A Study of Intrathecal Enzyme Therapy for Cognitive Decline in MPS I

• Status: Completed
• Trial end date: 2015-04-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a 24-month study of the use of laronidase administered into the spinal fluid to treat cognitive decline in mucopolysaccharidosis I (MPS I). MPS I is a rare genetic condition due to deficiency of the enzyme alpha-l-iduronidase. Laronidase is the manufactured form of the enzyme alpha-l-iduronidase.

MPS I is a heterogeneous disease with several clinical phenotypes ranging from the most severe, Hurler syndrome, to the attenuated forms, Hurler-Scheie and Scheie. Although patients with milder forms of MPS I may not have grossly observable problems with cognition, these patients do have learning difficulties that are apparent in school and with neuropsychological testing. The goal of this study is to evaluate whether intrathecal recombinant human alpha-l-iduronidase (rhIDU) injections can stabilize or improve cognitive decline in individuals with MPS I.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Patricia I. Dickson, M.D.
• Collaborators: BioMarin Pharmaceutical; National Center for Advancing Translational Science (NCATS); National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); National Institute of Neurological Disorders and Stroke (NINDS); Rare Diseases Clinical Research Network; The Ryan Foundation; University of California, Los Angeles; University of Minnesota; University of Minnesota - Clinical and Translational Science Institute

Criteria

Inclusion Criteria:

• The presence of MPS I disease as documented by low α-L-iduronidase activity

• Age six years or older.

• The presence of acquired cognitive deficits as demonstrated by:

1. A score of one standard deviation below mean on IQ testing or in one domain of neuropsychological function (language, memory, or non-verbal ability), OR

2. Documented historical evidence of a decline of greater than one standard deviation on sequential testing, OR

3. A score between 0.75 and 1 standard deviation below the mean, AND the cognitive deficit affects daily performance.

• The decline in function is not explainable by other neurological or psychiatric factors.

• 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 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 Aldurazyme® therapy that require ongoing medical intervention, special prophylaxis or altered rate or dose of enzyme administration

• The subject has a programmable VP shunt that is incompatible with the 3 Tesla MRI magnet and is unable or unwilling to undergo shunt revision to a MRI compatible device.

• The subject has another contraindication for MRI, such as nonremovable metal in the body.

• The subject has severely impaired spinal CSF flow, demonstrated by failure of appearance of 99mTechnetium-DTPA in the basal cisterns by 4 hours after intra-lumbar administration.