Extension Study of Intrathecal Enzyme Replacement Therapy for MPS I

Study Overview
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Brief Summary
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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

Detailed Description
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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.

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

Conditions
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Spinal Cord Compression, Mucopolysaccharidosis I, Hurler-Scheie Syndrome, Scheie Syndrome, Lysosomal Storage Disease

Intervention / Treatment
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* Drug: laronidase


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 8 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: intrathecal laronidase<br>drug laronidase, dose 1.74 mg, route intrathecal, frequency every 30-90 days, duration 1 year | Drug: laronidase<br>* 1.74 mg intrathecally every 1-3 months for 1 year<br>* Other names: recombinant human alpha-l-iduronidase;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mucopolysaccharidosis, Hurler-Scheie, Scheie, laronidase, spinal cord compression, central nervous system, enzyme replacement therapy, intrathecal