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

Study Overview
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Brief Summary
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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).

Official Title
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A Phase 4 Prospective Exploratory Muscle Biopsy, Biomarker, and Imaging Assessment Study in Patients With Late-Onset Pompe Disease Treated With Alglucosidase Alfa

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

Intervention / Treatment
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* Biological: Alglucosidase Alfa


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Alglucosidase Alfa<br> | Biological: Alglucosidase Alfa<br>* Alglucosidase alfa intravenous infusion 20 milligram per kilogram (mg/kg) every other week for 24 weeks.<br>* Other names: Lumizyme®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Tissue Glycogen Content in Quadriceps Muscle Biopsy Samples at Week 26 | Tissue glycogen content was measured by quadriceps biopsies as 'percent area of tissue occupied by glycogen'. | Baseline, Week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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. | Baseline, Week 26 | 
| Percent Change From Baseline in Degree of Fatty Infiltration Using 3-Point 3-Dimensional (3D) Dixon at Week 26 | Degree of Fatty Infiltration was assessed by 3-point 3D Dixon acquisition using skeletal muscle MRI in a subset of participants. | Baseline, Week 26 | 
| Percent Change From Baseline in Disease Activity Using T2 Magnetic Resonance Imaging (MRI) at 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. | Baseline, Week 26 |