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

• Register: ClinicalTrials.gov
• Last refreshed on: 1 February 2016
• Main ID: NCT00852358
• Date of registration: 25/02/2009
• Prospective Registration: Yes
• Primary sponsor: Patricia I. Dickson, M.D.
• Public title: A Study of Intrathecal Enzyme Therapy for Cognitive Decline in MPS I
• Scientific title: A Study of Intrathecal Enzyme Replacement for Cognitive Decline in Mucopolysaccharidosis I
• Date of first enrolment: June 2009
• Target sample size: 9
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT00852358
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment
• Phase: N/A

Countries of recruitment

United States

Contacts

• Name: Agnes Chen, MD
• Affiliation: Los Angeles Biomedical Institute at Harbor-UCLA

• Name: Patricia I Dickson, MD
• Affiliation: Los Angeles Biomedical Institute at Harbor-UCLA

Key inclusion & exclusion criteria

Inclusion Criteria:

- The presence of MPS I disease as documented by low a-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.



Age minimum: 6 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Lysosomal Storage Disease

Hurler-Scheie Syndrome

Cognitive Decline

Mucopolysaccharidosis I

Scheie Syndrome

Intervention(s)

Drug: laronidase

Primary Outcome(s)

The objective of this study is to assess the ability of intrathecal a-L-iduronidase to be administered safely [Time Frame: 24 months]

Secondary Outcome(s)

The objective of this study is to assess the ability of intrathecal a-L-iduronidase to stabilize or reverse cognitive decline. [Time Frame: 24 months]

Secondary ID(s)

IND 104,354

MIRC-002

U54NS065768

IRB Project No. 13270-01

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

BioMarin Pharmaceutical

University of Minnesota - Clinical and Translational Science Institute

National Center for Advancing Translational Science (NCATS)

The Ryan Foundation

University of California, Los Angeles

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

National Institute of Neurological Disorders and Stroke (NINDS)

Rare Diseases Clinical Research Network