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CompletedNCT02163577Updated May 6, 2024Results posted

Study of KRN23 (Burosumab), a Recombinant Fully Human Monoclonal Antibody Against Fibroblast Growth Factor 23 (FGF23), in Pediatric Subjects With X-linked Hypophosphatemia (XLH)

A Phase 2 interventional study of burosumab in X-linked Hypophosphatemia, sponsored by Kyowa Kirin, Inc.. Completed at 9 sites in 4 countries. Open to participants aged 5 Years to 12 Years. Per ClinicalTrials.gov, last updated 2024-05-06.

Sponsored by Kyowa Kirin, Inc. · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
52
Allocation
Randomized
Ages
5 Years to 12 Years
Sex
All
01

Study summary

The objectives of the study are to:

  • Identify a dose and dosing regimen of burosumab, based on safety and pharmacodynamic (PD) effect, in pediatric XLH participants
  • Establish the safety profile of burosumab for the treatment of children with XLH including ectopic mineralization risk, cardiovascular effects, and immunogenicity profile
  • Characterize the pharmacokinetic (PK)/PD profile of the KRN23 doses tested in the monthly (Q4) and biweekly (Q2) dose regimens in pediatric XLH patients
  • Determine the PD effects of burosumab treatment on markers of bone health in pediatric XLH patients
  • Obtain a preliminary assessment of the clinical effects of burosumab on bone health and deformity, muscle strength, and motor function
  • Obtain a preliminary assessment of the effects of burosumab on participant-reported outcomes, including pain, disability, and quality of life in pediatric XLH patients
  • Evaluate the long-term safety and efficacy of burosumab
02

Conditions studied

  • X-linked Hypophosphatemia

Keywords

  • X-linked hypophosphatemia
  • XLH
  • FGF23
  • KRN23
03

In context

Familial Hypophosphatemic Rickets

61 studies on the registry are indexed under Familial Hypophosphatemic Rickets; 9 are open to participants now.

This study's enrollment of 52 is above the median of 23 across 35 interventional studies indexed under Familial Hypophosphatemic Rickets.

Browse Familial Hypophosphatemic Rickets studies →

Lead sponsor

Kyowa Kirin, Inc. is the lead sponsor of 36 studies on the registry; 2 are open to participants now.

Of its 7 completed or terminated interventional studies of FDA-regulated products, 3 (43%) have results posted.

Browse Kyowa Kirin Co., Ltd. studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
5 Years to 12 Years
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  1. Male or female, aged 5 - 12 years, inclusive, with open growth plates
  2. Tanner stage of 2 or less based on breast and testicular development

  3. Diagnosis of XLH supported by ONE of the following:

    • Confirmed Phosphate regulating gene with homology to endopeptidases located on the X chromosome (PHEX) mutation in the patient or a directly related family member with appropriate X-linked inheritance
    • Serum FGF23 level > 30 pg/mL by Kainos assay

  4. Biochemical findings associated with XLH including:

    • Serum phosphorus ≤ 2.8 mg/dL (0.904 mmol/L)*
    • Serum creatinine within age-adjusted normal range*
  5. Standing height \< 50th percentile for age and gender using local normative data.
  6. Radiographic evidence of active bone disease including rickets in the wrists and/or knees, AND/OR femoral/tibial bowing, OR, for expansion subjects, a Rickets Severity Score (RSS) score in the knee of at least 1.5 as determined by central read.
  7. Willing to provide access to prior medical records for the collection of historical growth, biochemical and radiographic data, and disease history.
  8. Provide written or verbal assent (if possible) 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.
  9. 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.

  10. Females who have reached menarche must have a negative pregnancy test at Screening and undergo additional pregnancy testing during the study. If sexually active, male and female subjects must be willing to use an acceptable method of contraception for the duration of the study.

    • Criteria to be determined based on overnight fasting (minimum 4 hours) values collected at Screening Visit 2

Exclusion criteria

Exclusion

  1. Use of a pharmacologic vitamin D metabolite or analog (e.g. calcitriol, doxercalciferol, alfacalcidiol, and paricalcitol) within 14 days prior to Screening Visit 2; washout will take place during the Screening Period
  2. Use of oral phosphate within 7 days prior to Screening Visit 2; washout will take place during the Screening Period
  3. Use of calcimimetics, aluminum hydroxide antacids (e.g. Maalox® and Mylanta®), systemic corticosteroids, and thiazides within 7 days prior to Screening Visit 1
  4. Use of growth hormone therapy within 3 months before Screening Visit 1
  5. Use of bisphosphonates for 6 months or more in the 2 years prior to Screening Visit 1
  6. Presence of nephrocalcinosis on renal ultrasound graded ≥ 3 based on the following scale: 0 = Normal 1 = Faint hyperechogenic rim around the medullary pyramids 2 = More intense echogenic rim with echoes faintly filling the entire pyramid 3 = Uniformly intense echoes throughout the pyramid 4 = Stone formation: solitary focus of echoes at the tip of the pyramid
  7. Planned or recommended orthopedic surgery, including staples, 8-plates or osteotomy, within the clinical trial period
  8. Hypocalcemia or hypercalcemia, defined as serum calcium levels outside the age-adjusted normal limits *
  9. Evidence of tertiary hyperparathyroidism as determined by the Investigator
  10. Use of medication to suppress parathyroid hormone (PTH) (e.g. Sensipar®, cinacalcet, calcimimetics) within 2 months prior to Screening Visit 1
  11. 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
  12. Presence of a concurrent disease or condition that would interfere with study participation or affect safety
  13. Previously diagnosed with human immunodeficiency virus antibody, hepatitis B surface antigen, and/or hepatitis C antibody
  14. History of recurrent infection or predisposition to infection, or of known immunodeficiency
  15. Use of a therapeutic monoclonal antibody within 90 days prior to Screening Visit 1 or history of allergic or anaphylactic reactions to any monoclonal antibody
  16. Presence or history of any hypersensitivity to recombinant human immunoglobulin G1 (IgG1) monoclonal antibody to FGF23 (burosumab) excipients that, in the judgment of the investigator, places the subject at increased risk for adverse effects

  17. 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

    • Criteria to be determined based on overnight fasting (minimum 4 hours) values collected at Screening Visit 2
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
52 participants (actual)

Study arms

  • Experimental
    Burosumab Q2W

    Burosumab subcutaneous (SC) injections every 2 weeks (Q2W). Dose was determined by the participant's weight and prescribed dose by their study doctor.

    Biological: burosumab

  • Experimental
    Burosumab Q4W Then Q2W

    Burosumab SC injections every 4 weeks (Q4W). Dose was determined by the participant's weight and prescribed dose by their study doctor. Participants in Q4W were to switch to Q2W beginning with Week 64 dosing.

    Biological: burosumab

Interventions

  • Biologicalburosumab

    solution for SC injection

    Also known as: KRN23, Crysvita®, UX023

06

What researchers measure

Primary outcomes

  1. Change From Baseline in RSS Total Score Over Time

    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.

    Time frame: Baseline, Week 40, 64, 160

  2. Change From Baseline in Serum Phosphorus Over Time

    Time frame: Baseline, Week 40, 64, 160

  3. Change From Baseline in Serum 1,25(OH)2D Over Time

    Time frame: Baseline, Week 40, 64, 160

  4. Change From Baseline in TmP/GFR Over Time

    Data for urinary phosphorus and TRP were used in calculation TmP/GFR.

