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

Phase 3

Completed

• Conditions: Hurlers Syndrome; Mucopolysaccharidosis I; Hurler-Scheie Syndrome
• Interventions: Biological: Placebo; Biological: rhIDU (recombinant human-Alpha-L-Iduronidase)

• Registration Number: NCT00912925
• Lead Sponsor: Genzyme, a Sanofi Company

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study Start: 2000-12
• Primary Completion: 2001-09
• Study Completion: 2001-09
• Study First Submitted: 2009-06-02
• Study First Submitted QC: 2009-06-02
• Study First Posted: 2009-06-03
• Results First Submitted: 2009-07-02
• Results First Submitted QC: 2009-07-07
• Results First Posted: 2009-08-19
• Status Verified: 2015-03
• Last Update Submitted: 2015-03-19
• Last Update Posted: 2015-04-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 45

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	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.
Aldurazyme treatment	rhIDU (recombinant human-Alpha-L-Iduronidase)	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.

Primary Outcome Measures

Name	Time	Method
Overall Change From Baseline to Week 26 in Six Minute Walk Test (6MWT)	Baseline to Week 26	Six Minute Walk Test (6MWT): Distance walked (measured in meters) in 6 minutes. A longer distance indicates a greater response.
Overall Change From Baseline to Week 26 in Percent Predicted Forced Vital Capacity (FVC)	Baseline to Week 26	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.

Secondary Outcome Measures

Name	Time	Method
Overall Change From Baseline to Week 26 in Apnea/Hypopnea Index (AHI)	Baseline to Week 26	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.
Overall Percent Change From Baseline to Week 26 in Liver Volume	Baseline to Week 26	Liver Organ Volume: Volume of liver measured by Magnetic Resonance Imaging (MRI). Greater decrease in volume indicates a greater response.
Overall Change From Baseline to Week 26 in Child Health Assessment Questionnaire/Health Assessment Questionnaire (CHAQ/HAQ) Disability Index Score	Baseline to week 26	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.
Overall Change From Baseline to Week 26 in Active Joint Range of Motion (ROM)	Baseline to Week 26	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.
Overall Percent Change From Baseline to Week 26 in Urinary Glycosaminoglycan (GAG) Levels	Baseline to Week 26	Urinary Glycosaminoglycan (GAG) Levels: Concentration of GAG relative to creatinine in urine. A greater decrease in GAG level indicates a greater response.