Immune Tolerance Study With Aldurazyme® (Laronidase)

This study has been completed.
Sponsor:
Collaborator:
BioMarin/Genzyme LLC
Information provided by (Responsible Party):
Sanofi ( Genzyme, a Sanofi Company )
ClinicalTrials.gov Identifier:
NCT00741338
First received: August 13, 2008
Last updated: September 30, 2013
Last verified: September 2013
  Purpose

The purpose of this study is to see if treatment with an antigen-specific immunosuppressive can decrease or stop an antibody response to laronidase during enzyme replacement therapy with Aldurazyme in severe MPS I (Mucopolysaccharidosis I) patients.


Condition Intervention Phase
Mucopolysaccharidosis I
Biological: laronidase
Drug: Neoral® (CsA)
Drug: Imuran® (Aza)
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Trial of Antigen-specific Immune Tolerance Induction in Mucopolysaccharidosis I (MPS I) Patients Initiating Enzyme Replacement Therapy With Aldurazyme® (Laronidase)

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Antibody titer to laronidase less than or equal to 1:3200 [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • uGAG (Urinary Glycosaminoglycan) reduction [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Safety and tolerability [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 6
Study Start Date: September 2008
Study Completion Date: September 2012
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Aldurazyme® treatment with Neoral® and Imuran®
This study employs an adaptive design, in which a single cohort is enrolled initially, but which allows for the enrollment of up to 1 additional cohorts using modified immunosuppressive regimens (for a maximum of 2 cohorts).
Biological: laronidase
0.058-0.58 mg/kg iv (intravenous) qw (every week)
Other Name: Aldurazyme®
Drug: Neoral® (CsA)
6.7 mg/kg po tid [Per os (by mouth) 3 times a day] for 8 weeks
Drug: Imuran® (Aza)
5 mg/kg po qd [Per os (by mouth) every other day] for 8 weeks

  Eligibility

Ages Eligible for Study:   up to 5 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Written informed consent is required from the parent(s) or legal guardian(s) prior to any protocol-related procedures being performed. (A separate informed consent will be requested from the parent(s) for their genotyping, which is independent of the inclusion.)
  • Patient's parent(s) or legal guardian(s) allow their child's participation and are willing and able to comply with trial procedures.
  • The patient must be up to and including 5 years of age at the time of enrollment.
  • Clinical diagnosis of the severe (Hurler) phenotype of MPS I
  • Confirmed presence of 2 nonsense mutations in the IDUA (α-L-iduronidase) gene (ie, compound heterozygosity or homozygosity). For the purpose of enrollment, genotyping may be performed by a local laboratory. If no genotyping is performed by a local laboratory, a sample will be collected for analysis by a central laboratory before enrollment.
  • Documented α-L-iduronidase deficiency with fibroblast, plasma, serum, leukocyte or dried blood spot α-L-iduronidase enzyme activity assay.

Exclusion Criteria:

  • The patient has a clinically significant organ disease including: cardiovascular, hepatic, pulmonary, neurologic, or renal disease, other serious intercurrent illness or extenuating circumstances that, in the opinion of the Investigator, would preclude participation in the trial or potentially decrease survival.
  • The patient has previously received treatment with Aldurazyme®.
  • The patient has known severe hypersensitivity to any excipients of the delivery solution for Aldurazyme® or to any of the other investigational drugs used in the study.
  • The patient has undergone a haematopoietic stem cell transplant (HSCT), regardless of outcome, or is currently under consideration for such a transplant. If a family later decides to obtain HSCT, the patient will be discontinued from the trial.
  • The patient has received an investigational product within the 30 days prior to enrollment
  • The patient has prior treatment in any experimental protocol (eg., fibroblast injections) that might potentially induce antibodies to laronidase or might affect the interpretation of the patient's antibody response to laronidase.
  • The patient has received vaccination(s) within 1 month prior to enrollment, or is unwilling to postpone vaccinations during the Tolerance Induction Period in the trial.
  • The patient is homozygous for thiopurine methyltransferase (TPMT) deficiency, as determined by the genotype ( the presence of 2 known null alleles for TPMT) or phenotype (near to complete absence of TPMT enzyme activity).
  • The patient has a prior history of tuberculosis or a positive test for latent tuberculosis infection.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00741338

Locations
Brazil
HCPA
Porto Alegre, Brazil
Russian Federation
Moscow Research Institute for Pediatrics and Children Surgery
Moscow, Russian Federation
State Pediatric Medical Academy
St. Petersburg, Russian Federation
Ukraine
Kiev, Ukraine
Sponsors and Collaborators
Genzyme, a Sanofi Company
BioMarin/Genzyme LLC
Investigators
Study Director: Medical Monitor Genzyme Europe B.V.
  More Information

No publications provided

Responsible Party: Sanofi ( Genzyme, a Sanofi Company )
ClinicalTrials.gov Identifier: NCT00741338     History of Changes
Other Study ID Numbers: ALID02307, 2007-001163-30
Study First Received: August 13, 2008
Last Updated: September 30, 2013
Health Authority: Brazil: National Health Surveillance Agency
Russia: Ministry of Health of Russian Federation
Ukraine: State Expert Center of Ministry of Health of Ukraine

Keywords provided by Sanofi:
MPS I, Mucopolysaccharidosis, Hurler syndrome

Additional relevant MeSH terms:
Mucopolysaccharidosis I
Mucopolysaccharidoses
Carbohydrate Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lysosomal Storage Diseases
Mucinoses
Connective Tissue Diseases
Metabolic Diseases
Azathioprine
Cyclosporine
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antifungal Agents
Anti-Infective Agents
Dermatologic Agents
Enzyme Inhibitors

ClinicalTrials.gov processed this record on April 16, 2014