Safety and Efficacy Study of Asfotase Alfa in Adolescents and Adults With Hypophosphatasia (HPP)
- Conditions
- HypophosphatasiaMedDRA version: 20.0Level: PTClassification code 10049933Term: HypophosphatasiaSystem Organ Class: 10010331 - Congenital, familial and genetic disordersTherapeutic area: Body processes [G] - Genetic Phenomena [G05]
- Registration Number
- EUCTR2017-001831-38-Outside-EU/EEA
- Lead Sponsor
- Alexion Pharma GmbH
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- A
- Sex
- All
- Target Recruitment
- 19
Patients must meet all of the following criteria for enrollment in this study:
- Patients or their legal representative(s) must provide written informed consent prior to undergoing any study-related procedures
- Patients must be = 13 and = 65 years of age at the time of study enrollment
- Female patients of childbearing potential and sexually mature males must agree to use a medically acceptable form of birth control; for the purposes of this study, females are considered of non-childbearing potential if they are surgically sterile (i.e., have undergone a total hysterectomy, bilateral salpingo-oophorectomy or tubal ligation) or are post-menopausal, defined as having complete cessation of menstruation for at least 1 year after 45 years of age
- Patients must have a pre-established clinical diagnosis of HPP as indicated by:
?Serum alkaline phosphatase (ALP) below the age-adjusted normal range
?Plasma PLP at least twice the upper limit of normal (no vitamin B6 administered for at least 1 week prior to determination)
?Evidence of osteopenia or osteomalacia on skeletal radiographs
- Patients must have osteomalacia on bone biopsy, characterized by an MLT z-score of +2 or more (results from ENB-001-08 may be used)
- Patients must be willing to comply with study procedures and the visit schedule
Are the trial subjects under 18? yes
Number of subjects for this age range: 6
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 13
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0
Patients will be excluded from enrollment in this study if they meet any of the following exclusion criteria:
- Women who are pregnant or lactating
- History of sensitivity to tetracycline
- Serum calcium or phosphate levels below the normal range
- Serum 25(OH) vitamin D below 20 ng/mL
- Serum creatinine or parathyroid hormone (PTH) levels above the upper limit of normal
- Medical condition, serious intercurrent illness, or other extenuating circumstance that, in the opinion of the Investigator, may significantly interfere with study compliance, including all prescribed evaluations and follow-up activities
- Orthopedic surgery within 12 months prior to study entry that may interfere with the ability to perform functional assessments for the study
- Prior treatment with bisphosphonates within 2 years of study entry for any length of time or for more than 2 years at any time point; for patients with prior bisphosphonate use that is allowed, the bone resorption markers serum C-telopeptide and urine N-telopeptide or urine deoxypyridinoline must also be within the normal range or elevated to be eligible for study participation
- Treatment with PTH within 6 months prior to the start of asfotase alfa administration
- Participation in an interventional or investigational drug study within 30 days prior to study participation
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To determine the following:<br>- Effect of asfotase alfa on reduction in plasma inorganic pyrophosphate (PPi) and plasma pyridoxal-5’-phosphate (PLP)<br>- Tolerability of daily subcutaneous (SC) injections of asfotase alfa;Secondary Objective: To evaluate the following:<br>- Change in bone mineral content (BMC) and bone mineral density (BMD) as measured by dual-energy<br>X-ray absorptiometry (DEXA)<br>- Change in walking ability as measured by the Six-Minute Walk Test (6MWT)<br>- Change in HPP-related osteomalacia as measured by trans-iliac crest bone biopsy;Primary end point(s): - Effect of asfotase alfa on reduction in plasma inorganic pyrophosphate (PPi) and plasma pyridoxal-5' phosphate (PLP)<br>- Safety and Tolerability of asfotase alfa ;Timepoint(s) of evaluation of this end point: Efficacy endpoint: Baseline to Week 24<br>Safety Endpoint: continuous monitoring
- Secondary Outcome Measures
Name Time Method Secondary end point(s): - Change in bone mineral content and density as measured by dual-energy X-ray absorptiometry (DXA) <br>- Change in walking ability as measured by the Six-Minute Walk Test (6MWT)<br>- Change in HPP-related osteomalacia as measured by trans-iliac crest bone biopsy ;Timepoint(s) of evaluation of this end point: For DEXA and 6MWT measures: Every 24 weeks<br>for osteomalacia measure: Week 24, Week 48