Efficacy and Safety of Burosumab Versus Oral Phosphate an... | NCT02915705

Name	Class
Kyowa Kirin Co., Ltd.	INDUSTRY

Label	Type	Description	Intervention Names
Burosumab	Experimental	Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants continued to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.	Biological: burosumab
Active Control	Active Comparator	Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.	Biological: burosumab Drug: Oral Phosphate Supplement Drug: active vitamin D

Name	Type	Description	Arm Group Labels	Other Names
burosumab	Biological	solution for subcutaneous (SC) injection	Active Control Burosumab

Measure	Description	Time Frame
Radiographic Global Impression of Change (RGI-C) Global Score at Week 40	Changes in the severity of rickets and bowing were assessed using a disease specific qualitative RGI-C scoring system. The RGI-C is a 7-point ordinal scale with possible values: +3 = very much better (complete or near complete healing of rickets), +2 = much better (substantial healing of rickets), +1 = minimally better (i.e., minimal healing of rickets), 0 = unchanged, -1 = minimally worse (minimal worsening of rickets), -2 = much worse (moderate worsening of rickets), -3 = very much worse (severe worsening of rickets).	Week 40

Measure	Description	Time Frame
Percentage of Participants With a Mean RGI-C Global Score ≥ +2.0 (Responders) at Week 40	RGI-C responders are defined as participants with a mean RGI-C global score >= +2.0. The RGI-C is a 7-point ordinal scale with possible values: +3 = very much better (complete or near complete healing of rickets), +2 = much better (substantial healing of rickets), +1 = minimally better (i.e., minimal healing of rickets), 0 = unchanged, -1 = minimally worse (minimal worsening of rickets), -2 = much worse (moderate worsening of rickets), -3 = very much worse (severe worsening of rickets).

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Male or female, aged 1 to ≤12 years with radiographic evidence of rickets as determined by central readers
Phosphate-regulating endopeptidase homolog, X-linked (PHEX) mutation or variant of uncertain significance in either the patient or in a directly related family member with appropriate X-linked inheritance
Biochemical findings associated with XLH: serum phosphorus <3.0 mg/dL (<0.97 mmol/L)
Serum creatinine below the age-adjusted upper limit of normal
Serum 25(OH)D above the lower limit of normal (≥16 ng/mL) at the Screening Visit
Have received both oral phosphate and active vitamin D therapy for ≥ 12 consecutive months (for children ≥3 years of age) or ≥ 6 consecutive months (for children <3 years of age) 7 days prior to the Randomization Visit
Willing to provide access to prior medical records for the collection of historical growth and radiographic data and disease history
Provide written or verbal assent (as appropriate for the subject and region) and written informed consent by a legally authorized representative after the nature of the study has been explained, and prior to any research-related procedures.
Must, in the opinion of the investigator, be willing and able to complete all aspects of the study, adhere to the study visit schedule and comply with the assessments
Females who have reached menarche must have a negative pregnancy test at Screening and undergo additional pregnancy testing during the study. Female subjects of childbearing potential must be willing to use a highly effective method of contraception for the duration of the study plus 12 weeks after stopping the study drug. Sexually active male subjects with female partners of childbearing potential must consent to use a condom with spermicide or a highly effective method of contraception for the duration of the study plus 12 weeks after stopping the study drug

Exclusion Criteria:

Tanner stage 4 or higher in any of the following: genitals, breast, or pubic hair, based on physical examination
Height percentile > 50th based on country-specific norms
Use of aluminum hydroxide antacids (eg, Maalox® and Mylanta®), systemic corticosteroids, acetazolamide, and thiazides within 7 days prior to the Screening Visit
Current or prior use of leuprorelin (eg, Lupron®, Viadur®, Eligard®), triptorelin (TRELSTAR®), goserelin (Zoladex®), or other drugs known to delay puberty
Use of growth hormone therapy within 12 months before the Screening Visit
Presence of nephrocalcinosis on renal ultrasound grade 4
Planned orthopedic surgery, including osteotomy or implantation or removal of staples, 8 plates, or any other hardware, within the first 40 weeks of the study
Hypocalcemia or hypercalcemia, defined as serum calcium levels outside the age-adjusted normal limits
Evidence of hyperparathyroidism (parathyroid hormone [PTH] levels 2.5X upper limit of normal [ULN])
Use of medication to suppress PTH (eg, cinacalcet, calcimimetics) within 2 months prior to the Screening Visit
Presence or history of any condition that, in the view of the investigator, places the subject at high risk of poor treatment compliance or of not completing the study.
Presence of a concurrent disease or condition that would interfere with study participation or affect safety
History of recurrent infection or predisposition to infection, or of known immunodeficiency
Use of a therapeutic monoclonal antibody within 90 days prior to the Screening Visit or history of allergic or anaphylactic reactions to any monoclonal antibody
Presence or history of any hypersensitivity to KRN23 excipients that, in the judgment of the investigator, places the subject at increased risk for adverse effects
Use of any investigational product or investigational medical device within 30 days prior to screening, or requirement for any investigational agent prior to completion of all scheduled study assessments. OR, in Japan, use of any investigational product or investigational medical device within 4 months prior to screening, or requirement for any investigational agent prior to completion of all scheduled study assessments

Name	Affiliation	Role
Medical Director	Ultragenyx Pharmaceutical Inc	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Children's Hospital Los Angeles		Los Angeles	California	90027	United States
UCSF

PubMed Identifier	Type	Citation	Retractions
39151033	Derived	Portale AA, Ward L, Dahir K, Florenzano P, Ing SW, Jan de Beur SM, Martin RM, Meza-Martinez AI, Paloian N, Ashraf A, Dixon BP, Khan A, Langman C, Chen A, Wang C, Roberts MS, Tandon PK, Bedrosian C, Imel EA. Nephrocalcinosis and kidney function in children and adults with X-linked hypophosphatemia: baseline results from a large longitudinal study. J Bone Miner Res. 2024 Sep 26;39(10):1493-1502. doi: 10.1093/jbmr/zjae127.
37084401

ID	Title	Description
FG000	Active Control	Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Nov 3, 2017	Feb 27, 2019

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

age at first dose

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	OG0000.77± 0.107 OG0011.92± 0.110

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Least squares (LS) mean, standard error (SE), confidence interval (CI), and 2-sided p value per ANCOVA model, which included RGI-C as the dependent variable, treatment group and baseline age stratification factor as independent variables and baseline RSS score as a continuous covariate.	ANCOVA		< 0.0001		LS Mean Difference	1.14			2-Sided	95	0.83	1.45					Superiority

Secondary

Percentage of Participants With a Mean RGI-C Global Score ≥ +2.0 (Responders) at Week 40

RGI-C responders are defined as participants with a mean RGI-C global score >= +2.0. The RGI-C is a 7-point ordinal scale with possible values: +3 = very much better (complete or near complete healing of rickets), +2 = much better (substantial healing of rickets), +1 = minimally better (i.e., minimal healing of rickets), 0 = unchanged, -1 = minimally worse (minimal worsening of rickets), -2 = much worse (moderate worsening of rickets), -3 = very much worse (severe worsening of rickets).

Full Analysis Set: all randomized participants who received at least one dose of assigned medication and had at least one post-baseline assessment.

Posted

Number

percentage of participants

Week 40

ID	Title	Description
OG000	Active Control	Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
OG001	Burosumab	Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants continued to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.

Secondary

Percentage of Participants With a Mean RGI-C Global Score ≥ +2.0 (Responders) at Week 64

Full Analysis Set: all randomized participants who received at least one dose of assigned medication and had at least one post-baseline assessment.

Posted

Number

percentage of participants

Week 64

ID	Title	Description
OG000	Active Control	Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
OG001	Burosumab	Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants continued to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.

Secondary

RGI-C Global Score at Week 64

Full Analysis Set: all randomized participants who received at least one dose of assigned medication and had at least one post-baseline assessment.

Posted

Least Squares Mean

Standard Error

score on a scale

Week 64

ID	Title	Description
OG000	Active Control	Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
OG001	Burosumab	Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants continued to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.

Secondary

Change From Baseline in RSS Total Score at Week 40

The RSS system is a 10-point radiographic scoring method that was developed to assess the severity of nutritional rickets in the wrists and knees based on the degree of metaphyseal fraying, cupping, lucency, separation, and the proportion of the growth plate affected. Scores are assigned for the unilateral wrist and knee X-rays deemed by the rater to be the more severe of the bilateral images. The maximum total score on the RSS is 10 points and the minimum score is 0, with a total possible score of 4 points for the wrists and 6 points for the knees (the total score is the sum of the wrist and knee score). Higher scores indicate greater rickets severity.

Full Analysis Set: all randomized participants who received at least one dose of assigned medication and had at least one post-baseline RSS Total Score assessment.