    Time frame: Baseline, Week 40, 64, 160

Secondary outcomes

  1. Change From Baseline in RSS Knee Scores Over Time

    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.

    Time frame: Baseline, Week 40, 64, 160

  2. Change From Baseline in RSS Wrist Scores Over Time

    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.

    Time frame: Baseline, Week 40, 64, 160

  3. Radiographic Global Impression of Change (RGI-C) Global Scores Over Time

    Changes in the severity of rickets and bowing were assessed centrally by three independent pediatric radiologists contracted by a central imaging facility using a disease specific qualitative RGI-C scoring system. The RGI-C is a seven 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).

    Time frame: Baseline, Week 40, 64, 160

  4. RGI-C Knee Scores Over Time

    Changes in the severity of rickets and bowing were assessed centrally by three independent pediatric radiologists contracted by a central imaging facility using a disease specific qualitative RGI-C scoring system. The RGI-C is a seven 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).

    Time frame: Baseline, Week 40, 64, 160

  5. RGI-C Wrist Scores Over Time

    Changes in the severity of rickets and bowing were assessed centrally by three independent pediatric radiologists contracted by a central imaging facility using a disease specific qualitative RGI-C scoring system. The RGI-C is a seven 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).

    Time frame: Baseline, Week 40, 64, 160

  6. Change From Baseline in Growth Velocity Over Time

    Time frame: Baseline, Week 40, 64, 160

  7. Change From Baseline in Standing Height Z Score Over Time

    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.

    Time frame: Baseline, Week 40, 64, 160

  8. Change From Baseline in Growth (Standing Height) Over Time

    Time frame: Baseline, Week 40, 64, 160

  9. Change From Baseline in Growth (Sitting Height) Over Time

    Time frame: Baseline, Week 40, 64, 160

  10. Change From Baseline in Growth (Arm Length) Over Time

    Time frame: Baseline, Week 40, 64, 160

  11. Change From Baseline in Growth (Leg Length) Over Time

    Time frame: Baseline, Week 40, 64, 160

  12. 6MWT Distance (Predicted Percent of Normal) Change From Baseline Over Time

    The total distance walked (meters) in a 6-minute period was measured. The percent of predicted values were calculated using published normative data based on age, gender, and height (Geiger et al. 2007).

    Time frame: Baseline, Week 40, 64, 160

  13. Change From Baseline in POSNA-PODCI (Normative Score) Upper Extremity Scale Scores Over Time

    The POSNA-PODCI yields 4 functional assessment scores: Upper Extremity Function,Transfers and Basic Mobility, Sports and Physical Function, and Comfort/Pain. In addition, a Global Function score, which is an average of the 4 functional assessments, and a Happiness score are calculated. Raw, mean, standardized, and normative scores are calculated for each scale. Normative scores are calculated so that higher scores indicate better functioning. All scores are referenced to the general, healthy population with a normative mean score of 50 and a standard deviation of 10.

    Time frame: Baseline, Week 40, 64, 160

  14. Change From Baseline in POSNA-PODCI (Normative Score) Transfer and Basic Mobility Scale Scores Over Time

    The POSNA-PODCI yields 4 functional assessment scores: Upper Extremity Function,Transfers and Basic Mobility, Sports and Physical Function, and Comfort/Pain. In addition, a Global Function score, which is an average of the 4 functional assessments, and a Happiness score are calculated. Raw, mean, standardized, and normative scores are calculated for each scale. Normative scores are calculated so that higher scores indicate better functioning. All scores are referenced to the general, healthy population with a normative mean score of 50 and a standard deviation of 10.

    Time frame: Baseline, Week 40, 64, 160

  15. Change From Baseline in POSNA-PODCI (Normative Score) Sports/Physical Functioning Scale Scores Over Time

    The POSNA-PODCI yields 4 functional assessment scores: Upper Extremity Function,Transfers and Basic Mobility, Sports and Physical Function, and Comfort/Pain. In addition, a Global Function score, which is an average of the 4 functional assessments, and a Happiness score are calculated. Raw, mean, standardized, and normative scores are calculated for each scale. Normative scores are calculated so that higher scores indicate better functioning. All scores are referenced to the general, healthy population with a normative mean score of 50 and a standard deviation of 10.

    Time frame: Baseline, Week 40, 64, 160

  16. Change From Baseline in POSNA-PODCI (Normative Score) Pain/Comfort Scale Scores Over Time

    The POSNA-PODCI yields 4 functional assessment scores: Upper Extremity Function,Transfers and Basic Mobility, Sports and Physical Function, and Comfort/Pain. In addition, a Global Function score, which is an average of the 4 functional assessments, and a Happiness score are calculated. Raw, mean, standardized, and normative scores are calculated for each scale. Normative scores are calculated so that higher scores indicate better functioning. All scores are referenced to the general, healthy population with a normative mean score of 50 and a standard deviation of 10.

    Time frame: Baseline, Week 40, 64, 160

  17. Change From Baseline in POSNA-PODCI (Normative Score) Happiness Scale Scores Over Time

    The POSNA-PODCI yields 4 functional assessment scores: Upper Extremity Function,Transfers and Basic Mobility, Sports and Physical Function, and Comfort/Pain. In addition, a Global Function score, which is an average of the 4 functional assessments, and a Happiness score are calculated. Raw, mean, standardized, and normative scores are calculated for each scale. Normative scores are calculated so that higher scores indicate better functioning. All scores are referenced to the general, healthy population with a normative mean score of 50 and a standard deviation of 10.

    Time frame: Baseline, Week 40, 64, 160

  18. Change From Baseline in POSNA-PODCI (Normative Score) Global Functioning Scale Scores Over Time

    The POSNA-PODCI yields 4 functional assessment scores: Upper Extremity Function,Transfers and Basic Mobility, Sports and Physical Function, and Comfort/Pain. In addition, a Global Function score, which is an average of the 4 functional assessments, and a Happiness score are calculated. Raw, mean, standardized, and normative scores are calculated for each scale. Normative scores are calculated so that higher scores indicate better functioning. All scores are referenced to the general, healthy population with a normative mean score of 50 and a standard deviation of 10.

    Time frame: Baseline, Week 40, 64, 160

  19. Change From Baseline in FEP Over Time

    FEP is defined as 100% × (urine phosphorus × serum creatinine)/(urine creatinine × serum phosphorus), where the 2-hour urine sample was used for urine phosphorus and urine creatinine.

    Time frame: Baseline, Week 40, 64, 160

  20. Change From Baseline in P1NP Over Time

    Time frame: Baseline, Week 40, 64

  21. Change From Baseline in CTx Over Time

    Time frame: Baseline, Week 40, 64

  22. Change From Baseline in ALP Over Time

    Time frame: Baseline, Week 40, 64, 160

  23. Change From Baseline in BALP Over Time

    Time frame: Baseline, Week 40, 64, 160

  24. Serum Pre-Dose Concentrations of Burosumab

    Time frame: Week 40, 64, 160

  25. Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Discontinuations Due to Adverse Events (AEs)

    An AE is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An SAE is defined as an AE or suspected adverse reaction that at any dose results in any of the following outcomes: death; life-threatening AE; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; a congenital anomaly/birth defect. Severity was graded as 1 (mild), 2 (moderate), 3 (severe), 4 (life-threatening), 5 (death). TEAEs are defined as AEs with onset on or after the time of initiation of study drug administration.

    Time frame: Up to 216 weeks

07

Results

Posted May 22, 2019

Participant flow

Participant flow — Overall Study
MilestoneBurosumab Q2WBurosumab Q4W Then Q2W
Started2626
Completed2626
Not completed00

Outcome measures

PrimaryChange From Baseline in RSS Total Score Over Time

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.

Time frame:
Baseline, Week 40, 64, 160
Reported as:
Least squares mean · score on a scale
Change From Baseline in RSS Total Score Over Time
score on a scaleBurosumab Q2WBurosumab Q4W Then Q2W
Change to Week 40-1.06 ± 0.100-0.73 ± 0.100
Change to Week 64-1.00 ± 0.110-0.84 ± 0.098
Change to Week 160-0.98 ± 0.129-0.83 ± 0.122
Statistical analysis
  • Burosumab Q2W · GEE model · p = < 0.0001 (Per generalized estimating equations (GEE) model, which included visit, regimen, visit by regimen as factors, and RSS total score at baseline as a covariate, with exchangeable covariance structure.)
  • Burosumab Q4W Then Q2W · GEE model · p = < 0.0001 (Per GEE model, which included visit, regimen, visit by regimen as factors, and RSS total score at baseline as a covariate, with exchangeable covariance structure.)
  • Burosumab Q2W vs Burosumab Q4W Then Q2W · Difference in ls means: -0.33 · 95% CI -0.63 to -0.04
  • Burosumab Q2W · GEE model · p = < 0.0001 (Per GEE model, which included visit, regimen, visit by regimen as factors, and RSS total score at baseline as a covariate, with exchangeable covariance structure.)
  • Burosumab Q4W Then Q2W · GEE model · p = < 0.0001 (Per GEE model, which included visit, regimen, visit by regimen as factors, and RSS total score at baseline as a covariate, with exchangeable covariance structure.)
  • Burosumab Q2W vs Burosumab Q4W Then Q2W · Difference in ls means: -0.16 · 95% CI -0.45 to 0.13
  • Burosumab Q2W · GEE model · p = < 0.0001 (Per GEE model, which included visit, regimen, visit by regimen as factors, and RSS total score at baseline as a covariate, with exchangeable covariance structure.)
  • Burosumab Q4W Then Q2W · GEE model · p = < 0.0001 (Per GEE model, which included visit, regimen, visit by regimen as factors, and RSS total score at baseline as a covariate, with exchangeable covariance structure.)
PrimaryChange From Baseline in Serum Phosphorus Over Time
Time frame:
Baseline, Week 40, 64, 160
Reported as:
Mean · mg/dL
Change From Baseline in Serum Phosphorus Over Time
mg/dLBurosumab Q2WBurosumab Q4W Then Q2W
Change at Week 400.92 ± 0.4800.57 ± 0.265
Change at Week 640.99 ± 0.5020.69 ± 0.370
Change at Week 1600.97 ± 0.3381.08 ± 0.377
Statistical analysis
  • Burosumab Q2W · one sample t test · p = < 0.0001
  • Burosumab Q4W Then Q2W · one sample t test · p = < 0.0001
  • Burosumab Q2W · one sample t test · p = < 0.0001
  • Burosumab Q4W Then Q2W · one sample t test · p = < 0.0001
  • Burosumab Q2W · one sample t test · p = < 0.0001
  • Burosumab Q4W Then Q2W · one sample t test · p = < 0.0001
PrimaryChange From Baseline in Serum 1,25(OH)2D Over Time
Time frame:
Baseline, Week 40, 64, 160
Reported as:
Mean · pg/mL
Change From Baseline in Serum 1,25(OH)2D Over Time
pg/mLBurosumab Q2WBurosumab Q4W Then Q2W
Change at Week 4028.27 ± 29.31217.62 ± 18.802
Change at Week 6423.58 ± 24.50211.50 ± 16.522
Change at Week 16017.03 ± 24.88919.64 ± 22.857
Statistical analysis
  • Burosumab Q2W · one sample t test · p = < 0.0001
  • Burosumab Q4W Then Q2W · one sample t test · p = < 0.0001
  • Burosumab Q2W · one sample t test · p = < 0.0001
  • Burosumab Q4W Then Q2W · one sample t test · p = 0.0024
  • Burosumab Q2W · one sample t test · p = 0.0018
  • Burosumab Q4W Then Q2W · one sample t test · p = 0.0002
PrimaryChange From Baseline in TmP/GFR Over Time

Data for urinary phosphorus and TRP were used in calculation TmP/GFR.

Time frame:
Baseline, Week 40, 64, 160
Reported as:
Mean · mg/dL
Change From Baseline in TmP/GFR Over Time
mg/dLBurosumab Q2WBurosumab Q4W Then Q2W
Change at Week 401.14 ± 0.6860.80 ± 0.506
Change at Week 641.11 ± 0.6260.90 ± 0.632
Change at Week 1601.24 ± 0.5481.45 ± 0.653
Statistical analysis
  • Burosumab Q2W · one sample t test · p = < 0.0001
  • Burosumab Q4W Then Q2W · one sample t test · p = < 0.0001
  • Burosumab Q2W · one sample t test · p = < 0.0001
  • Burosumab Q4W Then Q2W · one sample t test · p = < 0.0001
  • Burosumab Q2W · one sample t test · p = < 0.0001
  • Burosumab Q4W Then Q2W · one sample t test · p = < 0.0001
SecondaryChange From Baseline in RSS Knee Scores Over Time

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.

Time frame:
Baseline, Week 40, 64, 160
Reported as:
Least squares mean · score on a scale
Change From Baseline in RSS Knee Scores Over Time
score on a scaleBurosumab Q2WBurosumab Q4W Then Q2W
Change at Week 40-0.62 ± 0.08-0.55 ± 0.08
Change at Week 64-0.70 ± 0.087-0.61 ± 0.072
Change at Week 160-0.70 ± 0.105-0.62 ± 0.093
Statistical analysis
  • Burosumab Q2W · ANCOVA · p = < 0.0001 (ANCOVA model includes the change from baseline in RSS as the dependent variable, regimen group as factor, and RSS at baseline as covariate.)
  • Burosumab Q4W Then Q2W · ANCOVA · p = < 0.0001 (ANCOVA model includes the change from baseline in RSS as the dependent variable, regimen group as factor, and RSS at baseline as covariate.)
  • Burosumab Q2W · GEE model · p = < 0.0001 (GEE model includes the change from baseline in RSS as the dependent variable, visit, regimen, visit by regimen as factors, and RSS at baseline as a covariate, with exchangeable covariance structure.)
  • Burosumab Q4W Then Q2W · GEE model · p = < 0.0001 (GEE model includes the change from baseline in RSS as the dependent variable, visit, regimen, visit by regimen as factors, and RSS at baseline as a covariate, with exchangeable covariance structure.)
  • Burosumab Q2W · GEE model · p = < 0.0001 (GEE model includes the change from baseline in RSS as the dependent variable, visit, regimen, visit by regimen as factors, and RSS at baseline as a covariate, with exchangeable covariance structure.)
  • Burosumab Q4W Then Q2W · GEE model · p = < 0.0001 (GEE model includes the change from baseline in RSS as the dependent variable, visit, regimen, visit by regimen as factors, and RSS at baseline as a covariate, with exchangeable covariance structure.)
SecondaryChange From Baseline in RSS Wrist Scores Over Time

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.

Time frame:
Baseline, Week 40, 64, 160
Reported as:
Least squares mean · score on a scale
Change From Baseline in RSS Wrist Scores Over Time
score on a scaleBurosumab Q2WBurosumab Q4W Then Q2W
Change at Week 40-0.44 ± 0.05-0.18 ± 0.05
Change at Week 64-0.30 ± 0.057-0.24 ± 0.051
Change at Week 160-0.27 ± 0.065-0.20 ± 0.047
Statistical analysis
  • Burosumab Q2W · ANCOVA · p = < 0.0001 (ANCOVA model includes the change from baseline in RSS as the dependent variable, regimen group as factor, and RSS at baseline as covariate.)
  • Burosumab Q4W Then Q2W · ANCOVA · p = 0.0015 (ANCOVA model includes the change from baseline in RSS as the dependent variable, regimen group as factor, and RSS at baseline as covariate.)
  • Burosumab Q2W · GEE model · p = < 0.0001 (GEE model includes the change from baseline in RSS as the dependent variable, visit, regimen, visit by regimen as factors, and RSS at baseline as a covariate, with exchangeable covariance structure.)
  • Burosumab Q4W Then Q2W · GEE model · p = < 0.0001 (GEE model includes the change from baseline in RSS as the dependent variable, visit, regimen, visit by regimen as factors, and RSS at baseline as a covariate, with exchangeable covariance structure.)
  • Burosumab Q2W · GEE model · p = < 0.0001 (GEE model includes the change from baseline in RSS as the dependent variable, visit, regimen, visit by regimen as factors, and RSS at baseline as a covariate, with exchangeable covariance structure.)
  • Burosumab Q4W Then Q2W · GEE model · p = < 0.0001 (GEE model includes the change from baseline in RSS as the dependent variable, visit, regimen, visit by regimen as factors, and RSS at baseline as a covariate, with exchangeable covariance structure.)
SecondaryRadiographic Global Impression of Change (RGI-C) Global Scores Over Time

Changes in the severity of rickets and bowing were assessed centrally by three independent pediatric radiologists contracted by a central imaging facility using a disease specific qualitative RGI-C scoring system. The RGI-C is a seven 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).

Time frame:
Baseline, Week 40, 64, 160
Reported as:
Least squares mean · score on a scale
Radiographic Global Impression of Change (RGI-C) Global Scores Over Time
score on a scaleBurosumab Q2WBurosumab Q4W Then Q2W
Change at Week 401.67 ± 0.121.46 ± 0.12
Change at Week 641.56 ± 0.1121.58 ± 0.112
Change at Week 1601.92 ± 0.1111.86 ± 0.119
Statistical analysis
  • Burosumab Q2W · ANCOVA · p = < 0.0001 (ANCOVA model includes RGI-C as the dependent variable, regimen group as factor, and RSS at baseline as covariate.)
  • Burosumab Q4W Then Q2W · ANCOVA · p = < 0.0001 (ANCOVA model includes RGI-C as the dependent variable, regimen group as factor, and RSS at baseline as covariate.)
  • Burosumab Q2W vs Burosumab Q4W Then Q2W · Difference in ls means: 0.21 · 95% CI -0.12 to 0.54
  • Burosumab Q2W · GEE model · p = < 0.0001 (Per GEE model, which included visit, regimen, visit by regimen as factors, and RSS total score at baseline as a covariate, with exchangeable covariance structure.)
  • Burosumab Q4W Then Q2W · GEE model · p = < 0.0001 (Per GEE model, which included visit, regimen, visit by regimen as factors, and RSS total score at baseline as a covariate, with exchangeable covariance structure.)
  • Burosumab Q2W vs Burosumab Q4W Then Q2W · Difference in ls means: -0.02 · 95% CI -0.34 to 0.29
  • Burosumab Q2W · GEE model · p = < 0.0001 (Per GEE model, which included visit, regimen, visit by regimen as factors, and RSS total score at baseline as a covariate, with exchangeable covariance structure.)
  • Burosumab Q4W Then Q2W · GEE model · p = < 0.0001 (Per GEE model, which included visit, regimen, visit by regimen as factors, and RSS total score at baseline as a covariate, with exchangeable covariance structure.)
SecondaryRGI-C Knee Scores Over Time

Changes in the severity of rickets and bowing were assessed centrally by three independent pediatric radiologists contracted by a central imaging facility using a disease specific qualitative RGI-C scoring system. The RGI-C is a seven 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).

Time frame:
Baseline, Week 40, 64, 160
Reported as:
Least squares mean · score on a scale
RGI-C Knee Scores Over Time
score on a scaleBurosumab Q2WBurosumab Q4W Then Q2W
Change at Week 401.60 ± 0.131.34 ± 0.13
Change at Week 641.57 ± 0.1041.53 ± 0.099
Change at Week 1602.01 ± 0.1061.85 ± 0.118
Statistical analysis
  • Burosumab Q2W · ANCOVA · p = < 0.0001 (ANCOVA model includes RGI-C as the dependent variable, regimen group as factor, and RSS at baseline as covariate.)
  • Burosumab Q4W Then Q2W · ANCOVA · p = < 0.0001 (ANCOVA model includes RGI-C as the dependent variable, regimen group as factor, and RSS at baseline as covariate.)
  • Burosumab Q2W · GEE model · p = < 0.0001 (GEE model includes RGI-C as the dependent variable, visit, regimen, visit by regimen as factors, and RSS total score at baseline as a covariate, with exchangeable covariance structure.)
  • Burosumab Q4W Then Q2W · GEE model · p = < 0.0001 (GEE model includes RGI-C as the dependent variable, visit, regimen, visit by regimen as factors, and RSS total score at baseline as a covariate, with exchangeable covariance structure.)
  • Burosumab Q2W · GEE model · p = < 0.0001 (GEE model includes RGI-C as the dependent variable, visit, regimen, visit by regimen as factors, and RSS total score at baseline as a covariate, with exchangeable covariance structure.)
  • Burosumab Q4W Then Q2W · GEE model · p = < 0.0001 (GEE model includes RGI-C as the dependent variable, visit, regimen, visit by regimen as factors, and RSS total score at baseline as a covariate, with exchangeable covariance structure.)
SecondaryRGI-C Wrist Scores Over Time

Changes in the severity of rickets and bowing were assessed centrally by three independent pediatric radiologists contracted by a central imaging facility using a disease specific qualitative RGI-C scoring system. The RGI-C is a seven 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).

