A Study Evaluating the Safety and Pharmacokinetics of Aldurazyme® (Laronidase) in MPS I Patients Less Than 5 Years Old

Genzyme

Status and phase: Completed; Phase 2

Conditions: Hurler-Scheie Syndrome; Mucopolysaccharidosis I; Scheie Syndrome; Hurler Syndrome

Treatments: Biological: Aldurazyme (Recombinant Human Alpha-L-Iduronidase)

Study type: Interventional

Funder types: Industry

Identifiers

NCT00146757

ALID-014-02

Details and patient eligibility

About

The main objectives of this study are to evaluate the safety and pharmacokinetics (PK) of enzyme replacement therapy with recombinant human alpha-L-iduronidase [Aldurazyme® (laronidase)] in mucopolysaccharidosis I (MPS I) patients less than 5 years old. Efficacy measurements will also be evaluated in this study.

Enrollment: 20 patients

Sex: All

Ages: Under 5 years old

Volunteers: No Healthy Volunteers

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.)
• Be less than 5 years of age at the time of enrollment.
• Have confirmed iduronidase deficiency with a fibroblast or leukocyte alpha-L-iduronidase enzyme activity level of less than 10.0 % of the lower limit of the normal range, or below the detection range of the measuring laboratory.
• Have a clinical diagnosis of MPS I based on genotyping.
• Documentation in his/her medical record that the parent(s) or legal guardian(s) have had counseling or a consultation regarding HSCT in order to assure that the parent(s) or legal guardian(s) are fully informed regarding the risks and benefits of this alternative treatment for patients eligible for the trial and with the severe manifestations of MPS I with neurodegeneration.

Exclusion criteria

• The patient is under consideration for or has undergone hematopoietic stem cell transplantation (HSCT).
• The patient has acute hydrocephalus at the time of enrollment.
• The patient has a clinically significant organic disease (with the exception of symptoms relating to MPS I) 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 received any investigational product within 30 days prior to trial enrollment.
• The patient has known severe hypersensitivity to Aldurazyme® (laronidase) or components of the delivery solution.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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20 participants in 2 patient groups

Aldurazyme (rhIDU) 100 U/kg ONLY every week

Experimental group

Description:

Patients received Aldurazyme (recombinant human alpha-L-iduronidase (rhIDU)) once per week at a dose of 100 Units/kg (approximately 0.58 mg/kg) for up to 52 weeks - labeled dose.

Treatment:

Biological: Aldurazyme (Recombinant Human Alpha-L-Iduronidase)

Aldurazyme (rhIDU) 100-200 U/kg every week

Experimental group

Description:

After receiving 100 Units/kg dose of Aldurazyme (rhIDU) for the first 25 weeks, patients enrolling after January 1, 2004 were eligible to receive an increased dose of 200 Units/kg from Week 26 onwards if the patient's urinary glycosaminoglycan (uGAG) levels were >200µg/mg creatinine at Week 22.

Treatment:

Biological: Aldurazyme (Recombinant Human Alpha-L-Iduronidase)