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

Genzyme

Status and phase: Completed; Phase 4

Conditions: Pompe Disease; Glycogen Storage Disease Type II

Treatments: Biological: Alglucosidase Alfa; Drug: Methotrexate; Drug: Rituximab

Study type: Interventional

Funder types: Industry

Identifiers

NCT00701129

MSC12862 (Other Identifier)

AGLU03807

Details and patient eligibility

About

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.

Enrollment: 4 patients

Sex: All

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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4 participants in 1 patient group

Alglucosidase Alfa

Experimental group

Description:

Alglucosidase alfa (Myozyme®) 20 milligrams per kilogram (mg/kg) intravenous (IV) infusion every other week (qow) (or optionally 20 mg/kg IV infusion every week \[qw\]) beginning from Day 0 to a minimum of 18 months or if the patient was less than (\<) 6 months of age at the time of enrollment, until the patient was 2 years of age, along with methotrexate 0.4 mg/kg subcutaneously for 3 consecutive days qow beginning from Day 0 to Week 6 (9 doses) and rituximab 375 milligrams per square meter (mg/m\^2) (or 12.5 mg/kg for patients with body surface area less than or equal to 0.5 m\^2) IV infusion qw beginning from Day -1 to Week 4 (4 doses) as per local prescribing information. An additional 4-week cycle of rituximab (up to 4 additional doses) and 6-week cycle of methotrexate (up to 9 additional doses) may have been administered within the first 6 months of the study as per local prescribing information.

Treatment:

Drug: Methotrexate

Biological: Alglucosidase Alfa

Drug: Rituximab