Clinical Trial: An Exploratory Study of the Safety and Efficacy of Prophylactic Immunomodulatory Treatment in Myozyme-naive Cross-Reacting Immunologic Material (CRIM[-]) Patients With Infantile-Onset Pompe Disease

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: An Exploratory Study of the Safety and Efficacy of Prophylactic Immunomodulatory Treatment in Myozyme®-Naive, CRIM(-) Patients With Infantile-onset Pompe Disease

Brief Summary:

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.


Detailed Summary:
Sponsor: Genzyme, a Sanofi Company

Current Primary Outcome:

  • Change From Baseline in Number of Patients With Anti-Recombinant Human Acid Alfa-glucosidase (Anti-rhGAA) Immunoglobulin G (IgG) Antibody at End of Study [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 abno

    Original Primary Outcome:

    • Evaluate the efficacy a prophylactic immunomodulatory regimen given prior to first Myozyme infusion [ Time Frame: 18 months ]
    • Evaluate the clinical benefit of this regimen. [ Time Frame: 18 months ]
    • Evaluate the safety of this regimen [ Time Frame: 18 months ]


    Current Secondary Outcome:

    Original Secondary Outcome:

    Information By: Sanofi

    Dates:
    Date Received: June 17, 2008
    Date Started: October 2009
    Date Completion:
    Last Updated: April 9, 2014
    Last Verified: April 2014