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Immune Tolerance Induction Study

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Sanofi
Sponsor:
Information provided by (Responsible Party):
Sanofi ( Genzyme, a Sanofi Company )
ClinicalTrials.gov Identifier:
NCT00701701
First received: June 17, 2008
Last updated: September 29, 2014
Last verified: September 2014
  Purpose

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.


Condition Intervention Phase
Pompe Disease
Glycogen Storage Disease Type II (GSD-II)
Glycogenesis 2 Acid Maltase Deficiency
Biological: Myozyme (alglucosidase alfa)
Phase 4

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

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • 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 [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • Evaluate Pompe disease activity in patients receiving the 2 ITI regimens as measured by overall survival. [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • Evaluate Pompe disease activity in patients receiving the 2 ITI regimens as measured by respiratory function. [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • Evaluate Pompe disease activity in patients receiving the 2 ITI regimens as measured by Left ventricular mass index (LVMI). [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • Evaluate Pompe disease activity in patients receiving the 2 ITI regimens as measured by motor function. [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • Evaluate Pompe disease activity in patients receiving the 2 ITI regimens as measured by disability index. [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 9
Study Start Date: December 2008
Estimated Study Completion Date: June 2017
Estimated Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Myozyme and Cyclophosphamide
Regimen A
Biological: Myozyme (alglucosidase alfa)
Myozyme: Intravenous (IV) infusion of 20 mg/kg every other week (qow); Cyclophosphamide: 250 mg/m2 IV every 4 wks after Myozyme infusion for 6 months
Other Name: Myozyme
Experimental: Myozyme, Rituximab and Methotrexate
Regimen B
Biological: Myozyme (alglucosidase alfa)
Myozyme: IV infusion of 20 mg/kg qow; Rituximab: 375 mg/m2 IV weekly beginning the day after MZ infusion for 4 weeks (an optional additional 2nd cycle may be administered at the discretion of the investigator); Methotrexate: 15mg/m2 subcutaneous every other week on the day after Myozyme infusion for 6 months
Other Name: Myozyme

  Eligibility

Ages Eligible for Study:   1 Month and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00701701

Contacts
Contact: Medical Information 800-745-4447 medinfo@genzyme.com
Contact: Medical Information 617-252-7832 MedInfo@genzyme.com

Locations
United States, Kentucky
Recruiting
Louisville, Kentucky, United States
United States, North Carolina
Recruiting
Durham, North Carolina, United States
United States, Utah
Recruiting
Salt Lake City, Utah, United States
United States, Virginia
Recruiting
Norfolk, Virginia, United States
Israel
Recruiting
Haifa, Israel
Sponsors and Collaborators
Genzyme, a Sanofi Company
Investigators
Study Director: Medical Monitor Genzyme, a Sanofi Company
  More Information

No publications provided

Responsible Party: Sanofi ( Genzyme, a Sanofi Company )
ClinicalTrials.gov Identifier: NCT00701701     History of Changes
Other Study ID Numbers: AGLU03707
Study First Received: June 17, 2008
Last Updated: September 29, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
Israel: Israeli Health Ministry Pharmaceutical Administration

Additional relevant MeSH terms:
Glycogen Storage Disease
Glycogen Storage Disease Type II
Brain Diseases
Brain Diseases, Metabolic
Brain Diseases, Metabolic, Inborn
Carbohydrate Metabolism, Inborn Errors
Central Nervous System Diseases
Genetic Diseases, Inborn
Lysosomal Storage Diseases
Lysosomal Storage Diseases, Nervous System
Metabolic Diseases
Metabolism, Inborn Errors
Nervous System Diseases

ClinicalTrials.gov processed this record on November 20, 2014