Time frame:
Baseline, Week 40, 64, 160
Reported as:
Least squares mean · score on a scale
RGI-C Wrist Scores Over Time
score on a scaleBurosumab Q2WBurosumab Q4W Then Q2W
Change at Week 401.64 ± 0.141.45 ± 0.14
Change at Week 641.65 ± 0.1531.55 ± 0.124
Change at Week 1601.78 ± 0.1331.83 ± 0.132
Statistical analysis
  • Burosumab Q2W · ANCOVA · p = < 0.0001 (ANCOVA model includes RGI-C as the dependent variable, regimen group as factor, and RSS at baseline as covariate.)
  • Burosumab Q4W Then Q2W · ANCOVA · p = < 0.0001 (ANCOVA model includes RGI-C as the dependent variable, regimen group as factor, and RSS at baseline as covariate.)
  • Burosumab Q2W · GEE model · p = < 0.0001 (GEE model includes RGI-C as the dependent variable, visit, regimen, visit by regimen as factors, and RSS total score at baseline as a covariate, with exchangeable covariance structure.)
  • Burosumab Q4W Then Q2W · GEE model · p = < 0.0001 (GEE model includes RGI-C as the dependent variable, visit, regimen, visit by regimen as factors, and RSS total score at baseline as a covariate, with exchangeable covariance structure.)
  • Burosumab Q2W · GEE model · p = < 0.0001 (GEE model includes RGI-C as the dependent variable, visit, regimen, visit by regimen as factors, and RSS total score at baseline as a covariate, with exchangeable covariance structure.)
  • Burosumab Q4W Then Q2W · GEE model · p = < 0.0001 (GEE model includes RGI-C as the dependent variable, visit, regimen, visit by regimen as factors, and RSS total score at baseline as a covariate, with exchangeable covariance structure.)
SecondaryChange From Baseline in Growth Velocity Over Time
Time frame:
Baseline, Week 40, 64, 160
Reported as:
Mean · cm/year
Change From Baseline in Growth Velocity Over Time
cm/yearBurosumab Q2WBurosumab Q4W Then Q2W
Week 0 to Week 40: Change from Baseline0.96 ± 1.6770.39 ± 2.559
Week 0 to Week 64: Change from Baseline0.73 ± 1.3990.37 ± 2.164
Week 64 to Week 112: Change from Baseline0.29 ± 2.2840.09 ± 2.523
Week 112 to Week 160: Change from Baseline0.67 ± 2.3180.54 ± 3.158
Statistical analysis
  • Burosumab Q2W · one sample t-test · p = 0.0088
  • Burosumab Q4W Then Q2W · one sample t-test · p = 0.4650
  • Burosumab Q2W · one sample t test · p = 0.0160
  • Burosumab Q4W Then Q2W · one sample t test · p = 0.4114
  • Burosumab Q2W · one sample t test · p = 0.5335
  • Burosumab Q4W Then Q2W · one sample t test · p = 0.8606
  • Burosumab Q2W · one sample t test · p = 0.1627
  • Burosumab Q4W Then Q2W · one sample t test · p = 0.4096
SecondaryChange From Baseline in Standing Height Z Score Over Time

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.

Time frame:
Baseline, Week 40, 64, 160
Reported as:
Least squares mean · Z score
Change From Baseline in Standing Height Z Score Over Time
Z scoreBurosumab Q2WBurosumab Q4W Then Q2W
Change to Week 400.17 ± 0.0420.10 ± 0.051
Change to Week 640.19 ± 0.0510.12 ± 0.061
Change to Week 1600.35 ± 0.0840.19 ± 0.089
Statistical analysis
  • Burosumab Q2W · GEE model · p = < 0.0001 (GEE model included change from baseline for standing height Z score as dependent variable; visit, regimen, visit by regimen, and gender as factors; and age and standing height Z score at baseline as covariates, with exchangeable covariance structure.)
  • Burosumab Q4W Then Q2W · GEE model · p = 0.0569 (GEE model included change from baseline for standing height Z score as dependent variable; visit, regimen, visit by regimen, and gender as factors; and age and standing height Z score at baseline as covariates, with exchangeable covariance structure.)
  • Burosumab Q2W · GEE model · p = 0.0002 (GEE model included change from baseline for standing height Z score as dependent variable; visit, regimen, visit by regimen, and gender as factors; and age and standing height Z score at baseline as covariates, with exchangeable covariance structure.)
  • Burosumab Q4W Then Q2W · GEE model · p = 0.0456 (GEE model included change from baseline for standing height Z score as dependent variable; visit, regimen, visit by regimen, and gender as factors; and age and standing height Z score at baseline as covariates, with exchangeable covariance structure.)
  • Burosumab Q2W · GEE model · p = < 0.0001 (GEE model included change from baseline for standing height Z score as dependent variable; visit, regimen, visit by regimen, and gender as factors; and age and standing height Z score at baseline as covariates, with exchangeable covariance structure.)
  • Burosumab Q4W Then Q2W · GEE model · p = 0.0343 (GEE model included change from baseline for standing height Z score as dependent variable; visit, regimen, visit by regimen, and gender as factors; and age and standing height Z score at baseline as covariates, with exchangeable covariance structure.)
SecondaryChange From Baseline in Growth (Standing Height) Over Time
Time frame:
Baseline, Week 40, 64, 160
Reported as:
Mean · cm
Change From Baseline in Growth (Standing Height) Over Time
cmBurosumab Q2WBurosumab Q4W Then Q2W
Change at Week 405.03 ± 1.2324.49 ± 1.455
Change at Week 647.48 ± 1.9346.98 ± 1.594
Change at Week 16018.38 ± 2.95817.22 ± 2.653
SecondaryChange From Baseline in Growth (Sitting Height) Over Time
Time frame:
Baseline, Week 40, 64, 160
Reported as:
Mean · cm
Change From Baseline in Growth (Sitting Height) Over Time
cmBurosumab Q2WBurosumab Q4W Then Q2W
Change at Week 402.66 ± 5.4962.39 ± 1.486
Change at Week 643.08 ± 2.4053.45 ± 1.390
Change at Week 1608.29 ± 2.9288.62 ± 2.163
SecondaryChange From Baseline in Growth (Arm Length) Over Time
Time frame:
Baseline, Week 40, 64, 160
Reported as:
Mean · cm
Change From Baseline in Growth (Arm Length) Over Time
cmBurosumab Q2WBurosumab Q4W Then Q2W
Change at Week 402.36 ± 1.0582.08 ± 0.905
Change at Week 643.99 ± 1.5564.77 ± 7.382
Change at Week 1608.50 ± 1.5378.32 ± 1.798
SecondaryChange From Baseline in Growth (Leg Length) Over Time
Time frame:
Baseline, Week 40, 64, 160
Reported as:
Mean · cm
Change From Baseline in Growth (Leg Length) Over Time
cmBurosumab Q2WBurosumab Q4W Then Q2W
Change to Week 402.90 ± 1.3652.82 ± 1.270
Change at Week 645.03 ± 1.8795.16 ± 1.283
Change at Week 16011.78 ± 3.04011.67 ± 2.338
Secondary6MWT Distance (Predicted Percent of Normal) Change From Baseline Over Time

The total distance walked (meters) in a 6-minute period was measured. The percent of predicted values were calculated using published normative data based on age, gender, and height (Geiger et al. 2007).

