Phase 2 AFFINITY Trial Evaluates Opicinumab in a Targeted Population of Patients With Relapsing Multiple Sclerosis: Rationale, Design and Baseline Characteristics (P3.2-072)

Objective: To present the design of the AFFINITY study (NCT03222973) as well as participant baseline characteristics. Background: Opicinumab is a human monoclonal antibody against LINGO-1, a negative regulator of oligodendrocyte differentiation and axonal regeneration. The Phase 2 SYNERGY study identified a dose (10 mg/kg) and subpopulation that were associated with enhanced treatment response. Design/Methods: AFFINITY is an ongoing Phase 2, 72-week, randomized, double-blind, placebo-controlled study evaluating the efficacy/safety of opicinumab (intravenous 750 mg every 4 weeks) versus placebo as an add-on to disease-modifying therapies (DMTs) in a population with relapsing MS. Inclusion criteria include: age 18–58 years with relapsing-remitting or secondary progressive MS; disease duration ≤20 years; Expanded Disability Status Scale (EDSS) 2.0–6.0; clinical relapse between 24 weeks–24 months or brain MRI evidence of disease activity ≤24 months; stable on IFN-beta, dimethyl fumarate, or natalizumab for ≥24 weeks; and characteristics on magnetization transfer ratio and diffusion tensor imaging-radial diffusivity, suggestive of lower myelin content and more preserved tissue integrity in brain T2 lesions by average. The primary endpoint is the Overall Response Score, an integrated assessment of disability improvement and worsening based on the EDSS, Timed 25-Foot Walk, and 9-Hole Peg Test (dominant and non-dominant). Results: Enrollment began in November 2017 and was completed in September 2018. As of August 20, 2018, AFFINITY enrolled 188 participants and 174 received ≥1 dose of placebo or opicinumab. Of the 174 participants who received study drug, mean (SD) age was 38.7 (9.1) years, median (range) EDSS score was 2.5 (2–6), and mean (SD) MS disease duration was 7.8 (5.4) years. Detailed baseline characteristics of all randomized participants (N=263) will be presented. Conclusions: AFFINITY is investigating the efficacy and safety of opicinumab as an add-on therapy to anti-inflammatory DMTs in a subpopulation of patients with MS with potentially enhanced responses to opicinumab. Disclosure: Dr. Zhu has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen. Dr. Zhu holds stock and/or stock options in Biogen. Dr. Calabresi has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with consulting fees from Biogen and Disarm Therapeutics. Dr. Calabresi has received personal compensation in an editorial capacity for The Journal of Clinical Investigation. Dr. Calabresi has received research support from research support to JHU from Annexon Biosciences, Biogen, MedImmune, and Novartis. Dr. Giovannoni has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with AbbVie, Biogen, Novartis, Teva Neuroscience and Roche Diagnostics Corporation. He has also received consultancy fees for advisory board meetings for Merck-Serono, Genzyme-Sanofi, Synthon BV, and Physicians’ Summit and several medical education meetings. Dr. Giovannoni has received personal compensation in an editorial capacity for Multiple Sclerosis and Related Disorders (Elsevier). Dr. Giovannoni has received research support from Takeda Pharmaceutical Company. Dr. Kapoor has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Actelion, Biogen, Sanofi Genzyme, Novartis Pharmaceuticals, Roche, and Teva. Dr. Kapoor has received research support from UK National Institute of Health Research UCL/H Biomedical Research Centre. Dr. Naismith has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Acorda, Alkermes, Biogen, Celgene, EMD Serono, Genentech, Genzyme, and Novartis. Dr. Naismith has received personal compensation in an editorial capacity as the Associate Editor NEJM Journal Watch. Dr. Naismith has received research support from Acorda, Alkermes, Biogen, Celgene, EMD Serono, Genentech, Genzyme, and Novartis. Dr. Hartung has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Bayer Healthcare, Biogen, Geneuro, Genzyme, Medimmune, Merck, Receptos Celgene, Novartis, Roche, CSL Behring. Dr. Arnold has nothing to disclose. Dr. Wolstencroft has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen. Dr. Wolstencroft holds stock and/or stock options in Biogen. Dr. Johnson has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen. Dr. Johnson holds stock and/or stock options in Biogen. Dr. Liu has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen. Dr. Liu holds stock and/or stock options in Biogen. Dr. Chang has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen. Dr. Chang holds stock and/or stock options in Biogen. Dr. Cheng has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen. Dr. Cheng holds stock and/or stock options in Biogen. Dr. Deykin has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen. Dr. Deykin holds stock and/or stock options in Biogen.