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A Study Evaluating the Safety and Pharmacokinetics of Aldurazyme® (Laronidase) in MPS I Patients Less Than 5 Years Old

This study has been completed.
Sponsor:
Collaborator:
BioMarin/Genzyme LLC
Information provided by:
Genzyme, a Sanofi Company
ClinicalTrials.gov Identifier:
NCT00146757
First received: September 2, 2005
Last updated: August 20, 2009
Last verified: April 2009
  Purpose

The main objectives of this study are to evaluate the safety and pharmacokinetics (PK) of enzyme replacement therapy with recombinant human alpha-L-iduronidase [Aldurazyme® (laronidase)] in mucopolysaccharidosis I (MPS I) patients less than 5 years old. Efficacy measurements will also be evaluated in this study.


Condition Intervention Phase
Mucopolysaccharidosis I
Hurler Syndrome
Hurler-Scheie Syndrome
Scheie Syndrome
Biological: Aldurazyme (Recombinant Human Alpha-L-Iduronidase)
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Open-Label Clinical Trial of Recombinant Human Alpha-L-iduronidase (Aldurazyme®) to Evaluate the Safety and Pharmacokinetics in Mucopolysaccharidosis I (MPS I) Patients Less Than 5 Years Old

Resource links provided by NLM:


Further study details as provided by Genzyme, a Sanofi Company:

Primary Outcome Measures:
  • Safety Evaluation [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]
  • Pharmacokinetics - Area Under the (Plasma Concentration-time) Curve (AUC∞) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Pharmacokinetics - Elimination Half Life (t1/2) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Pharmacokinetics - Total Plasma Clearance (CL) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Pharmacokinetics - Volume of Distribution (Vz) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]

Enrollment: 20
Study Start Date: October 2002
Study Completion Date: May 2005
Primary Completion Date: May 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Aldurazyme (rhIDU) 100 U/kg ONLY every week
Patients received Aldurazyme (recombinant human alpha-L-iduronidase (rhIDU)) once per week at a dose of 100 Units/kg (approximately 0.58 mg/kg) for up to 52 weeks - labeled dose.
Biological: Aldurazyme (Recombinant Human Alpha-L-Iduronidase)
100 U/kg every week
Experimental: Aldurazyme (rhIDU) 100-200 U/kg every week
After receiving 100 Units/kg dose of Aldurazyme (rhIDU) for the first 25 weeks, patients enrolling after January 1, 2004 were eligible to receive an increased dose of 200 Units/kg from Week 26 onwards if the patient's urinary glycosaminoglycan (uGAG) levels were >200µg/mg creatinine at Week 22.
Biological: Aldurazyme (Recombinant Human Alpha-L-Iduronidase)
200 U/kg every week (Week 26 onwards)

  Eligibility

Ages Eligible for Study:   up to 5 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Written informed consent is required from the parent(s) or legal guardian(s) prior to any protocol-related procedures being performed. (A separate informed consent will be requested from the parent(s) for their genotyping, which is independent of the inclusion.)
  • Be less than 5 years of age at the time of enrollment.
  • Have confirmed iduronidase deficiency with a fibroblast or leukocyte alpha-L-iduronidase enzyme activity level of less than 10.0 % of the lower limit of the normal range, or below the detection range of the measuring laboratory.
  • Have a clinical diagnosis of MPS I based on genotyping.
  • Documentation in his/her medical record that the parent(s) or legal guardian(s) have had counseling or a consultation regarding HSCT in order to assure that the parent(s) or legal guardian(s) are fully informed regarding the risks and benefits of this alternative treatment for patients eligible for the trial and with the severe manifestations of MPS I with neurodegeneration.

Exclusion Criteria:

  • The patient is under consideration for or has undergone hematopoietic stem cell transplantation (HSCT).
  • The patient has acute hydrocephalus at the time of enrollment.
  • The patient has a clinically significant organic disease (with the exception of symptoms relating to MPS I) including: cardiovascular, hepatic, pulmonary, neurologic, or renal disease, other serious intercurrent illness, or extenuating circumstances that, in the opinion of the Investigator, would preclude participation in the trial or potentially decrease survival.
  • The patient has received any investigational product within 30 days prior to trial enrollment.
  • The patient has known severe hypersensitivity to Aldurazyme® (laronidase) or components of the delivery solution.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00146757

Locations
France
Hôpital E. Herriot
Lyon, France
Germany
Johannes Gutenberg Universität
Kinderklinik, Mainz, Germany
Netherlands
Sophia Children's Hospital
Rotterdam, Netherlands
United Kingdom
Willink Biochemical Genetics Unit Royal Hospital for Children
Manchester, United Kingdom
Sponsors and Collaborators
Genzyme, a Sanofi Company
BioMarin/Genzyme LLC
Investigators
Study Director: Medical Monitor Genzyme, a Sanofi Company
  More Information

Additional Information:
No publications provided

Responsible Party: Medical Monitor, Genzyme Corporation
ClinicalTrials.gov Identifier: NCT00146757     History of Changes
Other Study ID Numbers: ALID-014-02
Study First Received: September 2, 2005
Results First Received: November 20, 2008
Last Updated: August 20, 2009
Health Authority: European Union: European Medicines Agency

Additional relevant MeSH terms:
Mucopolysaccharidosis I
Mucopolysaccharidoses
Syndrome
Carbohydrate Metabolism, Inborn Errors
Connective Tissue Diseases
Disease
Genetic Diseases, Inborn
Lysosomal Storage Diseases
Metabolic Diseases
Metabolism, Inborn Errors
Mucinoses
Pathologic Processes

ClinicalTrials.gov processed this record on November 24, 2014