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)

Phase 1

Active, not recruiting

• Conditions: X-linked hypophosphatemia (XLH) is a disorder of renal phosphate wasting, and the most common heritable form of rickets. In XLH patients, high circulating levels of fibroblast growth factor 23 (FGF23) impair normal phosphate reabsorption in the kidney. Low serum phosphorus levels result in hypomineralization of bone and associated abnormalities including rickets, bowing of the legs, and short stature.; MedDRA version: 20.0 Level: LLT Classification code 10016206 Term: Familial hypophosphataemic rickets System Organ Class: 100000004850; Therapeutic area: Body processes [G] - Bones and nerves physological processes [G11]

• Registration Number: EUCTR2016-000600-29-SE
• Lead Sponsor: ltragenyx Pharmaceuticals Inc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2016-07-20
• Last Update Posted: 10 December 2019

Recruitment & Eligibility

• Status: Not Recruiting
• Sex: Not specified
• Target Recruitment: 60

Inclusion Criteria

Individuals eligible to participate in this study must meet all of the following criteria:
1) Male or female, aged 1 to =12 years with radiographic evidence of rickets with a minimum rickets severity score (RSS) total score of 2 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 below age-adjusted upper normal limit” (Synopsis [Diagnosis and Criteria for Inclusion and Exclusion].
5) Serum 25(OH)D above the lower limit of normal (=16 ng/mL) at the Screening Visit**
6) conventional therapy should be discontinued …7 days prior to the Randomization Visit” rather than …prior to the Screening Visit” (Synopsis [Diagnosis and Criteria for Inclusion and Exclusion].
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) sexually active male subjects with female partners of childbearing potential to use a condom with spermicide or a highly effective method of contraception (rather than 2 methods) for the duration of the study plus 12 weeks after stopping the study drug.
Females who have reached menarche must have a negative pregnancy test at Screening and undergo additional pregnancy testing during the study. Female subjects of childbearing potential must be willing to use a highly effective method of contraception for the duration of the study plus 12 weeks after stopping the study drug.
Are the trial subjects under 18? yes
Number of subjects for this age range: 60
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Individuals who meet any of the following exclusion criteria will not be eligible to participate in the
study:
1) Tanner stage 4 or higher is assessed through physical examination in any of the following: genitals, breast, or pubic hair (Synopsis [Diagnosis and Criteria for Inclusion and Exclusion].
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 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 orthopedic surgery, including osteotomy or implantation or removal of staples, 8-plates, or any other hardware, within the first 40 weeks of the study” (Synopsis [Diagnosis and Criteria for Inclusion and Exclusion].
8) Hypocalcemia or hypercalcemia, defined as serum calcium levels outside the age-adjusted normal limits*
9) Evidence of hyperparathyroidism (parathyroid hormone [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 OR, in Japan, use of any investigational product or investigational medical device within 4 months 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 the
Screening and/or Baseline Visit
** If 25(OH)D levels are below the norma

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified