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

Pompe Disease (Late-Onset) Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01288027
• Other study ID #: AGLU07310
• Secondary ID: 2010-020611-36MS
• Status: Completed
• Phase: Phase 4
• First received: January 27, 2011
• Last updated: December 4, 2014
• Start date: June 2011
• Est. completion date: December 2013

Study information

• Verified date: December 2014
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationEuropean Union: European Medicines Agency
• Study type: Interventional

Clinical Trial 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 information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: December 2013
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

Biological:
• Alglucosidase Alfa
Alglucosidase alfa intravenous infusion 20 milligram per kilogram (mg/kg) every other week for 24 weeks.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Genzyme, a Sanofi Company

Countries where clinical trial is conducted

United States,  Germany,  Netherlands,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Glycogen Distribution		Baseline, Week 26	No
Secondary	Muscle Fiber Morphology		Baseline, Week 26	No
Secondary	Lysosomal Inclusions		Baseline, Week 26	No
Secondary	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	No
Secondary	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	No
Secondary	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	No