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Immune Tolerance Induction Study

This study is currently recruiting participants.
Verified October 2016 by Sanofi ( Genzyme, a Sanofi Company )
Sponsor:
ClinicalTrials.gov Identifier:
NCT00701701
First Posted: June 19, 2008
Last Update Posted: October 21, 2016
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Sanofi ( Genzyme, a Sanofi Company )
  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
Intervention Model: Parallel Assignment
Masking: None (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 ( Genzyme, a Sanofi Company ):

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 ]
  • Evaluate Pompe disease activity in patients receiving the 2 ITI regimens as measured by overall survival. [ Time Frame: 18 months ]
  • Evaluate Pompe disease activity in patients receiving the 2 ITI regimens as measured by respiratory function. [ Time Frame: 18 months ]
  • Evaluate Pompe disease activity in patients receiving the 2 ITI regimens as measured by Left ventricular mass index (LVMI). [ Time Frame: 18 months ]
  • Evaluate Pompe disease activity in patients receiving the 2 ITI regimens as measured by motor function. [ Time Frame: 18 months ]
  • Evaluate Pompe disease activity in patients receiving the 2 ITI regimens as measured by disability index. [ Time Frame: 18 months ]
  • 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 ]

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

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   1 Month and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00701701


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

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

Responsible Party: Genzyme, a Sanofi Company
ClinicalTrials.gov Identifier: NCT00701701     History of Changes
Other Study ID Numbers: AGLU03707
MSC12817 ( Other Identifier: Sanofi )
First Submitted: June 17, 2008
First Posted: June 19, 2008
Last Update Posted: October 21, 2016
Last Verified: October 2016

Additional relevant MeSH terms:
Brain Diseases, Metabolic, Inborn
Glycogen Storage Disease Type II
Glycogen Storage Disease
Lysosomal Storage Diseases, Nervous System
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Carbohydrate Metabolism, Inborn Errors
Lysosomal Storage Diseases
Metabolic Diseases
Cyclophosphamide
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists