Extension Study of Intrathecal Enzyme Replacement Therapy for MPS I

An Extension Study of Intrathecal Enzyme Replacement Therapy for Spinal Cord Compression in Mucopolysaccharidosis I

This is a one-year extension study of the use of laronidase into the spinal fluid to treat spinal cord compression in mucopolysaccharidosis I. Mucopolysaccharidosis I is a rare genetic condition due to deficiency of the enzyme alpha-l-iduronidase. Spinal cord compression occurs in this condition due to accumulation of material called glycosaminoglycans (GAG). Laronidase is the manufactured form of the enzyme alpha-l-iduronidase that is deficient in mucopolysaccharidosis I patients. The aim of this study is to determine whether laronidase is safe and effective when given into the spinal fluid as a potential non-surgical treatment for spinal cord compression due to mucopolysaccharidosis I disease. Funding Source -- FDA OOPD

Study Overview

• Status: Terminated
• Conditions: Mucopolysaccharidosis I; Scheie Syndrome; Lysosomal Storage Disease; Spinal Cord Compression; Hurler-Scheie Syndrome
• Intervention / Treatment: Drug: laronidase

Detailed Description

Enzyme replacement therapy (ERT) has been developed for mucopolysaccharidosis I (MPS I), a lysosomal storage disorder. ERT helps many physical ailments due to the disease, but does not treat the central nervous system, due to inability to cross the blood brain barrier. Our purpose is to test delivery of ERT to the spinal fluid via intrathecal injection in patients with MPS I. In this pilot study, we will use recombinant human α-L-iduronidase administered intrathecally once per month for four months to individuals with the Hurler-Scheie and Scheie forms of MPS I and spinal cord compression. If successful, intrathecal delivery could represent a practical, straightforward method of treating central nervous system disease due to lysosomal storage.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 1

Contacts and Locations

Study Locations

• Finland
  • Helsinki, Finland
    • Helsinki University Central Hospital
• United States
  • California
    • Torrance, California, United States, 90502
      • Los Angeles Biomedical Research Institute at Harbor-UCLA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Hurler-Scheie, Scheie form of MPS I, or Hurler 2 years after hematopoietic stem cell transplantation

  • Spinal cord compression
  • Has received intrathecal laronidase previously with good response and no significant safety concerns
  • Age greater than 8 years
  • Able to provide legal informed consent
  • Aware of clinical treatment option of observation without treatment or surgical decompression
  • Negative urine pregnancy test at screening (nonsterile females of child-bearing potential who are sexually active only)

Exclusion Criteria:

• Severe (Hurler) form of MPS I
• Desires surgical or medical treatment of spinal cord compression
• Spinal cord compression that warrants immediate surgical intervention
• Pregnancy or lactation
• Hematopoietic stem cell transplantation within 2 years of study enrollment
• Receipt of an investigational drug within 30 days of enrollment
• Infusion reactions to laronidase that required medical intervention, prophylaxis, or altered enzyme administration
• Significant anti-iduronidase antibody titer
• Recent initiation of intravenous laronidase (within past 6 months)
• Presence of cervical subluxation or similar external pathology as the major cause of cord compression symptoms for which surgical intervention should be immediately undertaken

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: intrathecal laronidase; drug laronidase, dose 1.74 mg, route intrathecal, frequency every 30-90 days, duration 1 year	Drug: laronidase; 1.74 mg intrathecally every 1-3 months for 1 year; Other Names: Aldurazyme; recombinant human alpha-l-iduronidase

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
safety of intrathecal enzyme treatment by blood and spinal fluid tests; improvement or stabilization in neurologic signs and symptoms of spinal cord compression	1 year

Collaborators and Investigators

• Sponsor: Patricia I. Dickson, M.D.
• Collaborators: The Ryan Foundation
• Investigators: Principal Investigator: Patricia I Dickson, MD, Los Angeles Biomedical Research Institute at Harbor-UCLA

Study record dates

Study Major Dates

• Study Start: January 1, 2008
• Primary Completion (ACTUAL): October 1, 2011
• Study Completion (ACTUAL): October 1, 2011

Study Registration Dates

• First Submitted: June 17, 2008
• First Submitted That Met QC Criteria: November 4, 2008
• First Posted (ESTIMATE): November 6, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): February 21, 2013
• Last Update Submitted That Met QC Criteria: February 19, 2013
• Last Verified: February 1, 2013

More Information

Terms related to this study

• Keywords: enzyme replacement therapy; laronidase; central nervous system; mucopolysaccharidosis; Hurler-Scheie; Scheie; spinal cord compression; intrathecal
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Disease; Genetic Diseases, Inborn; Connective Tissue Diseases; Spinal Cord Diseases; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Mucinoses; Spinal Cord Injuries; Syndrome; Mucopolysaccharidoses; Mucopolysaccharidosis I; Lysosomal Storage Diseases; Spinal Cord Compression
• Other Study ID Numbers: MIRC-001-01