Exploratory Muscle Biopsy Assessment Study in Patients With Late-Onset Pompe Disease Treated With Alglucosidase Alfa
This is an open-label, multicenter study of participants with late-onset Pompe disease naive to treatment with enzyme replacement therapy (ERT). The primary objective of this study is to evaluate glycogen clearance in muscle tissue samples collected pre and post alglucosidase alfa treatment in participants with Late-Onset Pompe disease.
The secondary objectives are to characterize the disease burden in participants with late-onset Pompe disease and explore imaging, histologic, and functional assessments in these participants and to explore potential plasma or urine biomarkers relative to late-onset Pompe disease and participant's response to treatment with alglucosidase alfa (Myozyme®/Lumizyme®/GZ419829).
|Pompe Disease (Late-Onset) Glycogen Storage Disease Type II (GSD II) Glycogenesis 2 Acid Maltase Deficiency||Biological: Alglucosidase Alfa||Phase 4|
|Study Design:||Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||A Phase 4 Prospective Exploratory Muscle Biopsy, Biomarker, and Imaging Assessment Study in Patients With Late-Onset Pompe Disease Treated With Alglucosidase Alfa|
- Change From Baseline in Tissue Glycogen Content in Quadriceps Muscle Biopsy Samples at Week 26 [ Time Frame: Baseline, Week 26 ]Tissue glycogen content was measured by quadriceps biopsies as 'percent area of tissue occupied by glycogen'.
- Glycogen Distribution [ Time Frame: Baseline, Week 26 ]
- Muscle Fiber Morphology [ Time Frame: Baseline, Week 26 ]
- Lysosomal Inclusions [ Time Frame: Baseline, Week 26 ]
- Percent Change From Baseline in Muscle Involvement Using Mercuri Scoring at Week 26 [ Time Frame: Baseline, Week 26 ]Muscle involvement was assessed by T1-weighted magnetic resonance imaging (MRI). T1-weighted MRI data was analyzed using the Mercuri scoring in both legs (Total score = 1-4; where 1=Normal appearance, 2=Mild involvement, 3=Moderate involvement, and 4=Severe involvement). For each participants, the average for each the upper (thigh) and lower leg was computed for Mercuri grading.
- Percent Change From Baseline in Degree of Fatty Infiltration Using 3-Point 3-Dimensional (3D) Dixon at Week 26 [ Time Frame: Baseline, Week 26 ]Degree of Fatty Infiltration was assessed by 3-point 3D Dixon acquisition using skeletal muscle MRI in a subset of participants.
- Percent Change From Baseline in Disease Activity Using T2 Magnetic Resonance Imaging (MRI) at Week 26 [ Time Frame: Baseline, Week 26 ]Disease activity (inflammation and/or water content within muscles) was quantitatively assessed by T2 MRI values in a subset of participants. A T2 MRI value of greater than (>) 39 millisecond (ms) was defined as abnormal. T2 estimation normally requires an additional acquisition for computing the B1 spatial deviation however, can still be estimated if this acquisition is missing.
|Study Start Date:||June 2011|
|Study Completion Date:||December 2013|
|Primary Completion Date:||December 2013 (Final data collection date for primary outcome measure)|
|Experimental: Alglucosidase Alfa||
Biological: Alglucosidase Alfa
Alglucosidase alfa intravenous infusion 20 milligram per kilogram (mg/kg) every other week for 24 weeks.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01288027
|United States, California|
|Orange, California, United States|
|United States, Florida|
|Gainesville, Florida, United States|
|United States, Kansas|
|Kansas City, Kansas, United States|
|United States, Missouri|
|St. Louis, Missouri, United States|
|United States, New York|
|New York, New York, United States|
|United States, North Carolina|
|Durham, North Carolina, United States|
|United States, Ohio|
|Colombus, Ohio, United States|
|United States, Pennsylvania|
|Heshey, Pennsylvania, United States|
|United States, Virginia|
|Fairfax, Virginia, United States|
|Newcastle upon Tyne, United Kingdom|
|Salford, United Kingdom|
|Study Director:||Medical Monitor||Genzyme, a Sanofi Company|