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

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

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.

Study Overview

• Status: Terminated
• Conditions: Mucopolysaccharidosis I; Cognitive Decline
• Intervention / Treatment: Drug: Intrathecal recombinant human alpha iduronidase

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Torrance, California, United States, 90509
      • Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. The subject has completed the MIRC-002 study of intrathecal enzyme replacement therapy for cognitive decline in mucopolysaccharidosis I
2. Age six years or older.
3. Subject and/or guardian willing and able to provide written informed consent.
4. Negative urine pregnancy test at screening (non-sterile females of child-bearing potential only)
5. 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)
6. 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:

1. The subject has undergone hematopoietic stem cell transplantation
2. 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
3. Pregnant or lactating, or considering pregnancy
4. Receipt of an investigational drug or procedure other than intrathecal Aldurazyme® within 30 days of enrollment
5. 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.
6. Infusion reactions to intravenous or intrathecal Aldurazyme® therapy that are life-threatening or require emergent intervention such as epinephrine, cardiopulmonary resuscitation, or hospitalization
7. 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.
8. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Open-label treatment; laronidase 1.74 mg IT q 3 months for five years	Drug: Intrathecal recombinant human alpha iduronidase; Intrathecal recombinant human alpha iduronidase every 3 months; Other Names: Aldurazyme

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: agnes chen
• Collaborators: University of California, Los Angeles; National Institute of Neurological Disorders and Stroke (NINDS); University of Minnesota; Rare Diseases Clinical Research Network; UCSF Benioff Children's Hospital Oakland; The Ryan Foundation

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2014
• Primary Completion (Actual): February 1, 2020
• Study Completion (Actual): February 1, 2020

Study Registration Dates

• First Submitted: September 3, 2014
• First Submitted That Met QC Criteria: September 3, 2014
• First Posted (Estimated): September 5, 2014

Study Record Updates

• Last Update Posted (Actual): October 31, 2023
• Last Update Submitted That Met QC Criteria: October 27, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Metabolic Diseases; Neurocognitive Disorders; Genetic Diseases, Inborn; Connective Tissue Diseases; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Mucinoses; Cognition Disorders; Mucopolysaccharidoses; Mucopolysaccharidosis I; Cognitive Dysfunction
• Other Study ID Numbers: MIRC-002 (100)