X-linked HypophosphatemiaPhase 2NCT02163577
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 study testing burosumab in people with X-linked Hypophosphatemia, run by Kyowa Kirin, Inc. at 9 sites in 4 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 5 to 12 years
- Conditions the study is for
- X-linked Hypophosphatemia
- What is being tested?
- burosumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 52 participants
- Where
- 9 sitesin 4 countries
- Study dates
- 2 Jul 2014to 30 Oct 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 to 12 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Male or female, aged 5 - 12 years, inclusive, with open growth plates
- Tanner stage of 2 or less based on breast and testicular development
- 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
- Biochemical findings associated with XLH including:
Show all 15Show fewer
- Serum phosphorus ≤ 2.8 mg/dL (0.904 mmol/L)*
- Serum creatinine within age-adjusted normal range*
- Standing height < 50th percentile for age and gender using local normative data.
- 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.
- Willing to provide access to prior medical records for the collection of historical growth, biochemical and radiographic data, and disease history.
- 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.
- 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. 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
Who cannot join
- 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
- Use of oral phosphate within 7 days prior to Screening Visit 2; washout will take place during the Screening Period
- Use of calcimimetics, aluminum hydroxide antacids (e.g. Maalox® and Mylanta®), systemic corticosteroids, and thiazides within 7 days prior to Screening Visit 1
- Use of growth hormone therapy within 3 months before Screening Visit 1
- Use of bisphosphonates for 6 months or more in the 2 years prior to Screening Visit 1
- 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
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- Planned or recommended orthopedic surgery, including staples, 8-plates or osteotomy, within the clinical trial period
- Hypocalcemia or hypercalcemia, defined as serum calcium levels outside the age-adjusted normal limits *
- Evidence of tertiary hyperparathyroidism as determined by the Investigator
- Use of medication to suppress parathyroid hormone (PTH) (e.g. Sensipar®, cinacalcet, calcimimetics) within 2 months prior to Screening Visit 1
- 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
- Previously diagnosed with human immunodeficiency virus antibody, hepatitis B surface antigen, and/or hepatitis C antibody
- History of recurrent infection or predisposition to infection, or of known immunodeficiency
- 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
- 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
- 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
Trial locations and contacts
9 sites in 4 countries.
9 sites in 4 countries
United States4 sites
Indiana University Hospital
Indianapolis, Indiana, 46202
Yale University School of Medicine
New Haven, Connecticut, 06520-8064
University of California San Francisco
San Francisco, California, 94158
Shriners Hospital for Children
St Louis, Missouri, 63110
United Kingdom3 sites
Birmingham Children's University
Birmingham, B4 6NH
Great Ormond Street Hospital
London, WC1N3JH
Royal Manchester Hospital
Manchester, Lancashire, M13 9WL
About this study
Official title: A Randomized, Open-Label, Dose Finding, Phase 2 Study to Assess the Pharmacodynamics and Safety of the Anti-FGF23 Antibody, KRN23, in Pediatric Patients With X-linked Hypophosphatemia (XLH)
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
- Conditions
- X-linked Hypophosphatemia
- Being tested
- burosumab
- Keywords
- X-linked hypophosphatemia, XLH, FGF23, KRN23
- Medical subject headings
- Familial Hypophosphatemic Rickets
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
burosumabBiological
Also called KRN23, Crysvita®, UX023
solution for SC injection
| Study group | Role | What they receive |
|---|---|---|
| Burosumab Q2W | Experimental | Burosumab subcutaneous (SC) injections every 2 weeks (Q2W). Dose was determined by the participant's weight and prescribed dose by their study doctor. Receives: Biological: burosumab |
| Burosumab Q4W Then Q2W | Experimental | 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. Receives: Biological: burosumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline, Week 40, 64, 160
Change From Baseline in Serum Phosphorus Over Time
Measured: Baseline, Week 40, 64, 160
Change From Baseline in Serum 1,25(OH)2D Over Time
Measured: Baseline, Week 40, 64, 160
Change From Baseline in TmP/GFR Over Time
Data for urinary phosphorus and TRP were used in calculation TmP/GFR.
Measured: Baseline, Week 40, 64, 160
Secondary outcomes (25)
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.
Measured: Baseline, Week 40, 64, 160
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.
Measured: Baseline, Week 40, 64, 160
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).