Time frame:
Baseline, Week 40, 64, 160
Reported as:
Least squares mean · percentage of predicted distance
6MWT Distance (Predicted Percent of Normal) Change From Baseline Over Time
percentage of predicted distanceBurosumab Q2WBurosumab Q4W Then Q2W
Change to Week 403.25 ± 1.8410.24 ± 2.153
Change to Week 645.29 ± 1.5683.70 ± 1.731
Change to Week 1601.96 ± 1.4832.15 ± 1.932
Statistical analysis
  • Burosumab Q2W · GEE model · p = 0.0771 (GEE model included change in 6MWT score as the dependent variable; visit, regimen, visit by regimen as factors; and 6MWT at baseline as a covariate, with exchangeable covariance structure.)
  • Burosumab Q4W Then Q2W · GEE model · p = 0.9098 (GEE model included change in 6MWT score as the dependent variable; visit, regimen, visit by regimen as factors; and 6MWT at baseline as a covariate, with exchangeable covariance structure.)
  • Burosumab Q2W · GEE model · p = 0.0007 (GEE model included change in percent of predicted 6MWT score as the dependent variable; visit, regimen, visit by regimen as factors; and 6MWT at baseline as a covariate, with exchangeable covariance structure.)
  • Burosumab Q4W Then Q2W · GEE model · p = 0.0327 (GEE model included change in percent of predicted 6MWT score as the dependent variable; visit, regimen, visit by regimen as factors; and 6MWT at baseline as a covariate, with exchangeable covariance structure.)
  • Burosumab Q2W · GEE model · p = 0.1865 (GEE model included change in percent of predicted 6MWT score as the dependent variable; visit, regimen, visit by regimen as factors; and 6MWT at baseline as a covariate, with exchangeable covariance structure.)
  • Burosumab Q4W Then Q2W · GEE model · p = 0.2654 (GEE model included change in percent of predicted 6MWT score as the dependent variable; visit, regimen, visit by regimen as factors; and 6MWT at baseline as a covariate, with exchangeable covariance structure.)
SecondaryChange From Baseline in POSNA-PODCI (Normative Score) Upper Extremity Scale Scores Over Time

The POSNA-PODCI yields 4 functional assessment scores: Upper Extremity Function,Transfers and Basic Mobility, Sports and Physical Function, and Comfort/Pain. In addition, a Global Function score, which is an average of the 4 functional assessments, and a Happiness score are calculated. Raw, mean, standardized, and normative scores are calculated for each scale. Normative scores are calculated so that higher scores indicate better functioning. All scores are referenced to the general, healthy population with a normative mean score of 50 and a standard deviation of 10.

Time frame:
Baseline, Week 40, 64, 160
Reported as:
Least squares mean · T-score
Change From Baseline in POSNA-PODCI (Normative Score) Upper Extremity Scale Scores Over Time
T-scoreBurosumab Q2WBurosumab Q4W Then Q2W
Change at Week 402.97 ± 0.7102.97 ± 1.212
Change at Week 641.89 ± 0.9143.20 ± 0.911
Change at Week 160-0.02 ± 0.7401.82 ± 1.449
Statistical analysis
  • Burosumab Q2W · GEE model · p = < 0.0001 (GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.)
  • Burosumab Q4W Then Q2W · GEE model · p = 0.0144 (GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.)
  • Burosumab Q2W · GEE model · p = 0.0384 (GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.)
  • Burosumab Q4W Then Q2W · GEE model · p = 0.0004 (GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.)
  • Burosumab Q2W · GEE model · p = 0.9795 (GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.)
  • Burosumab Q4W Then Q2W · GEE model · p = 0.2082 (GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.)
SecondaryChange From Baseline in POSNA-PODCI (Normative Score) Transfer and Basic Mobility Scale Scores Over Time

The POSNA-PODCI yields 4 functional assessment scores: Upper Extremity Function,Transfers and Basic Mobility, Sports and Physical Function, and Comfort/Pain. In addition, a Global Function score, which is an average of the 4 functional assessments, and a Happiness score are calculated. Raw, mean, standardized, and normative scores are calculated for each scale. Normative scores are calculated so that higher scores indicate better functioning. All scores are referenced to the general, healthy population with a normative mean score of 50 and a standard deviation of 10.

Time frame:
Baseline, Week 40, 64, 160
Reported as:
Least squares mean · T-score
Change From Baseline in POSNA-PODCI (Normative Score) Transfer and Basic Mobility Scale Scores Over Time
T-scoreBurosumab Q2WBurosumab Q4W Then Q2W
Change at Week 404.04 ± 0.8273.69 ± 1.648
Change at Week 64-0.34 ± 3.1234.32 ± 1.364
Change at Week 1601.88 ± 3.2855.44 ± 1.113
Statistical analysis
  • Burosumab Q2W · GEE model · p = < 0.0001 (GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.)
  • Burosumab Q4W Then Q2W · GEE model · p = 0.0251 (GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.)
  • Burosumab Q2W · GEE model · p = 0.9124 (GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.)
  • Burosumab Q4W Then Q2W · GEE model · p = 0.0016 (GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.)
  • Burosumab Q2W · GEE model · p = 0.5677 (GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.)
  • Burosumab Q4W Then Q2W · GEE model · p = < 0.0001 (GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.)
SecondaryChange From Baseline in POSNA-PODCI (Normative Score) Sports/Physical Functioning Scale Scores Over Time

The POSNA-PODCI yields 4 functional assessment scores: Upper Extremity Function,Transfers and Basic Mobility, Sports and Physical Function, and Comfort/Pain. In addition, a Global Function score, which is an average of the 4 functional assessments, and a Happiness score are calculated. Raw, mean, standardized, and normative scores are calculated for each scale. Normative scores are calculated so that higher scores indicate better functioning. All scores are referenced to the general, healthy population with a normative mean score of 50 and a standard deviation of 10.

Time frame:
Baseline, Week 40, 64, 160
Reported as:
Least squares mean · T-score
Change From Baseline in POSNA-PODCI (Normative Score) Sports/Physical Functioning Scale Scores Over Time
T-scoreBurosumab Q2WBurosumab Q4W Then Q2W
Change at Week 409.78 ± 1.6799.15 ± 2.249
Change at Week 647.74 ± 2.6369.84 ± 2.534
Change at Week 16012.04 ± 2.10214.33 ± 1.834
Statistical analysis
  • Burosumab Q2W · GEE model · p = < 0.0001 (GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.)
  • Burosumab Q4W Then Q2W · GEE model · p = < 0.0001 (GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.)
  • Burosumab Q2W · GEE model · p = 0.0033 (GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.)
  • Burosumab Q4W Then Q2W · GEE model · p = 0.0001 (GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.)
  • Burosumab Q2W · GEE model · p = < 0.0001 (GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.)
  • Burosumab Q4W Then Q2W · GEE model · p = < 0.0001 (GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.)
SecondaryChange From Baseline in POSNA-PODCI (Normative Score) Pain/Comfort Scale Scores Over Time

The POSNA-PODCI yields 4 functional assessment scores: Upper Extremity Function,Transfers and Basic Mobility, Sports and Physical Function, and Comfort/Pain. In addition, a Global Function score, which is an average of the 4 functional assessments, and a Happiness score are calculated. Raw, mean, standardized, and normative scores are calculated for each scale. Normative scores are calculated so that higher scores indicate better functioning. All scores are referenced to the general, healthy population with a normative mean score of 50 and a standard deviation of 10.

Time frame:
Baseline, Week 40, 64, 160
Reported as:
Least squares mean · T-score
Change From Baseline in POSNA-PODCI (Normative Score) Pain/Comfort Scale Scores Over Time
T-scoreBurosumab Q2WBurosumab Q4W Then Q2W
Change at Week 407.67 ± 2.3997.39 ± 2.477
Change at Week 645.60 ± 2.9047.74 ± 2.077
Change at Week 16013.06 ± 2.18712.38 ± 2.265
Statistical analysis
  • Burosumab Q2W · GEE model · p = 0.0014 (GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.)
  • Burosumab Q4W Then Q2W · GEE model · p = 0.0028 (GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.)
  • Burosumab Q2W · GEE model · p = 0.0536 (GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.)
  • Burosumab Q4W Then Q2W · GEE model · p = 0.0002 (GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.)
  • Burosumab Q2W · GEE model · p = < 0.0001 (GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.)
  • Burosumab Q4W Then Q2W · GEE model · p = < 0.0001 (GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.)
SecondaryChange From Baseline in POSNA-PODCI (Normative Score) Happiness Scale Scores Over Time

The POSNA-PODCI yields 4 functional assessment scores: Upper Extremity Function,Transfers and Basic Mobility, Sports and Physical Function, and Comfort/Pain. In addition, a Global Function score, which is an average of the 4 functional assessments, and a Happiness score are calculated. Raw, mean, standardized, and normative scores are calculated for each scale. Normative scores are calculated so that higher scores indicate better functioning. All scores are referenced to the general, healthy population with a normative mean score of 50 and a standard deviation of 10.

Time frame:
Baseline, Week 40, 64, 160
Reported as:
Least squares mean · T-score
Change From Baseline in POSNA-PODCI (Normative Score) Happiness Scale Scores Over Time
T-scoreBurosumab Q2WBurosumab Q4W Then Q2W
Change at Week 402.84 ± 2.3283.01 ± 1.902
Change at Week 642.18 ± 1.9143.34 ± 1.914
Change at Week 1606.46 ± 2.4869.19 ± 1.075
Statistical analysis
  • Burosumab Q2W · GEE model · p = 0.2230 (GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.)
  • Burosumab Q4W Then Q2W · GEE model · p = 0.1132 (GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.)
  • Burosumab Q2W · GEE model · p = 0.2558 (GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.)
  • Burosumab Q4W Then Q2W · GEE model · p = 0.0814 (GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.)
  • Burosumab Q2W · GEE model · p = 0.0093 (GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.)
  • Burosumab Q4W Then Q2W · GEE model · p = < 0.0001 (GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.)
SecondaryChange From Baseline in POSNA-PODCI (Normative Score) Global Functioning Scale Scores Over Time

The POSNA-PODCI yields 4 functional assessment scores: Upper Extremity Function,Transfers and Basic Mobility, Sports and Physical Function, and Comfort/Pain. In addition, a Global Function score, which is an average of the 4 functional assessments, and a Happiness score are calculated. Raw, mean, standardized, and normative scores are calculated for each scale. Normative scores are calculated so that higher scores indicate better functioning. All scores are referenced to the general, healthy population with a normative mean score of 50 and a standard deviation of 10.

Time frame:
Baseline, Week 40, 64, 160
Reported as:
Least squares mean · T-score
Change From Baseline in POSNA-PODCI (Normative Score) Global Functioning Scale Scores Over Time
T-scoreBurosumab Q2WBurosumab Q4W Then Q2W
Change at Week 409.06 ± 1.5608.12 ± 2.351
Change at Week 646.02 ± 2.7068.72 ± 2.019
Change at Week 16011.37 ± 1.80411.94 ± 2.024
Statistical analysis
  • Burosumab Q2W · GEE model · p = < 0.0001 (GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.)
  • Burosumab Q4W Then Q2W · GEE model · p = 0.0006 (GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.)
  • Burosumab Q2W · GEE model · p = 0.0260 (GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.)
  • Burosumab Q4W Then Q2W · GEE model · p = < 0.0001 (GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.)
  • Burosumab Q2W · GEE model · p = < 0.0001 (GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.)
  • Burosumab Q4W Then Q2W · GEE model · p = < 0.0001 (GEE model includes change in POSNA-PODCI score as the dependent variable, visit, regimen, visit by regimen as factors, and POSNA-PODCI at baseline as a covariate, with exchangeable covariance structure.)
SecondaryChange From Baseline in FEP Over Time

FEP is defined as 100% × (urine phosphorus × serum creatinine)/(urine creatinine × serum phosphorus), where the 2-hour urine sample was used for urine phosphorus and urine creatinine.

Time frame:
Baseline, Week 40, 64, 160
Reported as:
Mean · percentage of phosphorus excreted
Change From Baseline in FEP Over Time
percentage of phosphorus excretedBurosumab Q2WBurosumab Q4W Then Q2W
Change at Week 40-3.97 ± 7.161-4.85 ± 7.170
Change at Week 64-2.63 ± 4.446-3.96 ± 7.522
Change at Week 160-5.43 ± 6.985-6.47 ± 8.072
SecondaryChange From Baseline in P1NP Over Time
Time frame:
Baseline, Week 40, 64
Reported as:
Mean · ng/mL
Change From Baseline in P1NP Over Time
ng/mLBurosumab Q2WBurosumab Q4W Then Q2W
Change at Week 40275.98 ± 329.587224.91 ± 161.053
Change at Week 64137.35 ± 354.315133.56 ± 192.306
SecondaryChange From Baseline in CTx Over Time
Time frame:
Baseline, Week 40, 64
Reported as:
Mean · ng/mL
Change From Baseline in CTx Over Time
ng/mLBurosumab Q2WBurosumab Q4W Then Q2W
Change at Week 401.01 ± 0.8020.64 ± 0.578
Change at Week 641.08 ± 0.8700.81 ± 0.706
SecondaryChange From Baseline in ALP Over Time
Time frame:
Baseline, Week 40, 64, 160
Reported as:
Mean · U/L
Change From Baseline in ALP Over Time
U/LBurosumab Q2WBurosumab Q4W Then Q2W
Change at Week 40-79.4 ± 97.40-47.8 ± 70.86
Change at Week 64-113.9 ± 81.28-80.9 ± 67.11
Change at Week 160-153.1 ± 132.45-140.0 ± 115.82
Statistical analysis
  • Burosumab Q2W · one sample t test · p = 0.0003
  • Burosumab Q4W Then Q2W · one sample t test · p = 0.0021
  • Burosumab Q2W · one sample t test · p = < 0.0001
  • Burosumab Q4W Then Q2W · one sample t test · p = < 0.0001
  • Burosumab Q2W · one sample t test · p = < 0.0001
  • Burosumab Q4W Then Q2W · one sample t test · p = < 0.0001
SecondaryChange From Baseline in BALP Over Time
Time frame:
Baseline, Week 40, 64, 160
Reported as:
Mean · mcg/L
Change From Baseline in BALP Over Time
mcg/LBurosumab Q2WBurosumab Q4W Then Q2W
Change at Week 40-35.55 ± 46.738-27.80 ± 31.409
Change at Week 64-50.40 ± 36.478-47.13 ± 28.822
Change at Week 160-67.25 ± 59.309-56.73 ± 52.284
SecondarySerum Pre-Dose Concentrations of Burosumab
Time frame:
Week 40, 64, 160
Reported as:
Mean · ng/mL
Serum Pre-Dose Concentrations of Burosumab
ng/mLBurosumab Q2WBurosumab Q4W Then Q2W
Week 4013188.81 ± 7188.5886443.08 ± 3266.215
Week 6415846.65 ± 9385.3938525.63 ± 3968.821
Week 16013975.27 ± 8168.87713163.96 ± 6593.120
SecondaryNumber of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Discontinuations Due to Adverse Events (AEs)

An AE is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An SAE is defined as an AE or suspected adverse reaction that at any dose results in any of the following outcomes: death; life-threatening AE; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; a congenital anomaly/birth defect. Severity was graded as 1 (mild), 2 (moderate), 3 (severe), 4 (life-threatening), 5 (death). TEAEs are defined as AEs with onset on or after the time of initiation of study drug administration.

