search
Back to results

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

Primary Purpose

Mucopolysaccharidosis I, Hurlers Syndrome, Hurler-Scheie Syndrome

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
rhIDU (recombinant human-Alpha-L-Iduronidase)
Placebo
Sponsored by
Genzyme, a Sanofi Company
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Mucopolysaccharidosis I

Eligibility Criteria

5 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Active Comparator

Arm Label

Placebo

Aldurazyme treatment

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

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.
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.
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.
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.
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.

Full Information

First Posted
June 2, 2009
Last Updated
March 19, 2015
Sponsor
Genzyme, a Sanofi Company
Collaborators
BioMarin/Genzyme LLC
search

1. Study Identification

Unique Protocol Identification Number
NCT00912925
Brief Title
Clinical Study of Aldurazyme in Patients With Mucopolysaccharidosis (MPS) I
Official Title
A Randomized, Double-Blind, Placebo-Controlled, Multicenter, Multinational, Clinical Study of Recombinant Human Alpha L-Iduronidase In Patients With Mucopolysaccharidosis I
Study Type
Interventional

2. Study Status

Record Verification Date
March 2015
Overall Recruitment Status
Completed
Study Start Date
December 2000 (undefined)
Primary Completion Date
September 2001 (Actual)
Study Completion Date
September 2001 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Genzyme, a Sanofi Company
Collaborators
BioMarin/Genzyme LLC

4. Oversight

Data Monitoring Committee
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mucopolysaccharidosis I, Hurlers Syndrome, Hurler-Scheie Syndrome

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
45 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Arm Title
Aldurazyme treatment
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
rhIDU (recombinant human-Alpha-L-Iduronidase)
Intervention Description
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.
Intervention Type
Biological
Intervention Name(s)
Placebo
Intervention Description
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.
Primary Outcome Measure Information:
Title
Overall Change From Baseline to Week 26 in Percent Predicted Forced Vital Capacity (FVC)
Description
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.
Time Frame
Baseline to Week 26
Title
Overall Change From Baseline to Week 26 in Six Minute Walk Test (6MWT)
Description
Six Minute Walk Test (6MWT): Distance walked (measured in meters) in 6 minutes. A longer distance indicates a greater response.
Time Frame
Baseline to Week 26
Secondary Outcome Measure Information:
Title
Overall Change From Baseline to Week 26 in Apnea/Hypopnea Index (AHI)
Description
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.
Time Frame
Baseline to Week 26
Title
Overall Percent Change From Baseline to Week 26 in Liver Volume
Description
Liver Organ Volume: Volume of liver measured by Magnetic Resonance Imaging (MRI). Greater decrease in volume indicates a greater response.
Time Frame
Baseline to Week 26
Title
Overall Change From Baseline to Week 26 in Child Health Assessment Questionnaire/Health Assessment Questionnaire (CHAQ/HAQ) Disability Index Score
Description
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.
Time Frame
Baseline to week 26
Title
Overall Change From Baseline to Week 26 in Active Joint Range of Motion (ROM)
Description
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.
Time Frame
Baseline to Week 26
Title
Overall Percent Change From Baseline to Week 26 in Urinary Glycosaminoglycan (GAG) Levels
Description
Urinary Glycosaminoglycan (GAG) Levels: Concentration of GAG relative to creatinine in urine. A greater decrease in GAG level indicates a greater response.
Time Frame
Baseline to Week 26

10. Eligibility

Sex
All
Minimum Age & Unit of Time
5 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Monitor
Organizational Affiliation
Genzyme, a Sanofi Company
Official's Role
Study Director
Facility Information:
City
New York
State/Province
New York
Country
United States
City
Chapel Hill
State/Province
North Carolina
Country
United States
City
Vancouver
State/Province
British Columbia
Country
Canada
City
Mainz
Country
Germany

12. IPD Sharing Statement

Citations:
PubMed Identifier
33874971
Citation
Tandon PK, Kakkis ED. The multi-domain responder index: a novel analysis tool to capture a broader assessment of clinical benefit in heterogeneous complex rare diseases. Orphanet J Rare Dis. 2021 Apr 19;16(1):183. doi: 10.1186/s13023-021-01805-5.
Results Reference
derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs