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

Phase 2

Completed

Conditions: Scheie Syndrome
Hurler-Scheie Syndrome
Mucopolysaccharidosis I
Hurler Syndrome

Interventions: Biological: Aldurazyme (Recombinant Human Alpha-L-Iduronidase)

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.

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
Aldurazyme (rhIDU) 100 U/kg ONLY every week	Aldurazyme (Recombinant Human Alpha-L-Iduronidase)	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.
Aldurazyme (rhIDU) 100-200 U/kg every week	Aldurazyme (Recombinant Human Alpha-L-Iduronidase)	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.

Primary Outcome Measures

Name	Time	Method
Pharmacokinetics - Total Plasma Clearance (CL)	52 weeks	CL is volume of the body fluid cleared of the drug per unit of time.
Pharmacokinetics - Volume of Distribution (Vz)	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.
Safety Evaluation	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∞)	52 weeks	AUC∞ is a measure of the total exposure to a drug.
Pharmacokinetics - Elimination Half Life (t1/2)	52 weeks	Half-life is the time it takes for the concentration of drug in plasma to decline by 50%.

Secondary Outcome Measures

Name	Time	Method

Locations (4): Johannes Gutenberg Universität
🇩🇪
Kinderklinik, Mainz, Germany
Hôpital E. Herriot
🇫🇷
Lyon, France
Willink Biochemical Genetics Unit Royal Hospital for Children
🇬🇧
Manchester, United Kingdom
Sophia Children's Hospital
🇳🇱
Rotterdam, Netherlands