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Efficacy and Safety of KRN23 Versus Oral Phosphate and Active Vitamin D Treatment in Pediatric Patients With X Linked Hypophosphatemia (XLH) (PIXLES)

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02915705
First Posted: September 27, 2016
Last Update Posted: November 6, 2017
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.
Collaborator:
Kyowa Hakko Kirin Co., Ltd
Information provided by (Responsible Party):
Ultragenyx Pharmaceutical Inc
  Purpose
UX023-CL301 is a multicenter, randomized, open-label, Phase 3 study comparing the efficacy and safety of KRN23 with active control (oral phosphate/active vitamin D therapy) in children with XLH (aged 1 to ≤12 years) who have radiographic evidence of rickets, open epiphyses, and have received oral phosphate/active vitamin D therapy for ≥ 6-12 consecutive months prior to screening. Approximately 60 subjects will be randomized 1:1 to receive open-label KRN23 administered by subcutaneous injection or oral phosphate and active vitamin D therapy for a total of 64 weeks.

Condition Intervention Phase
X-Linked Hypophosphatemia Biological: KRN23 Drug: Oral Phosphate Drug: Active Vitamin D Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized, Open-Label, Phase 3 Study to Assess the Efficacy and Safety of KRN23 Versus Oral Phosphate and Active Vitamin D Treatment in Pediatric Patients With X Linked Hypophosphatemia (XLH)

Resource links provided by NLM:


Further study details as provided by Ultragenyx Pharmaceutical Inc:

Primary Outcome Measures:
  • Improvement in rickets in children with XLH [ Time Frame: 40 weeks ]
    Change in rickets at Week 40 as assessed by the RGI-C global score compared between the KRN23 and active control groups


Secondary Outcome Measures:
  • Change in Serum Phosphorous [ Time Frame: 64 weeks ]
    Effect of KRN23 as compared with active control by change from baseline in serum phosphorous

  • Change in Serum 1,25(OH)D [ Time Frame: 64 weeks ]
    Effect of KRN23 as compared with active control by change from baseline in serum 1,25(OH)D

  • Walking ability using the Six Minute Walk Test (6MWT) [ Time Frame: 24, 40 and 64 weeks ]
    Change from baseline in total distance walked

  • Growth [ Time Frame: 24, 40 and 64 weeks ]
    Change from baseline in standing height

  • Patient/Parent reported pain, fatigue and physical function/mobility [ Time Frame: 24, 40 and 64 weeks ]
    Change from baseline using the Patient Reported Outcomes Measurement Information System (PROMIS)

  • Phamacokinetics throughout the dosing cycle [ Time Frame: 64 weeks ]
    Measure the concentration of KRN23

  • Incidence, frequency, and severity of AE's and SAE's [ Time Frame: 64 weeks ]
    Incidence compared against active control group


Estimated Enrollment: 60
Study Start Date: September 2016
Estimated Study Completion Date: October 2018
Estimated Primary Completion Date: July 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: KRN23
Subjects randomized 1:1 to receive 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection.
Biological: KRN23
KRN23 is a recombinant human immunoglobulin G isotype 1 (IgG1) monoclonal antibody (mAb) that binds to and inhibits the activity of fibroblast growth factor 23 (FGF23).
Active Comparator: Active Control
Subjects randomized 1:1 to receive multiple daily doses of oral Phosphate and Active Vitamin D therapy, individualized for each subject at the Investigator's discretion.
Drug: Oral Phosphate Drug: Active Vitamin D

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   1 Year to 12 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female, aged 1 to ≤12 years with radiographic evidence of rickets as determined by central read
  2. PHEX mutation or variant of uncertain significance in either the patient or in a directly related family member with appropriate X-linked inheritance
  3. Biochemical findings associated with XLH: Serum phosphorus <3.0 mg/dL (0.97 mmol/L)
  4. Serum creatinine within age-adjusted normal range
  5. Serum 25(OH)D above the lower limit of normal (≥16 ng/mL) at the Screening Visit
  6. Have received both oral phosphate and active vitamin D therapy for ≥ 12 consecutive months (for children ≥3 years of age) or ≥ 6 consecutive months (for children <3 years of age) prior to the Screening Visit
  7. Willing to provide access to prior medical records for the collection of historical growth and radiographic data and disease history.
  8. Provide written or verbal assent (as appropriate for the subject and region) 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 highly effective method(s) of contraception for the duration of the study.

Exclusion Criteria:

  1. Tanner stage 4 or higher through physical examination
  2. Height percentile >50% based on country-specific norms
  3. Use of aluminum hydroxide antacids (e.g. Maalox® and Mylanta®), systemic corticosteroids, acetazolamide, and thiazides within 7 days prior to the Screening Visit
  4. Current or prior use of leuprorelin (e.g., Lupron®, Viadur®, Eligard®), triptorelin (TRELSTAR®), goserelin (Zoladex®), or other drugs known to delay puberty
  5. Use of growth hormone therapy within 12 months before the Screening Visit
  6. Presence of nephrocalcinosis on renal ultrasound grade 4
  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 hyperparathyroidism (PTH levels 2.5X upper limit of normal [ULN])
  10. Use of medication to suppress PTH (e.g., cinacalcet, calcimimetics) within 2 months prior to the Screening Visit
  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. History of recurrent infection or predisposition to infection, or of known immunodeficiency
  14. Use of a therapeutic monoclonal antibody within 90 days prior to the Screening Visit or history of allergic or anaphylactic reactions to any monoclonal antibody
  15. 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.
  16. 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.
  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): NCT02915705


  Hide Study Locations
Locations
United States, California
Children's Hospital Los Angeles
Los Angeles, California, United States, 90027
UCSF
San Francisco, California, United States, 94158
United States, Indiana
Indiana University School of Medicine
Indianapolis, Indiana, United States, 46202
United States, Missouri
Shriners Hospital For Children
Saint Louis, Missouri, United States, 63131
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232-9170
Australia, New South Wales
Sydney Children's Hospital Network
Westmead, New South Wales, Australia, 2145
Canada, Ontario
Children's Hospital of Eastern Ontario (CHEO) Research Institute
Ottawa, Ontario, Canada
SickKids
Toronto, Ontario, Canada, M5G1X8
Canada, Quebec
Shriners Hospital for Children - Canada
Montreal, Quebec, Canada, H4A 0A9
Denmark
ODense University Hospital
Odense C, Denmark, 5000
Italy
(IRCCS) - Ospedale San Raffaele (HSR) (Istituto Scientifico Universitario San Raffaele)
Milan, Italy, 20132
IRCCS Istituto Auxologico Italiano
Milan, Italy, 20145
Japan
Hyogo Prefectural Kobe Children's Hospital
Kobe, Hyogo, Japan, 654-0047
Kanagawa Children's Medical Center
Yokohama, Kanagawa, Japan, 232-8555
Osaka University Hospital
Suita, Osaka, Japan, 565-0871
Okayama Saiseikai General Hospital
Okayama, Japan, 700-0013
Japan Community Healthcare Organization Osaka Hospital
Osaka, Japan, 553-0003
National Center for Child Health and Development
Tokyo, Japan, 157-8535
Korea, Republic of
Seoul National University Hospital
Seoul, Korea, Republic of, 03080
Spain
Hospital Infantil Universitario Niño Jesús
Madrid, Spain, 28009
Sweden
Karolinska Institutet and University Hospital
Stockholm, Sweden, 17176
United Kingdom
Birmingham Children's Hospital
Birmingham, United Kingdom, B4 6NH
Royal Manchester Children's Hospital - University of Manchester
Manchester, United Kingdom, M13 9WL
Sponsors and Collaborators
Ultragenyx Pharmaceutical Inc
Kyowa Hakko Kirin Co., Ltd
  More Information

Responsible Party: Ultragenyx Pharmaceutical Inc
ClinicalTrials.gov Identifier: NCT02915705     History of Changes
Other Study ID Numbers: UX023-CL301
First Submitted: May 23, 2016
First Posted: September 27, 2016
Last Update Posted: November 6, 2017
Last Verified: November 2017

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
Vitamins
Vitamin D
Ergocalciferols
Micronutrients
Growth Substances
Physiological Effects of Drugs
Bone Density Conservation Agents