Trial Outcomes & Findings for Study of Burosumab (KRN23) in Adults With Tumor-Induced Osteomalacia (TIO) or Epidermal Nevus Syndrome (ENS) (NCT NCT02304367)

Last Updated: 2024-05-06

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

17 participants

Primary outcome timeframe

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])

Results posted on

2024-05-06

Participant Flow

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).

Participant milestones

Participant milestones
Measure	Burosumab 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 Study STARTED	17
Overall Study Completed 48 Weeks of Study Drug	16
Overall Study Completed 144 Weeks of Study Drug	12
Overall Study COMPLETED	9
Overall Study NOT COMPLETED	8

Reasons for withdrawal

Reasons for withdrawal
Measure	Burosumab 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 Study Lack of Response to Bruosumab	1
Overall Study Sponsor Decision	3
Overall Study Death	2
Overall Study Physician Decision	1
Overall Study Unable to Return Due to Corona Virus Pandemic	1

Baseline Characteristics

Tumor-induced osteomalacia (TIO) analysis set includes the 14 participants with TIO who received at least 1 dose of study drug.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Burosumab n=17 Participants 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.
Age, Continuous	53.1 years STANDARD_DEVIATION 13.86 • n=17 Participants
Sex: Female, Male Female	8 Participants n=17 Participants
Sex: Female, Male Male	9 Participants n=17 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=17 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	17 Participants n=17 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=17 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=17 Participants
Race/Ethnicity, Customized Asian	0 Participants n=17 Participants
Race/Ethnicity, Customized Black or African American	2 Participants n=17 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=17 Participants
Race/Ethnicity, Customized White	15 Participants n=17 Participants
Race/Ethnicity, Customized Other	0 Participants n=17 Participants
Diagnosis Tumor-Induced osteomalacia (TIO)	14 Participants n=17 Participants
Diagnosis Epidermal nevus syndrome-associated osteomalacia	1 Participants n=17 Participants
Diagnosis X-linked hypophosphatemia (XLH)	2 Participants n=17 Participants
Serum Total Fibroblast Growth Factor 23 (FGF23)	770.06 pg/mL STANDARD_DEVIATION 797.654 • n=14 Participants • Tumor-induced osteomalacia (TIO) analysis set includes the 14 participants with TIO who received at least 1 dose of study drug.
Serum Phosphorus	1.60 mg/dL STANDARD_DEVIATION 0.474 • n=14 Participants • TIO analysis set
Osteoid Volume/Bone Volume (OB/BV)	17.61 percentage of bone volume STANDARD_DEVIATION 19.485 • n=11 Participants • 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)	56.82 percentage of bone surface STANDARD_DEVIATION 31.003 • n=11 Participants • TIO biopsy analysis set
Osteoid Thickness (O.Th)	16.45 μm STANDARD_DEVIATION 12.044 • n=11 Participants • TIO biopsy analysis set
Mineralization Lag Time (Mlt)	1597.73 days STANDARD_DEVIATION 1326.832 • n=10 Participants • TIO biopsy analysis set for whom Mlt could be calculated or imputed

PRIMARY outcome

Timeframe: 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])

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

Outcome measures

Outcome measures
Measure	Burosumab n=14 Participants 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.	Elbow Extension 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.
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	50.0 percentage of participants Interval 26.8 to 73.2	—

PRIMARY outcome

Timeframe: Baseline, Week 48

Population: TIO bone biopsy analysis set

Histomorphometry of trans-iliac crest bone biopsies was assessed by a blinded, central reader. Osteoid thickness is the mean thickness of osteoid seams.

Outcome measures

Outcome measures
Measure	Burosumab n=11 Participants 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.	Elbow Extension 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.
Change From Baseline to Week 48 in Osteoid Thickness	-5.12 µm Interval -10.04 to -0.2	—

PRIMARY outcome

Timeframe: Baseline, Week 48

Population: TIO biopsy analysis set

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.

Outcome measures

Outcome measures
Measure	Burosumab n=11 Participants 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.	Elbow Extension 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.
Change From Baseline to Week 48 in Osteoid Surface/Bone Surface (OS/BS)	-0.18 percentage of bone surface Interval -13.86 to 13.5	—

PRIMARY outcome

Timeframe: Baseline, Week 48

Population: TIO bone biopsy analysis set

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).

Outcome measures

Outcome measures
Measure	Burosumab n=11 Participants 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.	Elbow Extension 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.
Change From Baseline to Week 48 in Osteoid Volume/Bone Volume (OV/BV)	-5.47 percentage of bone volume Interval -11.87 to 0.93	—

PRIMARY outcome

Timeframe: Baseline, Week 48

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

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.

Outcome measures

Outcome measures
Measure	Burosumab n=10 Participants 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.	Elbow Extension 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.
Change From Baseline to Week 48 in Mineralization Lag Time (MLt)	-565.20 days Interval -2037.42 to 907.02	—

SECONDARY outcome

Timeframe: End of each dose interval from Baseline to Week 24 (Weeks 4, 8, 12, 16, 20, and 24)

Population: TIO analysis set

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).

Outcome measures

Outcome measures
Measure	Burosumab n=14 Participants 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.	Elbow Extension 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.
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	21.4 percentage of participants Interval 7.57 to 47.59	—

SECONDARY outcome

Timeframe: Baseline and the mid-point of each dose interval from Baseline to Week 24 (Weeks 2, 6, 10, 14 and 22)

Population: TIO analysis set

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).

Outcome measures

Outcome measures
Measure	Burosumab n=14 Participants 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.	Elbow Extension 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.
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	1.039 mg/dL Standard Deviation 0.5622	—

SECONDARY outcome

Timeframe: Baseline and the mid-point of each dose interval from Baseline to Week 24 (Weeks 2, 6, 10, 14 and 22)

Population: TIO analysis set

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).

Outcome measures

Outcome measures
Measure	Burosumab n=14 Participants 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.	Elbow Extension 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.
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	69.77 percent change Standard Deviation 43.743	—

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8, 12, 16, 20, and 24

Population: TIO analysis set

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).

Outcome measures

Outcome measures
Measure	Burosumab n=14 Participants 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.	Elbow Extension 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.
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	0.550 mg/dL Standard Deviation 0.4260	—

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8, 12, 16, 20, and 24

Population: TIO analysis set

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).

Outcome measures

Outcome measures
Measure	Burosumab n=14 Participants 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.	Elbow Extension 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.
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	38.56 percent change Standard Deviation 33.027	—

SECONDARY outcome

Timeframe: Pre-dose on Day 1 and at Weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 21, 22, and 24

Population: TIO analysis set

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.

Outcome measures

Outcome measures
Measure	Burosumab n=14 Participants 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.	Elbow Extension 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.
Time-Adjusted Area Under the Curve (AUC) of Serum Phosphorus Levels Between Baseline and Week 24	2.36 mg/dL Standard Deviation 0.632	—

SECONDARY outcome

Timeframe: Baseline and Weeks 24, 48, 96, 144, 168, 192, 216, and 240

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

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.

Outcome measures

Outcome measures
Measure	Burosumab n=11 Participants 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.	Elbow Extension 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.
Change From Baseline Over Time in Serum 1,25-dihydroxyvitamin D (1,25(OH)2D) Concentration Week 24	9.90 pg/mL Standard Error 4.10	—
Change From Baseline Over Time in Serum 1,25-dihydroxyvitamin D (1,25(OH)2D) Concentration Week 48	10.49 pg/mL Standard Error 4.82	—
Change From Baseline Over Time in Serum 1,25-dihydroxyvitamin D (1,25(OH)2D) Concentration Week 96	4.28 pg/mL Standard Error 3.80	—
Change From Baseline Over Time in Serum 1,25-dihydroxyvitamin D (1,25(OH)2D) Concentration Week 144	3.15 pg/mL Standard Error 3.34	—
Change From Baseline Over Time in Serum 1,25-dihydroxyvitamin D (1,25(OH)2D) Concentration Week 168	4.91 pg/mL Standard Error 3.94	—
Change From Baseline Over Time in Serum 1,25-dihydroxyvitamin D (1,25(OH)2D) Concentration Week 192	0.67 pg/mL Standard Error 4.19	—
Change From Baseline Over Time in Serum 1,25-dihydroxyvitamin D (1,25(OH)2D) Concentration Week 216	9.78 pg/mL Standard Error 3.04	—
Change From Baseline Over Time in Serum 1,25-dihydroxyvitamin D (1,25(OH)2D) Concentration Week 240	6.56 pg/mL Standard Error 3.19	—

SECONDARY outcome

Timeframe: Baseline and Weeks 24, 48, 96, 144, 168, 192, 216, and 240

Population: TIO analysis set with available data at each time point

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.

Outcome measures

Outcome measures
Measure	Burosumab n=14 Participants 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.	Elbow Extension 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.
Change From Baseline Over Time in Total Serum Fibroblast Growth Factor 23 (FGF23) Concentration Week 48	180511.74 pg/mL Standard Error 33529.14	—
Change From Baseline Over Time in Total Serum Fibroblast Growth Factor 23 (FGF23) Concentration Week 96	331267.40 pg/mL Standard Error 103226.37	—
Change From Baseline Over Time in Total Serum Fibroblast Growth Factor 23 (FGF23) Concentration Week 144	275758.40 pg/mL Standard Error 102349.79	—
Change From Baseline Over Time in Total Serum Fibroblast Growth Factor 23 (FGF23) Concentration Week 168	185769.23 pg/mL Standard Error 65423.93	—
Change From Baseline Over Time in Total Serum Fibroblast Growth Factor 23 (FGF23) Concentration Week 192	234826.20 pg/mL Standard Error 82198.24	—
Change From Baseline Over Time in Total Serum Fibroblast Growth Factor 23 (FGF23) Concentration Week 216	254359.96 pg/mL Standard Error 81615.67	—
Change From Baseline Over Time in Total Serum Fibroblast Growth Factor 23 (FGF23) Concentration Week 240	210119.10 pg/mL Standard Error 76610.50	—
Change From Baseline Over Time in Total Serum Fibroblast Growth Factor 23 (FGF23) Concentration Week 24	246335.35 pg/mL Standard Error 61089.98	—

SECONDARY outcome

Timeframe: Baseline and Weeks 24, 48, 96, 144, 168, 192, 216, and 240

Population: TIO analysis set with available data at each time point

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.

Outcome measures

Outcome measures
Measure	Burosumab n=14 Participants 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.	Elbow Extension 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.
Change From Baseline Over Time in Free Serum Fibroblast Growth Factor 23 (FGF23) Concentration Week 24	624.91 pg/mL Standard Error 101.89	—
Change From Baseline Over Time in Free Serum Fibroblast Growth Factor 23 (FGF23) Concentration Week 48	578.07 pg/mL Standard Error 95.37	—
Change From Baseline Over Time in Free Serum Fibroblast Growth Factor 23 (FGF23) Concentration Week 96	736.59 pg/mL Standard Error 139.18	—
Change From Baseline Over Time in Free Serum Fibroblast Growth Factor 23 (FGF23) Concentration Week 144	801.69 pg/mL Standard Error 103.41	—
Change From Baseline Over Time in Free Serum Fibroblast Growth Factor 23 (FGF23) Concentration Week 168	787.16 pg/mL Standard Error 95.52	—
Change From Baseline Over Time in Free Serum Fibroblast Growth Factor 23 (FGF23) Concentration Week 192	717.71 pg/mL Standard Error 115.99	—
Change From Baseline Over Time in Free Serum Fibroblast Growth Factor 23 (FGF23) Concentration Week 216	704.87 pg/mL Standard Error 115.30	—
Change From Baseline Over Time in Free Serum Fibroblast Growth Factor 23 (FGF23) Concentration Week 240	625.16 pg/mL Standard Error 125.93	—

SECONDARY outcome

Timeframe: Baseline and Weeks 24, 48, 96, 144, 168, 192, 216, and 240

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

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.

Outcome measures

Outcome measures
Measure	Burosumab n=14 Participants 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.	Elbow Extension 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.
Change From Baseline Over Time in 24-hour Urinary Phosphorus Week 24	-3.66 mg/dL Standard Error 8.28	—
Change From Baseline Over Time in 24-hour Urinary Phosphorus Week 48	3.59 mg/dL Standard Error 6.73	—
Change From Baseline Over Time in 24-hour Urinary Phosphorus Week 96	3.22 mg/dL Standard Error 6.40	—
Change From Baseline Over Time in 24-hour Urinary Phosphorus Week 144	3.25 mg/dL Standard Error 6.971	—
Change From Baseline Over Time in 24-hour Urinary Phosphorus Week 168	4.98 mg/dL Standard Error 8.18	—
Change From Baseline Over Time in 24-hour Urinary Phosphorus Week 192	8.31 mg/dL Standard Error 4.54	—
Change From Baseline Over Time in 24-hour Urinary Phosphorus Week 216	13.93 mg/dL Standard Error 14.30	—
Change From Baseline Over Time in 24-hour Urinary Phosphorus Week 240	13.11 mg/dL Standard Error 9.35	—

SECONDARY outcome

Timeframe: Baseline and Weeks 24, 48, 96, 144, 168, 192, 216, and 240

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

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.

Outcome measures

Outcome measures
Measure	Burosumab n=13 Participants 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.	Elbow Extension 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.
Change From Baseline Over Time in Tubular Reabsorption of Phosphate (TRP) Week 24	0.13 fraction of phosphorus reabsorbed Standard Error 0.02	—
Change From Baseline Over Time in Tubular Reabsorption of Phosphate (TRP) Week 48	0.14 fraction of phosphorus reabsorbed Standard Error 0.02	—
Change From Baseline Over Time in Tubular Reabsorption of Phosphate (TRP) Week 96	0.10 fraction of phosphorus reabsorbed Standard Error 0.03	—
Change From Baseline Over Time in Tubular Reabsorption of Phosphate (TRP) Week 144	0.13 fraction of phosphorus reabsorbed Standard Error 0.02	—
Change From Baseline Over Time in Tubular Reabsorption of Phosphate (TRP) Week 168	0.12 fraction of phosphorus reabsorbed Standard Error 0.02	—
Change From Baseline Over Time in Tubular Reabsorption of Phosphate (TRP) Week 192	0.14 fraction of phosphorus reabsorbed Standard Error 0.02	—
Change From Baseline Over Time in Tubular Reabsorption of Phosphate (TRP) Week 216	0.14 fraction of phosphorus reabsorbed Standard Error 0.01	—
Change From Baseline Over Time in Tubular Reabsorption of Phosphate (TRP) Week 240	0.12 fraction of phosphorus reabsorbed Standard Error 0.02	—

SECONDARY outcome

Timeframe: Baseline and Weeks 24, 48, 96, 144, 168, 192, 216, and 240

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

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.

Outcome measures

Outcome measures
Measure	Burosumab n=13 Participants 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.	Elbow Extension 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.
Change From Baseline Over Time in Ratio of Renal Tubular Maximum Phosphate Reabsorption Rate to Glomerular Filtration Rate (TmP/GFR) Week 216	0.88 mg/dL Standard Error 0.12	—
Change From Baseline Over Time in Ratio of Renal Tubular Maximum Phosphate Reabsorption Rate to Glomerular Filtration Rate (TmP/GFR) Week 240	0.94 mg/dL Standard Error 0.15	—
Change From Baseline Over Time in Ratio of Renal Tubular Maximum Phosphate Reabsorption Rate to Glomerular Filtration Rate (TmP/GFR) Week 144	0.13 mg/dL Standard Error 0.02	—
Change From Baseline Over Time in Ratio of Renal Tubular Maximum Phosphate Reabsorption Rate to Glomerular Filtration Rate (TmP/GFR) Week 24	0.81 mg/dL Standard Error 0.13	—
Change From Baseline Over Time in Ratio of Renal Tubular Maximum Phosphate Reabsorption Rate to Glomerular Filtration Rate (TmP/GFR) Week 48	0.88 mg/dL Standard Error 0.14	—
Change From Baseline Over Time in Ratio of Renal Tubular Maximum Phosphate Reabsorption Rate to Glomerular Filtration Rate (TmP/GFR) Week 96	0.73 mg/dL Standard Error 0.23	—
Change From Baseline Over Time in Ratio of Renal Tubular Maximum Phosphate Reabsorption Rate to Glomerular Filtration Rate (TmP/GFR) Week 168	1.07 mg/dL Standard Error 0.29	—
Change From Baseline Over Time in Ratio of Renal Tubular Maximum Phosphate Reabsorption Rate to Glomerular Filtration Rate (TmP/GFR) Week 192	0.95 mg/dL Standard Error 0.16	—

SECONDARY outcome

Timeframe: Baseline and Weeks 24, 48, 96, 144, 168, 192, 216, and 240

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

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.

Outcome measures

Outcome measures
Measure	Burosumab n=14 Participants 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.	Elbow Extension 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.
Change From Baseline Over Time in Fractional Excretion of Phosphorus (FEP) Week 24	-0.14 percentage of phosphorus Standard Error 0.02	—
Change From Baseline Over Time in Fractional Excretion of Phosphorus (FEP) Week 48	-0.14 percentage of phosphorus Standard Error 0.02	—
Change From Baseline Over Time in Fractional Excretion of Phosphorus (FEP) Week 96	-0.10 percentage of phosphorus Standard Error 0.03	—
Change From Baseline Over Time in Fractional Excretion of Phosphorus (FEP) Week 240	-0.14 percentage of phosphorus Standard Error 0.02	—
Change From Baseline Over Time in Fractional Excretion of Phosphorus (FEP) Week 144	-0.15 percentage of phosphorus Standard Error 0.02	—
Change From Baseline Over Time in Fractional Excretion of Phosphorus (FEP) Week 168	-0.14 percentage of phosphorus Standard Error 0.02	—
Change From Baseline Over Time in Fractional Excretion of Phosphorus (FEP) Week 192	-0.14 percentage of phosphorus Standard Error 0.02	—
Change From Baseline Over Time in Fractional Excretion of Phosphorus (FEP) Week 216	-0.15 percentage of phosphorus Standard Error 0.01	—

SECONDARY outcome

Timeframe: Baseline and Weeks 24, 48, 96, 144, 168, 192, 216, and 240

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

Outcome measures

Outcome measures
Measure	Burosumab n=14 Participants 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.	Elbow Extension 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.
Change From Baseline Over Time in Serum Alkaline Phosphatase (ALP) Week 24	-1.68 U/L Standard Error 10.91	—
Change From Baseline Over Time in Serum Alkaline Phosphatase (ALP) Week 48	-20.36 U/L Standard Error 11.68	—
Change From Baseline Over Time in Serum Alkaline Phosphatase (ALP) Week 96	-38.23 U/L Standard Error 11.90	—
Change From Baseline Over Time in Serum Alkaline Phosphatase (ALP) Week 144	-57.45 U/L Standard Error 10.97	—
Change From Baseline Over Time in Serum Alkaline Phosphatase (ALP) Week 168	-62.80 U/L Standard Error 12.35	—
Change From Baseline Over Time in Serum Alkaline Phosphatase (ALP) Week 192	-60.40 U/L Standard Error 12.41	—
Change From Baseline Over Time in Serum Alkaline Phosphatase (ALP) Week 216	-50.14 U/L Standard Error 26.09	—
Change From Baseline Over Time in Serum Alkaline Phosphatase (ALP) Week 240	-49.71 U/L Standard Error 24.35	—

SECONDARY outcome

Timeframe: Baseline and Weeks 24, 48, 96, 144, 168, 192, 216, and 240

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

Outcome measures

Outcome measures
Measure	Burosumab n=14 Participants 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.	Elbow Extension 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.
Change From Baseline Over Time in Bone-Specific Alkaline Phosphatase (BALP) Week 24	-1.13 μg/L Standard Error 4.87	—
Change From Baseline Over Time in Bone-Specific Alkaline Phosphatase (BALP) Week 48	-9.65 μg/L Standard Error 4.74	—
Change From Baseline Over Time in Bone-Specific Alkaline Phosphatase (BALP) Week 96	-15.89 μg/L Standard Error 4.27	—
Change From Baseline Over Time in Bone-Specific Alkaline Phosphatase (BALP) Week 144	-19.81 μg/L Standard Error 4.42	—
Change From Baseline Over Time in Bone-Specific Alkaline Phosphatase (BALP) Week 168	-22.05 μg/L Standard Error 4.52	—
Change From Baseline Over Time in Bone-Specific Alkaline Phosphatase (BALP) Week 192	-21.54 μg/L Standard Error 4.87	—
Change From Baseline Over Time in Bone-Specific Alkaline Phosphatase (BALP) Week 216	-15.50 μg/L Standard Error 11.39	—
Change From Baseline Over Time in Bone-Specific Alkaline Phosphatase (BALP) Week 240	-21.58 μg/L Standard Error 6.17	—

SECONDARY outcome

Timeframe: Baseline and Weeks 24, 48, 96, 144, 168, 192, 216, and 240

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

Outcome measures

Outcome measures
Measure	Burosumab n=14 Participants 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.	Elbow Extension 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.
Percent Change From Baseline Over Time in BALP Week 24	5.15 percent change Standard Error 13.06	—
Percent Change From Baseline Over Time in BALP Week 48	-16.56 percent change Standard Error 8.35	—
Percent Change From Baseline Over Time in BALP Week 96	-30.40 percent change Standard Error 8.57	—
Percent Change From Baseline Over Time in BALP Week 144	-35.82 percent change Standard Error 9.47	—
Percent Change From Baseline Over Time in BALP Week 168	-40.97 percent change Standard Error 9.60	—
Percent Change From Baseline Over Time in BALP Week 192	-41.11 percent change Standard Error 9.93	—
Percent Change From Baseline Over Time in BALP Week 216	-28.41 percent change Standard Error 20.71	—
Percent Change From Baseline Over Time in BALP Week 240	-42.27 percent change Standard Error 11.65	—

SECONDARY outcome

Timeframe: Baseline and Weeks 24, 48, 96, 144, 168, 192, 216, and 240

Population: TIO analysis set participants with available data at each time point

Outcome measures

Outcome measures
Measure	Burosumab n=14 Participants 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.	Elbow Extension 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.
Change From Baseline Over Time in Carboxy Terminal Cross-Linked Telopeptide of Type 1 Collagen (CTx) Week 24	212.91 pg/mL Standard Error 125.76	—
Change From Baseline Over Time in Carboxy Terminal Cross-Linked Telopeptide of Type 1 Collagen (CTx) Week 48	97.02 pg/mL Standard Error 80.10	—
Change From Baseline Over Time in Carboxy Terminal Cross-Linked Telopeptide of Type 1 Collagen (CTx) Week 96	6.55 pg/mL Standard Error 63.66	—
Change From Baseline Over Time in Carboxy Terminal Cross-Linked Telopeptide of Type 1 Collagen (CTx) Week 144	-19.28 pg/mL Standard Error 38.49	—
Change From Baseline Over Time in Carboxy Terminal Cross-Linked Telopeptide of Type 1 Collagen (CTx) Week 168	-100.84 pg/mL Standard Error 49.31	—
Change From Baseline Over Time in Carboxy Terminal Cross-Linked Telopeptide of Type 1 Collagen (CTx) Week 192	-200.40 pg/mL Standard Error 65.80	—
Change From Baseline Over Time in Carboxy Terminal Cross-Linked Telopeptide of Type 1 Collagen (CTx) Week 216	-140.71 pg/mL Standard Error 94.55	—
Change From Baseline Over Time in Carboxy Terminal Cross-Linked Telopeptide of Type 1 Collagen (CTx) Week 240	-92.14 pg/mL Standard Error 102.27	—

SECONDARY outcome

Timeframe: Baseline and Weeks 24, 48, 96, 144, 168, 192, 216, and 240

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

Outcome measures

Outcome measures
Measure	Burosumab n=14 Participants 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.	Elbow Extension 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.
Percent Change From Baseline Over Time in CTx Week 24	33.77 percent change Standard Error 14.33	—
Percent Change From Baseline Over Time in CTx Week 48	31.05 percent change Standard Error 20.220	—
Percent Change From Baseline Over Time in CTx Week 96	11.96 percent change Standard Error 12.05	—
Percent Change From Baseline Over Time in CTx Week 144	10.92 percent change Standard Error 8.86	—
Percent Change From Baseline Over Time in CTx Week 168	-2.23 percent change Standard Error 8.29	—
Percent Change From Baseline Over Time in CTx Week 192	-15.90 percent change Standard Error 11.21	—
Percent Change From Baseline Over Time in CTx Week 216	-10.53 percent change Standard Error 7.40	—
Percent Change From Baseline Over Time in CTx Week 240	-5.68 percent change Standard Error 10.26	—

SECONDARY outcome

Timeframe: Baseline and Weeks 24, 48, 96, 144, 168, 192, 216, and 240

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

Outcome measures

Outcome measures
Measure	Burosumab n=14 Participants 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.	Elbow Extension 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.
Change From Baseline Over Time in Procollagen Type 1 N-Propeptide (P1NP) Week 24	34.07 ng/mL Standard Error 10.90	—
Change From Baseline Over Time in Procollagen Type 1 N-Propeptide (P1NP) Week 48	7.73 ng/mL Standard Error 7.05	—
Change From Baseline Over Time in Procollagen Type 1 N-Propeptide (P1NP) Week 96	11.28 ng/mL Standard Error 15.56	—
Change From Baseline Over Time in Procollagen Type 1 N-Propeptide (P1NP) Week 144	1.21 ng/mL Standard Error 5.55	—
Change From Baseline Over Time in Procollagen Type 1 N-Propeptide (P1NP) Week 168	-12.04 ng/mL Standard Error 3.36	—
Change From Baseline Over Time in Procollagen Type 1 N-Propeptide (P1NP) Week 192	-11.93 ng/mL Standard Error 8.11	—
Change From Baseline Over Time in Procollagen Type 1 N-Propeptide (P1NP) Week 216	-7.53 ng/mL Standard Error 14.58	—
Change From Baseline Over Time in Procollagen Type 1 N-Propeptide (P1NP) Week 240	-1.67 ng/mL Standard Error 14.39	—

SECONDARY outcome

Timeframe: Baseline and Weeks 24, 48, 96, 144, 168, 192, 216, and 240

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

Outcome measures

Outcome measures
Measure	Burosumab n=14 Participants 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.	Elbow Extension 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.
Percent Change From Baseline Over Time in P1NP Week 24	53.71 percent change Standard Error 16.35	—
Percent Change From Baseline Over Time in P1NP Week 48	15.64 percent change Standard Error 10.84	—
Percent Change From Baseline Over Time in P1NP Week 96	18.09 percent change Standard Error 20.29	—
Percent Change From Baseline Over Time in P1NP Week 144	13.65 percent change Standard Error 8.68	—
Percent Change From Baseline Over Time in P1NP Week 168	-12.40 percent change Standard Error 4.98	—
Percent Change From Baseline Over Time in P1NP Week 192	0.93 percent change Standard Error 19.78	—
Percent Change From Baseline Over Time in P1NP Week 216	-7.58 percent change Standard Error 17.45	—
Percent Change From Baseline Over Time in P1NP Week 240	4.47 percent change Standard Error 16.82	—

SECONDARY outcome

Timeframe: Baseline and Weeks 24, 48, 96, 144, 168, 192, 216, and 240

Population: TIO analysis set with available data at each time point

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.

Outcome measures

Outcome measures
Measure	Burosumab n=14 Participants 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.	Elbow Extension 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.
Change From Baseline Over Time in Osteocalcin Week 48	2.20 ng/mL Standard Error 3.48	—
Change From Baseline Over Time in Osteocalcin Week 96	-0.54 ng/mL Standard Error 2.75	—
Change From Baseline Over Time in Osteocalcin Week 24	9.51 ng/mL Standard Error 4.85	—
Change From Baseline Over Time in Osteocalcin Week 144	-0.52 ng/mL Standard Error 1.89	—
Change From Baseline Over Time in Osteocalcin Week 168	-3.14 ng/mL Standard Error 1.35	—
Change From Baseline Over Time in Osteocalcin Week 192	-6.91 ng/mL Standard Error 2.49	—
Change From Baseline Over Time in Osteocalcin Week 216	-7.97 ng/mL Standard Error 5.35	—
Change From Baseline Over Time in Osteocalcin Week 240	-8.55 ng/mL Standard Error 5.22	—

SECONDARY outcome

Timeframe: Baseline and Weeks 24, 48, 96, 144, 168, 192, 216, and 240

Population: TIO analysis set with available data at each time point

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.

Outcome measures

Outcome measures
Measure	Burosumab n=14 Participants 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.	Elbow Extension 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.
Percent Change From Baseline Over Time in Osteocalcin Week 48	16.28 percent change Standard Error 13.79	—
Percent Change From Baseline Over Time in Osteocalcin Week 24	41.49 percent change Standard Error 12.19	—
Percent Change From Baseline Over Time in Osteocalcin Week 96	15.04 percent change Standard Error 14.10	—
Percent Change From Baseline Over Time in Osteocalcin Week 144	14.08 percent change Standard Error 8.38	—
Percent Change From Baseline Over Time in Osteocalcin Week 168	-0.98 percent change Standard Error 7.11	—
Percent Change From Baseline Over Time in Osteocalcin Week 192	-19.67 percent change Standard Error 10.42	—
Percent Change From Baseline Over Time in Osteocalcin Week 216	-5.65 percent change Standard Error 11.48	—
Percent Change From Baseline Over Time in Osteocalcin Week 240	-8.37 percent change Standard Error 10.17	—

SECONDARY outcome

Timeframe: Baseline and Weeks 24 and 48

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

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.

Outcome measures

Outcome measures
Measure	Burosumab n=9 Participants 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.	Elbow Extension n=9 Participants 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.
Change From Baseline Over Time in Hand-Held Dynamometry (HHD) Elbow Measurements Week 24	0.12 kg Standard Error 0.512	0.75 kg Standard Error 0.704
Change From Baseline Over Time in Hand-Held Dynamometry (HHD) Elbow Measurements Week 48	0.32 kg Standard Error 0.753	1.06 kg Standard Error 0.760

SECONDARY outcome

Timeframe: Baseline and Weeks 24 and 48

Population: TIO analysis set with available knee dynamometry measurements at Baseline and each time point.

To assess muscle strength, hand-held dynamometry was conducted using a standardized technique. Bilateral strength (defined as the average of the left and the right scores, measured in kilograms) of the knee flexors and extensors was measured by the maximum voluntary isometric contraction against a dynamometer. Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline strength measurements, with compound symmetry covariance structure.

Outcome measures

Outcome measures
Measure	Burosumab n=10 Participants 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.	Elbow Extension n=10 Participants 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.
Change From Baseline Over Time in Hand-Held Dynamometry (HHD) Knee Measurements Week 24	0.94 kg Standard Error 1.139	-0.89 kg Standard Error 1.573
Change From Baseline Over Time in Hand-Held Dynamometry (HHD) Knee Measurements Week 48	1.21 kg Standard Error 1.297	0.75 kg Standard Error 1.158

SECONDARY outcome

Timeframe: Baseline and Weeks 24 and 48

Population: TIO analysis set with available STS data at each time point; One participant did not perform the test at Baseline as it was not included in the original protocol, and 2 participants were unable to perform the test due to underlying medical issues.

The STS test measures lower extremity strength and mobility as a participant moves repeatedly from a seated position to standing. This study used a modified STS test that allowed participants to use the arms of the chair to help them stand and sit if necessary. The number of sit-to-stand repetitions performed in a 30-second period was recorded. Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline measurement, with compound symmetry covariance structure.

Outcome measures

Outcome measures
Measure	Burosumab n=11 Participants 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.	Elbow Extension 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.
Change From Baseline Over Time in Sit-to-Stand (STS) Test Week 24	1.5 sit-to-stand repetitions Standard Error 0.54	—
Change From Baseline Over Time in Sit-to-Stand (STS) Test Week 48	1.6 sit-to-stand repetitions Standard Error 0.50	—

SECONDARY outcome

Timeframe: Baseline and Weeks 24 and 48

Population: TIO analysis set with available WAL measurements at Baseline and each time point.

The Weighted arm lift (WAL) test assesses upper extremity strength, mobility and reaching ability. The test was administered bilaterally to determine the number of times the participant could raise a 1 kg weight above the head in a 30-second period. The number of repetitions completed with each arm was recorded. Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline WAL measurements, with compound symmetry covariance structure.

Outcome measures

Outcome measures
Measure	Burosumab n=8 Participants 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.	Elbow Extension n=9 Participants 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.
Change From Baseline Over Time in Weighted Arm Lift (WAL) Test Week 24	-0.5 arm lifts Standard Error 1.09	0.6 arm lifts Standard Error 0.89
Change From Baseline Over Time in Weighted Arm Lift (WAL) Test Week 48	0.1 arm lifts Standard Error 1.25	1.7 arm lifts Standard Error 1.17

SECONDARY outcome

Timeframe: Baseline and Weeks 24 and 48

Population: TIO analysis set with available 6MWT measurements at Baseline and each time point. Six participants did not perform the test at Baseline as it was not included in the original protocol, and 2 participants were unable to perform the test due to underlying medical issues.

The 6MWT is a commonly used measure of mobility and was conducted in accordance with general principles set forth in the American Thoracic Society guidelines (ATS 2002). Participants were instructed to walk the length of a pre-measured course for 6 consecutive minutes (assistive devices could be used). The total distance walked at the end of 6 minutes was recorded in meters. Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline 6MWT measurement, with compound symmetry covariance structure.

Outcome measures

Outcome measures
Measure	Burosumab n=6 Participants 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.	Elbow Extension 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.
Change From Baseline Over Time in Six-Minute Walk Test (6MWT) Week 24	19.5 meters Standard Error 15.64	—
Change From Baseline Over Time in Six-Minute Walk Test (6MWT) Week 48	25.5 meters Standard Error 16.58	—

SECONDARY outcome

Timeframe: Baseline and Weeks 24, 48, 96, 144, 168, 192, 216, and 240

Population: TIO analysis set participants with available data at each time point

The Brief Pain Inventory (BPI) is a self-reported, pain-specific questionnaire with a recall period of 24 hours. Worst pain is defined as the answer to Question 3, in which participants rated their pain at its worst in the last 24 hours on a scale from 0 (no pain) to 10 (pain as bad as you can imagine). A negative change from Baseline score indicates improvement. Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline BPI measurement, with compound symmetry covariance structure.

Outcome measures

Outcome measures
Measure	Burosumab n=14 Participants 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.	Elbow Extension 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.
Change From Baseline Over Time in Brief Pain Inventory (BPI) Worst Pain Score Week 168	-0.9 score on a scale Standard Error 0.7	—
Change From Baseline Over Time in Brief Pain Inventory (BPI) Worst Pain Score Week 216	-0.9 score on a scale Standard Error 0.8	—
Change From Baseline Over Time in Brief Pain Inventory (BPI) Worst Pain Score Week 24	-0.6 score on a scale Standard Error 0.7	—
Change From Baseline Over Time in Brief Pain Inventory (BPI) Worst Pain Score Week 48	-0.9 score on a scale Standard Error 0.7	—
Change From Baseline Over Time in Brief Pain Inventory (BPI) Worst Pain Score Week 96	-0.7 score on a scale Standard Error 0.4	—
Change From Baseline Over Time in Brief Pain Inventory (BPI) Worst Pain Score Week 144	-1.1 score on a scale Standard Error 0.6	—
Change From Baseline Over Time in Brief Pain Inventory (BPI) Worst Pain Score Week 192	-0.9 score on a scale Standard Error 0.6	—
Change From Baseline Over Time in Brief Pain Inventory (BPI) Worst Pain Score Week 240	-0.9 score on a scale Standard Error 0.9	—

SECONDARY outcome

Timeframe: Baseline and Weeks 24, 48, 96, 144, 168, 192, 216, and 240

Population: TIO analysis set participants with available data at each time point

The Brief Pain Inventory (BPI) is a self-reported, pain-specific questionnaire with a recall period of 24 hours. Pain severity is defined as the average of 4 questions (Questions 3 through 6) assessing worst pain, least pain, average pain, and pain right now, rated on a scale from 0 (no pain) to 10 (pain as bad as you can imagine). Mild pain is defined as a score of 1 to 4, moderate pain is defined as a score of 5 to 6, and severe pain is defined as a score of 7 to 10. A negative change from Baseline score indicates improvement. Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline BPI measurement, with compound symmetry covariance structure.

