A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study to Assess the Efficacy and Safety of KRN23 in Adults with X-linked Hypophosphatemia (XLH) - Non applicabile
- Conditions
- XLF is a disorder of hyphophosphatemia,renal phosphate wasting,and the most common inheritable form of rickets. In XLH patients , excess circulating fibroblast growth factor (FGF23) impair phosphate reabsorption in the kidney. Chronic low serum phosphorum levels lead to defective bone mineralization and consequently to rickets in children and osteomalacia in adults, the two major pathologic outcomes of the hyphophosphatemiaMedDRA version: 19.0Level: LLTClassification code 10016206Term: Familial hypophosphataemic ricketsSystem Organ Class: 100000004850Therapeutic area: Body processes [G] - Bones and nerves physological processes [G11]
- Registration Number
- EUCTR2014-005529-11-IT
- Lead Sponsor
- TRAGENYX PHARMACEUTICAL INC
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 134
Individuals eligible to participate in this study must meet all of the following criteria:
1) Male or female, aged 18 – 65 years, inclusive
2) Diagnosis of XLH supported by classic clinical features of adult XLH (such as short stature or bowed legs) and at least ONE of the following at Screening:
• Documented PHEX mutation in either the patient, or in a directly related family member with appropriate X-linked inheritance
• Serum iFGF23 level > 30 pg/mL by Kainos assay
3) Biochemical findings consistent with XLH at Screening Visit 2 following overnight fasting (min. 8 hours):
• Serum phosphorus < 2.5 mg/dL (0.81 mmol/L)
• TmP/GFR of < 2.5 mg/dL
4) Presence of skeletal pain attributed to XLH/osteomalacia, as defined by a score of = 4 on the Brief Pain Inventory question 3 (BPI-Q3, Worst Pain) at Screening Visit 1. (Skeletal pain that, in the opinion of the investigator, is attributed solely to causes other than XLH/osteomalacia—for example, back pain or joint pain in the presence of severe osteoarthritis by radiograph in that anatomical location—in the absence of any skeletal pain likely attributed to XLH/osteomalacia should not be considered for eligibility)
5) Estimated glomerular filtration rate (eGFR) = 60 mL/min (using the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] equation) or eGFR of 45-60 mL/min at Screening Visit 2 with confirmation that the renal insufficiency is not due to nephrocalcinosis
6) If taking chronic pain medications (including narcotic pain medications/opioids), must be on a stable regimen for at least 21 days prior to Screening Visit 1, and be willing to maintain medications at the same stable dose(s) and schedule throughout the Placebo-controlled Treatment Period of the study. The dose must not exceed 60 mg oral morphine equivalents/day
7) Provide written informed consent or if a minor, provide written consent and have a legally authorized representative willing and able to provide written informed consent, after the nature of the study has been explained, and prior to any research-related procedures
8) Willing to provide access to prior medical records for the collection of biochemical and radiographic data and disease history
9) Females of child-bearing potential must have a negative urine pregnancy test at Screening and be willing to have additional pregnancy tests during the study. Females considered not to be of childbearing potential include those who have been in menopause for at least two years prior to Screening, or have had tubal ligation at least one year prior to Screening, or have had a total hysterectomy or bilateral salpingo-oophorectomy
10) Participants of child bearing potential or with partners of child-bearing potential who have not undergone a total hysterectomy or bilateral salpingo - oophorectomy and are sexually active must consent to use two effective methods of contraception as determined by the site investigator (i.e. oral hormonal contraceptives, patch hormonal contraceptives, vaginal ring, intrauterine device, physical double-barrier methods, surgical hysterectomy, vasectomy, tubal ligation, or true abstinence) from the period following the signing of the informed consent through 12 weeks after last dose of study drug
11) 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
12) Must have completed at least 4 of 7 days of the patient diaries bef
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 (calcitriol, doxercalciferol, and paricalcitol) within 14 days prior to Screening Visit 2
2) Use of oral phosphate within 14 days prior to Screening Visit 2
3) Use of aluminum hydroxide antacids, acetazolamides, and thiazides within 7 days prior to Screening Visit 2
4) Chronic use of systemic corticosteroids defined as more than 10 days in the 2 months prior to Screening Visit 1
5) Corrected serum calcium level = 10.8 mg/dL (2.7 mmol/L) at Screening Visit 2
6) Serum iPTH = 2.5 upper limit of normal (ULN) at Screening Visit 1
7) Use of medication to suppress PTH (cinacalcet, for example) within 60 days prior to Screening Visit 1
8) Use of bisphosphonates in the 2 years prior to Screening Visit 1
9) Use of denosumab in the 6 months prior to Screening Visit 1
10) Use of teriparatide in the 2 months prior to Screening Visit 1
11) Planned or recommended orthopedic surgery within the first 24 weeks of the clinical trial period
12) History of traumatic fracture or orthopedic surgery within 6 months prior to Screening Visit 1
13) Use of KRN23, or any other therapeutic monoclonal antibody within 90 days prior to Screening Visit 1
14) Use of any investigational product or investigational medical device within 30 days prior to Screening Visit 1, 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
15) Pregnant or breastfeeding at Screening /Baseline or planning to become pregnant (self or partner) at any time during the study
16) Unable or unwilling to withhold prohibited medications throughout the study
17) Presence or history of any hypersensitivity, allergic or anaphylactic reactions to any monoclonal antibody or KRN23 excipients that, in the judgment of the investigator, places the subject at increased risk for adverse effects
18) Prior history of positive test for human immunodeficiency virus antibody, hepatitis B surface antigen, and/or hepatitis C antibody
19) History of recurrent infection (other than dental abscesses, which are known to be associated with XLH) or predisposition to infection, or of known immunodeficiency
20) Presence of malignant neoplasm (except basal cell carcinoma)
21) Presence of a concurrent disease or condition that would interfere with study participation or affect safety
22) 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
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