Background: Ublituximab, a novel monoclonal antibody, targets a unique epitope on the CD20 antigen and is glycoengineered for enhanced B-cell cytolysis through anti-body-dependent cellular cytotoxicity (ADCC). The potent ADCC activity is thought to enhance B-cell depletion, and may allow for lower doses and shorter infusion times versus other presently available anti-CD20s mAbs.
Objectives: ULTIMATE I (NCT03277261) and ULTIMATE II (NCT03277248), are identical Phase 3, randomized, multi-center, double-blinded, active-controlled studies evaluating the efficacy and safety of UTX in patients with relapsing multiple sclerosis (RMS).
Patients are randomized (1:1) to receive either 450mg UTX via a one-hour intravenous infusion every 24 weeks (following day 1 infusion of 150mg UTX) or 14mg oral teriflunomide once daily, throughout a 96-week treatment period. Eligible patients have diagnosis of RMS (McDonald Criteria 2010), Expanded Disability Status Scale (EDSS) score of 0-5.5, and age of 18-55 years. Subjects are required to have at least 2 documented relapses within the two years prior, one relapse in the year prior, and/or > 1 or more Gd-enhancing lesions in the year prior to screening. The primary endpoint is annualized relapse rate (ARR). Key secondary endpoints include MRI-related outcomes, no evidence of disease activity (NEDA), and 3-month confirmed disability progression. Safety and tolerability are also assessed.
Results: Overall, 1094 patients were randomized in 10 countries (ULTIMATE I, N=549; ULTIMATE II, N=545). Baseline demographic and disease characteristics were previously reported including a mean age of ~37 and ~35 years, a mean MS duration since diagnosis of 4.7 and 5 years, and a mean EDSS of 2.9 and 2.9, respectively in ULTIMATE I&II. Efficacy and safety results from ULTIMATE I&II will be available at the Congress.
Conclusions: ULTIMATE I&II results will evaluate the therapeutic potential of a one-hour 450mg ublituximab infusion every six months, for patients with RMS