Hypophosphatasia MedDRA version: 20.0 Level: PT Classification code 10049933 Term: Hypophosphatasia System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Sponsors
Alexion Pharma GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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
Exclusion criteria
Exclusion criteria: 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the following: - Effect of asfotase alfa on reduction in plasma inorganic pyrophosphate (PPi) and plasma pyridoxal-5’-phosphate (PLP) - Tolerability of daily subcutaneous (SC) injections of asfotase alfa;Secondary Objective: To evaluate the following: - Change in bone mineral content (BMC) and bone mineral density (BMD) as measured by dual-energy X-ray absorptiometry (DEXA) - Change in walking ability as measured by the Six-Minute Walk Test (6MWT) - 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) - Safety and Tolerability of asfotase alfa ;Timepoint(s) of evaluation of this end point: Efficacy endpoint: Baseline to Week 24 Safety Endpoint: continuous monitoring | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Change in bone mineral content and density as measured by dual-energy X-ray absorptiometry (DXA) - Change in walking ability as measured by the Six-Minute Walk Test (6MWT) - 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 for osteomalacia measure: Week 24, Week 48 | — |
Countries
Canada, United States
Contacts
Public ContactEuropean Clinical Trial Information
Alexion Europe SAS
Outcome results
None listed