Intrathecal Enzyme Replacement for Hurler Syndrome

NCT00638547 | Completed Phase 1 DMC

• 2 other identifiers: MT2007-100707M11762
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

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.

Conditions

Hurler Syndrome

Keywords

Hurler Syndrome; mucopolysaccharidosis type I; Iduronidase deficiency

Outcome Measures

Primary Outcomes (1)

• To demonstrate the efficacy of intrathecally delivering alpha-L-iduronidase in patients with mucopolysaccharidosis type I in decreasing neurodevelopmental deterioration

  1 year

Secondary Outcomes (4)

• 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

Study Arms (1)

Intent-to-Treat

EXPERIMENTAL

All patients who have received at least one dose of Laronidase.

Drug: IRT Laronidase

Interventions

IRT Laronidase DRUG

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

Also known as: Aldurazyme

Intent-to-Treat

Eligibility Criteria

• Age: 6 Months - 3 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead

Study Sites (1)

University of Minnesota, Fairview

Minneapolis, Minnesota, 55455, United States

Location

MeSH Terms

Conditions

Mucopolysaccharidosis I

Interventions

Iduronidase

Condition Hierarchy (Ancestors)

Mucopolysaccharidoses; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lysosomal Storage Diseases; Mucinoses; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Glycoside Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes

Study Officials

• Paul Orchard, MD

  University of Minnesota Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2008
• First Posted: March 19, 2008
• Study Start: January 2, 2008
• Primary Completion: February 18, 2017
• Study Completion: November 18, 2018
• Last Updated: December 3, 2018

Record last verified: 2018-11

Locations

US (1)