Immune Tolerance Induction Study
Pompe Disease, Glycogen Storage Disease Type II (GSD-II), Glycogenesis 2 Acid Maltase Deficiency
About this trial
This is an interventional treatment trial for Pompe Disease
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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
Regimen A: Alglucosidase alfa and Cyclophosphamide
Regimen B: Alglucosidase alfa, Rituximab and Methotrexate
Participants exhibiting clinical decline since starting alglucosidase alfa (Myozyme®) therapy and having inhibitory antibodies and/or a sustained high recombinant human acid alpha-glucosidase (rhGAA) antibody titer (defined as at least 2 titers greater than or equal to [>=] 25,600 obtained at least 1 month apart), regardless of their CRIM status, were assigned to Regimen A. In Regimen A, participants received alglucosidase alfa (Myozyme®) Intravenous (IV) infusion of 20 milligram per kilogram (mg/kg) every other week (qow) for a minimum of 18 months or, until the participant reached the age of 2 years (if the participant was less than [<6] months of age at the time of enrollment). In addition, cyclophosphamide 250 milligram per square meter (mg/m^2) IV infusion was administered every 4 weeks (q4w) after Myozyme® infusion for 6 months.
CRIM-negative participants were assigned to Regimen B if they either(1)exhibited clinical decline since starting alglucosidase alfa (Myozyme®)therapy and did not have inhibitory antibodies and/or a sustained rhGAA antibody titer(defined as at least 2 titers >=25,600 obtained at least 1 month apart),or(2) did not exhibit clinical decline since starting alglucosidase alfa(Myozyme®) therapy, regardless of their anti-rhGAA or inhibitory antibody status. Regimen B participants with CRIM-negative status received alglucosidase alfa(Myozyme®) IV infusion of 20 mg/kg qow for a minimum of 18 months or,until participant reached the age of 2 years (if participant was <6 months of age at time of enrollment). In addition,rituximab 375 mg/m^2 IV was administered weekly beginning the day after Myozyme® infusion for 4 weeks(an optional 2nd cycle could be administered at the discretion of the investigator) and biweekly methotrexate 15 mg/m^2 subcutaneous on the day after Myozyme® infusion for 6 months.