Study of KRN23 (Burosumab), a Recombinant Fully Human Monoclonal Antibody Against Fibroblast Growth Factor 23 (FGF23), in Pediatric Subjects With X-linked Hypophosphatemia (XLH)
NCT ID: NCT02163577
Last Updated: 2024-05-06
Study Results
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
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COMPLETED
PHASE2
52 participants
INTERVENTIONAL
2014-07-02
2018-10-30
Brief Summary
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* 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
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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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.
burosumab
solution for SC injection
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.
burosumab
solution for SC injection
Interventions
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burosumab
solution for SC injection
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
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
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
5 Years
12 Years
ALL
No
Sponsors
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Kyowa Kirin Co., Ltd.
INDUSTRY
Kyowa Kirin, Inc.
INDUSTRY
Responsible Party
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Principal Investigators
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Medical Director
Role: STUDY_DIRECTOR
Ultragenyx Pharmaceutical Inc
Locations
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University of California San Francisco
San Francisco, California, United States
Yale University School of Medicine
New Haven, Connecticut, United States
Indiana University Hospital
Indianapolis, Indiana, United States
Shriners Hospital for Children
St Louis, Missouri, United States
Bicetre Hospital
Le Kremlin-Bicêtre, , France
University Medical Center Groningen
Groningen, , Netherlands
Royal Manchester Hospital
Manchester, Lancashire, United Kingdom
Birmingham Children's University
Birmingham, , United Kingdom
Great Ormond Street Hospital
London, , United Kingdom
Countries
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References
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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.
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.
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.
Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Other Identifiers
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UX023-CL201
Identifier Type: -
Identifier Source: org_study_id
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