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An Exploratory Study of the Safety and Efficacy of Prophylactic Immunomodulatory Treatment in Myozyme®-Naive, CRIM(-) Patients With Infantile-onset Pompe Disease
The purpose of this study was to evaluate the efficacy, clinical benefits and safety of a prophylactic immunomodulatory regimen given prior to first treatment with alglucosidase alfa (Myozyme®) in patients with infantile-onset Pompe disease. The objectives were to assess the efficacy of a prophylactic immunomodulatory regimen given prior to first treatment with alglucosidase alfa, as assessed by anti-recombinant human acid alpha-glucosidase (anti-rhGAA) antibody titers, and antibodies that inhibit the activity and/or uptake of alglucosidase alfa; to evaluate the clinical benefit as measured by overall survival, ventilator-free survival, left ventricular mass index (LVMI), gross motor function and development, disability index and the incidence of adverse events (AEs), serious adverse events (SAEs), and clinical laboratory abnormalities.
Details
| Lead sponsor | Genzyme, a Sanofi Company |
|---|---|
| Phase | Phase 4 |
| Status | COMPLETED |
| Enrolment | 4 |
| Start date | 2009-10 |
| Completion | 2013-03 |
Conditions
- Pompe Disease
- Glycogen Storage Disease Type II
Interventions
- Alglucosidase Alfa
- Methotrexate
- Rituximab
Primary outcomes
- Change From Baseline in Number of Patients With Anti-Recombinant Human Acid Alfa-glucosidase (Anti-rhGAA) Immunoglobulin G (IgG) Antibody at End of Study — Baseline, End of Study (up to Week 79 or early termination)
Serum samples from patients were analyzed for the presence of anti-rhGAA IgG antibodies. End of study (EOS) refers to the last post baseline observation during study period (up to Week 79). - Number of Patients With Recombinant Human Acid Alfa-glucosidase (rhGAA) Inhibitory Antibody at End of Study — End of study (up to Week 79)
Patients with positive anti-rhGAA IgG antibody were assessed for the presence of inhibitory antibodies (inhibition of enzyme activity and inhibition of enzyme uptake). Enzyme-linked immunosorbent assay (ELISA) was used to measure inhibition of rhGAA enzymatic activity in vitro and a cell-based assay was used to measure the inhibition of the uptake of rhGAA in normal fibroblast cells by flow cytometry. - Number of Patients Who Survived at End of Study — Baseline up to End of study (Week 79)
- Number of Patients With Normal/Abnormal Left Ventricular Mass (LVM) Z-Score and LVM Index at End of Study — End of study (up to Week 79 or early termination)
LVM Z-score and LVM index were assessed by ECHO. LVM Z-Score provides an indicator of degree of standard deviations from the mean in a normal distribution. Negative values indicate a smaller LVM than mean and values higher than 0 indicate a larger LVM than the mean. The normal range for LVM Z-Score is -2 to 2. Values \<-2 or \>2 indicate abnormal LVM Z-Score. LVM index is an index value derived by normalizing LVM by body surface area. LVM index provides evidence of cardiomyopathy. LVM index values \<65 gram per meter\^2 (g/m\^2) were considered as normal and LVM index values \>=65 g/m\^2 were considered as abnormal. End of study refers to the last post baseline observation during study period (up to Week 79). - Number of Patients With Ventilator Use at End of Study — End of study (up to Week 79 or early termination)
Number of patients who had ventilator support at end of study was reported. End of study refers to the last post baseline observation during study period (up to Week 79). - Gross Motor Disability Assessed by Gross Motor Function Measure-88 (GMFM-88) at End of Study — End of study (up to Week 79 or early termination)
GMFM-88 is an 88-item measure to detect gross motor function. It consists of 5 categories: lying and rolling; sitting; crawling and kneeling; standing; walking, running and jumping. Each item is scored on a 4-point Likert scale (0 = cannot do; 1 = initiates \[\<10% of the task\]; 2 = partially completes \[10% to \<100% of the task\]; 3 = task completion). The score for each dimension is expressed as a percentage of the maximum score for that dimension. Total score is obtained by adding the percentage scores for each dimension and dividing the sum by the total number of dimensions. Total score ranges from 0% to 100%, where higher scores indicate better motor functions. A total score of \<7.5% demonstrates gross motor disability. End of study refers to the last post baseline observation during study period (up to Week 79).
Countries
United States