Outcome measures

Outcome measures
Measure	Burosumab n=14 Participants 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.	Elbow Extension 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.
Change From Baseline Over Time in Brief Pain Inventory (BPI) Pain Severity Score Week 24	-0.51 score on a scale Standard Error 0.62	—
Change From Baseline Over Time in Brief Pain Inventory (BPI) Pain Severity Score Week 48	-0.87 score on a scale Standard Error 0.66	—
Change From Baseline Over Time in Brief Pain Inventory (BPI) Pain Severity Score Week 96	-0.62 score on a scale Standard Error 0.38	—
Change From Baseline Over Time in Brief Pain Inventory (BPI) Pain Severity Score Week 144	-0.99 score on a scale Standard Error 0.42	—
Change From Baseline Over Time in Brief Pain Inventory (BPI) Pain Severity Score Week 168	-1.21 score on a scale Standard Error 0.40	—
Change From Baseline Over Time in Brief Pain Inventory (BPI) Pain Severity Score Week 192	-0.81 score on a scale Standard Error 0.66	—
Change From Baseline Over Time in Brief Pain Inventory (BPI) Pain Severity Score Week 216	-0.75 score on a scale Standard Error 0.63	—
Change From Baseline Over Time in Brief Pain Inventory (BPI) Pain Severity Score Week 240	-0.91 score on a scale Standard Error 0.76	—

SECONDARY outcome

Timeframe: Baseline and Weeks 24, 48, 96, 144, 168, 192, 216, and 240

Population: TIO analysis set participants with available data at each time point

The Brief Pain Inventory (BPI) is a self-reported, pain-specific questionnaire with a recall period of 24 hours. Pain interference is defined as the average of 7 questions (9A through 9G) regarding the extent to which pain interfered with daily activities, including general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life in the last 24 hours, rated on a scale from 0 (does not interfere) to 10 (completely interferes). A negative change from Baseline score indicates improvement. Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline BPI measurement, with compound symmetry covariance structure.

Outcome measures

Outcome measures
Measure	Burosumab n=14 Participants 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.	Elbow Extension 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.
Change From Baseline Over Time in Brief Pain Inventory (BPI) Pain Interference Score Week 192	-1.11 score on a scale Standard Error 0.58	—
Change From Baseline Over Time in Brief Pain Inventory (BPI) Pain Interference Score Week 24	-1.15 score on a scale Standard Error 0.66	—
Change From Baseline Over Time in Brief Pain Inventory (BPI) Pain Interference Score Week 48	-1.09 score on a scale Standard Error 0.80	—
Change From Baseline Over Time in Brief Pain Inventory (BPI) Pain Interference Score Week 96	-1.08 score on a scale Standard Error 0.55	—
Change From Baseline Over Time in Brief Pain Inventory (BPI) Pain Interference Score Week 144	-1.46 score on a scale Standard Error 0.61	—
Change From Baseline Over Time in Brief Pain Inventory (BPI) Pain Interference Score Week 168	-1.76 score on a scale Standard Error 0.37	—
Change From Baseline Over Time in Brief Pain Inventory (BPI) Pain Interference Score Week 216	-1.56 score on a scale Standard Error 0.87	—
Change From Baseline Over Time in Brief Pain Inventory (BPI) Pain Interference Score Week 240	-2.00 score on a scale Standard Error 1.10	—

SECONDARY outcome

Timeframe: Baseline and Weeks 24, 48, 96, 144, 168, 192, 216, and 240

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

The Brief Fatigue Inventory (BFI) is a self-reported questionnaire consisting of 9 items related to fatigue that are rated on a 0 to 10 numerical rating scale with a recall period of 24 hours. Worst fatigue is defined as the answer to Question 3 in which participants rated their fatigue at its worst in the last 24 hours on a scale from 0 (no fatigue) to 10 (as bad as you can imagine). A negative change from Baseline score indicates improvement. Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline BFI measurement, with compound symmetry covariance structure.

Outcome measures

Outcome measures
Measure	Burosumab n=13 Participants 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.	Elbow Extension 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.
Change From Baseline Over Time in Brief Fatigue Inventory (BFI) Worst Fatigue Score Week 24	-1.3 score on a scale Standard Error 0.5	—
Change From Baseline Over Time in Brief Fatigue Inventory (BFI) Worst Fatigue Score Week 48	-0.9 score on a scale Standard Error 0.8	—
Change From Baseline Over Time in Brief Fatigue Inventory (BFI) Worst Fatigue Score Week 96	-1.0 score on a scale Standard Error 0.5	—
Change From Baseline Over Time in Brief Fatigue Inventory (BFI) Worst Fatigue Score Week 144	-0.9 score on a scale Standard Error 0.6	—
Change From Baseline Over Time in Brief Fatigue Inventory (BFI) Worst Fatigue Score Week 168	-1.6 score on a scale Standard Error 0.6	—
Change From Baseline Over Time in Brief Fatigue Inventory (BFI) Worst Fatigue Score Week 192	-1.0 score on a scale Standard Error 0.4	—
Change From Baseline Over Time in Brief Fatigue Inventory (BFI) Worst Fatigue Score Week 216	-2.1 score on a scale Standard Error 0.9	—
Change From Baseline Over Time in Brief Fatigue Inventory (BFI) Worst Fatigue Score Week 240	-2.6 score on a scale Standard Error 0.9	—

SECONDARY outcome

Timeframe: Baseline and Weeks 24, 48, 96, 144, 168, 192, 216, and 240

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

The Brief Fatigue Inventory (BFI) is a self-reported questionnaire consisting of 9 items related to fatigue that are rated on a 0 to 10 numerical rating scale with a recall period of 24 hours. Fatigue severity is defined as the average of 3 questions (Questions 1 through 3) assessing fatigue right now, usual level of fatigue, and worst fatigue, rated on a scale from 0 (no fatigue) to 10 (as bad as you can imagine). A negative change from Baseline score indicates improvement. Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline BFI measurement, with compound symmetry covariance structure.

Outcome measures

Outcome measures
Measure	Burosumab n=13 Participants 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.	Elbow Extension 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.
Change From Baseline Over Time in Brief Fatigue Inventory (BFI) Fatigue Severity Score Week 24	-1.47 score on a scale Standard Error 0.53	—
Change From Baseline Over Time in Brief Fatigue Inventory (BFI) Fatigue Severity Score Week 48	-1.31 score on a scale Standard Error 0.56	—
Change From Baseline Over Time in Brief Fatigue Inventory (BFI) Fatigue Severity Score Week 96	-1.58 score on a scale Standard Error 0.43	—
Change From Baseline Over Time in Brief Fatigue Inventory (BFI) Fatigue Severity Score Week 144	-1.44 score on a scale Standard Error 0.53	—
Change From Baseline Over Time in Brief Fatigue Inventory (BFI) Fatigue Severity Score Week 168	-2.34 score on a scale Standard Error 0.43	—
Change From Baseline Over Time in Brief Fatigue Inventory (BFI) Fatigue Severity Score Week 192	-1.62 score on a scale Standard Error 0.43	—
Change From Baseline Over Time in Brief Fatigue Inventory (BFI) Fatigue Severity Score Week 216	-2.62 score on a scale Standard Error 0.85	—
Change From Baseline Over Time in Brief Fatigue Inventory (BFI) Fatigue Severity Score Week 240	-2.57 score on a scale Standard Error 0.81	—

SECONDARY outcome

Timeframe: Baseline and Weeks 24, 48, 96, 144, 168, 192, 216, and 240

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

The Brief Fatigue Inventory (BFI) is a self-reported questionnaire consisting of 9 items related to fatigue that are rated on a 0 to 10 numerical rating scale with a recall period of 24 hours. The fatigue interference score is defined as the average of 6 questions (Questions 4A through 4F) regarding the extent to which fatigue interfered with daily activities, including general activity, mood, walking ability, work, relations with others, and enjoyment of life in the last 24 hours, rated on a scale from 0 (does not interfere) to 10 (completely interferes). A negative change from Baseline score indicates improvement. Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline BFI measurement, with compound symmetry covariance structure.

Outcome measures

Outcome measures
Measure	Burosumab n=13 Participants 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.	Elbow Extension 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.
Change From Baseline Over Time in Brief Fatigue Inventory (BFI) Fatigue Interference Score Week 24	-1.57 score on a scale Standard Error 0.65	—
Change From Baseline Over Time in Brief Fatigue Inventory (BFI) Fatigue Interference Score Week 48	-1.88 score on a scale Standard Error 0.66	—
Change From Baseline Over Time in Brief Fatigue Inventory (BFI) Fatigue Interference Score Week 96	-1.98 score on a scale Standard Error 0.47	—
Change From Baseline Over Time in Brief Fatigue Inventory (BFI) Fatigue Interference Score Week 144	-1.67 score on a scale Standard Error 0.44	—
Change From Baseline Over Time in Brief Fatigue Inventory (BFI) Fatigue Interference Score Week 168	-2.20 score on a scale Standard Error 0.38	—
Change From Baseline Over Time in Brief Fatigue Inventory (BFI) Fatigue Interference Score Week 192	-1.24 score on a scale Standard Error 0.59	—
Change From Baseline Over Time in Brief Fatigue Inventory (BFI) Fatigue Interference Score Week 216	-2.72 score on a scale Standard Error 1.02	—
Change From Baseline Over Time in Brief Fatigue Inventory (BFI) Fatigue Interference Score Week 240	-3.00 score on a scale Standard Error 1.14	—

SECONDARY outcome

Timeframe: Baseline and Weeks 24, 48, 96, 144, 168, 192, 216, and 240

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

The Brief Fatigue Inventory (BFI) is a self-reported questionnaire consisting of 9 items related to fatigue that are rated on a 0 to 10 numerical rating scale with a recall period of 24 hours. The first 3 questions measure fatigue severity and the next 6 questions assess the impact of fatigue on daily activities. The global fatigue score is defined as the average of all 9 questions on the BFI including severity and interference, and ranges from from 0 to 10, where higher scores correspond to greater levels of fatigue. A negative change from Baseline score indicates improvement. Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline BFI measurement, with compound symmetry covariance structure.

Outcome measures

Outcome measures
Measure	Burosumab n=13 Participants 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.	Elbow Extension 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.
Change From Baseline Over Time in Brief Fatigue Inventory (BFI) Global Fatigue Score Week 24	-1.54 score on a scale Standard Error 0.56	—
Change From Baseline Over Time in Brief Fatigue Inventory (BFI) Global Fatigue Score Week 48	-1.66 score on a scale Standard Error 0.56	—
Change From Baseline Over Time in Brief Fatigue Inventory (BFI) Global Fatigue Score Week 96	-1.83 score on a scale Standard Error 0.44	—
Change From Baseline Over Time in Brief Fatigue Inventory (BFI) Global Fatigue Score Week 144	-1.58 score on a scale Standard Error 0.44	—
Change From Baseline Over Time in Brief Fatigue Inventory (BFI) Global Fatigue Score Week 168	-2.23 score on a scale Standard Error 0.37	—
Change From Baseline Over Time in Brief Fatigue Inventory (BFI) Global Fatigue Score Week 192	-1.34 score on a scale Standard Error 0.50	—
Change From Baseline Over Time in Brief Fatigue Inventory (BFI) Global Fatigue Score Week 216	-2.66 score on a scale Standard Error 0.95	—
Change From Baseline Over Time in Brief Fatigue Inventory (BFI) Global Fatigue Score Week 240	-2.83 score on a scale Standard Error 1.02	—

SECONDARY outcome

Timeframe: Baseline and Weeks 24, 48, 96, 144, 168, 192, 216, and 240

Population: TIO analysis set participants with available data at each time point

The SF-36 v2 is a self-administered questionnaire that measures the impact of disease on overall quality of life during the past 4 weeks. The SF-36 consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The physical component summary score (PCS) is a weighted combination of the 8 subscales with positive weighting for physical functioning, role-physical, bodily pain, and general health. The PCS was calculated using norm-based scoring so that 50 is the average score and the standard deviation equals 10. Higher scores are associated with better functioning/quality of life; a positive change from Baseline score indicates an improvement. LS means and SEs were estimated from a GEE model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline SF-36, with compound symmetry covariance struct

Outcome measures

Outcome measures
Measure	Burosumab n=14 Participants 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.	Elbow Extension 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.
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Physical Component Summary Score Week 24	3.71 score on a scale Standard Error 1.42	—
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Physical Component Summary Score Week 48	5.43 score on a scale Standard Error 2.33	—
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Physical Component Summary Score Week 96	2.75 score on a scale Standard Error 1.37	—
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Physical Component Summary Score Week 144	7.98 score on a scale Standard Error 2.40	—
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Physical Component Summary Score Week 168	5.20 score on a scale Standard Error 2.14	—
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Physical Component Summary Score Week 192	3.82 score on a scale Standard Error 2.49	—
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Physical Component Summary Score Week 216	6.17 score on a scale Standard Error 2.17	—
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Physical Component Summary Score Week 240	5.82 score on a scale Standard Error 2.45	—

SECONDARY outcome

Timeframe: Baseline and Weeks 24, 48, 96, 144, 168, 192, 216, and 240

Population: TIO analysis set participants with available data at each time point

The SF-36 v2 is a self-administered questionnaire that measures the impact of disease on overall quality of life during the past 4 weeks. The SF-36 consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The physical functioning (PF) domain includes 10 questions that assess limitations in physical activities because of health problems. The PF domain score was calculated using norm-based scoring so that 50 is the average score and the standard deviation equals 10. Higher scores are associated with better functioning/quality of life; a positive change from Baseline score indicates an improvement. LS means and SEs were estimated from a GEE model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline SF-36, with compound symmetry covariance structure.

Outcome measures

Outcome measures
Measure	Burosumab n=14 Participants 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.	Elbow Extension 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.
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Physical Functioning Domain Score Week 24	2.29 score on a scale Standard Error 1.58	—
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Physical Functioning Domain Score Week 48	2.63 score on a scale Standard Error 2.51	—
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Physical Functioning Domain Score Week 96	3.77 score on a scale Standard Error 1.58	—
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Physical Functioning Domain Score Week 144	7.89 score on a scale Standard Error 2.00	—
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Physical Functioning Domain Score Week 168	5.50 score on a scale Standard Error 2.24	—
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Physical Functioning Domain Score Week 192	3.02 score on a scale Standard Error 2.04	—
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Physical Functioning Domain Score Week 216	6.75 score on a scale Standard Error 1.96	—
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Physical Functioning Domain Score Week 240	4.56 score on a scale Standard Error 3.11	—

SECONDARY outcome

Timeframe: Baseline and Weeks 24, 48, 96, 144, 168, 192, 216, and 240

Population: TIO analysis set participants with available data at each time point

The SF-36 v2 is a self-administered questionnaire that measures the impact of disease on overall quality of life during the past 4 weeks. The SF-36 consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The role-physical (RP) domain includes 4 questions that assess limitations in usual role activities because of physical health problems. The RP domain score was calculated using norm-based scoring so that 50 is the average score and the standard deviation equals 10. Higher scores are associated with better functioning/quality of life; a positive change from Baseline score indicates an improvement. LS means and SEs were estimated from a GEE model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline SF-36, with compound symmetry covariance structure.

Outcome measures

Outcome measures
Measure	Burosumab n=14 Participants 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.	Elbow Extension 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.
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Role Physical Domain Score Week 24	4.85 score on a scale Standard Error 1.74	—
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Role Physical Domain Score Week 48	5.00 score on a scale Standard Error 2.83	—
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Role Physical Domain Score Week 96	3.25 score on a scale Standard Error 1.63	—
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Role Physical Domain Score Week 144	5.53 score on a scale Standard Error 2.81	—
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Role Physical Domain Score Week 168	5.70 score on a scale Standard Error 1.93	—
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Role Physical Domain Score Week 192	5.03 score on a scale Standard Error 2.80	—
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Role Physical Domain Score Week 216	4.82 score on a scale Standard Error 3.01	—
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Role Physical Domain Score Week 240	8.99 score on a scale Standard Error 3.28	—

SECONDARY outcome

Timeframe: Baseline and Weeks 24, 48, 96, 144, 168, 192, 216, and 240

Population: TIO analysis set participants with available data at each time point

The SF-36 v2 is a self-administered questionnaire that measures the impact of disease on overall quality of life during the past 4 weeks. The SF-36 consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The bodily pain (BP) domain includes 2 questions that assess pain level and impact of pain on normal work. The BP domain score was calculated using norm-based scoring so that 50 is the average score and the standard deviation equals 10. Higher scores are associated with better functioning/quality of life; a positive change from Baseline score indicates an improvement. LS means and SEs were estimated from a GEE model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline SF-36, with compound symmetry covariance structure.

Outcome measures

Outcome measures
Measure	Burosumab n=14 Participants 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.	Elbow Extension 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.
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Bodily Pain Domain Score Week 24	1.61 score on a scale Standard Error 1.65	—
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Bodily Pain Domain Score Week 48	3.61 score on a scale Standard Error 1.48	—
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Bodily Pain Domain Score Week 96	2.52 score on a scale Standard Error 1.08	—
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Bodily Pain Domain Score Week 144	5.40 score on a scale Standard Error 1.90	—
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Bodily Pain Domain Score Week 168	5.01 score on a scale Standard Error 2.16	—
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Bodily Pain Domain Score Week 192	4.92 score on a scale Standard Error 2.81	—
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Bodily Pain Domain Score Week 216	6.64 score on a scale Standard Error 1.88	—
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Bodily Pain Domain Score Week 240	6.59 score on a scale Standard Error 2.20	—

SECONDARY outcome

Timeframe: Baseline and Weeks 24, 48, 96, 144, 168, 192, 216, and 240

Population: TIO analysis set participants with available data at each time point

The SF-36 v2 is a self-administered questionnaire that measures the impact of disease on overall quality of life during the past 4 weeks. The SF-36 consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The general health perceptions (GH) domain includes 5 questions that assess participants' perception of their own general health. The GH domain score was calculated using norm-based scoring so that 50 is the average score and the standard deviation equals 10. Higher scores are associated with better functioning/quality of life; a positive change from Baseline score indicates an improvement. LS means and SEs were estimated from a GEE model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline SF-36, with compound symmetry covariance structure.

Outcome measures

Outcome measures
Measure	Burosumab n=14 Participants 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.	Elbow Extension 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.
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) General Health Perceptions Domain Score Week 24	2.38 score on a scale Standard Error 1.88	—
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) General Health Perceptions Domain Score Week 48	6.09 score on a scale Standard Error 2.28	—
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) General Health Perceptions Domain Score Week 96	1.03 score on a scale Standard Error 1.96	—
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) General Health Perceptions Domain Score Week 144	3.12 score on a scale Standard Error 2.64	—
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) General Health Perceptions Domain Score Week 168	-0.32 score on a scale Standard Error 2.51	—
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) General Health Perceptions Domain Score Week 192	-1.60 score on a scale Standard Error 2.94	—
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) General Health Perceptions Domain Score Week 216	-1.51 score on a scale Standard Error 2.05	—
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) General Health Perceptions Domain Score Week 240	1.81 score on a scale Standard Error 3.30	—

SECONDARY outcome

Timeframe: Baseline and Weeks 24, 48, 96, 144, 168, 192, 216, and 240

Population: TIO analysis set participants with available data at each time point

The SF-36 v2 is a self-administered questionnaire that measures the impact of disease on overall quality of life during the past 4 weeks. The SF-36 consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The mental component summary score (MCS) is a weighted combination of the 8 subscales with positive weighting for vitality, social function, role limitations due to emotional problems, and mental health. The MCS was calculated using norm-based scoring so that 50 is the average score and the standard deviation equals 10. Higher scores are associated with better functioning/quality of life; a positive change from Baseline indicates an improvement. LS means and SEs were estimated from a GEE model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline SF-36, with compound symmetry covariance structure.

Outcome measures

Outcome measures
Measure	Burosumab n=14 Participants 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.	Elbow Extension 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.
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Mental Component Summary Score Week 24	1.07 score on a scale Standard Error 2.38	—
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Mental Component Summary Score Week 48	1.37 score on a scale Standard Error 2.47	—
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Mental Component Summary Score Week 96	3.91 score on a scale Standard Error 2.53	—
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Mental Component Summary Score Week 144	-0.85 score on a scale Standard Error 2.29	—
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Mental Component Summary Score Week 168	2.05 score on a scale Standard Error 1.81	—
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Mental Component Summary Score Week 192	0.55 score on a scale Standard Error 2.95	—
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Mental Component Summary Score Week 216	0.51 score on a scale Standard Error 2.67	—
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Mental Component Summary Score Week 240	5.13 score on a scale Standard Error 3.59	—

SECONDARY outcome

Timeframe: Baseline and Weeks 24, 48, 96, 144, 168, 192, 216, and 240

Population: TIO analysis set participants with available data at each time point

The SF-36 v2 is a self-administered questionnaire that measures the impact of disease on overall quality of life during the past 4 weeks. The SF-36 consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The vitality (VT) domain includes 4 questions that assess energy levels and fatigue. The VT domain score was calculated using norm-based scoring so that 50 is the average score and the standard deviation equals 10. Higher scores are associated with better functioning/quality of life; a positive change from Baseline score indicates an improvement. LS means and SEs were estimated from a GEE model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline SF-36, with compound symmetry covariance structure.

Outcome measures

Outcome measures
Measure	Burosumab n=14 Participants 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.	Elbow Extension 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.
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Vitality Domain Score Week 24	5.98 score on a scale Standard Error 1.96	—
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Vitality Domain Score Week 48	5.27 score on a scale Standard Error 2.42	—
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Vitality Domain Score Week 96	6.71 score on a scale Standard Error 2.64	—
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Vitality Domain Score Week 144	3.05 score on a scale Standard Error 2.30	—
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Vitality Domain Score Week 168	6.04 score on a scale Standard Error 2.74	—
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Vitality Domain Score Week 192	2.78 score on a scale Standard Error 2.85	—
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Vitality Domain Score Week 216	6.79 score on a scale Standard Error 3.77	—
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Vitality Domain Score Week 240	8.06 score on a scale Standard Error 4.03	—

SECONDARY outcome

Timeframe: Baseline and Weeks 24, 48, 96, 144, 168, 192, 216, and 240

Population: TIO analysis set participants with available data at each time point

The SF-36 v2 is a self-administered questionnaire that measures the impact of disease on overall quality of life during the past 4 weeks. The SF-36 consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The social functioning (SF) domain includes 2 questions that assess limitations in social activities because of physical health or emotional problems. The SF domain score was calculated using norm-based scoring so that 50 is the average score and the standard deviation equals 10. Higher scores are associated with better functioning/quality of life; a positive change from Baseline score indicates an improvement. LS means and SEs were estimated from a GEE model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline SF-36, with compound symmetry covariance structure.

Outcome measures

Outcome measures
Measure	Burosumab n=14 Participants 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.	Elbow Extension 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.
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Social Functioning Domain Score Week 24	2.02 score on a scale Standard Error 2.24	—
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Social Functioning Domain Score Week 48	5.54 score on a scale Standard Error 2.48	—
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Social Functioning Domain Score Week 96	4.63 score on a scale Standard Error 1.34	—
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Social Functioning Domain Score Week 144	3.22 score on a scale Standard Error 2.71	—
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Social Functioning Domain Score Week 168	5.34 score on a scale Standard Error 2.06	—
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Social Functioning Domain Score Week 192	2.84 score on a scale Standard Error 2.62	—
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Social Functioning Domain Score Week 216	4.15 score on a scale Standard Error 2.08	—
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Social Functioning Domain Score Week 240	6.30 score on a scale Standard Error 2.98	—

SECONDARY outcome

Timeframe: Baseline and Weeks 24, 48, 96, 144, 168, 192, 216, and 240

Population: TIO analysis set participants with available data at each time point

The SF-36 v2 is a self-administered questionnaire that measures the impact of disease on overall quality of life during the past 4 weeks. The SF-36 consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The role-emotional (RE) domain includes 3 questions that assess limitations in usual role activities because of emotional problems. The RE domain score was calculated using norm-based scoring so that 50 is the average score and the standard deviation equals 10. Higher scores are associated with better functioning/quality of life; a positive change from Baseline score indicates an improvement. LS means and SEs were estimated from a GEE model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline SF-36, with compound symmetry covariance structure.

Outcome measures

Outcome measures
Measure	Burosumab n=14 Participants 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.	Elbow Extension 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.
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Role Emotional Domain Score Week 24	1.52 score on a scale Standard Error 1.98	—
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Role Emotional Domain Score Week 48	1.13 score on a scale Standard Error 2.72	—
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Role Emotional Domain Score Week 96	6.73 score on a scale Standard Error 3.03	—
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Role Emotional Domain Score Week 144	2.10 score on a scale Standard Error 2.60	—
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Role Emotional Domain Score Week 168	4.90 score on a scale Standard Error 2.22	—
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Role Emotional Domain Score Week 192	3.51 score on a scale Standard Error 3.47	—
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Role Emotional Domain Score Week 216	3.56 score on a scale Standard Error 3.08	—
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Role Emotional Domain Score Week 240	6.04 score on a scale Standard Error 3.69	—

SECONDARY outcome

Timeframe: Baseline and Weeks 24, 48, 96, 144, 168, 192, 216, and 240

Population: TIO analysis set participants with available data at each time point

The SF-36 v2 is a self-administered questionnaire that measures the impact of disease on overall quality of life during the past 4 weeks. The SF-36 consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The mental health (MH) domain includes 5 questions that assess general mental health (psychological distress and well-being). The MH domain score was calculated using norm-based scoring so that 50 is the average score and the standard deviation equals 10. Higher scores are associated with better functioning/quality of life; a positive change from Baseline score indicates an improvement. LS means and SEs were estimated from a GEE model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline SF-36, with compound symmetry covariance structure.

Outcome measures

Outcome measures
Measure	Burosumab n=14 Participants 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.	Elbow Extension 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.
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Mental Health Domain Score Week 24	-0.46 score on a scale Standard Error 2.54	—
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Mental Health Domain Score Week 48	-0.32 score on a scale Standard Error 2.48	—
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Mental Health Domain Score Week 96	-0.58 score on a scale Standard Error 2.12	—
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Mental Health Domain Score Week 144	-0.17 score on a scale Standard Error 1.97	—
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Mental Health Domain Score Week 168	-0.97 score on a scale Standard Error 1.61	—
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Mental Health Domain Score Week 192	-1.24 score on a scale Standard Error 2.23	—
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Mental Health Domain Score Week 216	-2.11 score on a scale Standard Error 2.87	—
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Mental Health Domain Score Week 240	3.50 score on a scale Standard Error 3.10	—

OTHER_PRE_SPECIFIED outcome

Timeframe: From first dose of study drug up to database lock date (July 07, 2021); median duration of treatment in the TIO analysis set was 1594.0 (range: 168-2106) days.

Population: TIO analysis set

An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug, whether or not considered drug related. A serious AE was defined as an AE that at any dose, in the view of either the Investigator or Sponsor, results in any of the following outcomes: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant incapacity or disability, a congenital anomaly/birth defect, or other important medical events (according to the investigator). An AE was considered a TEAE if it occurred on or after the first dose and was not present prior to the first dose, or it was present prior to the first dose but increased in severity during the study. Events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0: grade 1 (mild), grade 2 (moderate), grade 3 (severe), grade 4 (life-threatening), grade 5 (death).

