Study of Aldurazyme® Replacement Therapy in Patients With Mucopolysaccharidosis I (MPS I) Disease

Study Overview
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Brief Summary
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This is a multi-center, open label, study conducted to evaluate the safety of laronidase administered by intravenous drip infusion in Japanese patients with MPS I disease. Following baseline evaluation, patients will receive weekly infusions of JC0498 at an intravenous dose of 100 units/kg. Patient safety will be monitored continuously throughout the trial. In addition, the effects of JC0498 treatment in this patient population will be assessed by periodically evaluating aspects of MPS I disease in patients at scheduled intervals over the duration of the trial. Since patients may be eligible for the trial if they have received JC0498, a portion of the data may be captured retrospectively and recorded onto the case report forms (CRFs). This study represents the first good clinical practice (GCP) effort to characterize MPS I in the Japanese population and evaluate the effects of JC0498 on disease manifestations.

Official Title
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A Safety Confirmatory Study of JC0498 (Laronidase) in Mucopolysaccharidosis I (MPS I) Patients

Conditions
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Mucopolysaccharidosis I, Hurler Syndrome, Hurler-Scheie Syndrome, Scheie Syndrome

Intervention / Treatment
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* Biological: Aldurazyme (Recombinant Human Alpha-L-Iduronidase)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent/assent of the patient or written informed consent of the parent(s) or the legal guardian(s), depending on the age of the patient, is required prior to any protocol-related procedures being performed; this includes information regarding hematopoietic stem cell transplantation (HSCT) in order to assure that the guardian(s) is fully informed regarding the risks and benefits of this alternative treatment for patients eligible for the trial and who have severe manifestations of MPS I with neurodegeneration. Have a clinical diagnosis of MPS, confirmed by measurable clinical signs and symptoms of MPS I. Have confirmed iduronidase deficiency with a leukocyte alpha-L-iduronidase enzyme activity level of less than 10.0% of the lower limit of the normal range of the measuring laboratory (SRL) Exclusion Criteria: The patient is under consideration for or has previously undergone hematopoietic stem cell transplantation. 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 (exception: JC0498). The patient has known severe hypersensitivity to JC0498 or components of the delivery solution.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aldurazyme (laronidase) treatment<br>Patients received weekly infusions of JC0498 (laronidase) at an intravenous dose of 100 Units/kg (0.58 mg/kg) body weight for up to 73 weeks. | Biological: Aldurazyme (Recombinant Human Alpha-L-Iduronidase)<br>* 0.58 mg/kg every week<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety Evaluation | Overall Safety Summary of Adverse Events (AEs) during Treatment Safety assessment was based on the incidence of AE reports. | Up to 73 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urinary Glycosaminoglycan (GAG) Excretion | Percentage change in the concentration of GAG relative to creatinine in urine (ug GAG/mg creatinine) from baseline to last study visit. Greater decrease indicates greater response. | Up to 73 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MPS I Disease