Safety Study of Human Recombinant Tissue Non-Specific Alkaline Phosphatase Fusion Protein Asfotase Alfa in Adults With Hypophosphatasia (HPP)
This clinical trial studies the safety, tolerability, and pharmacology of asfotase alfa when given to adults with HPP.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Multicenter, Open-Label, Dose Escalating Study of the Safety, Tolerability and Pharmacology of Human Recombinant Tissue Non-Specific Alkaline Phosphatase Fusion Protein Asfotase Alfa in Adults With Hypophosphatasia (HPP)|
- To determine the safety and tolerability of Asfotase Alfa given intravenously and given subcutaneously. [ Time Frame: Within the first 2 months (8 weeks). ] [ Designated as safety issue: Yes ]
- To assess the pharmacokinetics (PK) of Asfotase Alfa given intravenously and subcutaneously [ Time Frame: Within the first 2 months (8 weeks) ] [ Designated as safety issue: No ]
- To assess the bioavailability of the subcutaneous Asfotase Alfa [ Time Frame: Within the first 2 months (8 weeks) ] [ Designated as safety issue: No ]
|Study Start Date:||August 2008|
|Study Completion Date:||February 2009|
|Primary Completion Date:||January 2009 (Final data collection date for primary outcome measure)|
Experimental: Cohort 1
3 HPP patients are to be enrolled in Cohort 1 and receive a single IV dose and three weekly SC doses of Asfotase Alfa . End of Study for patients in Cohort 1 is at 8 weeks.
Biological: Asfotase Alfa
The initial IV dose to be administered to patients was set at one-tenth the no adverse effect level (NOAEL) as determined by one month toxicology studies in animals in which Asfotase Alfa was administered as a single weekly IV dose. The SC doses to be administered are lower than the IV doses and are thought to be near or at the anticipated daily efficacious dose. Dosing will be as follows:
Cohort 1: In Week 1, patients will receive an IV infusion of Asfotase Alfa at a dose of 3 mg/kg. In Weeks 2, 3 and 4, patients will receive weekly SC injections of Asfotase Alfa at a dose of 1 mg/kg SC.
Experimental: Cohort 2
Cohort 2 will begin when the safety and PK data for Cohort 1 weeks 1-4 has been reviewed by the DSMB. Cohort 2 will enroll 3 HPP patients and will receive a higher dose level than Cohort 1. Cohort 2 patients will have a single IV dose and three weekly SC doses of Asfotase Alfa . End of Study for patients in Cohort 2 is at 8 weeks.
Biological: Asfotase Alfa
Cohort 2: In Week 1, patients will receive an IV infusion of Asfotase Alfa at a dose of 7 mg/kg. In Weeks 2, 3 and 4, patients will receive weekly SC injections of Asfotase Alfa at a dose of 1.5 mg/kg SC.
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: NCT00739505
|United States, Missouri|
|Barnes Jewish Hospital- Washington University School of Medicine|
|St. Louis, Missouri, United States, 63110|
|United States, North Carolina|
|Duke University Medical Center|
|Durham, North Carolina, United States, 27710|
|Department of Pediatrics & Child Health, Health Sciences Centre Winnipeg, University of Manitoba|
|Winnipeg, Manitoba, Canada, R3A 1S1|