Intrathecal Enzyme Replacement for Hurler Syndrome

Phase 1

Completed

• Conditions: Hurler Syndrome
• Interventions: Drug: IRT Laronidase

• Registration Number: NCT00638547
• Lead Sponsor: Masonic Cancer Center, University of Minnesota

Brief Summary

This protocol will examine whether the enzyme alpha-L-iduronidase (Laronidase), delivered into the spinal fluid of patients with Hurler syndrome at intervals before and after bone marrow transplant, is a safe and effective approach to slow the neurologic degeneration seen in Hurler patients undergoing transplantation.

Detailed Description

Subjects will receive an infusion of Laronidase into his/her spinal fluid approximately 12 weeks before, 2 weeks before, 100 days after and 6 months after transplant. This procedure is done by lumbar puncture (also called a "spinal tap").

Study Timeline

• Study Start: 2008-01-02
• Study First Submitted: 2008-03-11
• Study First Submitted QC: 2008-03-18
• Study First Posted: 2008-03-19
• Primary Completion: 2017-02-18
• Status Verified: 2018-11
• Study Completion: 2018-11-18
• Last Update Submitted: 2018-11-30
• Last Update Posted: 2018-12-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 26

Inclusion Criteria

• Patients with a diagnosis of MPS IH (Hurler syndrome) are candidates for this protocol if they are being considered for hematopoietic stem cell transplantation according the University of Minnesota guidelines.

Exclusion Criteria

• Patients are less than 6 months old, or older than 3 years of age.
• There is a history of clinically-severe hypersensitivity to Laronidase.
• There is a contraindication for repeated lumbar puncture.
• The family is not willing to undergo the necessary procedures and evaluations inherent in the study.
• Consent has not been signed for participation in the 2004-09 study of intravenous Laronidase administration.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Intent-to-Treat	IRT Laronidase	All patients who have received at least one dose of Laronidase.

Primary Outcome Measures

Name	Time	Method
To demonstrate the efficacy of intrathecally delivering alpha-L-iduronidase in patients with mucopolysaccharidosis type I in decreasing neurodevelopmental deterioration	1 year

Secondary Outcome Measures

Name	Time	Method
To determine the safety and toxicity of intrathecally delivering alpha-L-iduronidase in patients with mucopolysaccharidosis type I	1 year
To determine brain changes with magnetic resonance imaging	1 and 2 years
To determine neurocognitive changes present in patients with Hurler syndrome	6, 12, and 24 months
To determine cerebral spinal fluid levels of glycosaminoglycans, cytokines and antibodies to Laronidase at baseline and at each point CSF is obtained	through 1 year

Trial Locations

Locations (1)

University of Minnesota, Fairview; 🇺🇸 Minneapolis, Minnesota, United States