Outcome measures

Outcome measures
Measure	Burosumab n=14 Participants 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.	Elbow Extension 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.
Number of Participants With Adverse Events (AEs), Treatment Emergent AEs (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation Any adverse event	14 Participants	—
Number of Participants With Adverse Events (AEs), Treatment Emergent AEs (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation Serious adverse events (SAEs)	8 Participants	—
Number of Participants With Adverse Events (AEs), Treatment Emergent AEs (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation Related adverse events	9 Participants	—
Number of Participants With Adverse Events (AEs), Treatment Emergent AEs (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation Serious related adverse events	0 Participants	—
Number of Participants With Adverse Events (AEs), Treatment Emergent AEs (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation Grade 3 or 4 adverse event	8 Participants	—
Number of Participants With Adverse Events (AEs), Treatment Emergent AEs (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation TEAE leading to study discontinuation	0 Participants	—
Number of Participants With Adverse Events (AEs), Treatment Emergent AEs (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation TEAE leading to treatment discontinuation	1 Participants	—
Number of Participants With Adverse Events (AEs), Treatment Emergent AEs (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation TEAE leading to death	2 Participants	—

OTHER_PRE_SPECIFIED outcome

Timeframe: From first dose of study drug up to database lock date (July 07, 2021); median duration of treatment in the TIO analysis set was 1594.0 (range: 168-2106) days.

Population: TIO analysis set

Outcome measures

Outcome measures
Measure	Burosumab n=14 Participants 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.	Elbow Extension 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.
Number of Participants With Anti-burosumab Antibodies Anti-burosumab binding antibodies	2 Participants	—
Number of Participants With Anti-burosumab Antibodies Anti-burosumab neutralizing antibodies	0 Participants	—

Adverse Events

KRN23 TIO

Serious events: 8 serious events

Other events: 14 other events

Deaths: 2 deaths

KRN23 XLH and ENS

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Information

Ultragenyx Pharmaceutical Inc

Phone: 1-888-756-8657

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.
Publication restrictions are in place

Restriction type: OTHER

Measure	KRN23 TIO n=14 participants at risk Participants with TIO 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.	KRN23 XLH and ENS n=3 participants at risk Participants with XLH and ENS 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.
Cardiac disorders Cardiac Arrest	14.3% 2/14 • From first dose of study drug up to database lock date (July 07, 2021); median duration of treatment in the TIO analysis set was 1594.0 (range: 168-2106) days.	0.00% 0/3 • From first dose of study drug up to database lock date (July 07, 2021); median duration of treatment in the TIO analysis set was 1594.0 (range: 168-2106) days.
Cardiac disorders Pulseless Electrical Activity	7.1% 1/14 • From first dose of study drug up to database lock date (July 07, 2021); median duration of treatment in the TIO analysis set was 1594.0 (range: 168-2106) days.	0.00% 0/3 • From first dose of study drug up to database lock date (July 07, 2021); median duration of treatment in the TIO analysis set was 1594.0 (range: 168-2106) days.
Gastrointestinal disorders Ascites	7.1% 1/14 • From first dose of study drug up to database lock date (July 07, 2021); median duration of treatment in the TIO analysis set was 1594.0 (range: 168-2106) days.	0.00% 0/3 • From first dose of study drug up to database lock date (July 07, 2021); median duration of treatment in the TIO analysis set was 1594.0 (range: 168-2106) days.
Gastrointestinal disorders Pancreatitis	7.1% 1/14 • From first dose of study drug up to database lock date (July 07, 2021); median duration of treatment in the TIO analysis set was 1594.0 (range: 168-2106) days.	0.00% 0/3 • From first dose of study drug up to database lock date (July 07, 2021); median duration of treatment in the TIO analysis set was 1594.0 (range: 168-2106) days.
General disorders Multi-Organ Failure	7.1% 1/14 • From first dose of study drug up to database lock date (July 07, 2021); median duration of treatment in the TIO analysis set was 1594.0 (range: 168-2106) days.	0.00% 0/3 • From first dose of study drug up to database lock date (July 07, 2021); median duration of treatment in the TIO analysis set was 1594.0 (range: 168-2106) days.
Hepatobiliary disorders Cholangitis	7.1% 1/14 • From first dose of study drug up to database lock date (July 07, 2021); median duration of treatment in the TIO analysis set was 1594.0 (range: 168-2106) days.	0.00% 0/3 • From first dose of study drug up to database lock date (July 07, 2021); median duration of treatment in the TIO analysis set was 1594.0 (range: 168-2106) days.
Infections and infestations Septic Shock	7.1% 1/14 • From first dose of study drug up to database lock date (July 07, 2021); median duration of treatment in the TIO analysis set was 1594.0 (range: 168-2106) days.	0.00% 0/3 • From first dose of study drug up to database lock date (July 07, 2021); median duration of treatment in the TIO analysis set was 1594.0 (range: 168-2106) days.
Infections and infestations Sialoadenitis	7.1% 1/14 • From first dose of study drug up to database lock date (July 07, 2021); median duration of treatment in the TIO analysis set was 1594.0 (range: 168-2106) days.	0.00% 0/3 • From first dose of study drug up to database lock date (July 07, 2021); median duration of treatment in the TIO analysis set was 1594.0 (range: 168-2106) days.
Infections and infestations Tooth Abscess	7.1% 1/14 • From first dose of study drug up to database lock date (July 07, 2021); median duration of treatment in the TIO analysis set was 1594.0 (range: 168-2106) days.	0.00% 0/3 • From first dose of study drug up to database lock date (July 07, 2021); median duration of treatment in the TIO analysis set was 1594.0 (range: 168-2106) days.
Metabolism and nutrition disorders Hypophosphataemia	7.1% 1/14 • From first dose of study drug up to database lock date (July 07, 2021); median duration of treatment in the TIO analysis set was 1594.0 (range: 168-2106) days.	0.00% 0/3 • From first dose of study drug up to database lock date (July 07, 2021); median duration of treatment in the TIO analysis set was 1594.0 (range: 168-2106) days.
Musculoskeletal and connective tissue disorders Rheumatoid Arthritis	7.1% 1/14 • From first dose of study drug up to database lock date (July 07, 2021); median duration of treatment in the TIO analysis set was 1594.0 (range: 168-2106) days.	0.00% 0/3 • From first dose of study drug up to database lock date (July 07, 2021); median duration of treatment in the TIO analysis set was 1594.0 (range: 168-2106) days.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases To Lung	7.1% 1/14 • From first dose of study drug up to database lock date (July 07, 2021); median duration of treatment in the TIO analysis set was 1594.0 (range: 168-2106) days.	0.00% 0/3 • From first dose of study drug up to database lock date (July 07, 2021); median duration of treatment in the TIO analysis set was 1594.0 (range: 168-2106) days.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm Progression	28.6% 4/14 • From first dose of study drug up to database lock date (July 07, 2021); median duration of treatment in the TIO analysis set was 1594.0 (range: 168-2106) days.	0.00% 0/3 • From first dose of study drug up to database lock date (July 07, 2021); median duration of treatment in the TIO analysis set was 1594.0 (range: 168-2106) days.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian Cancer	7.1% 1/14 • From first dose of study drug up to database lock date (July 07, 2021); median duration of treatment in the TIO analysis set was 1594.0 (range: 168-2106) days.	0.00% 0/3 • From first dose of study drug up to database lock date (July 07, 2021); median duration of treatment in the TIO analysis set was 1594.0 (range: 168-2106) days.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour Compression	7.1% 1/14 • From first dose of study drug up to database lock date (July 07, 2021); median duration of treatment in the TIO analysis set was 1594.0 (range: 168-2106) days.	0.00% 0/3 • From first dose of study drug up to database lock date (July 07, 2021); median duration of treatment in the TIO analysis set was 1594.0 (range: 168-2106) days.
Renal and urinary disorders Acute Kidney Injury	7.1% 1/14 • From first dose of study drug up to database lock date (July 07, 2021); median duration of treatment in the TIO analysis set was 1594.0 (range: 168-2106) days.	0.00% 0/3 • From first dose of study drug up to database lock date (July 07, 2021); median duration of treatment in the TIO analysis set was 1594.0 (range: 168-2106) days.
Respiratory, thoracic and mediastinal disorders Acute Respiratory Failure	14.3% 2/14 • From first dose of study drug up to database lock date (July 07, 2021); median duration of treatment in the TIO analysis set was 1594.0 (range: 168-2106) days.	0.00% 0/3 • From first dose of study drug up to database lock date (July 07, 2021); median duration of treatment in the TIO analysis set was 1594.0 (range: 168-2106) days.
Respiratory, thoracic and mediastinal disorders Pickwickian Syndrome	7.1% 1/14 • From first dose of study drug up to database lock date (July 07, 2021); median duration of treatment in the TIO analysis set was 1594.0 (range: 168-2106) days.	0.00% 0/3 • From first dose of study drug up to database lock date (July 07, 2021); median duration of treatment in the TIO analysis set was 1594.0 (range: 168-2106) days.
Respiratory, thoracic and mediastinal disorders Pleural Effusion	7.1% 1/14 • From first dose of study drug up to database lock date (July 07, 2021); median duration of treatment in the TIO analysis set was 1594.0 (range: 168-2106) days.	0.00% 0/3 • From first dose of study drug up to database lock date (July 07, 2021); median duration of treatment in the TIO analysis set was 1594.0 (range: 168-2106) days.
Respiratory, thoracic and mediastinal disorders Pulmonary Embolism	7.1% 1/14 • From first dose of study drug up to database lock date (July 07, 2021); median duration of treatment in the TIO analysis set was 1594.0 (range: 168-2106) days.	0.00% 0/3 • From first dose of study drug up to database lock date (July 07, 2021); median duration of treatment in the TIO analysis set was 1594.0 (range: 168-2106) days.