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

A Multicenter, Multinational, Open-Label Extension Study of the Safety and Efficacy of Aldurazyme® (Laronidase) in Patients With Mucopolysaccharidosis I

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.

Study Overview

• Status: Completed
• Conditions: Mucopolysaccharidosis I; Scheie Syndrome; Hurler's Syndrome; Hurler-Scheie Syndrome
• Intervention / Treatment: Biological: Aldurazyme; Biological: Aldurazyme; Biological: placebo

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • Florianopolis, Brazil, 88040-500
    • Hospital Universatario de Universidade Federal de Santa Catarina
  • Florianopolis, Brazil, CEP 88025-301
    • Hospital Infantil Joana de Gusmão
• Canada
  • Calgary, Canada, T2T 5C7
    • Alberta Children's Hospital
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • The Hospital for Sick Children
• Germany
  • Hamburg, Germany, 22143
    • Children's Hospital Klinikum Nord Heidberg
  • Hannover, Germany, 30625
    • Medizinishe Hochshule Hannover
  • Heidelberg, Germany, 69120
    • Children's Hospital at the University Hospital of Heidelberg
  • Jena, Germany, 07740
    • Children's Hospital Klinikum der F.S. Universitat
• Italy
  • Rome, Italy, 00168
    • Catholic University Sacro Cuore
• Netherlands
  • Rotterdam, Netherlands, 3000 GR
    • Academisch Ziekenhuis Rotterdam
• United Kingdom
  • Belfast, United Kingdom, BT9 78A
    • Belfast City Hospital
  • Birmingham, United Kingdom, B4 6NH
    • Birmingham Children's Hospital
  • Bristol, United Kingdom, BS16 1LE
    • Bristol Royal Hospital for Children and Frenchay Hospital
  • Glasgow, United Kingdom, G11 6NT
    • Gartnavel Hospital
  • London, United Kingdom, WC1N 3GH
    • Great Ormond Street Hospital for Sick Children and NHS Trust
  • Newcastle upon Tyne, United Kingdom, NE1 4LB
    • Royal Victoria Hospital
  • Lancashire
    • Blackpool, Lancashire, United Kingdom, FY3 8NR
      • Blackpool Victoria Hospital
• United States
  • Alabama
    • Mobile, Alabama, United States, 36604
      • University of South Alabama
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University School of Medicine
  • New York
    • Rochester, New York, United States, 14542
      • University of Rochester
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina at Chapel Hill
  • Ohio
    • Toledo, Ohio, United States, 43606
      • Toledo Children's Hospital
  • Oregon
    • Klamath Falls, Oregon, United States, 97601
      • Merle West Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • The Childrens Hospital of Philadelphia
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / 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: Aldurazyme; 0.58 mg/kg Aldurazyme every week for 208 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; Placebo for 26 weeks then 0.58 mg/kg Aldurazyme every week for 182 weeks; Biological: Aldurazyme; 0.58 mg/kg Aldurazyme every week for 208 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline to Week 182
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.	Baseline to Week 182

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline to Week 182
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.	Baseline to Week 182
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.	Baseline to Week 182
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.	Baseline to Week182

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Week 182 in Urinary GAG Level	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 182

Collaborators and Investigators

• Sponsor: Genzyme, a Sanofi Company
• Collaborators: BioMarin/Genzyme LLC

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: May 1, 2001
• Primary Completion (ACTUAL): March 1, 2005
• Study Completion (ACTUAL): March 1, 2005

Study Registration Dates

• First Submitted: September 2, 2005
• First Submitted That Met QC Criteria: September 2, 2005
• First Posted (ESTIMATE): September 7, 2005

Study Record Updates

• Last Update Posted (ESTIMATE): April 3, 2015
• Last Update Submitted That Met QC Criteria: March 17, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Disease; Genetic Diseases, Inborn; Connective Tissue Diseases; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Mucinoses; Syndrome; Mucopolysaccharidoses; Mucopolysaccharidosis I
• Other Study ID Numbers: ALID-006-01