Posted

Least Squares Mean

Standard Error

score on a scale

Baseline, Week 40

ID	Title	Description
OG000	Active Control	Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
OG001	Burosumab

Secondary

Change From Baseline in RSS Total Score at Week 64

The RSS system is a 10-point radiographic scoring method that was developed to assess the severity of nutritional rickets in the wrists and knees based on the degree of metaphyseal fraying, cupping, and the proportion of the growth plate affected. Scores are assigned for the unilateral wrist and knee X-rays deemed by the rater to be the more severe of the bilateral images. The maximum total score on the RSS is 10 points and the minimum score is 0, with a total possible score of 4 points for the wrists and 6 points for the knees. Higher scores indicate greater rickets severity.

Full Analysis Set: all randomized participants who received at least one dose of assigned medication and had at least one post-baseline RSS Total Score assessment.

Posted

Least Squares Mean

Standard Error

score on a scale

Baseline, Week 64

ID	Title	Description
OG000	Active Control	Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
OG001	Burosumab	Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants continued to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.

Secondary

RGI-C Long Leg Score at Week 40

Changes in the severity of lower extremity skeletal abnormalities, including genu varum and genu valgus, were assessed using a disease specific qualitative RGI-C scoring system. The RGI-C is a 7-point ordinal scale with possible values: +3 = very much better (complete or near complete healing), +2 = much better (substantial healing), +1 = minimally better (i.e., minimal healing), 0 = unchanged, -1 = minimally worse (minimal worsening), -2 = much worse (moderate worsening), -3 = very much worse (severe worsening).

Full Analysis Set: all randomized participants who received at least one dose of assigned medication and had at least one post-baseline assessment.

Posted

Least Squares Mean

Standard Error

score on a scale

Week 40

ID	Title	Description
OG000	Active Control	Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
OG001	Burosumab	Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants continued to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.

Secondary

RGI-C Long Leg Score at Week 64

Full Analysis Set: all randomized participants who received at least one dose of assigned medication and had at least one post-baseline assessment.

Posted

Least Squares Mean

Standard Error

score on a scale

Week 64

ID	Title	Description
OG000	Active Control	Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
OG001	Burosumab	Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants continued to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.

Secondary

Change From Baseline in Height-For-Age Z-Scores to Week 40

Full Analysis Set: all randomized participants who received at least one dose of assigned medication and had at least one post-baseline assessment. Participants with an assessment at Week 40.

Posted

Least Squares Mean

Standard Error

Z score

Baseline, Week 40

ID	Title	Description
OG000	Active Control	Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
OG001	Burosumab	Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants continued to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.

Secondary

Change From Baseline in Height-For-Age Z-Scores to Week 64

Recumbent length/Standing height z scores are measures of height adjusted for a child's age and sex. The Z-score indicates the number of standard deviations away from a reference population (from the CDC growth charts) in the same age range and with the same sex. A Z-score of 0 is equal to the mean with negative numbers indicating values lower than the mean and positive values higher. Higher Z-scores indicate a better outcome.

Full Analysis Set: all randomized participants who received at least one dose of assigned medication and had at least one post-baseline assessment. Participants with an assessment at Week 64.

Posted

Least Squares Mean

Standard Error

Z score

Baseline, Week 64

ID	Title	Description
OG000	Active Control	Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
OG001	Burosumab	Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants continued to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.

Secondary

Change in Growth Velocity Z Score From Baseline to Week 40

A growth velocity Z score was calculated based on Tanner's standard. The Z score indicates the number of standard deviations away from a reference population (from Tanner's standard) in the same age range and with the same sex. The baseline growth velocity was calculated for participants who had data available from within 1.5 years prior to baseline. The Week 64 growth velocity was calculated using data between baseline and Week 64. The mid-point of the age interval was used to locate the closest reference age provided by Tanner's Standard. Children with a mid-point age under 2.25 years were excluded, because younger ages are not available in Tanner's standard. To smoothly transition from recumbent length to standing height, 0·8 cm was subtracted from recumbent length before pooling with standing height. A Z score of 0 is equal to the mean with negative numbers indicating values lower than the mean and positive values higher. Higher Z scores indicate a better outcome.

Full Analysis Set: all randomized participants who received at least one dose of assigned medication and had at least one post-baseline assessment. Participants with Baseline growth velocity.

Posted

Least Squares Mean

Standard Error

Z score

Baseline, Week 40

ID	Title	Description
OG000	Active Control	Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.

