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

Purpose

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	Intervention	Phase
Mucopolysaccharidosis I Hurler's Syndrome Hurler-Scheie Syndrome Scheie Syndrome	Biological: Aldurazyme Biological: placebo	Phase 3


Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: 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

Resource links provided by NLM:

Genetics Home Reference related topics: Schindler disease mucopolysaccharidosis type I

Drug Information available for: Laronidase

Genetic and Rare Diseases Information Center resources: Mucopolysaccharidosis Hurler Syndrome Mucopolysaccharidosis Type I Scheie Syndrome Hurlerâ€“Scheie Syndrome

U.S. FDA Resources

Further study details as provided by Sanofi:

Primary Outcome Measures:

Change From Baseline to Week 182 in Percent Predicted Forced Vital Capacity (FVC) [ Time Frame: Baseline to Week 182 ] [ Designated as safety issue: No ]
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.
Change From Baseline to Week 182 in Six Minute Walk Test (6MWT) [ Time Frame: Baseline to Week 182 ] [ Designated as safety issue: No ]
Six Minute Walk Test: Distance walked (measured in Meters) in 6 minutes. A longer distance indicates a greater response.

Secondary Outcome Measures:

Change From Baseline to Week 182 in Apnea/Hypopnea Index (AHI) [ Time Frame: Baseline to Week 182 ] [ Designated as safety issue: No ]
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.
Change From Baseline to Week 182 in Liver Volume [ Time Frame: Baseline to Week 182 ] [ Designated as safety issue: No ]
Liver Organ Volume: Volume of liver measured by Magnetic Resonance Imaging (MRI). Greater decrease in volume indicates a greater response.
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 ] [ Designated as safety issue: No ]
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.
Change From Baseline to Week 182 in Active Joint Range of Motion (ROM) [ Time Frame: Baseline to Week182 ] [ Designated as safety issue: No ]
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:

Change From Baseline to Week 182 in Urinary GAG Level [ Time Frame: Baseline to Week 182 ] [ Designated as safety issue: No ]
Urinary Glycosaminoglycan (GAG) Levels:

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


Enrollment:	45
Study Start Date:	May 2001
Study Completion Date:	March 2005
Primary Completion Date:	March 2005 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

Eligibility


Ages Eligible for Study:	Child, Adult, Senior
Genders Eligible for Study:	Both
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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00146770

Show 25 Study Locations

Sponsors and Collaborators

Genzyme, a Sanofi Company

BioMarin/Genzyme LLC

Investigators


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.


Responsible Party:	Medical Monitor, Genzyme Corporation
ClinicalTrials.gov Identifier:	NCT00146770 History of Changes
Other Study ID Numbers:	ALID-006-01
Study First Received:	September 2, 2005
Results First Received:	January 7, 2009
Last Updated:	March 17, 2015
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:


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

ClinicalTrials.gov processed this record on September 27, 2016