Try our beta test site
IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...

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

This study has been completed.
BioMarin/Genzyme LLC
Information provided by:
Sanofi Identifier:
First received: September 2, 2005
Last updated: March 17, 2015
Last verified: March 2015
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
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 Sanofi:

Primary Outcome Measures:
  • Safety Evaluation [ Time Frame: 52 weeks ]
    Overall Safety Summary of Adverse Events (AEs) during Treatment Safety assessment was based on the incidence of AE reports.

  • Pharmacokinetics - Area Under the (Plasma Concentration-time) Curve (AUC∞) [ Time Frame: 52 weeks ]
    AUC∞ is a measure of the total exposure to a drug.

  • Pharmacokinetics - Elimination Half Life (t1/2) [ Time Frame: 52 weeks ]
    Half-life is the time it takes for the concentration of drug in plasma to decline by 50%.

  • Pharmacokinetics - Total Plasma Clearance (CL) [ Time Frame: 52 weeks ]
    CL is volume of the body fluid cleared of the drug per unit of time.

  • Pharmacokinetics - Volume of Distribution (Vz) [ Time Frame: 52 weeks ]
    Vz is the volume that relates the amount of drug in the body after absorption is complete to the concentration of drug in the plasma.

Other Outcome Measures:
  • Percent Change From Baseline to Week 52 in Urinary Glycosaminoglycan (uGAG) Level [ Time Frame: Baseline to 52 weeks ]
    Percentage change in the concentration of GAG relative to creatinine (ug GAG/mg creatinine) in urine from Baseline to Week 52; A greater decrease in percent change indicates a greater response.

  • Percent Change From Baseline to Week 52 in Liver Size (Hepatomegaly) [ Time Frame: Baseline to 52 weeks ]
    Percent change in extent of Liver Edge Below Right Costal Margin (BRCM) measured in centimeters from Baseline to Week 52; A greater decrease in percent change indicates a greater response.

  • Change From Baseline to Week 52 in Apnea/Hypopnea Index (AHI) [ Time Frame: Baseline to 52 weeks ]
    Number of absent (apnea) and shallow (hypopnea) breaths per hour of sleep. A greater decrease in events per hour indicates a greater response.

  • Expert Global Assessment of Sleep Study Results at Week 52 Compared With Baseline [ Time Frame: Baseline to 52 weeks ]
    Independent experts provided a global assessment for each sleep study visit as well as the degree of clinically meaningful change over the course of the study. Assessment was based on AHI, severity and frequency of oxygen desaturations and sleep quality.

  • Change From Baseline to Week 52 in Left Ventricular Mass (LVM) Z-Score [ Time Frame: Baseline to 52 weeks ]
    Change in LVM Z-scores as measured by echocardiography from Baseline to Week 52. Z-score=number of standard deviations from mean. Z-scores greater than +2 and less than -2 are abnormal. A greater decrease in abnormally high z-score indicates a greater response.

  • Change From Baseline to Week 52 in Height [ Time Frame: Baseline to 52 weeks ]
    Change in Z-scores for standing height/lying-length-for-age from Baseline to Week 52. Z-score=number of standard deviations from mean. Z-scores greater than +2 and less than -2 are abnormal. A greater decrease in abnormally high z-score indicates a greater response.

  • Investigator's Clinical Assessment at Week 52 Compared With Baseline [ Time Frame: Baseline to 52 weeks ]
    The Investigator's impression of the patient's overall clinical status at Week 52 compared with Baseline.

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)


Ages Eligible for Study:   up to 5 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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 identifier: NCT00146757

Hôpital E. Herriot
Lyon, France
Johannes Gutenberg Universität
Kinderklinik, Mainz, Germany
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
Study Director: Medical Monitor Genzyme, a Sanofi Company
  More Information

Responsible Party: Medical Monitor, Genzyme Corporation 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: March 17, 2015

Additional relevant MeSH terms:
Mucopolysaccharidosis I
Pathologic Processes
Carbohydrate Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lysosomal Storage Diseases
Connective Tissue Diseases
Metabolic Diseases processed this record on May 24, 2017