We updated the design of this site on December 18, 2017. Learn more.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02163577
Recruitment Status : Active, not recruiting
First Posted : June 13, 2014
Last Update Posted : October 23, 2017
Sponsor:
Collaborator:
Information provided by (Responsible Party):

Study Description
Brief Summary:
UX023-CL201 is a randomized, multicenter, open-label, dose finding, Phase 2 study. The study will be conducted in prepubescent children aged 5-12 years with XLH to assess the pharmacodynamics and safety of KRN23 administered via subcutaneous injections monthly (every 4 weeks) or biweekly (every 2 weeks) for a total of 64 weeks. The study consists of a 16-week individual dose Titration Period, followed by a 48-week Treatment Period. The study will enroll approximately 50 pediatric patients with XLH and radiographic evidence of bone disease. Subjects will need to discontinue oral phosphate and vitamin D metabolite therapy prior to randomization and throughout the duration of the study.

Condition or disease Intervention/treatment Phase
X-linked Hypophosphatemia Drug: KRN23 Phase 2

Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 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 : June 30, 2014
Primary Completion Date : June 16, 2016
Estimated Study Completion Date : December 2018


Arms and Interventions

Arm Intervention/treatment
Experimental: KRN23 Q4 (every 4) weeks
Study drug is administered every 4 weeks. Dose is determined by subject's weight and prescribed dose by their study doctor.
Drug: KRN23
Experimental: KRN23 Q2 (every 2) weeks
Study drug is administered every 2 weeks. Dose is determined by subject's weight and prescribed dose by their study doctor.
Drug: KRN23


Outcome Measures

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


Other Outcome Measures:
  1. Change From Baseline at Week 64 in Severity of Rickets as Measured by RSS Knee and Wrist Scores [ Time Frame: Baseline, Week 64 ]
  2. Change from Baseline at Week 64 in the Radiographic Appearance of Rickets and Bowing as Measured by Radiographic Global Impression of Change (RGI-C) RSS Global, Knee, Wrist and Long Leg Scores [ Time Frame: Baseline, Week 64 ]
  3. Growth (Standing Height, Sitting Height, Arm Length, and Leg Length) at Week 64 [ Time Frame: Baseline, Week 64 ]
  4. Walking Ability at Week 64, as Measured by the 6-Minute Walk Test (6MWT) [ Time Frame: Baseline, Week 64 ]
  5. Functional Disability and Pain at Week 64, as measured by POSNA-PODCI [ Time Frame: Week 64 ]
    Functional Disability and Pain at Week 64, as measured by the Pediatric Orthopedic Society of North America-Pediatric Outcomes Data Collection Instrument (POSNA-PODCI)


Eligibility Criteria

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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 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 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 (min. 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 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 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 (min. 4 hours) values collected at Screening Visit 2
Contacts and Locations

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, 94143
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
Birmingham Children's University
Birmingham, United Kingdom, B4 6NH
Royal Manchester Hospital
Greater Manchester, United Kingdom
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
More Information

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: October 23, 2017
Last Verified: October 2017

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