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

• Sponsor: Genzyme, a Sanofi Company
• Collaborator: BioMarin/Genzyme LLC
• Information provided by: Sanofi

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Mucopolysaccharidosis I; Hurler's Syndrome; Hurler-Scheie Syndrome; Scheie Syndrome	Biological: Aldurazyme; Biological: placebo	Phase 3

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	45 participants
Allocation:	Non-Randomized
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	A Multicenter, Multinational, Open-Label Extension Study of the Safety and Efficacy of Aldurazyme® (Laronidase) in Patients With Mucopolysaccharidosis I
Study Start Date :	May 2001
Actual Primary Completion Date :	March 2005
Actual Study Completion Date :	March 2005

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Placebo/Aldurazyme; 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; Placebo for 26 weeks then 0.58 mg/kg Aldurazyme every week for 182 weeks; Biological: placebo; Placebo for 26 weeks
Active Comparator: Aldurazyme/Aldurazyme; 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; 0.58 mg/kg Aldurazyme every week for 208 weeks

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline to Week 182 in Percent Predicted Forced Vital Capacity (FVC) [ Time Frame: Baseline to Week 182 ]
   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.
2. Change From Baseline to Week 182 in Six Minute Walk Test (6MWT) [ Time Frame: Baseline to Week 182 ]
   Six Minute Walk Test: Distance walked (measured in Meters) in 6 minutes. A longer distance indicates a greater response.

Secondary Outcome Measures :

1. Change From Baseline to Week 182 in Apnea/Hypopnea Index (AHI) [ Time Frame: Baseline to Week 182 ]
   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.
2. Change From Baseline to Week 182 in Liver Volume [ Time Frame: Baseline to Week 182 ]
   Liver Organ Volume: Volume of liver measured by Magnetic Resonance Imaging (MRI). Greater decrease in volume indicates a greater response.
3. Change From Baseline to Week 182 in Child Health Assessment Questionnaire/Health Assessment Questionnaire (CHAQ/HAQ) Disability Index Score [ Time Frame: Baseline to Week 182 ]
   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.
4. Change From Baseline to Week 182 in Active Joint Range of Motion (ROM) [ Time Frame: Baseline to Week182 ]
   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.

Other Outcome Measures:

1. Change From Baseline to Week 182 in Urinary GAG Level [ Time Frame: Baseline to Week 182 ]

   Urinary Glycosaminoglycan (GAG) Levels:

   >> Concentration of GAG relative to creatinine in urine. A greater decrease in GAG level indicates a greater response.

Eligibility Criteria

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Ages Eligible for Study:	Child, Adult, Older Adult
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

  Show 25 Study Locations

Sponsors and Collaborators

Genzyme, a Sanofi Company

BioMarin/Genzyme LLC

Investigators

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Study Director:	Medical Monitor	Genzyme, a Sanofi Company

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Clarke LA, Wraith JE, Beck M, Kolodny EH, Pastores GM, Muenzer J, Rapoport DM, Berger KI, Sidman M, Kakkis ED, Cox GF. Long-term efficacy and safety of laronidase in the treatment of mucopolysaccharidosis I. Pediatrics. 2009 Jan;123(1):229-40. doi: 10.1542/peds.2007-3847.

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Responsible Party:	Medical Monitor, Genzyme Corporation
ClinicalTrials.gov Identifier:	NCT00146770 History of Changes
Other Study ID Numbers:	ALID-006-01
First Posted:	September 7, 2005
Results First Posted:	June 16, 2009
Last Update Posted:	April 3, 2015
Last Verified:	March 2015

Additional relevant MeSH terms:

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Syndrome; Mucopolysaccharidoses; Mucopolysaccharidosis I; Disease; Pathologic Processes; Carbohydrate Metabolism, Inborn Errors	Metabolism, Inborn Errors; Genetic Diseases, Inborn; Lysosomal Storage Diseases; Mucinoses; Connective Tissue Diseases; Metabolic Diseases