Extension Study of Intrathecal Enzyme Replacement Therapy for MPS I

Mucopolysaccharidosis I Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00786968
• Other study ID #: MIRC-001-01
• Status: Terminated
• Phase: Phase 1
• First received: June 17, 2008
• Last updated: February 19, 2013
• Start date: January 2008
• Est. completion date: October 2011

Study information

• Verified date: February 2013
• Source: Dickson, Patricia I., M.D.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: October 2011
• Est. primary completion date: October 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 8 Years and older

Eligibility

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 Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hurler-Scheie Syndrome
• Lysosomal Storage Disease
• Lysosomal Storage Diseases
• Mucopolysaccharidoses
• Mucopolysaccharidosis I
• Scheie Syndrome
• Spinal Cord Compression
• Syndrome

Intervention

Drug:
• laronidase
1.74 mg intrathecally every 1-3 months for 1 year

Locations

Country	Name	City	State
Finland	Helsinki University Central Hospital	Helsinki
United States	Los Angeles Biomedical Research Institute at Harbor-UCLA	Torrance	California

Sponsors (2)

Lead Sponsor	Collaborator
Patricia I. Dickson, M.D.	The Ryan Foundation

Countries where clinical trial is conducted

United States,  Finland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes