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

Mucopolysaccharidosis I Clinical Trial

Official title:

A Multicenter, Multinational, Randomized, Dose-Optimization Study of the Safety and Pharmacodynamic Response of Aldurazyme® (Laronidase) in Patients With Mucopolysaccharidosis I

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00144781
• Other study ID #: ALID-017-03
• Status: Completed
• Phase: Phase 4
• First received: September 2, 2005
• Last updated: March 17, 2015
• Start date: December 2004
• Est. completion date: January 2006

Study information

• Verified date: March 2015
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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 information / eligibility

• Status: Completed
• Enrollment: 34
• Est. completion date: January 2006
• Est. primary completion date: January 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

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 a-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 ß-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.

Study Design

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

Related Conditions & MeSH terms

• Hurler's Syndrome
• Hurler-Scheie Syndrome
• Mucopolysaccharidoses
• Mucopolysaccharidosis I
• Scheie Syndrome
• Syndrome

Intervention

Biological:
• Aldurazyme (Recombinant Human Alpha-L-Iduronidase)
0.58 mg/kg every week
• Aldurazyme (Recombinant Human Alpha-L-Iduronidase)
1.2 mg/kg every week
• Aldurazyme (Recombinant Human Alpha-L-Iduronidase)
1.2 mg/kg every other week
• Aldurazyme (Recombinant Human Alpha-L-Iduronidase)
1.8 mg/kg every other week

Locations

Country	Name	City	State
Brazil	Universidade Federal de Minas Gerais	Belo Horizonte
Brazil	Hospital Infantil Joana de Gusmao	Florianopolis	Santa Catarina
Brazil	Hospital de Clinical de Porto Alegre	Porto Alegre
Brazil	Universidade Federal de Sao Paulo	San Paulo
Canada	Division of Clinical and Metabolic Genetics	Toronto	Ontario

Sponsors (2)

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

Countries where clinical trial is conducted

Brazil,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent Change From Baseline to Week 26 in Urinary Glycosaminoglycan (GAG) Level	Urinary GAG Level - Concentration of GAG relative to creatinine in urine. A greater decrease in GAG level indicates a greater response.	Baseline to 26 Weeks	No
Secondary	Percent Change From Baseline to Week 26 in Liver Organ Volume	A greater decrease in liver volume indicates a greater response.	Baseline to 26 Weeks	No
Secondary	Change From Baseline to Week 26 in Six Minute Walk Test (6MWT)	Six Minute Walk Test: Distance walked (measured in Meters) in 6 minutes. A longer distance indicates a greater response.	Baseline to 26 Weeks	No