Baseline Demographics, Disease Characteristics, and Clinical Measures of Patients with Relapsing MS in Enlighten: A Phase 3b Study of Ozanimod on Cognitive Processing Speed

Background: In patients with multiple sclerosis (MS), slowed cognitive processing speed emerges as an early deficit. The Symbol Digit Modalities Test (SDMT) is a preferred measure of cognitive performance in patients with MS. The primary objective of the ongoing ENLIGHTEN study (NCT04140305) is to describe clinically meaningful changes in SDMT over a 3-yr period in patients with early relapsing MS (RMS) treated with ozanimod.

Objectives: We describe baseline demographics, MS disease characteristics, and clinical measures of patients enrolled in ENLIGHTEN as of November 3, 2021.

Methods: ENLIGHTEN is a multicenter, phase 3b study currently recruiting in the US and Canada. Patients will receive ozanimod 0.92 mg/d for 3 yrs following a 7-d dose-titration. Eligible patients must be 18–65 years of age at screening, have a diagnosis of MS per the 2010 or 2017 McDonald criteria within the last 5 years, be taking ≤1 MS disease-modifying therapy (DMT), have an Expanded Disability Status Scale (EDSS) score of ≤3.5, and have had no relapses within 30 days before screening.

Results: A total of 82 patients with a mean (SD) age of 40.9 (11.7) yrs are enrolled in ENLIGHTEN and received ≥1 dose of ozanimod; most are white (74; 90.2%), female (66; 80.5%), and DMT-naive (52; 63.4%). Mean (SD) time since MS diagnosis was 1.2 (1.3) yrs, with relapsing-remitting MS being the most prevalent type (81; 98.8%). Within the 12 months prior to screening, mean (SD) number of relapses was 0.8 (0.7; n=81). Mean (SD) EDSS score was 2.0 (1.1; n=82). Among 81 patients with baseline MRI data, 29 (35.8%) had gadolinium-enhancing (GdE) lesions at baseline; the mean (SD) number of GdE and T2 lesions were 0.7 (1.3) and 25.3 (18.9), respectively. Of the tests that constitute the Brief International Assessment of Cognition for MS (BICAMS), mean (SD) scores were 53.3 (12.5; n=77) for SDMT, 53.1 (9.8; n=74) for the California Verbal Learning Test-Second Edition, and 23.6 (6.8; n=68) for the Brief Visuospatial Memory Test-Revised. Fatigue Severity Scale mean (SD) total score was 4.4 (1.7; n=82), and Hospital Anxiety and Depression Scale mean (SD) total score was 12.8 (6.5; n=82). Mean (SD) MS Quality of Life-54 physical and mental health composite summary scores were 59 (20.5; n=80) and 66.7 (19.8; n=81), respectively.

Conclusions: BICAMS cognitive assessments in patients with RMS currently enrolled in ENLIGHTEN and treated with ozanimod are consistent with early disease. As of early 2022, ENLIGHTEN is actively recruiting.