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

Purpose

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).

Condition	Intervention	Phase
Pompe Disease (Late-Onset) Glycogen Storage Disease Type II (GSD II) Glycogenesis 2 Acid Maltase Deficiency	Biological: Alglucosidase Alfa	Phase 4


Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: 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

Resource links provided by NLM:

Genetics Home Reference related topics: Pompe disease Schindler disease glycogen storage disease type IX succinic semialdehyde dehydrogenase deficiency

MedlinePlus related topics: Biopsy

Drug Information available for: Alglucosidase Alfa

Genetic and Rare Diseases Information Center resources: Glycogen Storage Disease Type 2

U.S. FDA Resources

Further study details as provided by Sanofi:

Primary Outcome Measures:

Change From Baseline in Tissue Glycogen Content in Quadriceps Muscle Biopsy Samples at Week 26 [ Time Frame: Baseline, Week 26 ] [ Designated as safety issue: No ]
Tissue glycogen content was measured by quadriceps biopsies as 'percent area of tissue occupied by glycogen'.

Secondary Outcome Measures:

Glycogen Distribution [ Time Frame: Baseline, Week 26 ] [ Designated as safety issue: No ]
Muscle Fiber Morphology [ Time Frame: Baseline, Week 26 ] [ Designated as safety issue: No ]
Lysosomal Inclusions [ Time Frame: Baseline, Week 26 ] [ Designated as safety issue: No ]
Percent Change From Baseline in Muscle Involvement Using Mercuri Scoring at Week 26 [ Time Frame: Baseline, Week 26 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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.


Enrollment:	16
Study Start Date:	June 2011
Study Completion Date:	December 2013
Primary Completion Date:	December 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Alglucosidase Alfa	Biological: Alglucosidase Alfa Alglucosidase alfa intravenous infusion 20 milligram per kilogram (mg/kg) every other week for 24 weeks. Other Names: GZ419829 Myozyme® Lumizyme®

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01288027

Locations


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
Germany

Mainz, Germany

Munster, Germany

München, Germany
Netherlands

Rotterdam, Netherlands
United Kingdom

Newcastle upon Tyne, United Kingdom

Salford, United Kingdom

Sponsors and Collaborators

Genzyme, a Sanofi Company

Investigators


Study Director:	Medical Monitor	Genzyme, a Sanofi Company

More Information


Responsible Party:	Genzyme, a Sanofi Company
ClinicalTrials.gov Identifier:	NCT01288027 History of Changes
Other Study ID Numbers:	AGLU07310 2010-020611-36 MSC12823
Study First Received:	January 27, 2011
Results First Received:	November 24, 2014
Last Updated:	December 4, 2014
Health Authority:	United States: Food and Drug Administration European Union: European Medicines Agency

Additional relevant MeSH terms:


Glycogen Storage Disease Type II Glycogen Storage Disease Lysosomal Storage Diseases, Nervous System Brain Diseases, Metabolic, Inborn Brain Diseases, Metabolic Brain Diseases Central Nervous System Diseases	Nervous System Diseases Metabolism, Inborn Errors Genetic Diseases, Inborn Carbohydrate Metabolism, Inborn Errors Lysosomal Storage Diseases Metabolic Diseases

ClinicalTrials.gov processed this record on September 23, 2016