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

NCT00146770 | Completed Phase 3 Results

• 1 other identifier: ALID-006-01
• Study Type: interventional
• Target: 45
• Locations: 7 countries
• Sites: 25

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.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (4)

• Change From Baseline to Week 182 in Apnea/Hypopnea Index (AHI)

  Baseline to Week 182

• Change From Baseline to Week 182 in Liver Volume

  Baseline to Week 182

• Change From Baseline to Week 182 in Child Health Assessment Questionnaire/Health Assessment Questionnaire (CHAQ/HAQ) Disability Index Score

  Baseline to Week 182

• Change From Baseline to Week 182 in Active Joint Range of Motion (ROM)

  Baseline to Week182

Other Outcomes (1)

• Change From Baseline to Week 182 in Urinary GAG Level

  Baseline to Week 182

Study Arms (2)

Placebo/Aldurazyme

ACTIVE COMPARATOR

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; Biological: placebo

Aldurazyme/Aldurazyme

ACTIVE COMPARATOR

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

Interventions

Aldurazyme BIOLOGICAL

Placebo for 26 weeks then 0.58 mg/kg Aldurazyme every week for 182 weeks

Placebo/Aldurazyme

placebo BIOLOGICAL

Placebo for 26 weeks

Placebo/Aldurazyme

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Genzyme, a Sanofi Company: lead
• BioMarin/Genzyme LLC: collaborator

Study Sites (25)

University of South Alabama

Mobile, Alabama, 36604, United States

Location

Emory University School of Medicine

Atlanta, Georgia, 30322, United States

Location

University of Rochester

Rochester, New York, 14542, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Toledo Children's Hospital

Toledo, Ohio, 43606, United States

Location

Merle West Medical Center

Klamath Falls, Oregon, 97601, United States

Location

The Childrens Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

Hospital Universatario de Universidade Federal de Santa Catarina

Florianópolis, 88040-500, Brazil

Location

Hospital Infantil Joana de Gusmao

Florianópolis, CEP 88025-301, Brazil

Location

The Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Alberta Children's Hospital

Calgary, T2T 5C7, Canada

Location

Children's Hospital Klinikum Nord Heidberg

Hamburg, 22143, Germany

Location

Medizinishe Hochshule Hannover

Hanover, 30625, Germany

Location

Children's Hospital at the University Hospital of Heidelberg

Heidelberg, 69120, Germany

Location

Children's Hospital Klinikum der F.S. Universitat

Jena, 07740, Germany

Location

Catholic University Sacro Cuore

Rome, 00168, Italy

Location

Academisch Ziekenhuis Rotterdam

Rotterdam, 3000 GR, Netherlands

Location

Blackpool Victoria Hospital

Blackpool, Lancashire, FY3 8NR, United Kingdom

Location

Belfast City Hospital

Belfast, BT9 78A, United Kingdom

Location

Birmingham Children's Hospital

Birmingham, B4 6NH, United Kingdom

Location

Bristol Royal Hospital for Children and Frenchay Hospital

Bristol, BS16 1LE, United Kingdom

Location

Gartnavel Hospital

Glasgow, G11 6NT, United Kingdom

Location

Great Ormond Street Hospital for Sick Children and NHS Trust

London, WC1N 3GH, United Kingdom

Location

Royal Victoria Hospital

Newcastle upon Tyne, NE1 4LB, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 33874971 DERIVED

• 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.

  PMID: 19117887 DERIVED

MeSH Terms

Conditions

Mucopolysaccharidosis I

Interventions

Iduronidase

Condition Hierarchy (Ancestors)

Mucopolysaccharidoses; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lysosomal Storage Diseases; Mucinoses; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Glycoside Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes

Limitations and Caveats

Rare disease with limited sample size, lack of control group.FVC calculations less reliable for patients whose height is below the 3rdpercent of general population.Height term used to calculate FVC may be influenced by joint contractures and posture.

Results Point of Contact

• Title: Genzyme Medical Information
• Organization: Genzyme Corporation

800-745-4447

Study Officials

• Medical Monitor

  Genzyme, a Sanofi Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: September 2, 2005
• First Posted: September 7, 2005
• Study Start: May 1, 2001
• Primary Completion: March 1, 2005
• Study Completion: March 1, 2005
• Last Updated: April 3, 2015
• Results First Posted: June 16, 2009

Record last verified: 2015-03

Locations

DE (4); IT (1); NL (1); CA (2); GB (7); US (8); BR (2)