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Trial record 1 of 26 for:    xlh
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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 currently recruiting participants.
See Contacts and Locations
Verified May 2017 by Ultragenyx Pharmaceutical Inc
Sponsor:
Collaborator:
Kyowa Hakko Kirin Co., Ltd
Information provided by (Responsible Party):
Ultragenyx Pharmaceutical Inc
ClinicalTrials.gov Identifier:
NCT02915705
First received: May 23, 2016
Last updated: May 2, 2017
Last verified: May 2017
  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: No masking
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: September 2018
Estimated Primary Completion Date: May 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

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
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02915705

Contacts
Contact: Patient Advocacy patientadvocacy@ultragenyx.com

  Show 29 Study Locations
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
Study First Received: May 23, 2016
Last Updated: May 2, 2017

Additional relevant MeSH terms:
Familial Hypophosphatemic Rickets
Hypophosphatemia
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

ClinicalTrials.gov processed this record on June 28, 2017