Immune Tolerance Induction Study
Condition: Pompe Disease; Glycogen Storage Disease Type II (GSD-II); Glycogenesis 2 Acid Maltase Deficiency
MeSH terms: Glycogen Storage Disease Type II; Glycogen Storage Disease
Intervention: Myozyme® (alglucosidase alfa); Myozyme® (alglucosidase alfa)
Intervention description: Myozyme®: IV infusion of 20 mg/kg qow; Cyclophosphamide: 250 mg/m^2 IV q4w after Myozyme infusion for 6 months.; Myozyme®: IV infusion of 20 mg/kg qow; Rituximab: 375 mg/m^2 IV weekly beginning the day after Myozyme infusion for 4 weeks (an optional additional 2nd cycle could be administered at the discretion of the investigator); Methotrexate: 15 mg/m^2 subcutaneous qow on the day after Myozyme infusion for 6 months.
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 4.0
Sex: All
Minimum age: 1 Month
Healthy volunteers: No

Summary:

      An exploratory, open-labeled study of participants with Pompe disease, who had previously
      received Myozyme® (alglucosidase alfa) treatment, to evaluate the efficacy, safety and
      clinical benefit of 2 Immune Tolerance Induction (ITI) regimens in combination with Myozyme®.
      Eligible participants who were then receiving Myozyme® therapy were enrolled into the study,
      and were followed for a minimum of 18 months on-study (a 6-month ITI treatment module and a
      12-month follow-up module on Myozyme® alone). Eligible participants were followed for a
      minimum of 18 months on treatment or, if a participant was <6 months of age at the time of
      enrollment, until the participant was 2 years of age. Both cross-reacting immunologic
      material (CRIM)-negative and CRIM-positive participants were eligible for Regimen A depending
      if they met the required criteria. Regimen B, however, was limited to CRIM-negative
      participants.
    

Eligibility criteria:

        Inclusion Criteria:

          -  The participant (and/or participant's legal guardian if participant was < 18 years)
             provided written informed consent prior to any study-related procedures that were
             performed.

          -  The participants had a confirmed diagnosis of Pompe disease defined as a documented
             acid α-glucosidase (GAA) enzyme deficiency from any tissue source or 2 GAA gene
             mutations.

          -  The participant (and/or legal guardian) had ability to comply with clinical protocol.

          -  If the participant was CRIM-positive, he/she had received at least 6 consecutive
             months of Myozyme® infusions (20 mg/kg qow).

          -  If the participant was CRIM-negative, he/she had received at least 1 Myozyme® infusion
             prior to enrollment.

          -  Regimen A only: The participants exhibits clinical decline; The participant had
             persistent high anti-recombinant human acid α-glucosidase (anti-rhGAA) antibody titers
             and/or tested positive for antibodies that inhibit enzymatic activity and/or uptake of
             Myozyme®;

          -  Regimen B only: The participant was CRIM-negative AND The participant did not exhibit
             clinical decline; OR all of the following: The participant was CRIM-negative AND The
             participant exhibited clinical decline AND The participant did not exhibit high
             anti-rhGAA antibody titers and had not tested positive for antibodies that inhibit
             enzymatic activity and/or uptake of Myozyme®.

        Exclusion Criteria:

          -  The participant had a clinical condition unrelated to Pompe disease that would
             interfere with program assessments.

          -  The participant was at risk of reactivation or was a carrier of Hepatitis B or
             Hepatitis C.

          -  The participant was at risk of reactivation or had positive serology suggestive of
             active infection for cytomegalovirus, Herpes simplex, JC virus, Parvovirus or Epstein
             Barr virus.

          -  The participant was at risk of reactivation of tuberculosis or had regular contact
             with individuals who were being actively treated for tuberculosis.

          -  The participant had low serum albumin.

          -  The participant had a major congenital abnormality.

          -  The participant had used any investigational product (other than alglucosidase alfa)
             within 30 days prior to study enrollment.

          -  The participant was pregnant or lactating.

          -  The participant has had or was required to have any live vaccination within one month
             prior to enrollment.