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

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

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).

Study Overview

• Status: Completed
• Conditions: Mucopolysaccharidosis I; Scheie Syndrome; Hurler's Syndrome; Hurler-Scheie Syndrome
• Intervention / Treatment: Biological: Aldurazyme (Recombinant Human Alpha-L-Iduronidase); Biological: Aldurazyme (Recombinant Human Alpha-L-Iduronidase); Biological: Aldurazyme (Recombinant Human Alpha-L-Iduronidase); Biological: Aldurazyme (Recombinant Human Alpha-L-Iduronidase)

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 4

Contacts and Locations

Study Locations

• Brazil
  • Belo Horizonte, Brazil, CEP 30130-100
    • Universidade Federal de Minas Gerais
  • Porto Alegre, Brazil, CEP 90035-003
    • Hospital de Clinical de Porto Alegre
  • San Paulo, Brazil, CEP 04023-062
    • Universidade Federal de São Paulo
  • Santa Catarina
    • Florianopolis, Santa Catarina, Brazil, CEP 88025-601
      • Hospital Infantil Joana de Gusmão
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • Division of Clinical and Metabolic Genetics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1; 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.	Biological: Aldurazyme (Recombinant Human Alpha-L-Iduronidase); 0.58 mg/kg every week; Biological: Aldurazyme (Recombinant Human Alpha-L-Iduronidase); 1.2 mg/kg every week; Biological: Aldurazyme (Recombinant Human Alpha-L-Iduronidase); 1.2 mg/kg every other week; Biological: Aldurazyme (Recombinant Human Alpha-L-Iduronidase); 1.8 mg/kg every other week
Active Comparator: 2; 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.	Biological: Aldurazyme (Recombinant Human Alpha-L-Iduronidase); 0.58 mg/kg every week; Biological: Aldurazyme (Recombinant Human Alpha-L-Iduronidase); 1.2 mg/kg every week; Biological: Aldurazyme (Recombinant Human Alpha-L-Iduronidase); 1.2 mg/kg every other week; Biological: Aldurazyme (Recombinant Human Alpha-L-Iduronidase); 1.8 mg/kg every other week
Active Comparator: 3; 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.	Biological: Aldurazyme (Recombinant Human Alpha-L-Iduronidase); 0.58 mg/kg every week; Biological: Aldurazyme (Recombinant Human Alpha-L-Iduronidase); 1.2 mg/kg every week; Biological: Aldurazyme (Recombinant Human Alpha-L-Iduronidase); 1.2 mg/kg every other week; Biological: Aldurazyme (Recombinant Human Alpha-L-Iduronidase); 1.8 mg/kg every other week
Active Comparator: 4; 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.	Biological: Aldurazyme (Recombinant Human Alpha-L-Iduronidase); 0.58 mg/kg every week; Biological: Aldurazyme (Recombinant Human Alpha-L-Iduronidase); 1.2 mg/kg every week; Biological: Aldurazyme (Recombinant Human Alpha-L-Iduronidase); 1.2 mg/kg every other week; Biological: Aldurazyme (Recombinant Human Alpha-L-Iduronidase); 1.8 mg/kg every other week

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

Collaborators and Investigators

• Sponsor: Genzyme, a Sanofi Company
• Collaborators: BioMarin/Genzyme LLC
• Investigators: Study Director: Medical Information, Genzyme, a Sanofi Company

Study record dates

Study Major Dates

• Study Start: December 1, 2004
• Primary Completion (Actual): January 1, 2006
• Study Completion (Actual): January 1, 2006

Study Registration Dates

• First Submitted: September 2, 2005
• First Submitted That Met QC Criteria: September 2, 2005
• First Posted (Estimate): September 5, 2005

Study Record Updates

• Last Update Posted (Estimate): April 3, 2015
• Last Update Submitted That Met QC Criteria: March 17, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Disease; Genetic Diseases, Inborn; Connective Tissue Diseases; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Mucinoses; Syndrome; Mucopolysaccharidoses; Mucopolysaccharidosis I
• Other Study ID Numbers: ALID-017-03