Phase 3 Extension Study of the Safety and Efficacy of Aldurazyme® (Laronidase) in Mucopolysaccharidosis I (MPS I) Patients

Study Overview
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Brief Summary
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This study is being conducted to collect additional long-term efficacy and safety data of Aldurazyme® (laronidase) patients with MPS I disease. Patients who were previously enrolled in the Phase 3 Double-Blind Study will be enrolled in this study.

Official Title
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A Multicenter, Multinational, Open-Label Extension Study of the Safety and Efficacy of Aldurazyme® (Laronidase) in Patients With Mucopolysaccharidosis I

Conditions
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Scheie Syndrome, Mucopolysaccharidosis I, Hurler's Syndrome, Hurler-Scheie Syndrome

Intervention / Treatment
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* Biological: Aldurazyme
* Biological: Aldurazyme
* Biological: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patient or patient's legal guardian must provide written informed consent prior to any protocol-related procedures being performed. The patient must have successfully completed Study ALID-003-99 (who received 21 of 26 consecutive weekly infusions). The patient has not experienced any safety issues that would contraindicate participation in the Extension study. A female patient of childbearing potential must have a negative pregnancy test at entry Exclusion Criteria: The patient is pregnant or lactating. The patient has received an investigational drug within 30 days prior to the study enrollment. The patient has a medical condition, serious intercurrent illness, or other extenuating circumstance that may significantly interfere with study compliance including all prescribed evaluations and follow-up activities
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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Placebo/Aldurazyme<br>Patients received placebo for 26 weeks in the Double-Blind Study then received 182 weeks of Aldurazyme (0.58 mg/kg every week) in this Extension Study; patients received a total of 182 weeks of Aldurazyme. | Biological: Aldurazyme<br>* Placebo for 26 weeks then 0.58 mg/kg Aldurazyme every week for 182 weeks<br>Biological: placebo<br>* Placebo for 26 weeks<br>|
| Active Comparator: Aldurazyme/Aldurazyme<br>Patients received 26 weeks of Aldurazyme in the Double-Blind Study and then received 182 weeks of Aldurazyme in this Extension Study; patients received a total of 208 weeks of Aldurazyme. | Biological: Aldurazyme<br>* 0.58 mg/kg Aldurazyme every week for 208 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 182 in Percent Predicted Forced Vital Capacity (FVC) | Percent Predicted Forced Vital Capacity: the maximal exhaled breath volume following a maximal inhaled breath. Overall change from Baseline to Week 182 in percent predicted FVC = (observed value)/(predicted value) * 100%). A higher value indicates a greater response. | Baseline to Week 182 | 
| Change From Baseline to Week 182 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 Week 182 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 182 in Apnea/Hypopnea Index (AHI) | Apnea/Hypopnea Index (AHI): Number of absent (apnea) and shallow (hypopnea) breaths per hour of sleep. A greater decrease in events indicates a greater response. | Baseline to Week 182 | 
| Change From Baseline to Week 182 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 182 | 
| Change From Baseline to Week 182 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 182 | 
| Change From Baseline to Week 182 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 Week182 |