Immune Tolerance Induction Study

Condition(s) targeted: Pompe Disease; Glycogen Storage Disease Type II (GSD-II); Glycogenesis 2 Acid Maltase Deficiency

Intervention: Myozyme (alglucosidase alfa) (Biological); Myozyme (alglucosidase alfa) (Biological)

Phase: Phase 4

Status: Recruiting

Sponsored by: Genzyme

Official(s) and/or principal investigator(s):
Medical Monitor, Study Director, Affiliation: Genzyme

Overall contact:
Medical Information, Phone: 800-745-4447, Email: medinfo@genzyme.com

An exploratory, open-labeled study of patients with Pompe disease, who have 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 patients who are currently receiving Myozyme therapy will be enrolled into the study, and will be 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 patients will be followed for a minimum of 18 months on treatment or, if a patient is <6 months of age at the time of enrollment, until the patient is 2 years of age. Both cross-reacting immunologic material (CRIM)-negative and CRIM-positive patients can be eligible for Regimen A depending if they meet the required criteria. Regimen B however, is limited to CRIM-negative patients.

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

Study design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

Evaluate the efficacy of ITI regimens as assessed by anti-recombinant human acid α-glucosidase (anti-rhGAA) antibody titers and antibodies that inhibit the enzymatic activity and/or uptake of Myozyme

Evaluate Pompe disease activity in patients receiving the 2 ITI regimens as measured by overall survival.

Evaluate Pompe disease activity in patients receiving the 2 ITI regimens as measured by respiratory function.

Evaluate Pompe disease activity in patients receiving the 2 ITI regimens as measured by Left ventricular mass index (LVMI).

Evaluate Pompe disease activity in patients receiving the 2 ITI regimens as measured by motor function.

Evaluate Pompe disease activity in patients receiving the 2 ITI regimens as measured by disability index.

Evaluate the safety of the 2 ITI regimens as assessed by the incidence of adverse events (AEs), serious adverse events (SAEs), and clinical laboratory abnormalities.

Minimum age: 1 Month. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- The patient (and/or patient's legal guardian if patient is < 18years) must provide

written informed consent prior to any study-related procedures that are performed;

- The patient must have 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 patient (and/or legal guardian) must have ability to comply with clinical

protocol;

- If the patient is Cross-reacting immunologic material (CRIM)-positive, he/she must

have received at least 6 consecutive months of Myozyme infusions (20mg/kg qow)

- If the patient is CRIM-negative, he/she must have received at least 1 Myozyme

infusion prior to enrollment

- Regimen A only: The patient exhibits clinical decline; The patient has 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 patient is CRIM-negative AND The patient does not exhibit

clinical decline; OR ALL OF THE FOLLOWING: The patient is CRIM-negative AND The patient exhibits clinical decline AND The patient does NOT exhibit high anti-rhGAA antibody titers and has NOT tested positive for antibodies that inhibit enzymatic activity and/or uptake of Myozyme.

Exclusion Criteria:

- The patient has a clinical condition unrelated to Pompe disease that would interfere

with program assessments;

- The patient is at risk of reactivation or is a carrier of Hepatitis B or Hepatitis C;

- The patient is at risk of reactivation or has positive serology suggestive of active

infection for cytomegalovirus, Herpes simplex, JC virus, Parvovirus or Epstein Barr virus;

- The patient is at risk of reactivation of tuberculosis or has regular contact with

individuals who are being actively treated for tuberculosis;

- The patient has low serum albumin;

- The patient has a major congenital abnormality;

- The patient has used any investigational product (other than alglucosidase alfa)

within 30 days prior to study enrollment;

- The patient is pregnant or lactating;

- The patient has had or is required to have any live vaccination within one month

prior to enrollment.

Medical Information, Phone: 800-745-4447, Email: medinfo@genzyme.com

Haifa 31096, Israel; Recruiting

Louisville, Kentucky, United States; Recruiting

Durham, North Carolina, United States; Recruiting

Salt Lake City, Utah, United States; Recruiting

Norfolk, Virginia, United States; Recruiting

Starting date: December 2008
Last updated: October 3, 2012