Open-Label Phase III Extension Studies to Evaluate the Long-Term Safety and Efficacy of Ocrelizumab in Relapsing MS and Primary Progressive MS

Background: Ocrelizumab (OCR) is a humanized monoclonal antibody that selectively targets CD20⁺ B cells. OPERA I and OPERA II are 2 identical randomized, double-blind, double-dummy, Phase III, interferon β-1a–controlled trials that showed superior efficacy and favorable safety of OCR in relapsing multiple sclerosis (RMS). Further, OCR met primary and key secondary efficacy outcomes and showed a favorable safety profile in the randomized, double-blind, placebo-controlled Phase III ORATORIO study in primary progressive MS (PPMS).

Objectives: Following completion of the double-blind, controlled treatment phases of OPERA I, OPERA II and ORATORIO, patients are eligible to enter open-label extension (OLE) studies, designed to evaluate the long-term safety, tolerability and efficacy of OCR in patients with RMS and PPMS.

Methods: Key eligibility criteria for inclusion in the OPERA I, OPERA II and ORATORIO OLE phases included completion of the double-blind treatment phases, indication of potential benefit from treatment with OCR as determined by the investigator and meeting predefined retreatment criteria. Eligible patients will receive a single infusion of OCR 600 mg every 24 weeks (except for the first dose, which will be administered as two 300-mg infusions 14 days apart) for the OPERA OLE phase or OCR 600 mg (as two 300-mg infusions 14 days apart) every 24 weeks for the ORATORIO OLE phase. Safety assessments include routine safety laboratory tests, concomitant treatments, antibody titers against common antigens and antidrug antibodies. Key efficacy assessments include potential relapses, neurological examination and Expanded Disability Status Scale, annual magnetic resonance imaging tests and EQ-5D. Additional efficacy assessments in the ORATORIO OLE phase include Multiple Sclerosis Functional Composite Scale, Modified Fatigue Impact Scale and SF-36.

Results: As of 1 December 2015, 630 and 616 patients are ongoing in the OPERA I and OPERA II OLE phases, respectively. Transition into the ORATORIO OLE phase started in November 2015 and as of 1 December 2015, 185 patients have entered the OLE phase.

Conclusions: The long-term safety, tolerability and efficacy of OCR in RMS and PPMS will continue to be assessed in the OPERA I, OPERA II and ORATORIO OLE studies. 

Supported by F. Hoffmann-La Roche Ltd.