Effects of Teriflunomide (Aubagio) on Cognitive and Vocational Outcomes in Multiple Sclerosis

Summary:

Objectives: The primary aim of this study is to define the effect of teriflunomide (Aubagio®)
on cognitive abilities in patients with relapsing multiple sclerosis (MS). There are two
secondary objectives, to [a] relate changes in cognition to vocational problems, and [b]
determine MRI correlates of change in cognition, more specifically gray-matter (GM) volume
metrics which the investigators believe reflect neurodegeneration.

Design: This is a prospective, observational, single-blinded, longitudinal study of
teriflunomide effects on cognitive performance in MS patients over 24 months.
Neuropsychological status and 3T MRI will be assessed at baseline, 12 months and 24 months.
Vocational status will be assessed every three months via the internet. Statistical analysis
will emphasize within-subjects changes in all metrics to maximize statistical power.

Study Population: Thirty (30) relapsing MS patients and 30 healthy controls (HC) will be
enrolled in the study.

Outcomes: An information processing speed index and a memory composite index will be
calculated from conventional, validated neuropsychological tests as recommended by consensus
opinion publications. Conventional clinical metrics for overall neurological disability will
also be assessed. Vocational performance will be monitored using a newly developed online
survey called the Multiple Sclerosis Vocational Monitoring Survey (MSVMS). Regional GM
atrophy, as defined by measurement of thalamic and cortical atrophy, will serve as
neurodegeneration outcomes.

Significance of the research: The effect of teriflunomide on the development of cognitive
impairment and vocational capacity is unknown. This study will elucidate the effect of
teriflunomide on these important outcomes.

Inclusion Criteria:

- Patient diagnosed with MS according to McDonald criteria

- Age 18-60

- Have a relapsing disease course

- Have Expanded Disability Status Scale scores of 0-6.5

- Have a disease duration <20 years

- Treatment naïve to teriflunomide

- Be willing and able to comply with the study procedures for the duration of the trial

- Have given written informed consent and signed Health Insurance Portability and
Accountability Act (HIPAA) Authorization before any study-related activities are
carried out

- Normal kidney functioning (creatinine clearance >59)

- None of the exclusion criteria

Exclusion Criteria:

- MS patients with hepatic impairment

- Nursing mothers or pregnant women who will need to undergo 12 months follow-up

- Women of childbearing potential not using reliable contraception

- Patients currently treated with teriflunomide

- A clinically significant infectious or neurological (for Healthy Controls only)
illness (e.g., cellulitis, abscess, pneumonia, septicemia) within 30 days prior to
treatment assignment

- Unwillingness or inability to comply with the requirements of this protocol including
the presence of any condition (physical, mental, or social) that is likely to affect
the subject's ability to comply with the study protocol

- History of neurological disorder other than MS

- History of developmental learning disorder or other developmental anomaly

- History of major depressive disorder, or other psychiatric disorder that could impact
cognitive capacity, preceding diagnosis of MS

- Current major depressive episode

- Other pathology related to MRI abnormalities