search
Back to results

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

Primary Purpose

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

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Aldurazyme
Aldurazyme
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

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

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

Sites / Locations

  • University of South Alabama
  • Emory University School of Medicine
  • University of Rochester
  • University of North Carolina at Chapel Hill
  • Toledo Children's Hospital
  • Merle West Medical Center
  • The Childrens Hospital of Philadelphia
  • Rhode Island Hospital
  • Hospital Universatario de Universidade Federal de Santa Catarina
  • Hospital Infantil Joana de Gusmao
  • The Hospital for Sick Children
  • Alberta Children's Hospital
  • Children's Hospital Klinikum Nord Heidberg
  • Medizinishe Hochshule Hannover
  • Children's Hospital at the University Hospital of Heidelberg
  • Children's Hospital Klinikum der F.S. Universitat
  • Catholic University Sacro Cuore
  • Academisch Ziekenhuis Rotterdam
  • Blackpool Victoria Hospital
  • Belfast City Hospital
  • Birmingham Children's Hospital
  • Bristol Royal Hospital for Children and Frenchay Hospital
  • Gartnavel Hospital
  • Great Ormond Street Hospital for Sick Children and NHS Trust
  • Royal Victoria Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Placebo/Aldurazyme

Aldurazyme/Aldurazyme

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

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.
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.
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.
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.

Full Information

First Posted
September 2, 2005
Last Updated
March 17, 2015
Sponsor
Genzyme, a Sanofi Company
Collaborators
BioMarin/Genzyme LLC
search

1. Study Identification

Unique Protocol Identification Number
NCT00146770
Brief Title
Phase 3 Extension Study of the Safety and Efficacy of Aldurazyme® (Laronidase) in Mucopolysaccharidosis I (MPS I) Patients
Official Title
A Multicenter, Multinational, Open-Label Extension Study of the Safety and Efficacy of Aldurazyme® (Laronidase) in Patients With Mucopolysaccharidosis I
Study Type
Interventional

2. Study Status

Record Verification Date
March 2015
Overall Recruitment Status
Completed
Study Start Date
May 2001 (undefined)
Primary Completion Date
March 2005 (Actual)
Study Completion Date
March 2005 (Actual)

3. Sponsor/Collaborators

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

4. Oversight

5. 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.

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
45 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo/Aldurazyme
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Aldurazyme/Aldurazyme
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
Aldurazyme
Intervention Description
Placebo for 26 weeks then 0.58 mg/kg Aldurazyme every week for 182 weeks
Intervention Type
Biological
Intervention Name(s)
Aldurazyme
Intervention Description
0.58 mg/kg Aldurazyme every week for 208 weeks
Intervention Type
Biological
Intervention Name(s)
placebo
Intervention Description
Placebo for 26 weeks
Primary Outcome Measure Information:
Title
Change From Baseline to Week 182 in Percent Predicted Forced Vital Capacity (FVC)
Description
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.
Time Frame
Baseline to Week 182
Title
Change From Baseline to Week 182 in Six Minute Walk Test (6MWT)
Description
Six Minute Walk Test: Distance walked (measured in Meters) in 6 minutes. A longer distance indicates a greater response.
Time Frame
Baseline to Week 182
Secondary Outcome Measure Information:
Title
Change From Baseline to Week 182 in Apnea/Hypopnea Index (AHI)
Description
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.
Time Frame
Baseline to Week 182
Title
Change From Baseline to Week 182 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 182
Title
Change From Baseline to Week 182 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 182
Title
Change From Baseline to Week 182 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 Week182
Other Pre-specified Outcome Measures:
Title
Change From Baseline to Week 182 in Urinary GAG Level
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 182

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
Eligibility 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
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:
Facility Name
University of South Alabama
City
Mobile
State/Province
Alabama
ZIP/Postal Code
36604
Country
United States
Facility Name
Emory University School of Medicine
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
University of Rochester
City
Rochester
State/Province
New York
ZIP/Postal Code
14542
Country
United States
Facility Name
University of North Carolina at Chapel Hill
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
Toledo Children's Hospital
City
Toledo
State/Province
Ohio
ZIP/Postal Code
43606
Country
United States
Facility Name
Merle West Medical Center
City
Klamath Falls
State/Province
Oregon
ZIP/Postal Code
97601
Country
United States
Facility Name
The Childrens Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Rhode Island Hospital
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02903
Country
United States
Facility Name
Hospital Universatario de Universidade Federal de Santa Catarina
City
Florianopolis
ZIP/Postal Code
88040-500
Country
Brazil
Facility Name
Hospital Infantil Joana de Gusmao
City
Florianopolis
ZIP/Postal Code
CEP 88025-301
Country
Brazil
Facility Name
The Hospital for Sick Children
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 1X8
Country
Canada
Facility Name
Alberta Children's Hospital
City
Calgary
ZIP/Postal Code
T2T 5C7
Country
Canada
Facility Name
Children's Hospital Klinikum Nord Heidberg
City
Hamburg
ZIP/Postal Code
22143
Country
Germany
Facility Name
Medizinishe Hochshule Hannover
City
Hannover
ZIP/Postal Code
30625
Country
Germany
Facility Name
Children's Hospital at the University Hospital of Heidelberg
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
Facility Name
Children's Hospital Klinikum der F.S. Universitat
City
Jena
ZIP/Postal Code
07740
Country
Germany
Facility Name
Catholic University Sacro Cuore
City
Rome
ZIP/Postal Code
00168
Country
Italy
Facility Name
Academisch Ziekenhuis Rotterdam
City
Rotterdam
ZIP/Postal Code
3000 GR
Country
Netherlands
Facility Name
Blackpool Victoria Hospital
City
Blackpool
State/Province
Lancashire
ZIP/Postal Code
FY3 8NR
Country
United Kingdom
Facility Name
Belfast City Hospital
City
Belfast
ZIP/Postal Code
BT9 78A
Country
United Kingdom
Facility Name
Birmingham Children's Hospital
City
Birmingham
ZIP/Postal Code
B4 6NH
Country
United Kingdom
Facility Name
Bristol Royal Hospital for Children and Frenchay Hospital
City
Bristol
ZIP/Postal Code
BS16 1LE
Country
United Kingdom
Facility Name
Gartnavel Hospital
City
Glasgow
ZIP/Postal Code
G11 6NT
Country
United Kingdom
Facility Name
Great Ormond Street Hospital for Sick Children and NHS Trust
City
London
ZIP/Postal Code
WC1N 3GH
Country
United Kingdom
Facility Name
Royal Victoria Hospital
City
Newcastle upon Tyne
ZIP/Postal Code
NE1 4LB
Country
United Kingdom

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
PubMed Identifier
19117887
Citation
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.
Results Reference
derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs