Immune Tolerance Study With Aldurazyme® (Laronidase)
This study has been completed.
Information provided by (Responsible Party):
Sanofi ( Genzyme, a Sanofi Company )
First received: August 13, 2008
Last updated: September 30, 2013
Last verified: September 2013
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.
Drug: Neoral® (CsA)
Drug: Imuran® (Aza)
||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
||A Trial of Antigen-specific Immune Tolerance Induction in Mucopolysaccharidosis I (MPS I) Patients Initiating Enzyme Replacement Therapy With Aldurazyme® (Laronidase)
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 ]
| Study Start Date:
| Study Completion Date:
| Primary Completion Date:
||September 2012 (Final data collection date for primary outcome measure)
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).
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
|Ages Eligible for Study:
||up to 5 Years
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- 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.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00741338
|Porto Alegre, Brazil |
|Moscow Research Institute for Pediatrics and Children Surgery
|Moscow, Russian Federation |
|State Pediatric Medical Academy
|St. Petersburg, Russian Federation |
|Kiev, Ukraine |
Genzyme, a Sanofi Company
||Genzyme Europe B.V.
No publications provided
||Sanofi ( Genzyme, a Sanofi Company )
History of Changes
|Other Study ID Numbers:
|Study First Received:
||August 13, 2008
||September 30, 2013
||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:
ClinicalTrials.gov processed this record on March 09, 2014
Carbohydrate Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lysosomal Storage Diseases
Connective Tissue Diseases
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs