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

A Randomized, Double-Blind, Placebo-Controlled, Multicenter, Multinational, Clinical Study of Recombinant Human Alpha L-Iduronidase In Patients With Mucopolysaccharidosis I

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

Study Overview

• Status: Completed
• Conditions: Mucopolysaccharidosis I; Hurler-Scheie Syndrome; Hurlers Syndrome
• Intervention / Treatment: Biological: Placebo; Biological: rhIDU (recombinant human-Alpha-L-Iduronidase)

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada
• Germany
  • Mainz, Germany
• United States
  • New York
    • New York, New York, United States
  • North Carolina
    • Chapel Hill, North Carolina, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; 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; 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.
Active Comparator: Aldurazyme treatment; 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); 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Change From Baseline to Week 26 in Apnea/Hypopnea Index (AHI)	Apnea/Hypopnea Index (AHI): Number of absent (apnea) and shallow (hypopnea) breaths per hour of sleep. Overall change from Baseline to Week 26 in AHI. A greater decrease in events indicates a greater response.	Baseline to Week 26
Overall Percent Change From Baseline to Week 26 in Liver Volume	Liver Organ Volume: Volume of liver measured by Magnetic Resonance Imaging (MRI). Greater decrease in volume indicates a greater response.	Baseline to Week 26
Overall Change From Baseline to Week 26 in Child Health Assessment Questionnaire/Health Assessment Questionnaire (CHAQ/HAQ) Disability Index Score	CHAQ/HAQ) = Patient questionnaire that measures the degree of disability on a scale of 0 (no disability) to 3 (maximal disability). A lower score indicates a greater response.	Baseline to week 26
Overall Change From Baseline to Week 26 in Active Joint Range of Motion (ROM)	Active Joint Range of Motion (ROM): Shoulder Flexion Ability to maximally raise one's arm overhead without assistance. Shoulder range of motion (mean of left and right arms) measured in degrees (0-180) by goniometry. Greater degree of flexion indicates greater response.	Baseline to Week 26
Overall Percent Change From Baseline to Week 26 in Urinary Glycosaminoglycan (GAG) Levels	Urinary Glycosaminoglycan (GAG) Levels: Concentration of GAG relative to creatinine in urine. A greater decrease in GAG level indicates a greater response.	Baseline to Week 26

Collaborators and Investigators

• Sponsor: Genzyme, a Sanofi Company
• Collaborators: BioMarin/Genzyme LLC

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: December 1, 2000
• Primary Completion (Actual): September 1, 2001
• Study Completion (Actual): September 1, 2001

Study Registration Dates

• First Submitted: June 2, 2009
• First Submitted That Met QC Criteria: June 2, 2009
• First Posted (Estimate): June 3, 2009

Study Record Updates

• Last Update Posted (Estimate): April 7, 2015
• Last Update Submitted That Met QC Criteria: March 19, 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-003-99