Clinical Study of Aldurazyme in Patients With Mucopolysaccharidosis (MPS) I

NCT00912925 | Completed Phase 3 Results

• 1 other identifier: ALID-003-99
• Study Type: interventional
• Target: 45
• Locations: 3 countries
• Sites: 4

Brief Summary

This study is being conducted to demonstrate the safety and clinical efficacy of Aldurazyme treatment in MPS I patients

Conditions

Mucopolysaccharidosis I; Hurlers Syndrome; Hurler-Scheie Syndrome

Outcome Measures

Primary Outcomes (2)

• Overall Change From Baseline to Week 26 in Percent Predicted Forced Vital Capacity (FVC)

  Percent Predicted Forced Vital Capacity (FVC): the maximal exhaled breathe volume following a maximal inhaled breath. Overall Change from Baseline to Week 26 in percent predicted FVC = (observed value)/(predicted value) \* 100%). A higher value indicates a greater response.

  Baseline to Week 26

• Overall Change From Baseline to Week 26 in Six Minute Walk Test (6MWT)

  Six Minute Walk Test (6MWT): Distance walked (measured in meters) in 6 minutes. A longer distance indicates a greater response.

  Baseline to Week 26

Secondary Outcomes (5)

• Overall Change From Baseline to Week 26 in Apnea/Hypopnea Index (AHI)

  Baseline to Week 26

• Overall Percent Change From Baseline to Week 26 in Liver Volume

  Baseline to Week 26

• Overall Change From Baseline to Week 26 in Child Health Assessment Questionnaire/Health Assessment Questionnaire (CHAQ/HAQ) Disability Index Score

  Baseline to week 26

• Overall Change From Baseline to Week 26 in Active Joint Range of Motion (ROM)

  Baseline to Week 26

• Overall Percent Change From Baseline to Week 26 in Urinary Glycosaminoglycan (GAG) Levels

  Baseline to Week 26

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Patients in the placebo-control group were administered a solution of 100 millimolar (mM) sodium phosphate, 150 mM sodium chloride, and 0.001% polysorbate-80, adjusted to a pH of 5.8 administered intravenously over approximately 4 hours once weekly for 26 weeks.

Biological: Placebo

Aldurazyme treatment

ACTIVE COMPARATOR

Patients in the active treatment group received Aldurazyme intravenously at a dose of 100 Units/kg (approximately 0.58 mg/kg = labeled dose) administered intravenously over approximately 4 hours once weekly for 26 weeks.

Biological: rhIDU (recombinant human-Alpha-L-Iduronidase)

Interventions

rhIDU (recombinant human-Alpha-L-Iduronidase) BIOLOGICAL

Patients in the active treatment group received Aldurazyme intravenously at a dose of 100 units/kg (approximately 0.58mg/kg) administered intravenously over approximately 4 hours once weekly for 26 weeks.

Aldurazyme treatment

Placebo BIOLOGICAL

Patients in the Placebo-control group were administered a solution of 100mM sodium phosphate , 150mM sodium chloride, and 0.001% polysorbate-80, adjusted to a pH of 5.8 administered intravenously over a time period of approximately 4 hours once weekly for 26 weeks.

Placebo

Eligibility Criteria

• Age: 5 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• The patient had a documented diagnosis of MPS I confirmed by measurable clinical signs and symptoms of MPS I and a fibroblast or leukocyte alpha-L-iduronidase enzyme activity level of less than 10% of the lower limit of the normal range of the measuring laboratory.
• Female patients of childbearing potential had a negative pregnancy test (urine-beta-human chorionic gonadotropin (hCG)) at baseline (all female patients of childbearing potential and sexually mature male patients were advised to use a medically accepted method of contraception throughout the study).
• The patient was capable of standing independently for 6 minutes and walking a minimum of 5 meters within 6 minutes.
• The patient was capable of performing a reproducible FVC maneuver.
• The patient had a baseline FVC value that was less than or equal to 80% of the patient's predicted normal FVC value based on polgar predicted values for standing height for children 5 through 7 years of age and the Hankinson predicted values for ages 8 and above.

You may not qualify if:

• The patient had undergone a tracheostomy.
• The patient had previously undergone a bone marrow transplantation.
• The patient was pregnant or lactating.
• The patient has received an investigational drug within 30 days prior to study enrollment.
• The patient had a medical condition, serious intercurrent illness, or other extenuating circumstance that could have significantly interfered with study compliance including all prescribing evaluations and follow-up activities.
• The patient had a known hypersensitivity to rhIDU or to components of the active or placebo test solutions.

Sponsors & Collaborators

• Genzyme, a Sanofi Company: lead
• BioMarin/Genzyme LLC: collaborator

Study Sites (4)

Unknown Facility

New York, New York, United States

Location

Unknown Facility

Chapel Hill, North Carolina, United States

Location

Unknown Facility

Vancouver, British Columbia, Canada

Location

Unknown Facility

Mainz, Germany

Location

Related Publications (1)

• Tandon PK, Kakkis ED. The multi-domain responder index: a novel analysis tool to capture a broader assessment of clinical benefit in heterogeneous complex rare diseases. Orphanet J Rare Dis. 2021 Apr 19;16(1):183. doi: 10.1186/s13023-021-01805-5.

  PMID: 33874971 DERIVED

MeSH Terms

Conditions

Mucopolysaccharidosis I

Condition Hierarchy (Ancestors)

Mucopolysaccharidoses; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lysosomal Storage Diseases; Mucinoses; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Limitations and Caveats

Rare disease with limited sample size, FVC calculations less reliable for patients whose height is below the 3rd% for general population.

Results Point of Contact

• Title: Genzyme Medical Information
• Organization: Genzyme Corporation

medinfo@genzyme.com

Study Officials

• Medical Monitor

  Genzyme, a Sanofi Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: June 2, 2009
• First Posted: June 3, 2009
• Study Start: December 1, 2000
• Primary Completion: September 1, 2001
• Study Completion: September 1, 2001
• Last Updated: April 7, 2015
• Results First Posted: August 19, 2009

Record last verified: 2015-03

Locations

DE (1); CA (1); US (2)