.659
	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.

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	0.752
	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.

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	0.594
	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.

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	0.614
	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.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Burosumab
	Comments	Week 168
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.542
	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.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Burosumab
	Comments	Week 192
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.067
	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.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Burosumab
	Comments	Week 216
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.330
	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.

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Burosumab
	Comments	Week 240
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.161
	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.

16. Secondary Outcome

Title	Change From Baseline Over Time in Tubular Reabsorption of Phosphate (TRP)
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, 144, 168, 192, 216, and 240

Outcome Measure Data

Analysis Population Description

TIO analysis set participants with available data at Baseline and each time point.

Arm/Group Title		Burosumab
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 (0.02)
Week 48	Number Analyzed	12 participants
		0.14 (0.02)
Week 96	Number Analyzed	11 participants
		0.10 (0.03)
Week 144	Number Analyzed	9 participants
		0.13 (0.02)
Week 168	Number Analyzed	9 participants
		0.12 (0.02)
Week 192	Number Analyzed	7 participants
		0.14 (0.02)
Week 216	Number Analyzed	6 participants
		0.14 (0.01)
Week 240	Number Analyzed	6 participants
		0.12 (0.02)

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	< 0.001
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline TRP.

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	< 0.001
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline TRP.

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	0.001
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline TRP.

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	< 0.001
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline TRP.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Burosumab
	Comments	Week 168
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline TRP.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Burosumab
	Comments	Week 192
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline TRP.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Burosumab
	Comments	Week 216
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline TRP.

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Burosumab
	Comments	Week 240
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline TRP.

17. Secondary Outcome

Title	Change From Baseline Over Time in Ratio of Renal Tubular Maximum Phosphate Reabsorption Rate to Glomerular Filtration Rate (TmP/GFR)
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, 144, 168, 192, 216, and 240

Outcome Measure Data

Analysis Population Description

TIO analysis set participants with available data at Baseline and each time point.

Arm/Group Title		Burosumab
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
		0.81 (0.13)
Week 48	Number Analyzed	12 participants
		0.88 (0.14)
Week 96	Number Analyzed	11 participants
		0.73 (0.23)
Week 144	Number Analyzed	9 participants
		0.13 (0.02)
Week 168	Number Analyzed	9 participants
		1.07 (0.29)
Week 192	Number Analyzed	7 participants
		0.95 (0.16)
Week 216	Number Analyzed	6 participants
		0.88 (0.12)
Week 240	Number Analyzed	6 participants
		0.94 (0.15)

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	< 0.001
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline TmP/GFR

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	< 0.001
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline TmP/GFR

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	0.002
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline TmP/GFR

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	< 0.001
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline TmP/GFR

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Burosumab
	Comments	Week 168
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline TmP/GFR.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Burosumab
	Comments	Week 192
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline TmP/GFR.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Burosumab
	Comments	Week 216
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline TmP/GFR.

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Burosumab
	Comments	Week 240
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline TmP/GFR.

18. Secondary Outcome

Title	Change From Baseline Over Time in Fractional Excretion of Phosphorus (FEP)
Description	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, 144, 168, 192, 216, and 240

Outcome Measure Data

Analysis Population Description

TIO analysis set participants with available data at each time point.

Arm/Group Title		Burosumab
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
		-0.14 (0.02)
Week 48	Number Analyzed	13 participants
		-0.14 (0.02)
Week 96	Number Analyzed	12 participants
		-0.10 (0.03)
Week 144	Number Analyzed	10 participants
		-0.15 (0.02)
Week 168	Number Analyzed	10 participants
		-0.14 (0.02)
Week 192	Number Analyzed	8 participants
		-0.14 (0.02)
Week 216	Number Analyzed	7 participants
		-0.15 (0.01)
Week 240	Number Analyzed	7 participants
		-0.14 (0.02)

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	< 0.001
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline FEP.

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	< 0.001
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline FEP.

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	< 0.001
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline FEP.

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	< 0.001
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline FEP.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Burosumab
	Comments	Week 168
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline FEP.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Burosumab
	Comments	Week 192
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline FEP.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Burosumab
	Comments	Week 216
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline FEP.

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Burosumab
	Comments	Week 240
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline FEP.

19. Secondary Outcome

Title	Change From Baseline Over Time in Serum Alkaline Phosphatase (ALP)
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, 144, 168, 192, 216, and 240

Outcome Measure Data

Analysis Population Description

TIO analysis set participants with available data at each time point.

Arm/Group Title		Burosumab
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
		-1.68 (10.91)
Week 48	Number Analyzed	13 participants
		-20.36 (11.68)
Week 96	Number Analyzed	12 participants
		-38.23 (11.90)
Week 144	Number Analyzed	11 participants
		-57.45 (10.97)
Week 168	Number Analyzed	10 participants
		-62.80 (12.35)
Week 192	Number Analyzed	10 participants
		-60.40 (12.41)
Week 216	Number Analyzed	7 participants
		-50.14 (26.09)
Week 240	Number Analyzed	7 participants
		-49.71 (24.35)

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	0.878
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline ALP.

