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

NCT ID: NCT00701129

Last Updated: 2014-05-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 4 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-10-31
• Study Completion Date: 2013-03-31

Brief 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.

Conditions

Pompe Disease; Glycogen Storage Disease Type II

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Alglucosidase Alfa

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.

Group Type: EXPERIMENTAL

Alglucosidase Alfa

Intervention Type: BIOLOGICAL

Administered as IV infusion.

Methotrexate

Intervention Type: DRUG

Administered subcutaneously.

Rituximab

Intervention Type: DRUG

Administered as IV infusion.

Interventions

Alglucosidase Alfa

Administered as IV infusion.

Intervention Type: BIOLOGICAL

Methotrexate

Administered subcutaneously.

Intervention Type: DRUG

Rituximab

Administered as IV infusion.

Intervention Type: DRUG

Other Intervention Names

Myozyme®

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

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genzyme, a Sanofi Company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Monitor

Role: STUDY_DIRECTOR

Genzyme Coorporation

Locations

Kosair Children's Hospital

Louisville, Kentucky, United States

Duke University Medical Center

Durham, North Carolina, United States

Countries

United States

Other Identifiers

MSC12862

Identifier Type: OTHER

Identifier Source: secondary_id

AGLU03807

Identifier Type: -

Identifier Source: org_study_id