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
Condition: Pompe Disease; Glycogen Storage Disease Type II
MeSH terms: Glycogen Storage Disease Type II; Glycogen Storage Disease
Intervention: Alglucosidase Alfa; Methotrexate; Rituximab
Intervention description: Administered as IV infusion.; Administered subcutaneously.; Administered as IV infusion.
Intervention MeSH terms: Rituximab; Methotrexate
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 4.0
Sex: All
Healthy volunteers: No
Keywords: Glycogenesis 2; Acid; Maltase; Deficiency

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  The patient's legal guardian(s) must have provided written informed consent prior to
             any study-related procedures being performed

          -  The patient must have had a clinical diagnosis of Pompe disease as defined by
             documented acid alpha-glucosidase (GAA) deficiency (deficient endogenous GAA activity)
             in skin fibroblasts, muscle, or blood, or 2 GAA mutations. Consent was also sought
             from the biological parent(s) for parental GAA mutational analysis, but was not a
             requirement for study eligibility

          -  The patient must have not received Myozyme® or any rhGAA therapies prior to enrollment
             in the study

          -  The patient must be CRIM negative via Western Blot analysis performed on skin
             fibroblasts or via 2 known CRIM negative mutations (in which case CRIM status was to
             be confirmed by Western Blot analysis after enrollment)

          -  The patient's legal guardian(s) must have the ability to comply with the clinical
             protocol

        Exclusion Criteria:

          -  The patient had any medical condition that, in the opinion of the Investigator, could
             be exacerbated/precipitated by or interfere with the study regimen or assessments;
             such conditions may include but were not limited to human immunodeficiency virus,
             cancer, Hepatitis B, Hepatitis C, Cytomegalovirus, Herpes Simplex, John Cunningham
             (JC) virus, Parvovirus, or Epstein Barr virus or tuberculosis

          -  The patient had used any investigational product within 30 days prior to study
             enrollment

          -  The patient had or was required to have any live vaccination within 1 month prior to
             enrollment