Secondary

Change in Growth Velocity Z Score From Baseline to Week 64

Full Analysis Set: all randomized participants who received at least one dose of assigned medication and had at least one post-baseline assessment. Participants with Baseline growth velocity.

Posted

Least Squares Mean

Standard Error

Z score

Baseline, Week 64

ID	Title	Description
OG000	Active Control	Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.

Secondary

Change From Baseline Over Time in Serum Phosphorus Concentration, up to Week 64

The GEE model includes change from baseline for serum phosphorous measurement as the dependent variable, treatment group, visit, interaction between treatment group by visit, baseline age and baseline RSS stratification as factors, baseline phosphorous measure as a covariate, with exchangeable covariance structure. The GEE model included data up to Week 64.

Pharmacodynamic (PD) Analysis Set: all participants who received at least one dose of study therapy and had evaluable serum data. Participants with data at given time point.

Posted

Least Squares Mean

Standard Error

mg/dL

Baseline, Weeks 1, 2, 4, 8, 12, 16, 24, 32, 33, 40, 52, 64

ID	Title	Description
OG000	Active Control	Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
OG001	Burosumab	Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants continued to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.

Secondary

Change From Baseline Over Time in Serum Phosphorus Concentration, Weeks 66-112

PD Analysis Set: all participants who received at least one dose of study therapy and had evaluable serum data. Participants with an assessment at given time point.

Posted

Mean

Standard Deviation

mg/dL

Baseline, Weeks 66, 68, 76, 88, 100, 112

ID	Title	Description
OG000	Active Control	Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
OG001	Burosumab	Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants continued to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.

Units	Counts

Secondary

Change From Baseline in Mean Post-Baseline Serum Phosphorus Level to Week 64

The ANCOVA model includes change in serum phosphorus from baseline to mean post-baseline as the dependent variable, treatment group, baseline age and baseline RSS stratification as factors, baseline phosphorous measure as a covariate.

PD Analysis Set: all participants who received at least one dose of study therapy and had evaluable serum data.

Posted

Least Squares Mean

Standard Error

mg/dL

Baseline, Weeks 1, 4, 8, 16, 24, 32, 40, 52, 64

ID	Title	Description
OG000	Active Control	Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
OG001	Burosumab	Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants continued to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.

Secondary

Change From Baseline in Mean Post-Baseline Serum Phosphorus Level to Week 140 (During Treatment With Burosumab)

PD Analysis Set: all participants who received at least one dose of study therapy and had evaluable serum data.

Posted

Mean

Standard Deviation

mg/dL

Burosumab arm: Baseline, Week 1, 4, 8, 16, 24, 32, 40, 52, 64, 66, 68, 76, 88, 100, 112, 124, 140; Active Control arm: Baseline, Week 68, 76, 88, 100, 112, 124, 140

ID	Title	Description
OG000	Active Control	Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
OG001	Burosumab	Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants continued to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.

Secondary

Percentage of Participants Reaching the Normal Range of Serum Phosphorus Concentration (3.2 - 6.1 mg/dL)

PD Analysis Set: all participants who received at least one dose of study therapy and had evaluable serum data.

Posted

Number

percentage of participants

Burosumab arm: Baseline, up to Week 140; Active Control arm: Baseline, Week 68 up to Week 140

ID	Title	Description
OG000	Active Control	Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
OG001	Burosumab	Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants continued to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.

Units	Counts

Secondary

Change From Baseline Over Time in 1,25-Dihydroxyvitamin D, up to Week 64

The GEE model includes change from baseline for 1, 25-Dihydroxyvitamin D measurement as the dependent variable, treatment group, visit, interaction between treatment group by visit, baseline age and baseline RSS stratification as factors, baseline 1, 25-Dihydroxyvitamin D measure as a covariate, with exchangeable covariance structure. The GEE model included data up to Week 64.

PD Analysis Set: all participants who received at least one dose of study therapy and had evaluable serum data. Participants with an assessment at given time point.

Posted

Least Squares Mean

Standard Error

pg/mL

Baseline, Weeks 1, 2, 4, 8, 12, 16, 24, 32, 33, 40, 52, 64

ID	Title	Description
OG000	Active Control	Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
OG001	Burosumab	Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants continued to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.

Secondary

Change From Baseline Over Time in 1,25-Dihydroxyvitamin D, Weeks 68 to 112

PD Analysis Set: all participants who received at least one dose of study therapy and had evaluable serum data. Participants with an assessment at given time point.

Posted

Mean

Standard Deviation

pg/mL

Baseline, Weeks 68, 76, 88, 100, 112

ID	Title	Description
OG000	Active Control	Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
OG001	Burosumab	Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants continued to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.

Units	Counts
Participants

Secondary

Change From Baseline Over Time in TmP/GFR, up to Week 64

Serum phosphorus and TRP measurements were used in the calculation of TmP/GFR.

The GEE model includes change from baseline for TmP/GFR measurement as the dependent variable, treatment group, visit, interaction between treatment group by visit, baseline age and baseline RSS stratification as factors, baseline TmP/GFR measure as a covariate, with exchangeable covariance structure. The GEE model included data up to Week 64.

PD Analysis Set: all participants who received at least one dose of study therapy and had evaluable serum data. Participants with an assessment at given time point.

Posted

Least Squares Mean

Standard Error

mg/dL

Baseline, Weeks 4, 8, 16, 24, 32, 40, 52, 64

ID	Title	Description
OG000	Active Control	Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
OG001	Burosumab	Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants continued to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.

Secondary

Change From Baseline Over Time in TmP/GFR, Week 68 to 112

Serum phosphorus and TRP measurements were used in the calculation of TmP/GFR.

PD Analysis Set: all participants who received at least one dose of study therapy and had evaluable serum data. Participants with data at given time point.

Posted

Mean

Standard Deviation

mg/dL

Baseline, Weeks 68, 76, 88, 112

ID	Title	Description
OG000	Active Control	Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
OG001	Burosumab	Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants continued to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.

Secondary

Change From Baseline Over Time in Serum ALP, up to Week 64

The GEE model includes change from baseline for ALP measurement as the dependent variable, treatment group, visit, interaction between treatment group by visit, baseline age and baseline RSS stratification as factors, baseline ALP measure as a covariate, with exchangeable covariance structure. The GEE model included data up to Week 64.

PD Analysis Set: all participants who received at least one dose of study therapy and had evaluable serum data.

Posted

Least Squares Mean

Standard Error

U/L

Baseline, Weeks 16, 24, 40, 52, 64

ID	Title	Description
OG000	Active Control	Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
OG001	Burosumab	Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants continued to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.

Secondary

Change From Baseline Over Time in Serum ALP, Week 68 to 112

PD Analysis Set: all participants who received at least one dose of study therapy and had evaluable serum data.

Posted

Mean

Standard Deviation

U/L

Baseline, Weeks 68, 76, 88, 100, 112

ID	Title	Description
OG000	Active Control	Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
OG001	Burosumab	Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants continued to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.

Units	Counts
Participants

Secondary

Percent Change From Baseline Over Time in Serum ALP, up to Week 112

Decreases indicate improvement.

PD Analysis Set: all participants who received at least one dose of study therapy and had evaluable serum data.

Posted

Mean

Standard Deviation

percent change

Baseline, Weeks 16, 24, 40, 52, 64, 68, 76, 88, 100, 112

ID	Title	Description
OG000	Active Control	Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
OG001	Burosumab	Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants continued to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.

Units	Counts

Secondary

Change From Baseline in the PROMIS Pediatric Pain Interference, Physical Function Mobility and Fatigue Domain Scores (For Participants ≥ 5 Years of Age at the Screening Visit) at Week 40

Full Analysis Set: all randomized participants who received at least one dose of assigned medication and had at least one post-baseline assessment. Participants with an assessment at Week 40.

Posted

Least Squares Mean

Standard Error

T-score

Baseline, Week 40

ID	Title	Description
OG000	Active Control	Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
OG001	Burosumab

Secondary

Change From Baseline in the PROMIS Pediatric Pain Interference, Physical Function Mobility and Fatigue Domain Scores (For Participants ≥ 5 Years of Age at the Screening Visit) at Week 64

Full Analysis Set: all randomized participants who received at least one dose of assigned medication and had at least one post-baseline assessment. Participants with an assessment at Week 64.

Posted

Least Squares Mean

Standard Error

T-score

Baseline, Week 64

ID	Title	Description
OG000	Active Control	Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
OG001	Burosumab

Secondary

Change From Baseline in the FPS-R (For Participants ≥ 5 Years of Age at the Screening Visit) at Week 40

Full Analysis Set: all randomized participants who received at least one dose of assigned medication and had at least one post-baseline assessment. Participants with an assessment at Week 40.

Posted

Least Squares Mean

Standard Error

units on a scale

Baseline, Week 40

ID	Title	Description
OG000	Active Control	Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
OG001	Burosumab	Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants continued to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.

Secondary

Change From Baseline in the FPS-R (For Participants ≥ 5 Years of Age at the Screening Visit) at Week 64

Full Analysis Set: all randomized participants who received at least one dose of assigned medication and had at least one post-baseline assessment. Participants with an assessment at Week 64.

Posted

Least Squares Mean

Standard Error

units on a scale

Baseline, Week 64

ID	Title	Description
OG000	Active Control	Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
OG001	Burosumab	Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants continued to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.

Secondary

Change From Baseline in the 6MWT Total Distance at Week 40

The total distance walked (meters) in a 6-minute period was measured in participants ≥ 5 years of age at the Screening Visit who were able to complete the test.

Full Analysis Set: all randomized participants who received at least one dose of assigned medication and had at least one post-baseline assessment. Participants with an assessment at Week 40 in subjects ≥ 5 years who were able to complete the test.

Posted

Least Squares Mean

Standard Error

meters

Baseline, Week 40

ID	Title	Description
OG000	Active Control	Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
OG001	Burosumab	Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants continued to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.

Secondary

Change From Baseline in the 6MWT Total Distance at Week 64

The total distance walked (meters) in a 6-minute period was measured in participants ≥ 5 years of age at the Screening Visit who were able to complete the test.

Full Analysis Set: all randomized participants who received at least one dose of assigned medication and had at least one post-baseline assessment. Participants with an assessment at Week 64.

Posted

Least Squares Mean

Standard Error

meters

Baseline, Week 64

ID	Title	Description
OG000	Active Control	Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
OG001	Burosumab	Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants continued to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.

Secondary

Percent of Predicted Normal in the 6MWT Total Distance at Week 40

The total distance walked (meters) in a 6-minute period was measured in participants ≥ 5 years of age at the Screening Visit who were able to complete the test, and the percent predicted distance based on normative data for age and gender was estimated.

Full Analysis Set: all randomized participants who received at least one dose of assigned medication and had at least one post-baseline assessment. Participants with an assessment at Week 40.

Posted

Least Squares Mean

Standard Error

percent of predicted meters

Baseline, Week 40

ID	Title	Description
OG000	Active Control	Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
OG001	Burosumab	Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants continued to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.

Secondary

Percent of Predicted Normal in the 6MWT Total Distance at Week 64

Full Analysis Set: all randomized participants who received at least one dose of assigned medication and had at least one post-baseline assessment. Participants with an assessment at Week 64.

