Safety and PK/PD Study With Agalsidase Alfa in Canadian Patients With Fabry Disease
This study is designed to evaluate safety and PK/PD in Canadian Fabry patients.
|Study Design:||Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
|Official Title:||A Phase II Comparability Study Between Replagal® Produced From Agalsidase Alfa Manufactured by 2 Different Processes in Adult Male Patients With Fabry Disease|
- Urine sediment globotriaosylceramide (Gb3) [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]Change from baseline to the end of study in urine sediment Gb3
- Plasma globotriaosylceramide (Gb3) [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]Change from baseline to end of study in plasma Gb3
- Dose-normalized area under the concentration-time curve from time 0 to the time of the last quantifiable sample (AUC last/Dose) [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
- Dose-normalized area under the concentration-time curve (AUC) extrapolated to infinity (AUC∞/Dose) [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
- Dose-normalized maximum serum concentration (C max/Dose) [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
- Number of participants with adverse events [ Time Frame: 20 weeks ] [ Designated as safety issue: Yes ]Safety and tolerability, as assessed by adverse events, changes in vital signs, physical examinations, electrocardiogram (ECG), concomitant medication usage, and anti-agalsidase alfa antibodies (in serum).
|Study Start Date:||March 2011|
|Study Completion Date:||December 2012|
|Primary Completion Date:||December 2012 (Final data collection date for primary outcome measure)|
Experimental: agalsidase alfa
Patients will receive a single infusion of agalsidase alfa (0.2 mg/kg) on Day 1 and thereafter receive 0.2 mg/kg agalsidase alfa manufactured with the new process every other week (EOW) through week 14.
Biological: agalsidase alfa
0.2 mg/kg doses of agalsidase alfa and 0.2 mg/kg doses of agalsidase alfa (manufactured by the new process) administered as intravenous (IV) infusions over 40 minutes (+/- 10 minutes) EOW
Other Name: Replagal
In 2008, a change in the agalsidase alfa drug substance manufacturing process was made. There are no changes to the drug product formulation, manufacturing site, manufacturing process, or container closure.
This study is designed to provide safety and PD/PK data. The assessment schedule is designed to capture the PK profile of drug uptake in the blood as well the pharmacologic effect which manifests over the course of weeks. Each patient will serve as his own control.
|University of Alberta Hospital|
|Edmonton, Alberta, Canada, T6G 2H7|
|Canada, Nova Scotia|
|Queen Elizabeth II Health Sciences Centre|
|Halifax, Nova Scotia, Canada, B3H 1V8|
|The Hospital for Sick Children|
|Toronto, Ontario, Canada, M5G 1X8|
|Toronto, Ontario, Canada, M5V 2T3|
|Hopital du Sacre-Coeur de Montreal|
|Montreal, Quebec, Canada, H4J 1C5|
|Study Director:||Anna Wijatyk, MD||Shire Human Genetic Therapies, Inc.|