Measured: Baseline, Week 40, 64, 160
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).
Measured: Baseline, Week 40, 64, 160
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).
Measured: Baseline, Week 40, 64, 160
Change From Baseline in Growth Velocity Over Time
Measured: Baseline, Week 40, 64, 160
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.
Measured: Baseline, Week 40, 64, 160
Change From Baseline in Growth (Standing Height) Over Time
Measured: Baseline, Week 40, 64, 160
Change From Baseline in Growth (Sitting Height) Over Time
Measured: Baseline, Week 40, 64, 160
Change From Baseline in Growth (Arm Length) Over Time
Measured: Baseline, Week 40, 64, 160
Change From Baseline in Growth (Leg Length) Over Time
Measured: Baseline, Week 40, 64, 160
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).
Measured: Baseline, Week 40, 64, 160
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.
Measured: Baseline, Week 40, 64, 160
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.
Measured: Baseline, Week 40, 64, 160
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.
Measured: Baseline, Week 40, 64, 160
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.
Measured: Baseline, Week 40, 64, 160
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.
Measured: Baseline, Week 40, 64, 160
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.
Measured: Baseline, Week 40, 64, 160
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.
Measured: Baseline, Week 40, 64, 160
Change From Baseline in P1NP Over Time
Measured: Baseline, Week 40, 64
Change From Baseline in CTx Over Time
Measured: Baseline, Week 40, 64
Change From Baseline in ALP Over Time
Measured: Baseline, Week 40, 64, 160
Change From Baseline in BALP Over Time
Measured: Baseline, Week 40, 64, 160
Serum Pre-Dose Concentrations of Burosumab
Measured: Week 40, 64, 160
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.
Measured: Up to 216 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jun 2014 (estimated)
- Study start2 Jul 2014
- Primary completion30 Oct 2018
- Study completion30 Oct 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for X-linked HypophosphatemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 52 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kyowa Kirin, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Kyowa Kirin Co., Ltd.
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Ultragenyx Pharmaceutical Inc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02163577
- Sponsor's protocol ID
- UX023-CL201
- Status last verified
- May 2024
- First submitted
- 9 Jun 2014
- Last updated
- 6 May 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Expanded access
- Available
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 39151033Linglart 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 34636899Mao 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 32721016Carpenter 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 at a glance
From the registry record, last updated by the sponsor on 6 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Open-Label, Dose Finding, Phase 2 Study to Assess the Pharmacodynamics and Safety of the Anti-FGF23 Antibody, KRN23, in Pediatric Patients With X-linked Hypophosphatemia (XLH)
- ClinicalTrials.gov ID
- NCT02163577
- Acronym / sponsor ID
- UX023-CL201
- Conditions
- X-linked Hypophosphatemia
- Keywords
- X-linked hypophosphatemia, XLH, FGF23, KRN23
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 52 participants (actual)
- Lead sponsor
- Kyowa Kirin, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Kyowa Kirin Co., Ltd.
- Study start
- 2 Jul 2014 (actual)
- Primary completion
- 30 Oct 2018 (actual)
- Study completion
- 30 Oct 2018 (actual)
- First posted
- 13 Jun 2014 (estimated)
- Results
- Posted 22 May 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Burosumab Q2W | Experimental | Biological: burosumabBurosumab subcutaneous (SC) injections every 2 weeks (Q2W). Dose was determined by the participant's weight and prescribed dose by their study doctor. |
| Burosumab Q4W Then Q2W | Experimental | Biological: burosumabBurosumab 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. |
Who may qualify
- Ages
- 5 to 12 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (15 listed)
- Male or female, aged 5 - 12 years, inclusive, with open growth plates
- Tanner stage of 2 or less based on breast and testicular development
- Diagnosis of XLH supported by ONE of the following:
- Biochemical findings associated with XLH including:
- Standing height < 50th percentile for age and gender using local normative data.
