A Dose-optimization Study of Aldurazyme® (Laronidase) in Patients With Mucopolysaccharidosis I (MPS I) Disease

Phase 4

Completed

Conditions: Hurler's Syndrome
Hurler-Scheie Syndrome
Mucopolysaccharidosis I
Scheie Syndrome

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

Brief Summary: The main purpose of this study is to evaluate differences in the pharmacodynamic response of 4 Aldurazyme® (laronidase) dose regimens in patients with Mucopolysaccharidosis I (MPS I).

Recruitment & Eligibility

Inclusion Criteria

Have a documented diagnosis of MPS I, confirmed by measurable clinical signs and symptoms of MPS I, and a documented fibroblast or leukocyte α-L-iduronidase enzyme activity level of less than 10% of the lower limit of the normal range of the measuring laboratory.
Weigh at least 12.5 kg.
Have serum creatinine and blood urea nitrogen (BUN) values within age appropriate normal ranges.
Provide signed, written informed consent prior to any protocol-related procedures being performed. Consent of a legally authorized guardian(s) is (are) required for patients under 18 years. If the patient is under 18 years old and can understand the consent, written informed consent will be required from both the patient and the authorized guardian(s).

Exclusion Criteria

Have previously received Aldurazyme® (laronidase).
Have a suspected hypersensitivity to Aldurazyme® (laronidase) or known hypersensitivity to components of the infusion solution.
Have previously undergone hematopoietic stem cell transplantation (HSCT; i.e., from bone marrow [BMT], peripheral blood, or umbilical cord blood) or other major organ transplantation.
Have a medical condition, serious inter-current illness, or other extenuating circumstance that may interfere with study compliance including all prescribed evaluations and follow-up activities, except the 6MWT. (Note: All patients may not be capable of performing the 6MWT due to age and/or maturity level. Exemption from performing the 6MWT must be obtained in writing by the investigator from the sponsor's medical monitor prior to enrollment).
Have an acute illness that requires surgical intervention, and/or anticipates surgery during study participation, and/or has had surgery within 30 days prior to study enrollment.
Have received an investigational drug within 30 days prior to study enrollment.
Is pregnant or lactating. Female patients of childbearing potential must have a negative pregnancy test [urine β-human chronic gonadotropin (hCG)] at entry (prior to the first infusion). Note: All female patients of childbearing potential and sexually mature males must be advised to use a medically accepted method of contraception throughout the study.

Arm && Interventions

Group	Intervention	Description
2	Aldurazyme (Recombinant Human Alpha-L-Iduronidase)	1.2 mg Aldurazyme/kg of body weight (200 U/kg) administered every week. Final Visit is Week 27 for patients randomized to every week regimen.
1	Aldurazyme (Recombinant Human Alpha-L-Iduronidase)	0.58 mg Aldurazyme/kg of body weight (100 U/kg) administered every week (labeled dose). Final Visit is Week 27 for patients randomized to every week regimen.
4	Aldurazyme (Recombinant Human Alpha-L-Iduronidase)	1.8 mg Aldurazyme/kg of body weight (300 U/kg) administered every 2 weeks. Final Visit is Week 26 for patients randomized to every 2 week regimen.
3	Aldurazyme (Recombinant Human Alpha-L-Iduronidase)	1.2 mg Aldurazyme/kg of body weight (200 U/kg) administered every 2 weeks. Final Visit is Week 26 for patients randomized to every 2 week regimen.

Primary Outcome Measures

Name	Time	Method
Percent Change From Baseline to Week 26 in Urinary Glycosaminoglycan (GAG) Level	Baseline to 26 Weeks	Urinary GAG Level - Concentration of GAG relative to creatinine in urine. A greater decrease in GAG level indicates a greater response.

Secondary Outcome Measures

Name	Time	Method
Percent Change From Baseline to Week 26 in Liver Organ Volume	Baseline to 26 Weeks	A greater decrease in liver volume indicates a greater response.
Change From Baseline to Week 26 in Six Minute Walk Test (6MWT)	Baseline to 26 Weeks	Six Minute Walk Test: Distance walked (measured in Meters) in 6 minutes. A longer distance indicates a greater response.

Locations (5): Universidade Federal de Sao Paulo
🇧🇷
San Paulo, Brazil
Hospital de Clinical de Porto Alegre
🇧🇷
Porto Alegre, Brazil
Universidade Federal de Minas Gerais
🇧🇷
Belo Horizonte, Brazil
Division of Clinical and Metabolic Genetics
🇨🇦
Toronto, Ontario, Canada
Hospital Infantil Joana de Gusmao
🇧🇷
Florianopolis, Santa Catarina, Brazil