Safety and Efficacy Study of Asfotase Alfa in Adolescents and Adults With Hypophosphatasia (HPP)
This clinical trial is being conducted to study hypophosphatasia (HPP), a bone disorder caused by gene mutations or changes. These gene mutations cause low levels of an enzyme needed to harden bone. The purpose of this study is to test the safety and efficacy of two doses of the study drug called asfotase alfa as compared to a control group to see what effects it has adolescents and adults with HPP.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Randomized, Open-Label, Multicenter, Multinational, Dose-Ranging, Concurrent Control Study of the Safety, Efficacy, Pharmacokinetic of ENB-0040 (Human Recombinant Tissue Nonspecific Alkaline Phosphatase Fusion Protein) in Adolescents and Adults With Hypophosphatasia (HPP)|
- Effect of asfotase alfa on reduction in plasma inorganic pyrophosphate (PPi) and plasma pyridoxal-5' phosphate (PLP) [ Time Frame: Week 24 ] [ Designated as safety issue: No ]Blood samples will be collected to evaluate the effect of Asfotase Alfa on reduction in plasma inorganic pyrophosphate (PPi) and plasma pyridoxal-5' phosphate (PLP)
- Safety and Tolerability of asfotase alfa [ Time Frame: Up to 96 weeks or until regulatory approval ] [ Designated as safety issue: Yes ]The safety and tolerability of daily subcutaneous (SC) injections of asfotase alfa will be assessed by routine monitoring of patients for adverse events (AEs) and injection-associated reactions (IARs) and monitoring changes from Baseline in physical examination findings, vital signs, clinical laboratory evaluations, renal ultrasound findings, funduscopic examinations, antibody evaluations, and results of pregnancy testing (in women of childbearing potential only). Monitoring for changes in concomitant medications and therapies will also occur.
- Change in bone mineral content and density as measured by dual-energy X-ray absorptiometry (DXA) [ Time Frame: Every 24 weeks ] [ Designated as safety issue: No ]A DXA scan will be performed to evaluate bone mineral content and density of the spine, hip, and whole body.
- Change in walking ability as measured by the Six-Minute Walk Test (6MWT) [ Time Frame: Every 24 weeks ] [ Designated as safety issue: No ]The patient will be instructed to walk the length of a pre-measured hallway for 6 minutes. The primary measurement will be the distance walked (in meters).
- Change in HPP-related osteomalacia as measured by trans-iliac crest bone biopsy [ Time Frame: Week 24, Week 48 ] [ Designated as safety issue: No ]A trans-iliac crest bone biopsy will be performed to quantify osteomalacia severity.
|Study Start Date:||June 2010|
|Estimated Study Completion Date:||December 2015|
|Estimated Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
Experimental: Cohort 1
Cohort 1: Daily SC injections of 0.3 mg/kg asfotase alfa (2.1 mg/kg/week total)
Drug: asfotase alfa
Cohort 1: Daily SC injections of 0.3 mg/kg asfotase alfa (tota1 of 2.1 mg/kg/week)
Experimental: Cohort 2
Cohort 2: Daily SC injections of 0.5 mg/kg asfotase alfa (3.5 mg/kg/week total)
Drug: asfotase alfa
Cohort 2: Daily SC injections of 0.5 mg/kg Asfotase Alfa (3.5 mg/kg/week total)
No Intervention: Concurrent Control
Following completion of the Week 24 visit, all patients (including those randomized to the concurrent control cohort) may be eligible to participate in an open-label extension study of asfotase alfa. In this extension period, all patients will be treated with daily SC injections of 0.5 mg/kg/day asfotase alfa (a total of 3.5 mg/kg/week) for approximately 24 weeks, then subjects will receive 1 mg/kg/day 6 days/week for an additional 48 weeks or until regulatory approval of the drug.
Asfotase alfa was formerly referred to as ENB-0040
Hypophosphatasia (HPP) is a life-threatening, genetic, and ultra-rare metabolic disease characterized by defective bone mineralization and impaired phosphate and calcium regulation that can lead to progressive damage to multiple vital organs, including destruction and deformity of bones, profound muscle weakness, seizures, impaired renal function, and respiratory failure. There are no approved disease-modifying treatments for patients with this disease. There is also limited data available on the natural course of this disease over time, particularly in patients with the juvenile-onset form.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01163149
|United States, Missouri|
|Shriner's Hospital for Children|
|St. Louis, Missouri, United States, 63131|
|United States, North Carolina|
|Duke University Medical Center|
|Durham, North Carolina, United States, 27710|
|Health Sciences Centre Winnipeg, University of Manitoba|
|Winnipeg, Manitoba, Canada, R3A 1S1|