Immune Tolerance Induction Study

An Exploratory Study of the Safety and Efficacy of Immune Tolerance Induction (ITI) in Patients With Pompe Disease Who Have Previously Received Myozyme

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.

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.