Safety Study of Human Recombinant Tissue Non-Specific Alkaline Phosphatase Fusion Protein Asfotase Alfa in Adults With Hypophosphatasia (HPP)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT00739505|
Recruitment Status : Completed
First Posted : August 21, 2008
Last Update Posted : May 29, 2014
|Condition or disease||Intervention/treatment||Phase|
|Hypophosphatasia (HPP)||Biological: Asfotase Alfa||Phase 1|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||6 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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)|
|Study Start Date :||August 2008|
|Primary Completion Date :||January 2009|
|Study Completion Date :||February 2009|
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.
- To determine the safety and tolerability of Asfotase Alfa given intravenously and given subcutaneously. [ Time Frame: Within the first 2 months (8 weeks). ]
- To assess the pharmacokinetics (PK) of Asfotase Alfa given intravenously and subcutaneously [ Time Frame: Within the first 2 months (8 weeks) ]
- To assess the bioavailability of the subcutaneous Asfotase Alfa [ Time Frame: Within the first 2 months (8 weeks) ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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|