Clinical trial NCT00741338: Immune Tolerance Study With Aldurazyme® (Laronidase)
Official title: A Trial of Antigen-specific Immune Tolerance Induction in Mucopolysaccharidosis I (MPS I) Patients Initiating Enzyme Replacement Therapy With Aldurazyme® (Laronidase)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Mucopolysaccharidosis I
Keywords: MPS I, Mucopolysaccharidosis, Hurler syndrome
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: BioMarin/Genzyme LLC
First posted: 2008-08-26
Enrollment: 7
Sex: ALL
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility 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)
* Participant's parent(s) or legal guardian(s) allow their child's participation and are willing and able to comply with trial procedures
* The participant 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 alfa-L-iduronidase (IDUA) gene (that is, 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 is collected for analysis by a central laboratory before enrollment
* Documented IDUA deficiency with fibroblast, plasma, serum, leukocyte or dried blood spot IDUA enzyme activity assay

Exclusion Criteria:

* The participant 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, precludes participation in the trial or potentially decrease survival
* The participant has previously received treatment with laronidase
* The participant has known severe hypersensitivity to any excipients of the delivery solution for laronidase or to any of the other investigational drugs used in the study
* The participant 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 participant will be discontinued from the trial
* The participant has received an investigational product within the 30 days prior to enrollment
* The participant has prior treatment in any experimental protocol (for example, fibroblast injections) that might potentially induce antibodies to laronidase or might affect the interpretation of the participant's antibody response to laronidase
* The participant 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 participant 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 participant has a prior history of tuberculosis or a positive test for latent tuberculosis infection

Primary outcomes:
measure: Number of Participants Who Achieved Immune Tolerance Induction
timeFrame: 24 weeks after start of full-dose laronidase therapy
Secondary outcomes:
measure: Percent Reduction of Urinary Glycosaminoglycan (uGAG) Level From Baseline to the End of Treatment/Early Withdrawal
timeFrame: Baseline, end of treatment/early withdrawal (up to 24 weeks after start of full-dose laronidase therapy)
Other outcomes:
Locations:
city: Porto Alegre
country: Brazil
facility: HCPA
city: Moscow
country: Russian Federation
facility: Moscow Research Institute for Pediatrics and Children Surgery
Study officials:
affiliation: Genzyme Europe B.V.
name: Medical Monitor
role: STUDY_DIRECTOR
References:
citation: Giugliani R, Vieira TA, Carvalho CG, Munoz-Rojas MV, Semyachkina AN, Voinova VY, Richards S, Cox GF, Xue Y. Immune tolerance induction for laronidase treatment in mucopolysaccharidosis I. Mol Genet Metab Rep. 2017 Jan 13;10:61-66. doi: 10.1016/j.ymgmr.2017.01.004. eCollection 2017 Mar.