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

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

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

Conditions
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Mucopolysaccharidosis I, Hurlers Syndrome, Hurler-Scheie Syndrome

Intervention / Treatment
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* Biological: rhIDU (recombinant human-Alpha-L-Iduronidase)
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 5 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>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<br>* 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.<br>|
| Active Comparator: Aldurazyme treatment<br>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)<br>* 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.<br>|

What is the study measuring?
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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 |