Extension Study of Intrathecal Enzyme Replacement for Cognitive Decline in MPS I

Study Overview
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Brief Summary
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This is a five-year extension study of the pilot study, Intrathecal Enzyme Replacement for Cognitive Decline in MPS I. Participants must have completed the pilot study to participate in this study.

Official Title
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An Extension Study of Intrathecal Enzyme Replacement for Cognitive Decline in Mucopolysaccharidosis I

Conditions
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Mucopolysaccharidosis I, Cognitive Decline

Intervention / Treatment
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* Drug: Intrathecal recombinant human alpha iduronidase


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The subject has completed the MIRC-002 study of intrathecal enzyme replacement therapy for cognitive decline in mucopolysaccharidosis I Age six years or older. Subject and/or guardian willing and able to provide written informed consent. Negative urine pregnancy test at screening (non-sterile females of child-bearing potential only) Currently using two acceptable methods of birth control as determined by the investigator and willing to continue to use acceptable birth control during their participation in the study (non-sterile females of child-bearing potential who are sexually active only) Willing and able to comply with study procedures. For example, the subjects must be able to complete written and computer-based testing. The subjects must be able to lie still in the MRI scanner for at least 40 minutes without sedation. Exclusion Criteria: The subject has undergone hematopoietic stem cell transplantation Recent initiation of intravenous Aldurazyme® therapy with less than 6 months of therapy. Subjects who have been receiving Aldurazyme® therapy for more than 6 months, and those who have never received Aldurazyme® therapy, will be allowed to enroll Pregnant or lactating, or considering pregnancy Receipt of an investigational drug or procedure other than intrathecal Aldurazyme® within 30 days of enrollment A condition, medical or other, that prevents participation in the study, including severe auditory or visual impairment, significant lumbar pathology, lumbar catheter, or recent major surgery within 6 weeks that would preclude their ability to participate. Infusion reactions to intravenous or intrathecal Aldurazyme® therapy that are life-threatening or require emergent intervention such as epinephrine, cardiopulmonary resuscitation, or hospitalization The subject has severely impaired spinal CSF flow, demonstrated by failure of appearance of radionuclide in the basal cisterns by 4 hours after intra-lumbar administration. The subject has a coagulopathy, as identified by a platelet count of less than 50,000, an INR of 1.5 or greater, or a PTT that is 1.5 times the upper limit of normal for the laboratory from which it was drawn.

Ages Eligible for Study
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Minimum Age: 6 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: Open-label treatment<br>laronidase 1.74 mg IT q 3 months for five years | Drug: Intrathecal recombinant human alpha iduronidase<br>* Intrathecal recombinant human alpha iduronidase every 3 months<br>* Other names: Aldurazyme;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hopkins Verbal Learning Test | Mean intra-subject change in total recall score on the Hopkins Verbal Learning Test between baseline/screening for MIRC-002 and the subject's final visit. The Hopkins Verbal Learning Test measures verbal memory. The subject is read a list of words and asked to memorize as many words as possible. The scale ranges from 0 to 36, with higher scores indicating a better outcome. Two relevant time points: Baseline and the subject's final visit. Because this study ended prematurely for due to the pandemic, the subject's final visit was at the 12-month time point for one subject, 24-months for one subject, 36-months for two subjects, and 48-months for two subjects. Calculation: The total recall score at Baseline was subtracted from the total recall score at the subject's final visit and mean change and standard deviation were reported. | zero to 48 months |