Clinical trial NCT00146757: A Study Evaluating the Safety and Pharmacokinetics of Aldurazyme® (Laronidase) in MPS I Patients Less Than 5 Years Old
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Mucopolysaccharidosis I
Hurler Syndrome
Hurler-Scheie Syndrome
Scheie Syndrome
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: BioMarin/Genzyme LLC
First posted: 2005-09-07
Enrollment: 20
Sex: ALL
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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.

Primary outcomes:
measure: Safety Evaluation
timeFrame: 52 weeks
measure: Pharmacokinetics - Area Under the (Plasma Concentration-time) Curve (AUC∞)
timeFrame: 52 weeks
measure: Pharmacokinetics - Elimination Half Life (t1/2)
timeFrame: 52 weeks
measure: Pharmacokinetics - Total Plasma Clearance (CL)
timeFrame: 52 weeks
measure: Pharmacokinetics - Volume of Distribution (Vz)
timeFrame: 52 weeks
Secondary outcomes:
Other outcomes:
measure: Percent Change From Baseline to Week 52 in Urinary Glycosaminoglycan (uGAG) Level
timeFrame: Baseline to 52 weeks
measure: Percent Change From Baseline to Week 52 in Liver Size (Hepatomegaly)
timeFrame: Baseline to 52 weeks
measure: Change From Baseline to Week 52 in Apnea/Hypopnea Index (AHI)
timeFrame: Baseline to 52 weeks
measure: Expert Global Assessment of Sleep Study Results at Week 52 Compared With Baseline
timeFrame: Baseline to 52 weeks
measure: Change From Baseline to Week 52 in Left Ventricular Mass (LVM) Z-Score
timeFrame: Baseline to 52 weeks
measure: Change From Baseline to Week 52 in Height
timeFrame: Baseline to 52 weeks
measure: Investigator's Clinical Assessment at Week 52 Compared With Baseline
timeFrame: Baseline to 52 weeks
Locations:
city: Lyon
country: France
facility: Hôpital E. Herriot
city: Kinderklinik
country: Germany
facility: Johannes Gutenberg Universität
state: Mainz
city: Rotterdam
country: Netherlands
facility: Sophia Children's Hospital
city: Manchester
country: United Kingdom
facility: Willink Biochemical Genetics Unit Royal Hospital for Children
Study officials:
affiliation: Genzyme, a Sanofi Company
name: Medical Monitor
role: STUDY_DIRECTOR
References: