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

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ClinicalTrials.gov Identifier: NCT02163577
Recruitment Status : Active, not recruiting
First Posted : June 13, 2014
Last Update Posted : June 13, 2018
Sponsor:
Collaborator:
Kyowa Hakko Kirin Co., Ltd
Information provided by (Responsible Party):
Ultragenyx Pharmaceutical Inc

Brief Summary:

The objectives of the study are to:

  • Identify a dose and dosing regimen of KRN23, based on safety and pharmacodynamic (PD) effect, in pediatric XLH patients
  • Establish the safety profile of KRN23 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 KRN23 treatment on markers of bone health in pediatric XLH patients
  • Obtain a preliminary assessment of the clinical effects of KRN23 on bone health and deformity, muscle strength, and motor function
  • Obtain a preliminary assessment of the effects of KRN23 on patient-reported outcomes, including pain, disability, and quality of life in pediatric XLH patients
  • Evaluate the long-term safety and efficacy of KRN23 Evaluate the long-term safety and efficacy of KRN23

Condition or disease Intervention/treatment Phase
X-linked Hypophosphatemia Biological: burosumab Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 52 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : July 2, 2014
Actual Primary Completion Date : June 16, 2016
Estimated Study Completion Date : September 30, 2018


Arm Intervention/treatment
Experimental: Burosumab Q4W
Burosumab subcutaneous (SC) injections every 4 weeks (Q4W). Dose is determined by the participant's weight and prescribed dose by their study doctor.
Biological: burosumab
solution for SC injection
Other Names:
  • KRN23
  • Crysvita®

Experimental: Burosumab Q2W
Burosumab SC injections every 2 weeks (Q2W). Dose is determined by the participant's weight and prescribed dose by their study doctor.
Biological: burosumab
solution for SC injection
Other Names:
  • KRN23
  • Crysvita®




Primary Outcome Measures :
  1. Change from Baseline at Week 40 in Severity of Rickets as Measured by Rickets Severity Score (RSS) Total Score [ Time Frame: Baseline, Week 40 ]

Secondary Outcome Measures :
  1. Change From Baseline at Week 40 in Severity of Rickets as Measured by RSS Knee and Wrist Scores [ Time Frame: Baseline, Week 40 ]
  2. Change from Baseline at Week 40 in the Radiographic Appearance of Rickets and Bowing as Measured by Radiographic Global Impression of Change (RGI-C) Global, Knee, Wrist and Long Leg Scores [ Time Frame: Baseline, Week 40 ]
  3. Change in Growth Velocity (cm/year) From Pre-Treatment to Post-Treatment [ Time Frame: Pre-treatment, Baseline, Weeks 16, 24, 40 ]
  4. Change From Baseline at Week 40 in Standing Height Z-Score [ Time Frame: Baseline, Week 40 ]
  5. Growth (Standing Height, Sitting Height, Arm Length, Leg Length) up to Week 40 [ Time Frame: Baseline, Weeks 16, 24, 40 ]
  6. Change from Baseline at Week 40 in 6-Minute Walk Test (6MWT), Distance (m) [ Time Frame: Baseline, Week 40 ]
  7. Change from Baseline in Pediatric Orthopedic Society of North America Pediatric Outcomes Data Collection Instrument (POSNA-PODCI) Scores at Week 40 [ Time Frame: Baseline, Week 40 ]


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Ages Eligible for Study:   5 Years to 12 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion

  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

  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 alcimimetics) 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 (KRN23) 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02163577


Locations
United States, California
University of California San Francisco
San Francisco, California, United States, 94158
United States, Connecticut
Yale University School of Medicine
New Haven, Connecticut, United States, 06520-8064
United States, Indiana
Indiana University Hospital
Indianapolis, Indiana, United States, 46202
United States, Missouri
Shriners Hospital for Children
Saint Louis, Missouri, United States, 63110
France
Bicetre Hospital
Le Kremlin- Bicetre, France, 94275
Netherlands
University Medical Center Groningen
Groningen, Netherlands, 9700RB
United Kingdom
Royal Manchester Hospital
Manchester, Lancashire, United Kingdom, M13 9WL
Birmingham Children's University
Birmingham, United Kingdom, B4 6NH
Great Ormond Street Hospital
London, United Kingdom, WC1N3JH
Sponsors and Collaborators
Ultragenyx Pharmaceutical Inc
Kyowa Hakko Kirin Co., Ltd
Investigators
Principal Investigator: Thomas Carpenter, MD Yale University

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Ultragenyx Pharmaceutical Inc
ClinicalTrials.gov Identifier: NCT02163577     History of Changes
Other Study ID Numbers: UX023-CL201
First Posted: June 13, 2014    Key Record Dates
Last Update Posted: June 13, 2018
Last Verified: June 2018

Keywords provided by Ultragenyx Pharmaceutical Inc:
X-linked hypophosphatemia
XLH
FGF23
KRN23

Additional relevant MeSH terms:
Hypophosphatemia
Familial Hypophosphatemic Rickets
Phosphorus Metabolism Disorders
Metabolic Diseases
Rickets, Hypophosphatemic
Rickets
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Hypophosphatemia, Familial
Renal Tubular Transport, Inborn Errors
Kidney Diseases
Urologic Diseases
Metal Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Calcium Metabolism Disorders
Vitamin D Deficiency
Avitaminosis
Deficiency Diseases
Malnutrition
Nutrition Disorders
Antibodies
Immunologic Factors
Physiological Effects of Drugs