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

Mucopolysaccharidosis I Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00912925
• Other study ID #: ALID-003-99
• Status: Completed
• Phase: Phase 3
• First received: June 2, 2009
• Last updated: March 19, 2015
• Start date: December 2000
• Est. completion date: September 2001

Study information

• Verified date: March 2015
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationCanada: Health CanadaEuropean Union: European Medicines AgencyGermany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: September 2001
• Est. primary completion date: September 2001
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 5 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hurler-Scheie Syndrome
• Hurlers Syndrome
• Mucopolysaccharidoses
• Mucopolysaccharidosis I
• Syndrome

Intervention

Biological:
• rhIDU (recombinant human-Alpha-L-Iduronidase)
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.
• Placebo
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.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Genzyme, a Sanofi Company	BioMarin/Genzyme LLC

Countries where clinical trial is conducted

United States,  Canada,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No