Exploratory Muscle Biopsy Assessment Study in Patients With Late-Onset Pompe Disease Treated With Alglucosidase Alfa

Phase 4

Completed

Conditions: Pompe Disease (Late-Onset)
Glycogen Storage Disease Type II (GSD II)
Glycogenesis 2 Acid Maltase Deficiency

Brief Summary: 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).

Recruitment & Eligibility

Inclusion Criteria

The participant has confirmed acid alpha-glucosidase (GAA) enzyme deficiency from any tissue source and/or confirmed GAA gene mutations and without known cardiac hypertrophy
The participant is able to ambulate a distance without stopping and without an assistive device. Use of assistive device for community ambulation is appropriate
The participant has a certain forced vital capacity (FVC) in upright position
The participant, if female and of childbearing potential, must have a negative pregnancy test (urine beta-human chorionic gonadotropin [beta-hCG]) at baseline

Exclusion Criteria

The participant has had previous treatment with ERT
The participant is wheelchair dependent
The participant requires invasive-ventilation (non-invasive ventilation is allowed)
The participant is participating in another clinical study using investigational treatment
The participant cannot submit to magnetic resonance imaging (MRI) examination because of a formal contraindication such as a pacemaker, implanted ferromagnetic metals, etc
The participant, in the opinion of the Investigator, is unable to adhere to the requirements of the study

Arm && Interventions

Group	Intervention	Description
Alglucosidase Alfa	Alglucosidase Alfa	-

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Tissue Glycogen Content in Quadriceps Muscle Biopsy Samples at Week 26	Baseline, Week 26	Tissue glycogen content was measured by quadriceps biopsies as 'percent area of tissue occupied by glycogen'.

Secondary Outcome Measures

Name	Time	Method
Glycogen Distribution	Baseline, Week 26
Muscle Fiber Morphology	Baseline, Week 26
Lysosomal Inclusions	Baseline, Week 26
Percent Change From Baseline in Muscle Involvement Using Mercuri Scoring at Week 26	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	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	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.