Immune Tolerance Study With Aldurazyme® (Laronidase)

Condition(s) targeted: Mucopolysaccharidosis I

Intervention: laronidase (Biological); Neoral® (CsA) (Drug); Imuran® (Aza) (Drug)

Phase: Phase 1/Phase 2

Status: Recruiting

Sponsored by: Genzyme

Official(s) and/or principal investigator(s):
Eric Ginosian, Study Director, Affiliation: Genzyme Europe B.V.

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

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.

Official title: A Trial of Antigen-specific Immune Tolerance Induction in Mucopolysaccharidosis I (MPS I) Patients Initiating Enzyme Replacement Therapy With Aldurazyme® (Laronidase)

Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Antibody titer to laronidase less than or equal to 1:3200

Secondary outcome:

uGAG (Urinary Glycosaminoglycan) reduction

Safety and tolerability

Minimum age: N/A. Maximum age: 5 Years. Gender(s): Both.

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.

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

Porto Alegre, Brazil; Active, not recruiting

Moscow, Russian Federation; Active, not recruiting

St. Petersburg, Russian Federation; Recruiting

Kiev, Ukraine; Not yet recruiting

Starting date: September 2008
Last updated: October 24, 2012