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

Primary Purpose

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

Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Alglucosidase Alfa
Sponsored by
Genzyme, a Sanofi Company
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pompe Disease (Late-Onset)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Alglucosidase Alfa

Arm Description

Outcomes

Primary Outcome Measures

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'.

Secondary Outcome Measures

Glycogen Distribution
Muscle Fiber Morphology
Lysosomal Inclusions
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.
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.
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.

Full Information

First Posted
January 27, 2011
Last Updated
December 4, 2014
Sponsor
Genzyme, a Sanofi Company
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1. Study Identification

Unique Protocol Identification Number
NCT01288027
Brief Title
Exploratory Muscle Biopsy Assessment Study in Patients With Late-Onset Pompe Disease Treated With Alglucosidase Alfa
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
Study Type
Interventional

2. Study Status

Record Verification Date
December 2014
Overall Recruitment Status
Completed
Study Start Date
June 2011 (undefined)
Primary Completion Date
December 2013 (Actual)
Study Completion Date
December 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Genzyme, a Sanofi Company

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pompe Disease (Late-Onset), Glycogen Storage Disease Type II (GSD II), Glycogenesis 2 Acid Maltase Deficiency

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
16 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Alglucosidase Alfa
Arm Type
Experimental
Intervention Type
Biological
Intervention Name(s)
Alglucosidase Alfa
Other Intervention Name(s)
GZ419829, Myozyme®, Lumizyme®
Intervention Description
Alglucosidase alfa intravenous infusion 20 milligram per kilogram (mg/kg) every other week for 24 weeks.
Primary Outcome Measure Information:
Title
Change From Baseline in Tissue Glycogen Content in Quadriceps Muscle Biopsy Samples at Week 26
Description
Tissue glycogen content was measured by quadriceps biopsies as 'percent area of tissue occupied by glycogen'.
Time Frame
Baseline, Week 26
Secondary Outcome Measure Information:
Title
Glycogen Distribution
Time Frame
Baseline, Week 26
Title
Muscle Fiber Morphology
Time Frame
Baseline, Week 26
Title
Lysosomal Inclusions
Time Frame
Baseline, Week 26
Title
Percent Change From Baseline in Muscle Involvement Using Mercuri Scoring at Week 26
Description
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.
Time Frame
Baseline, Week 26
Title
Percent Change From Baseline in Degree of Fatty Infiltration Using 3-Point 3-Dimensional (3D) Dixon at Week 26
Description
Degree of Fatty Infiltration was assessed by 3-point 3D Dixon acquisition using skeletal muscle MRI in a subset of participants.
Time Frame
Baseline, Week 26
Title
Percent Change From Baseline in Disease Activity Using T2 Magnetic Resonance Imaging (MRI) at Week 26
Description
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.
Time Frame
Baseline, Week 26

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Monitor
Organizational Affiliation
Genzyme, a Sanofi Company
Official's Role
Study Director
Facility Information:
City
Orange
State/Province
California
Country
United States
City
Gainesville
State/Province
Florida
Country
United States
City
Kansas City
State/Province
Kansas
Country
United States
City
St. Louis
State/Province
Missouri
Country
United States
City
New York
State/Province
New York
Country
United States
City
Durham
State/Province
North Carolina
Country
United States
City
Colombus
State/Province
Ohio
Country
United States
City
Heshey
State/Province
Pennsylvania
Country
United States
City
Fairfax
State/Province
Virginia
Country
United States
City
Mainz
Country
Germany
City
Munster
Country
Germany
City
München
Country
Germany
City
Rotterdam
Country
Netherlands
City
Newcastle upon Tyne
Country
United Kingdom
City
Salford
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
27473031
Citation
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.
Results Reference
derived

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

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