Key exclusion criteria (18 listed)
- 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
- Use of oral phosphate within 7 days prior to Screening Visit 2; washout will take place during the Screening Period
- Use of calcimimetics, aluminum hydroxide antacids (e.g. Maalox® and Mylanta®), systemic corticosteroids, and thiazides within 7 days prior to Screening Visit 1
- Use of growth hormone therapy within 3 months before Screening Visit 1
- Use of bisphosphonates for 6 months or more in the 2 years prior to Screening Visit 1
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| burosumabAlso: KRN23, Crysvita®, UX023solution for SC injection | Biological | Burosumab Q2W, Burosumab Q4W Then Q2W |
Primary outcome
Change From Baseline in RSS Total Score Over Time
Time frame: Baseline, Week 40, 64, 160
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.
Change From Baseline in Serum Phosphorus Over Time
Time frame: Baseline, Week 40, 64, 160
Change From Baseline in Serum 1,25(OH)2D Over Time
Time frame: Baseline, Week 40, 64, 160
Change From Baseline in TmP/GFR Over Time
Time frame: Baseline, Week 40, 64, 160
Data for urinary phosphorus and TRP were used in calculation TmP/GFR.
25 secondary outcomes
Change From Baseline in RSS Knee Scores Over Time
Time frame: Baseline, Week 40, 64, 160
Change From Baseline in RSS Wrist Scores Over Time
Time frame: Baseline, Week 40, 64, 160
Radiographic Global Impression of Change (RGI-C) Global Scores Over Time
Time frame: Baseline, Week 40, 64, 160
RGI-C Knee Scores Over Time
Time frame: Baseline, Week 40, 64, 160
RGI-C Wrist Scores Over Time
Time frame: Baseline, Week 40, 64, 160
Change From Baseline in Growth Velocity Over Time
Time frame: Baseline, Week 40, 64, 160
Change From Baseline in Standing Height Z Score Over Time
Time frame: Baseline, Week 40, 64, 160
Change From Baseline in Growth (Standing Height) Over Time
Time frame: Baseline, Week 40, 64, 160
Change From Baseline in Growth (Sitting Height) Over Time
Time frame: Baseline, Week 40, 64, 160
Change From Baseline in Growth (Arm Length) Over Time
Time frame: Baseline, Week 40, 64, 160
Change From Baseline in Growth (Leg Length) Over Time
Time frame: Baseline, Week 40, 64, 160
6MWT Distance (Predicted Percent of Normal) Change From Baseline Over Time
Time frame: Baseline, Week 40, 64, 160
Change From Baseline in POSNA-PODCI (Normative Score) Upper Extremity Scale Scores Over Time
Time frame: Baseline, Week 40, 64, 160
Change From Baseline in POSNA-PODCI (Normative Score) Transfer and Basic Mobility Scale Scores Over Time
Time frame: Baseline, Week 40, 64, 160
Change From Baseline in POSNA-PODCI (Normative Score) Sports/Physical Functioning Scale Scores Over Time
Time frame: Baseline, Week 40, 64, 160
Change From Baseline in POSNA-PODCI (Normative Score) Pain/Comfort Scale Scores Over Time
Time frame: Baseline, Week 40, 64, 160
Change From Baseline in POSNA-PODCI (Normative Score) Happiness Scale Scores Over Time
Time frame: Baseline, Week 40, 64, 160
Change From Baseline in POSNA-PODCI (Normative Score) Global Functioning Scale Scores Over Time
Time frame: Baseline, Week 40, 64, 160
Change From Baseline in FEP Over Time
Time frame: Baseline, Week 40, 64, 160
Change From Baseline in P1NP Over Time
Time frame: Baseline, Week 40, 64
Change From Baseline in CTx Over Time
Time frame: Baseline, Week 40, 64
Change From Baseline in ALP Over Time
Time frame: Baseline, Week 40, 64, 160
Change From Baseline in BALP Over Time
Time frame: Baseline, Week 40, 64, 160
Serum Pre-Dose Concentrations of Burosumab
Time frame: Week 40, 64, 160
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Discontinuations Due to Adverse Events (AEs)
Time frame: Up to 216 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39151033Portale 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.
- Derived from this study: PubMed 34636899Linglart 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.
- Derived from this study: PubMed 32721016Mao 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.
- Derived from this study: PubMed 29791829Carpenter 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Ultragenyx Pharmaceutical Inc
9 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing burosumab in people with X-linked Hypophosphatemia, run by Kyowa Kirin, Inc. at 9 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United States, United Kingdom, France, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 May 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in RSS Total Score Over Time (time frame: Baseline, Week 40, 64, 160). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02163577, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 May 2024.