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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01288027
Recruitment Status : Completed
First Posted : February 2, 2011
Results First Posted : December 2, 2014
Last Update Posted : December 19, 2014
Information provided by (Responsible Party):
Sanofi ( Genzyme, a Sanofi Company )

January 27, 2011
February 2, 2011
November 24, 2014
December 2, 2014
December 19, 2014
June 2011
December 2013   (Final data collection date for primary outcome measure)
Change From Baseline in Tissue Glycogen Content in Quadriceps Muscle Biopsy Samples at Week 26 [ Time Frame: Baseline, Week 26 ]
Tissue glycogen content was measured by quadriceps biopsies as 'percent area of tissue occupied by glycogen'.
Percent reduction from baseline in tissue glycogen content in muscle biopsy samples. [ Time Frame: Week 26 ]
Complete list of historical versions of study NCT01288027 on Archive Site
  • Glycogen Distribution [ Time Frame: Baseline, Week 26 ]
  • Muscle Fiber Morphology [ Time Frame: Baseline, Week 26 ]
  • Lysosomal Inclusions [ Time Frame: Baseline, Week 26 ]
  • Percent Change From Baseline in Muscle Involvement Using Mercuri Scoring at Week 26 [ Time Frame: Baseline, 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 [ Time Frame: Baseline, 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 [ Time Frame: Baseline, 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.
  • Glycogen Distribution [ Time Frame: Baseline and Week 26 ]
  • Muscle Fiber Morphology [ Time Frame: Baseline and Week 26 ]
  • Lysosomal Inclusions [ Time Frame: Baseline and Week 26 ]
  • change from baseline in intact muscle and fatty replacement [ Time Frame: Week 26 ]
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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).

Not Provided
Phase 4
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • Pompe Disease (Late-Onset)
  • Glycogen Storage Disease Type II (GSD II)
  • Glycogenesis 2 Acid Maltase Deficiency
Biological: Alglucosidase Alfa
Alglucosidase alfa intravenous infusion 20 milligram per kilogram (mg/kg) every other week for 24 weeks.
Other Names:
  • GZ419829
  • Myozyme®
  • Lumizyme®
Experimental: Alglucosidase Alfa
Intervention: Biological: Alglucosidase Alfa
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.

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
December 2013
December 2013   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
Contact information is only displayed when the study is recruiting subjects
Germany,   Netherlands,   United Kingdom,   United States
2010-020611-36 ( EudraCT Number )
MSC12823 ( Other Identifier: Sanofi )
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Sanofi ( Genzyme, a Sanofi Company )
Genzyme, a Sanofi Company
Not Provided
Study Director: Medical Monitor Genzyme, a Sanofi Company
December 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP