A clinical study (phase 2) in hereditary Rickets (XLH) in children to assess the safety and working of the antibody anti-FGF23
- 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: 18.0 Level: LLT Classification code 10016206 Term: Familial hypophosphataemic rickets System Organ Class: 100000004850Therapeutic area: Body processes [G] - Bones and nerves physological processes [G11]
- Registration Number
- EUCTR2014-000406-35-FR
- Lead Sponsor
- ltragenyx Pharmaceuticals Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 52
Individuals eligible to participate in this study must meet all of the following criteria:
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 (assessed only in children = 8 years of age)
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 iFGF23 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)Short stature as defined by standing height < 25% percentile for age and gender (per CDC 2000)
6)Radiographic evidence of active bone disease including rickets in the wrists and/or knees, AND/OR femoral/tibial bowing
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.
Are the trial subjects under 18? yes
Number of subjects for this age range: 30
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)Use of a pharmacologic vitamin D metabolite or analog (e.g. calcitriol, doxercalciferol, 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 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 within 1 year prior to 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) 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)Positive for 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.
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