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Completed

NCT Number: NCT00146757

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

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.

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Key information

Conditions

Mucopolysaccharidosis I Carbohydrate Metabolism, Inborn Errors Congenital, Hereditary, and Neonatal Diseases and Abnormalities Connective Tissue Diseases Genetic Diseases, Inborn Hurler Syndrome Hurler-Scheie Syndrome Lysosomal Storage Diseases Metabolic Diseases Metabolism, Inborn Errors Mucinoses Mucopolysaccharidoses Nutritional and Metabolic Diseases Scheie Syndrome Skin and Connective Tissue Diseases

Age range

Up to 5 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Hôpital E. Herriot, Lyon, France

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Aldurazyme (Recombinant Human Alpha-L-Iduronidase)

Biological

100 U/kg every week

Primary outcomes

  1. 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.

  2. Pharmacokinetics - Area Under the (Plasma Concentration-time) Curve (AUC∞)

    Time frame: 52 weeks

    AUC∞ is a measure of the total exposure to a drug.

  3. 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%.

  4. Pharmacokinetics - Total Plasma Clearance (CL)

    Time frame: 52 weeks

    CL is volume of the body fluid cleared of the drug per unit of time.

  5. 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 outcomes

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

Sponsors and collaborators

Lead sponsor

Genzyme, a Sanofi Company

Industry

Collaborators

  • BioMarin/Genzyme LLC

Registry information

Official study 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

Important dates

Study start
2002
Primary completion
2005
Study completion
2005
First posted
Sep 7, 2005
Registry last updated
Apr 3, 2015

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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