Background: B-cell depletion in patients with relapsing multiple sclerosis (RMS) using anti-CD20 monoclonal antibodies (mAbs) reduces annualized relapse rates and inflammatory lesion activity on MRI, and delays time to confirmed disability worsening. Anti-CD20 mAbs ocrelizumab and rituximab are administered intravenously in clinic; ofatumumab is administered subcutaneously with an autoinjector pen, facilitating patient-administration at home. No outcome data exist relating to transition from ocrelizumab/rituximab treatment to ofatumumab. Objectives: OLIKOS, a 12-month, prospective, single-arm, multicenter Phase 3b study, will explore maintained efficacy in patients with RMS transitioning from intravenous anti-CD20 mAb therapy to ofatumumab. Methods: Approximately 100 adults with RMS will be enrolled at 10-20 US centers. Eligible patients will have been previously treated with at least 2 consecutive courses of ocrelizumab/rituximab, with last dose 4-9 months before OLIKOS baseline. Other inclusion criteria are EDSS score ?5.5 at screening and stable disease while on prior anti-CD20 therapy. Patients with suboptimal response to anti-CD20 therapy (relapse, ?2 active gadolinium-enhancing [Gd+] lesions, any new/enlarging T2 lesions, clinical worsening), or who discontinued anti-CD20 therapy because of severe infusion-related reactions or recurrent infections, or with progressive disease, will be excluded. All participants will receive ofatumumab 20 mg via autoinjector on Days 1, 7, and 14, then once monthly through Month 12. The primary endpoint will be no change or a reduction in Gd+ lesion count at Month 12. Secondary endpoints will be participant retention and changes in immune biomarkers, treatment satisfaction, safety, and tolerability at Months 6 and 12. There will be a 6-month interim analysis. Results: The detailed study design for the OLIKOS trial will be presented. The trial will generate efficacy, retention, and satisfaction data from RMS patients transitioning from intravenous anti-CD20 therapies to ofatumumab. Conclusions: OLIKOS will provide important data on the maintenance of efficacy in RMS patients transitioning from intravenous anti-CD20 therapies to ofatumumab.