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)
- Conditions
- X-linked hypophosphatemia (XLH) is a disorder of renal phosphate wasting, defective bone mineralization, and impaired growth plate or endochondral ossification caused by inactivatingmutations in the PHEX gene (phosphate-regulating gene with homologies to endopeptidases on theX chromosome), and is the most common form of heritable rickets.MedDRA version: 20.0Level: LLTClassification code 10016206Term: Familial hypophosphataemic ricketsSystem Organ Class: 100000004850Therapeutic area: Body processes [G] - Bones and nerves physological processes [G11]
- Registration Number
- EUCTR2016-000600-29-IT
- Lead Sponsor
- TRAGENYX PHARMACEUTICAL INC.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 60
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 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.
Are the trial subjects under 18? yes
Number of subjects for this age range: 1
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
Individuals who meet any of the following exclusion criteria will not be eligible to participate in the
study:
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 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 (implantation or removal), including staples, 8-plates or osteotomy, within first 40 weeks of the study
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 normal range, 25(OH)D supplementation will be prescribed.
Assuming a subject meets all other eligibility requirements, the subject may be rescreened
after a minimum of 7 days of treatment.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method