Immune Tolerance Study With Aldurazyme® (Laronidase)

Mucopolysaccharidosis I Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00741338
• Other study ID #: ALID02307
• Secondary ID: 2007-001163-30
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: August 13, 2008
• Last updated: June 2, 2014
• Start date: September 2008
• Est. completion date: September 2012

Study information

• Verified date: June 2014
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: Brazil: National Health Surveillance AgencyRussia: Ministry of Health of Russian FederationUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 7
• Est. completion date: September 2012
• Est. primary completion date: September 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 5 Years

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Mucopolysaccharidoses
• Mucopolysaccharidosis I

Intervention

Biological:
• Laronidase
0.058 mg/kg - 0.58 mg/kg IV infusion weekly.

Drug:
• Cyclosporine A (CsA)
Orally three times daily.
• Azathioprine (Aza)
Orally either every day for Cohort 1 or every other day for Cohort 2.

Locations

Country	Name	City	State
Brazil	HCPA	Porto Alegre
Russian Federation	Moscow Research Institute for Pediatrics and Children Surgery	Moscow

Sponsors (2)

Lead Sponsor	Collaborator
Genzyme, a Sanofi Company	BioMarin/Genzyme LLC

Countries where clinical trial is conducted

Brazil,  Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants Who Achieved Immune Tolerance Induction	Immune tolerance induction success was defined as development of an anti-laronidase immunoglobulin G (IgG) antibody titer less than or equal to (<=) 1:3200 after 24 weeks of receiving full-dose (0.58 mg/kg) laronidase therapy.	24 weeks after start of full-dose laronidase therapy	Yes
Secondary	Percent Reduction of Urinary Glycosaminoglycan (uGAG) Level From Baseline to the End of Treatment/Early Withdrawal	Urinary Glycosaminoglycan (uGAG) Levels: concentration of glycosaminoglycan (GAG) relative to creatinine in urine. A greater decrease in uGAG level indicates a greater response.	Baseline, end of treatment/early withdrawal (up to 24 weeks after start of full-dose laronidase therapy)	No