Intrathecal Enzyme Replacement for Hurler Syndrome

Intrathecal Enzyme Replacement Therapy For Patients With Mucopolysaccharidosis Type I (Hurler Syndrome)

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.

Study Overview

• Status: Completed
• Conditions: Hurler Syndrome
• Intervention / Treatment: Drug: IRT Laronidase

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 Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of MInnesota, Fairview

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 3 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Intent-to-Treat; All patients who have received at least one dose of Laronidase.

Drug: IRT Laronidase; Laronidase belongs to a class of drugs called enzyme replacement therapies or ERT that provides people with sufficient quantities of an important enzyme that they cannot create on their own. The main ingredient in laronidase is a protein that is identical to a naturally occurring form of the human enzyme alpha-L-iduronidase. Laronidase replaces the missing enzyme alpha-L-iduronidase and restores sufficient enzyme activity to break down GAG buildup. 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; Other Names: Aldurazyme

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Masonic Cancer Center, University of Minnesota

Study record dates

Study Major Dates

• Study Start (Actual): January 2, 2008
• Primary Completion (Actual): February 18, 2017
• Study Completion (Actual): November 18, 2018

Study Registration Dates

• First Submitted: March 11, 2008
• First Submitted That Met QC Criteria: March 18, 2008
• First Posted (Estimate): March 19, 2008

Study Record Updates

• Last Update Posted (Actual): December 3, 2018
• Last Update Submitted That Met QC Criteria: November 30, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: Hurler Syndrome; mucopolysaccharidosis type I; Iduronidase deficiency
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Disease; Genetic Diseases, Inborn; Connective Tissue Diseases; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Mucinoses; Syndrome; Mucopolysaccharidoses; Mucopolysaccharidosis I
• Other Study ID Numbers: MT2007-10; 0707M11762 (Other Identifier: IRB, University of Minnesota)