Posted

Least Squares Mean

Standard Error

percent of predicted meters

Baseline, Week 64

ID	Title	Description
OG000	Active Control	Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
OG001	Burosumab	Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants continued to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Tooth Hypoplasia	Congenital, familial and genetic disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected32 at risk EG0012 affected29 at risk EG0020 affected26 at risk EG0032 affected29 at risk EG0042 affected55 at risk
Ear Discomfort	Ear and labyrinth disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected32 at risk EG0011 affected29 at risk EG0020 affected26 at risk EG003
Ear Pain	Ear and labyrinth disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected32 at risk EG0014 affected29 at risk EG0022 affected26 at risk EG003
Abdominal Discomfort	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0002 affected32 at risk EG0012 affected29 at risk EG0021 affected26 at risk EG003
Abdominal Pain	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected32 at risk EG0012 affected29 at risk EG0021 affected26 at risk EG003
Abdominal Pain Upper	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0003 affected32 at risk EG0013 affected29 at risk EG0022 affected26 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected32 at risk EG0015 affected29 at risk EG0022 affected26 at risk EG003
Dental Caries	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0002 affected32 at risk EG0019 affected29 at risk EG0020 affected26 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0002 affected32 at risk EG0017 affected29 at risk EG0021 affected26 at risk EG003
Haematochezia	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected32 at risk EG0011 affected29 at risk EG0020 affected26 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected32 at risk EG0013 affected29 at risk EG0022 affected26 at risk EG003
Teething	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected32 at risk EG0012 affected29 at risk EG0021 affected26 at risk EG003
Tooth Loss	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected32 at risk EG0011 affected29 at risk EG0021 affected26 at risk EG003
Toothache	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected32 at risk EG0014 affected29 at risk EG0021 affected26 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0008 affected32 at risk EG00112 affected29 at risk EG0025 affected26 at risk EG003
Fatigue	General disorders	MedDRA 18.1	Systematic Assessment	EG0002 affected32 at risk EG0011 affected29 at risk EG0021 affected26 at risk EG003
Injection Site Bruising	General disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected32 at risk EG0010 affected29 at risk EG0022 affected26 at risk EG003
Injection Site Erosion	General disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected32 at risk EG0012 affected29 at risk EG0020 affected26 at risk EG003
Injection Site Erythema	General disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected32 at risk EG0019 affected29 at risk EG0026 affected26 at risk EG003
Injection Site Pruritus	General disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected32 at risk EG0013 affected29 at risk EG0022 affected26 at risk EG003
Injection Site Rash	General disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected32 at risk EG0013 affected29 at risk EG0020 affected26 at risk EG003
Injection Site Reaction	General disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected32 at risk EG0017 affected29 at risk EG0022 affected26 at risk EG003
Injection Site Swelling	General disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected32 at risk EG0013 affected29 at risk EG0021 affected26 at risk EG003
Injection Site Urticaria	General disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected32 at risk EG0012 affected29 at risk EG0020 affected26 at risk EG003
Pain	General disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected32 at risk EG0012 affected29 at risk EG0020 affected26 at risk EG003
Pyrexia	General disorders	MedDRA 18.1	Systematic Assessment	EG0007 affected32 at risk EG00116 affected29 at risk EG0027 affected26 at risk EG003
Hypersensitivity	Immune system disorders	MedDRA 18.1	Systematic Assessment	EG0002 affected32 at risk EG0011 affected29 at risk EG0020 affected26 at risk EG003
Seasonal Allergy	Immune system disorders	MedDRA 18.1	Systematic Assessment	EG0002 affected32 at risk EG0014 affected29 at risk EG0021 affected26 at risk EG003
Ear Infection	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0003 affected32 at risk EG0012 affected29 at risk EG0021 affected26 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0003 affected32 at risk EG0012 affected29 at risk EG0020 affected26 at risk EG003
Gastroenteritis Viral	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0003 affected32 at risk EG0012 affected29 at risk EG0020 affected26 at risk EG003
Influenza	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0006 affected32 at risk EG0014 affected29 at risk EG0020 affected26 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG00014 affected32 at risk EG00111 affected29 at risk EG0026 affected26 at risk EG003
Otitis Externa	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0003 affected32 at risk EG0010 affected29 at risk EG0020 affected26 at risk EG003
Otitis Media	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0004 affected32 at risk EG0012 affected29 at risk EG0020 affected26 at risk EG003
Pharyngitis Streptococcal	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0001 affected32 at risk EG0011 affected29 at risk EG0021 affected26 at risk EG003
Pneumonia	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0000 affected32 at risk EG0012 affected29 at risk EG0020 affected26 at risk EG003
Rhinitis	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0002 affected32 at risk EG0012 affected29 at risk EG0020 affected26 at risk EG003
Tooth Abscess	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0003 affected32 at risk EG0018 affected29 at risk EG0022 affected26 at risk EG003
Upper Respiratory Tract Infection	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0003 affected32 at risk EG0013 affected29 at risk EG0020 affected26 at risk EG003
Varicella	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0000 affected32 at risk EG0012 affected29 at risk EG0021 affected26 at risk EG003
Viral Upper Respiratory Tract Infection	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0002 affected32 at risk EG0010 affected29 at risk EG0020 affected26 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA 18.1	Systematic Assessment	EG0000 affected32 at risk EG0014 affected29 at risk EG0020 affected26 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA 18.1	Systematic Assessment	EG0000 affected32 at risk EG0013 affected29 at risk EG0020 affected26 at risk EG003
Procedural Pain	Injury, poisoning and procedural complications	MedDRA 18.1	Systematic Assessment	EG0000 affected32 at risk EG0012 affected29 at risk EG0020 affected26 at risk EG003
Vitamin D Decreased	Investigations	MedDRA 18.1	Systematic Assessment	EG0001 affected32 at risk EG0016 affected29 at risk EG0021 affected26 at risk EG003
Decreased Appetite	Metabolism and nutrition disorders	MedDRA 18.1	Systematic Assessment	EG0002 affected32 at risk EG0011 affected29 at risk EG0020 affected26 at risk EG003
Vitamin D Deficiency	Metabolism and nutrition disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected32 at risk EG0015 affected29 at risk EG0020 affected26 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG00010 affected32 at risk EG00113 affected29 at risk EG0023 affected26 at risk EG003
Back Pain	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0003 affected32 at risk EG0012 affected29 at risk EG0020 affected26 at risk EG003
Pain In Extremity	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG00010 affected32 at risk EG00111 affected29 at risk EG0023 affected26 at risk EG003
Headache	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0006 affected32 at risk EG00110 affected29 at risk EG0023 affected26 at risk EG003
Migraine	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0002 affected32 at risk EG0011 affected29 at risk EG0021 affected26 at risk EG003
Attention Deficit/Hyperactivity Disorder	Psychiatric disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected32 at risk EG0010 affected29 at risk EG0020 affected26 at risk EG003
Dysuria	Renal and urinary disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected32 at risk EG0012 affected29 at risk EG0020 affected26 at risk EG003
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected32 at risk EG0014 affected29 at risk EG0020 affected26 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0006 affected32 at risk EG00115 affected29 at risk EG0024 affected26 at risk EG003
Nasal Congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected32 at risk EG0015 affected29 at risk EG0021 affected26 at risk EG003
Oropharyngeal Pain	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected32 at risk EG0015 affected29 at risk EG0023 affected26 at risk EG003
Rhinitis Allergic	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected32 at risk EG0012 affected29 at risk EG0020 affected26 at risk EG003
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0002 affected32 at risk EG0017 affected29 at risk EG0023 affected26 at risk EG003
Wheezing	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected32 at risk EG0011 affected29 at risk EG0020 affected26 at risk EG003
Erythema	Skin and subcutaneous tissue disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected32 at risk EG0012 affected29 at risk EG0020 affected26 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA 18.1	Systematic Assessment	EG0002 affected32 at risk EG0013 affected29 at risk EG0020 affected26 at risk EG003
Skin Lesion	Skin and subcutaneous tissue disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected32 at risk EG0011 affected29 at risk EG0020 affected26 at risk EG003
Swelling Face	Skin and subcutaneous tissue disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected32 at risk EG0011 affected29 at risk EG0020 affected26 at risk EG003

