Clinical trial NCT01288027: 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
Overall status: COMPLETED
Phase: PHASE4
Conditions: Pompe Disease (Late-Onset)
Glycogen Storage Disease Type II (GSD II)
Glycogenesis 2 Acid Maltase Deficiency
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2011-02-02
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).


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

Primary outcomes:
measure: Change From Baseline in Tissue Glycogen Content in Quadriceps Muscle Biopsy Samples at Week 26
timeFrame: Baseline, Week 26
Secondary outcomes:
measure: Glycogen Distribution
timeFrame: Baseline, Week 26
measure: Muscle Fiber Morphology
timeFrame: Baseline, Week 26
measure: Lysosomal Inclusions
timeFrame: Baseline, Week 26
measure: Percent Change From Baseline in Muscle Involvement Using Mercuri Scoring at Week 26
timeFrame: Baseline, Week 26
measure: Percent Change From Baseline in Degree of Fatty Infiltration Using 3-Point 3-Dimensional (3D) Dixon at Week 26
timeFrame: Baseline, Week 26
measure: Percent Change From Baseline in Disease Activity Using T2 Magnetic Resonance Imaging (MRI) at Week 26
timeFrame: Baseline, Week 26
Other outcomes:
Locations:
city: Orange
country: United States
state: California
city: Gainesville
country: United States
state: Florida
city: Kansas City
country: United States
state: Kansas
city: St. Louis
country: United States
state: Missouri
city: New York
country: United States
state: New York
city: Durham
country: United States
state: North Carolina
city: Colombus
country: United States
state: Ohio
city: Heshey
country: United States
state: Pennsylvania
city: Fairfax
country: United States
state: Virginia
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
Study officials:
affiliation: Genzyme, a Sanofi Company
name: Medical Monitor
role: STUDY_DIRECTOR
References:
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.