Pompe Disease (Late-Onset), Glycogen Storage Disease Type II (GSD II), Glycogenesis 2 Acid Maltase Deficiency
Conditions
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).
Interventions
BIOLOGICALAlglucosidase Alfa
Alglucosidase alfa intravenous infusion 20 milligram per kilogram (mg/kg) every other week for 24 weeks.
Sponsors
Genzyme, a Sanofi Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Tissue Glycogen Content in Quadriceps Muscle Biopsy Samples at Week 26 | Baseline, Week 26 | Tissue glycogen content was measured by quadriceps biopsies as 'percent area of tissue occupied by glycogen'. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Muscle Fiber Morphology | Baseline, Week 26 | — |
| Lysosomal Inclusions | Baseline, Week 26 | — |
| Glycogen Distribution | Baseline, Week 26 | — |
| Percent Change From Baseline in Degree of Fatty Infiltration Using 3-Point 3-Dimensional (3D) Dixon at Week 26 | 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 | 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. |
| Percent Change From Baseline in Muscle Involvement Using Mercuri Scoring at Week 26 | 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. |
Countries
Germany, Netherlands, United Kingdom, United States
Participant flow
Recruitment details
The study was conducted at 11 centers between July 06, 2011 and December 19, 2013.
Participants by arm
| Arm | Count |
|---|---|
| Alglucosidase Alfa Alglucosidase alfa intravenous infusion 20 milligram per kilogram (mg/kg) every other week for 24 weeks. | 16 |
| Total | 16 |
Baseline characteristics
| Characteristic | Alglucosidase Alfa |
|---|---|
| Age, Continuous | 51.6 years STANDARD_DEVIATION 13.69 |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 15 / 16 |
| serious Total, serious adverse events | 1 / 16 |
Outcome results
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'.
Time frame: Baseline, Week 26
Population: FAS population included all participants who received at least one complete infusion of alglucosidase alfa. Here, n = number of participants with both Baseline and Week 26 assessment of tissue glycogen content.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Alglucosidase Alfa | Change From Baseline in Tissue Glycogen Content in Quadriceps Muscle Biopsy Samples at Week 26 | Baseline (n=14) | 5.3 percent area occupied by glycogen | Standard Deviation 4.59 |
| Alglucosidase Alfa | Change From Baseline in Tissue Glycogen Content in Quadriceps Muscle Biopsy Samples at Week 26 | Change at Week 26 (n=13) | -1.6 percent area occupied by glycogen | Standard Deviation 4.11 |
Comparison: Statistical significance for change from Baseline was measured using one sample t-testp-value: 0.186one sample t-test
Secondary
Glycogen Distribution
Time frame: Baseline, Week 26
Population: No quantitative data could be reported for this outcome as the assessment was qualitative in nature.
Secondary
Lysosomal Inclusions
Time frame: Baseline, Week 26
Population: No quantitative data could be reported for this outcome as the assessment was qualitative in nature.
Secondary
Muscle Fiber Morphology
Time frame: Baseline, Week 26
Population: No quantitative data could be reported for this outcome as the assessment was qualitative in nature.
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.
Time frame: Baseline, Week 26
Population: FAS population included all participants who received at least one complete infusion of alglucosidase alfa. Here, number of participants analyzed = number of participants with both Baseline and Week 26 assessment of degree of fatty infiltration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alglucosidase Alfa | Percent Change From Baseline in Degree of Fatty Infiltration Using 3-Point 3-Dimensional (3D) Dixon at Week 26 | 2.0 percent change | Standard Deviation 12.83 |
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.
Time frame: Baseline, Week 26
Population: FAS population included all participants who received at least one complete infusion of alglucosidase alfa. Here Number of participants analyzed = number of participants with both baseline and Week 26 assessment of disease activity.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Alglucosidase Alfa | Percent Change From Baseline in Disease Activity Using T2 Magnetic Resonance Imaging (MRI) at Week 26 | T2 with B1 | 8.1 percent change | Standard Deviation 14.19 |
| Alglucosidase Alfa | Percent Change From Baseline in Disease Activity Using T2 Magnetic Resonance Imaging (MRI) at Week 26 | T2 without B1 | 7.2 percent change | Standard Deviation 13.58 |
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.
Time frame: Baseline, Week 26
Population: FAS population included all participants who received at least one complete infusion of alglucosidase alfa. Here, Number of participants analyzed= participants with both Baseline and Week 26 assessment of muscle involvement, n= number of participants with both Baseline and Week 26 assessment of muscle involvement for specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Alglucosidase Alfa | Percent Change From Baseline in Muscle Involvement Using Mercuri Scoring at Week 26 | Mercuri Scoring - Upper Leg (n=13) | 2.6 percent change | Standard Deviation 9.24 |
| Alglucosidase Alfa | Percent Change From Baseline in Muscle Involvement Using Mercuri Scoring at Week 26 | Mercuri Scoring - Lower Leg (n=14) | 0.0 percent change | Standard Deviation 0 |