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

A Phase 4 Prospective Exploratory Muscle Biopsy, Biomarker, and Imaging 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).

Study Overview

• Status: Completed
• Conditions: Glycogenesis 2 Acid Maltase Deficiency; Pompe Disease (Late-Onset); Glycogen Storage Disease Type II (GSD II)
• Intervention / Treatment: Biological: Alglucosidase Alfa

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 4

Contacts and Locations

Study Locations

• Germany
  • Mainz, Germany
  • Munster, Germany
  • München, Germany
• Netherlands
  • Rotterdam, Netherlands
• United Kingdom
  • Newcastle upon Tyne, United Kingdom
  • Salford, United Kingdom
• United States
  • California
    • Orange, California, United States
  • Florida
    • Gainesville, Florida, United States
  • Kansas
    • Kansas City, Kansas, United States
  • Missouri
    • St. Louis, Missouri, United States
  • New York
    • New York, New York, United States
  • North Carolina
    • Durham, North Carolina, United States
  • Ohio
    • Colombus, Ohio, United States
  • Pennsylvania
    • Heshey, Pennsylvania, United States
  • Virginia
    • Fairfax, Virginia, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Alglucosidase Alfa	Biological: Alglucosidase Alfa; Alglucosidase alfa intravenous infusion 20 milligram per kilogram (mg/kg) every other week for 24 weeks.; Other Names: Myozyme®; Lumizyme®; GZ419829

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Genzyme, a Sanofi Company

Publications and helpful links

General Publications

• van der Ploeg A, Carlier PG, Carlier RY, Kissel JT, Schoser B, Wenninger S, Pestronk A, Barohn RJ, Dimachkie MM, Goker-Alpan O, Mozaffar T, Pena LD, Simmons Z, Straub V, Guglieri M, Young P, Boentert M, Baudin PY, Wens S, Shafi R, Bjartmar C, Thurberg BL. Prospective exploratory muscle biopsy, imaging, and functional assessment in patients with late-onset Pompe disease treated with alglucosidase alfa: The EMBASSY Study. Mol Genet Metab. 2016 Sep;119(1-2):115-23. doi: 10.1016/j.ymgme.2016.05.013. Epub 2016 May 19.

Study record dates

Study Major Dates

• Study Start: June 1, 2011
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: January 27, 2011
• First Submitted That Met QC Criteria: January 31, 2011
• First Posted (Estimate): February 2, 2011

Study Record Updates

• Last Update Posted (Estimate): December 19, 2014
• Last Update Submitted That Met QC Criteria: December 4, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Lysosomal Storage Diseases, Nervous System; Glycogen Storage Disease Type II; Glycogen Storage Disease
• Other Study ID Numbers: AGLU07310; 2010-020611-36 (EudraCT Number); MSC12823 (Other Identifier: Sanofi)