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	0.081
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline ALP.

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	0.001
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline ALP.

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	< 0.001
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline ALP.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Burosumab
	Comments	Week 168
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline ALP.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Burosumab
	Comments	Week 192
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline ALP.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Burosumab
	Comments	Week 216
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.055
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline ALP.

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Burosumab
	Comments	Week 240
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.041
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline ALP.

20. Secondary Outcome

Title	Change From Baseline Over Time in Bone-Specific Alkaline Phosphatase (BALP)
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, 144, 168, 192, 216, and 240

Outcome Measure Data

Analysis Population Description

TIO analysis set participants with available data at each time point.

Arm/Group Title		Burosumab
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
		-1.13 (4.87)
Week 48	Number Analyzed	12 participants
		-9.65 (4.74)
Week 96	Number Analyzed	12 participants
		-15.89 (4.27)
Week 144	Number Analyzed	11 participants
		-19.81 (4.42)
Week 168	Number Analyzed	10 participants
		-22.05 (4.52)
Week 192	Number Analyzed	10 participants
		-21.54 (4.87)
Week 216	Number Analyzed	7 participants
		-15.50 (11.39)
Week 240	Number Analyzed	7 participants
		-21.58 (6.17)

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	0.817
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline BALP.

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	0.042
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline BALP.

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	< 0.001
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline BALP.

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	< 0.001
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline BALP.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Burosumab
	Comments	Week 168
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline BALP.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Burosumab
	Comments	Week 192
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline BALP.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Burosumab
	Comments	Week 216
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.174
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline BALP.

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Burosumab
	Comments	Week 240
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.001
	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
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, 144, 168, 192, 216, and 240

Outcome Measure Data

Analysis Population Description

TIO analysis set participants with available data at each time point.

Arm/Group Title		Burosumab
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
		5.15 (13.06)
Week 48	Number Analyzed	12 participants
		-16.56 (8.35)
Week 96	Number Analyzed	12 participants
		-30.40 (8.57)
Week 144	Number Analyzed	11 participants
		-35.82 (9.47)
Week 168	Number Analyzed	10 participants
		-40.97 (9.60)
Week 192	Number Analyzed	10 participants
		-41.11 (9.93)
Week 216	Number Analyzed	7 participants
		-28.41 (20.71)
Week 240	Number Analyzed	7 participants
		-42.27 (11.65)

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	0.694
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline BALP.

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	0.047
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline BALP.

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	< 0.001
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline BALP.

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	< 0.001
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline BALP.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Burosumab
	Comments	Week 168
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline BALP.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Burosumab
	Comments	Week 192
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline BALP.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Burosumab
	Comments	Week 216
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.170
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline BALP.

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Burosumab
	Comments	Week 240
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.001
	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)
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, 144, 168, 192, 216, and 240

Outcome Measure Data

Analysis Population Description

TIO analysis set participants with available data at each time point

Arm/Group Title		Burosumab
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
		212.91 (125.76)
Week 48	Number Analyzed	13 participants
		97.02 (80.10)
Week 96	Number Analyzed	12 participants
		6.55 (63.66)
Week 144	Number Analyzed	11 participants
		-19.28 (38.49)
Week 168	Number Analyzed	10 participants
		-100.84 (49.31)
Week 192	Number Analyzed	9 participants
		-200.40 (65.80)
Week 216	Number Analyzed	7 participants
		-140.71 (94.55)
Week 240	Number Analyzed	7 participants
		-92.14 (102.27)

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	0.090
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline CTx.

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	0.226
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline CTx.

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	0.918
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline CTx.

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	0.616
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline CTx.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Burosumab
	Comments	Week 168
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.041
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline CTx.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Burosumab
	Comments	Week 192
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.002
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline CTx.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Burosumab
	Comments	Week 216
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.137
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline CTx.

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Burosumab
	Comments	Week 240
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.368
	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
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, 144, 168, 192, 216, and 240

Outcome Measure Data

Analysis Population Description

TIO analysis set participants with available data at each time point.

Arm/Group Title		Burosumab
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
		33.77 (14.33)
Week 48	Number Analyzed	13 participants
		31.05 (20.220)
Week 96	Number Analyzed	12 participants
		11.96 (12.05)
Week 144	Number Analyzed	11 participants
		10.92 (8.86)
Week 168	Number Analyzed	10 participants
		-2.23 (8.29)
Week 192	Number Analyzed	9 participants
		-15.90 (11.21)
Week 216	Number Analyzed	7 participants
		-10.53 (7.40)
Week 240	Number Analyzed	7 participants
		-5.68 (10.26)

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	0.018
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline CTx.

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	0.133
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline CTx.

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	0.321
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline CTx.

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	0.218
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline CTx.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Burosumab
	Comments	Week 168
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.788
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline CTx.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Burosumab
	Comments	Week 192
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.156
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline CTx.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Burosumab
	Comments	Week 216
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.155
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline CTx.

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Burosumab
	Comments	Week 240
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.580
	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)
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, 144, 168, 192, 216, and 240

Outcome Measure Data

Analysis Population Description

TIO analysis set participants with available data at each time point.

Arm/Group Title		Burosumab
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
		34.07 (10.90)
Week 48	Number Analyzed	13 participants
		7.73 (7.05)
Week 96	Number Analyzed	12 participants
		11.28 (15.56)
Week 144	Number Analyzed	11 participants
		1.21 (5.55)
Week 168	Number Analyzed	9 participants
		-12.04 (3.36)
Week 192	Number Analyzed	10 participants
		-11.93 (8.11)
Week 216	Number Analyzed	7 participants
		-7.53 (14.58)
Week 240	Number Analyzed	7 participants
		-1.67 (14.39)

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	0.002
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline P1NP.

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	0.273
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline P1NP.

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	0.469
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline P1NP.

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	0.828
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline P1NP.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Burosumab
	Comments	Week 168
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline P1NP.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Burosumab
	Comments	Week 192
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.141
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline P1NP.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Burosumab
	Comments	Week 216
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.606
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline P1NP.

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Burosumab
	Comments	Week 240
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.907
	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
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, 144, 168, 192, 216, and 240

Outcome Measure Data

Analysis Population Description

TIO analysis set participants with available data at each time point.

Arm/Group Title		Burosumab
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
		53.71 (16.35)
Week 48	Number Analyzed	13 participants
		15.64 (10.84)
Week 96	Number Analyzed	12 participants
		18.09 (20.29)
Week 144	Number Analyzed	11 participants
		13.65 (8.68)
Week 168	Number Analyzed	9 participants
		-12.40 (4.98)
Week 192	Number Analyzed	10 participants
		0.93 (19.78)
Week 216	Number Analyzed	7 participants
		-7.58 (17.45)
Week 240	Number Analyzed	7 participants
		4.47 (16.82)

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	0.001
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline P1NP.

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	0.149
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline P1NP.

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	0.372
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline P1NP.

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	0.116
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline P1NP.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Burosumab
	Comments	Week 168
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.013
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline P1NP.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Burosumab
	Comments	Week 192
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.962
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline P1NP.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Burosumab
	Comments	Week 216
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.664
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline P1NP.

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Burosumab
	Comments	Week 240
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.790
	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
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, 144, 168, 192, 216, and 240

Outcome Measure Data

Analysis Population Description

TIO analysis set with available data at each time point

Arm/Group Title		Burosumab
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
		9.51 (4.85)
Week 48	Number Analyzed	11 participants
		2.20 (3.48)
Week 96	Number Analyzed	12 participants
		-0.54 (2.75)
Week 144	Number Analyzed	10 participants
		-0.52 (1.89)
Week 168	Number Analyzed	10 participants
		-3.14 (1.35)
Week 192	Number Analyzed	10 participants
		-6.91 (2.49)
Week 216	Number Analyzed	6 participants
		-7.97 (5.35)
Week 240	Number Analyzed	7 participants
		-8.55 (5.22)

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	0.050
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline osteocalcin.

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	0.526
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline osteocalcin.

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	0.845
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline osteocalcin.

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	0.782
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline osteocalcin.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Burosumab
	Comments	Week 168
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.020
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline osteocalcin.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Burosumab
	Comments	Week 192
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.005
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline osteocalcin.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Burosumab
	Comments	Week 216
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.136
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline osteocalcin.

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Burosumab
	Comments	Week 240
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.101
	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
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, 144, 168, 192, 216, and 240

Outcome Measure Data

Analysis Population Description

TIO analysis set with available data at each time point

Arm/Group Title		Burosumab
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
		41.49 (12.19)
Week 48	Number Analyzed	11 participants
		16.28 (13.79)
Week 96	Number Analyzed	12 participants
		15.04 (14.10)
Week 144	Number Analyzed	10 participants
		14.08 (8.38)
Week 168	Number Analyzed	10 participants
		-0.98 (7.11)
Week 192	Number Analyzed	10 participants
		-19.67 (10.42)
Week 216	Number Analyzed	6 participants
		-5.65 (11.48)
Week 240	Number Analyzed	7 participants
		-8.37 (10.17)

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	< 0.001
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline osteocalcin.

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	0.238
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline osteocalcin.

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	0.286
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline osteocalcin.

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	0.093
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline osteocalcin.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Burosumab
	Comments	Week 168
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.890
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline osteocalcin.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Burosumab
	Comments	Week 192
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.059
	Comments	[Not Specified]
	Method	GEE model
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline osteocalcin.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Burosumab
	Comments	Week 216
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.623
	Comments	Generalized estimation equation (GEE) model includes time as the categorical variable and adjusted for Baseline osteocalcin.
	Method	GEE model
	Comments	[Not Specified]

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Burosumab
	Comments	Week 240
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.411
	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
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

Outcome Measure Data

Analysis Population Description

TIO analysis set with available elbow dynamometry measurements at Baseline and each time point.

Arm/Group Title		Elbow Flexion	Elbow Extension
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)

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.

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.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Elbow Flexion
	Comments	Week 48
	Type of Statistical Test	Other
	Comments	[Not Specified]