ID	Term
D063730	Rickets, Hypophosphatemic
D012279	Rickets
D001851	Bone Diseases, Metabolic
D001847	Bone Diseases
D009140	Musculoskeletal Diseases
D007015	Hypophosphatemia, Familial
D015499	Renal Tubular Transport, Inborn Errors
D007674	Kidney Diseases
D014570	Urologic Diseases
D052776	Female Urogenital Diseases
D005261	Female Urogenital Diseases and Pregnancy Complications
D000091642	Urogenital Diseases
D052801	Male Urogenital Diseases
D008664	Metal Metabolism, Inborn Errors
D008661	Metabolism, Inborn Errors
D030342	Genetic Diseases, Inborn
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases
D002128	Calcium Metabolism Disorders
D017674	Hypophosphatemia
D010760	Phosphorus Metabolism Disorders
D014808	Vitamin D Deficiency
D001361	Avitaminosis
D003677	Deficiency Diseases
D044342	Malnutrition
D009748	Nutrition Disorders

ID	Title	Description
BG000	Active Control	Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
BG001	Burosumab	Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants continued to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Oral Phosphate/Active Vitamin D (Treatment Period)	Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64).	32	3	32	23	32
EG001	Burosumab (Treatment Period)	Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection during the Treatment Period (up to Week 64).	29	3	29	21	29
EG002	Oral Phosphate/Active Vitamin D->Burosumab (Extension Period)	Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.	26	0	26	9	26
EG003	Burosumab->Burosumab (Treatment Period and Extension Period)	Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants continued to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.	29	4	29	25	29
EG004	Total Burosumab (Treatment Period and Extension Period)	Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection at any time during the study.	55	4	55	34	55

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Craniosynostosis	Congenital, familial and genetic disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected32 at risk EG0011 affected29 at risk EG0020 affected26 at risk EG0031 affected29 at risk EG004
Papilloedema	Eye disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected32 at risk EG0010 affected29 at risk EG0020 affected26 at risk EG003
Viral Infection	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0000 affected32 at risk EG0011 affected29 at risk EG0020 affected26 at risk EG003
Knee Deformity	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected32 at risk EG0010 affected29 at risk EG0020 affected26 at risk EG003
Migraine	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected32 at risk EG0011 affected29 at risk EG0020 affected26 at risk EG003
Haematuria	Renal and urinary disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected32 at risk EG0010 affected29 at risk EG0020 affected26 at risk EG003