Time frame:
Up to 216 weeks
Reported as:
Count of participants · Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Discontinuations Due to Adverse Events (AEs)
ParticipantsBurosumab Q2WBurosumab Q4W Then Q2W
All TEAEs2626
Serious TEAE01
Related TEAE1721
Serious Related TEAE01
Grade 3 or 4 TEAE11
TEAE Leading to Study Discontinuation00
TEAE Leading to Treatment Discontinuation00
TEAE Leading to Death00

Adverse events

Collected over Up to 216 weeks. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Burosumab Q2W0/26 (0%)0/26 (0%)26/26 (100%)
Burosumab Q4W Then Q2W0/26 (0%)1/26 (3.8%)26/26 (100%)
Most frequent serious events
Most frequent serious events
EventBurosumab Q2WBurosumab Q4W Then Q2W
PyrexiaGeneral disorders0/261/26
MyalgiaMusculoskeletal and connective tissue disorders0/261/26
HeadacheNervous system disorders0/261/26
Most frequent other events
Showing 10 of 107
Most frequent other events
EventBurosumab Q2WBurosumab Q4W Then Q2W
CoughRespiratory, thoracic and mediastinal disorders21/2615/26
HeadacheNervous system disorders20/2619/26
ArthralgiaMusculoskeletal and connective tissue disorders11/2617/26
Pain In ExtremityMusculoskeletal and connective tissue disorders10/2617/26
VomitingGastrointestinal disorders13/2616/26
NasopharyngitisInfections and infestations13/2615/26
Injection Site ErythemaGeneral disorders14/269/26
Oropharyngeal PainRespiratory, thoracic and mediastinal disorders14/2612/26
Injection Site ReactionGeneral disorders13/2613/26
PyrexiaGeneral disorders12/2613/26

Baseline characteristics

Age, Continuous
Age, Continuous(years)Burosumab Q2WBurosumab Q4W Then Q2WTotal
Mean8.7 ± 1.728.3 ± 2.048.5 ± 1.87
Sex: Female, Male
Sex: Female, Male(Participants)Burosumab Q2WBurosumab Q4W Then Q2WTotal
Female141428
Male121224
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)Burosumab Q2WBurosumab Q4W Then Q2WTotal
Black or African American202
White232346
Other, Not Specified134
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)Burosumab Q2WBurosumab Q4W Then Q2WTotal
Hispanic or Latino022
Not Hispanic or Latino262450
Rickets Severity Score (RSS) Total Score
Rickets Severity Score (RSS) Total Score(score on a scale)Burosumab Q2WBurosumab Q4W Then Q2WTotal
Mean1.92 ± 1.1721.67 ± 0.9991.80 ± 1.086
Serum Phosphorus
Serum Phosphorus(mg/dL)Burosumab Q2WBurosumab Q4W Then Q2WTotal
Mean2.38 ± 0.4052.28 ± 0.2992.33 ± 0.356
Serum 1, 25-Dihydroxyvitamin D
Serum 1, 25-Dihydroxyvitamin D(pg/mL)Burosumab Q2WBurosumab Q4W Then Q2WTotal
Mean41.28 ± 21.96741.37 ± 15.29341.33 ± 18.740
Ratio of Renal Tubular Maximum Reabsorption Rate of Phosphate to Glomerular Filtration Rate(TmP/GFR)
Ratio of Renal Tubular Maximum Reabsorption Rate of Phosphate to Glomerular Filtration Rate(TmP/GFR)(mg/dL)Burosumab Q2WBurosumab Q4W Then Q2WTotal
Mean2.176 ± 0.49251.978 ± 0.34742.077 ± 0.4335

12 further baseline measures are reported on the registry.

08

Study locations

9 sites
  • University of California San Francisco
    San Francisco, California 94158, United States
  • Yale University School of Medicine
    New Haven, Connecticut 06520-8064, United States
  • Indiana University Hospital
    Indianapolis, Indiana 46202, United States
  • Shriners Hospital for Children
    St Louis, Missouri 63110, United States
  • Bicetre Hospital
    Le Kremlin-Bicêtre, 94275, France
  • University Medical Center Groningen
    Groningen, 9700RB, Netherlands
  • Royal Manchester Hospital
    Manchester, Lancashire M13 9WL, United Kingdom
  • Birmingham Children's University
    Birmingham, B4 6NH, United Kingdom
  • Great Ormond Street Hospital
    London, WC1N3JH, United Kingdom
09

References and documents

Publications

  • 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. PubMed 39151033 ↗
  • Linglart A, Imel EA, Whyte MP, Portale AA, Hogler W, Boot AM, Padidela R, Van't Hoff W, Gottesman GS, Chen A, Skrinar A, Scott Roberts M, Carpenter TO. Sustained Efficacy and Safety of Burosumab, a Monoclonal Antibody to FGF23, in Children With X-Linked Hypophosphatemia. J Clin Endocrinol Metab. 2022 Feb 17;107(3):813-824. doi: 10.1210/clinem/dgab729. PubMed 34636899 ↗
  • Mao M, Carpenter TO, Whyte MP, Skrinar A, Chen CY, San Martin J, Rogol AD. Growth Curves for Children with X-linked Hypophosphatemia. J Clin Endocrinol Metab. 2020 Oct 1;105(10):3243-9. doi: 10.1210/clinem/dgaa495. PubMed 32721016 ↗
  • Carpenter TO, Whyte MP, Imel EA, Boot AM, Hogler W, Linglart A, Padidela R, Van't Hoff W, Mao M, Chen CY, Skrinar A, Kakkis E, San Martin J, Portale AA. Burosumab Therapy in Children with X-Linked Hypophosphatemia. N Engl J Med. 2018 May 24;378(21):1987-1998. doi: 10.1056/NEJMoa1714641. PubMed 29791829 ↗

Study documents

  • Study protocol · May 8, 2017
  • Statistical analysis plan · Apr 26, 2016

Documents are hosted by the registry — open the source record to download them.

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on May 6, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT02163577
Lead sponsor
Kyowa Kirin, Inc.
Collaborators
Kyowa Kirin Co., Ltd.
Responsible party
Sponsor
First posted
Jun 13, 2014
Start date
Jul 2, 2014
Primary completion
Oct 30, 2018
Completion
Oct 30, 2018
Results posted
May 22, 2019
Last update
May 6, 2024

Study contacts

Medical Director
study director · Ultragenyx Pharmaceutical Inc

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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