A Study of Ocrelizumab in Comparison With Interferon Beta-1a (Rebif) in Participants With Relapsing Multiple Sclerosis

Summary

This randomized, double-blind, double-dummy, parallel-group study will evaluate the efficacy and safety of ocrelizumab in comparison with interferon beta-1a (Rebif) in participants with relapsing multiple sclerosis. Participants will be randomized to receive either ocrelizumab 600 mg or matching placebo intravenous (IV) as 300 mg infusions on Days 1 and 15 for the first dose and as a single infusion of 600 mg for all subsequent infusions every 24 weeks, with placebo injections matching interferon beta-1a SC three times per week; or interferon beta-1a 44 mcg SC injections three times per week (with placebo infusions matching ocrelizumab infusions every 24 weeks).

Timeline

Start

2011-09-20

Primary completion

2015-05-12

Completion

2022-12-30

Outcome

Met primary endpoint

registry Interferon Beta-1a 44 mcg SC vs Ocrelizumab; p < 0.0001; Rate Ratio 0.532 (95% CI 0.397 to 0.714); Negative Binomial Model NCT01412333 ↗

Publications

• Kappos L, Yiu S, Reucassel J, Oh J, Granziera C, Killestein J, Bermel RA, Berge C, Kazlauskaite A, Schneble HM, Dahlke F, Cree BAC. Performance of Composite Endpoints Defining Progression Independent of Relapse Activity in Multiple Sclerosis. Ann Clin Transl Neurol. 2025 Sep;12(9):1805-1812. doi: 10.1002/acn3.70111. Epub 2025 Jul 8.
• Montobbio N, Bovis F, Signori A, Carmisciano L, Schiavetti I, Ponzano M, Tur C, Granziera C, Cagol A, Arnold DL, Kappos L, Sormani MP. Uncovering a bias in estimated treatment effects on PIRA in multiple sclerosis clinical trials. EBioMedicine. 2025 Jul;117:105802. doi: 10.1016/j.ebiom.2025.105802. Epub 2025 Jun 18.
• Kappos L, Yiu S, Dahlke F, Coetzee T, Cutter GR, Yuen S, Bonati U, Lublin FD. Composite Confirmed Disability Worsening/Progression Is a Useful Clinical Endpoint for Multiple Sclerosis Clinical Trials. Neurology. 2025 May 27;104(10):e213558. doi: 10.1212/WNL.0000000000213558. Epub 2025 Apr 21.
• Benedict RH, Kappos L, Miller A, Hartung HP, Overell J, Pei J, Dahlke F, Bernasconi C, Koendgen H, Wang Q, Bonati U, Cohan S. Cognitive effects of ocrelizumab vs interferon beta-1a in relapsing multiple sclerosis: A post hoc analysis of the OPERA I/II trials. Mult Scler Relat Disord. 2025 Mar;95:106310. doi: 10.1016/j.msard.2025.106310. Epub 2025 Feb 2.
• Muros-Le Rouzic E, Heer Y, Yiu S, Tozzi V, Braune S, van Hovell P, Bergmann A, Bernasconi C, Model F, Craveiro L; NTD study group. Five-year efficacy outcomes of ocrelizumab in relapsing multiple sclerosis: A propensity-matched comparison of the OPERA studies with other disease-modifying therapies in real-world lines of treatments. J Cent Nerv Syst Dis. 2024 Sep 13;16:11795735241260563. doi: 10.1177/11795735241260563. eCollection 2024.
• Loomis SJ, Sadhu N, Fisher E, Gafson AR, Huang Y, Yang C, Hughes EE, Marshall E, Herman A, John S, Runz H, Jia X, Bhangale T, Bronson PG. Genome-wide study of longitudinal brain imaging measures of multiple sclerosis progression across six clinical trials. Sci Rep. 2023 Aug 31;13(1):14313. doi: 10.1038/s41598-023-41099-0.
• Kolind S, Gaetano L, Assemlal HE, Bernasconi C, Bonati U, Elliott C, Hagenbuch N, Magon S, Arnold DL, Traboulsee A. Ocrelizumab-treated patients with relapsing multiple sclerosis show volume loss rates similar to healthy aging. Mult Scler. 2023 May;29(6):741-747. doi: 10.1177/13524585231162586. Epub 2023 May 6.
• Hauser SL, Bar-Or A, Weber MS, Kletzl H, Gunther A, Manfrini M, Model F, Mercier F, Petry C, Wing Q, Koendgen H, Smith T, Kappos L. Association of Higher Ocrelizumab Exposure With Reduced Disability Progression in Multiple Sclerosis. Neurol Neuroimmunol Neuroinflamm. 2023 Feb 15;10(2):e200094. doi: 10.1212/NXI.0000000000200094. Print 2023 Mar.
• Falet JR, Durso-Finley J, Nichyporuk B, Schroeter J, Bovis F, Sormani MP, Precup D, Arbel T, Arnold DL. Estimating individual treatment effect on disability progression in multiple sclerosis using deep learning. Nat Commun. 2022 Sep 26;13(1):5645. doi: 10.1038/s41467-022-33269-x.
• Arnold DL, Sprenger T, Bar-Or A, Wolinsky JS, Kappos L, Kolind S, Bonati U, Magon S, van Beek J, Koendgen H, Bortolami O, Bernasconi C, Gaetano L, Traboulsee A. Ocrelizumab reduces thalamic volume loss in patients with RMS and PPMS. Mult Scler. 2022 Oct;28(12):1927-1936. doi: 10.1177/13524585221097561. Epub 2022 Jun 7.
• Krishnan AP, Song Z, Clayton D, Gaetano L, Jia X, de Crespigny A, Bengtsson T, Carano RAD. Joint MRI T1 Unenhancing and Contrast-enhancing Multiple Sclerosis Lesion Segmentation with Deep Learning in OPERA Trials. Radiology. 2022 Mar;302(3):662-673. doi: 10.1148/radiol.211528. Epub 2021 Dec 14.
• Giovannoni G, Kappos L, de Seze J, Hauser SL, Overell J, Koendgen H, Manfrini M, Wang Q, Wolinsky JS. Risk of requiring a walking aid after 6.5 years of ocrelizumab treatment in patients with relapsing multiple sclerosis: Data from the OPERA I and OPERA II trials. Eur J Neurol. 2022 Apr;29(4):1238-1242. doi: 10.1111/ene.14823. Epub 2021 May 5.
• Hauser SL, Kappos L, Arnold DL, Bar-Or A, Brochet B, Naismith RT, Traboulsee A, Wolinsky JS, Belachew S, Koendgen H, Levesque V, Manfrini M, Model F, Hubeaux S, Mehta L, Montalban X. Five years of ocrelizumab in relapsing multiple sclerosis: OPERA studies open-label extension. Neurology. 2020 Sep 29;95(13):e1854-e1867. doi: 10.1212/WNL.0000000000010376. Epub 2020 Jul 20.
• Kappos L, Wolinsky JS, Giovannoni G, Arnold DL, Wang Q, Bernasconi C, Model F, Koendgen H, Manfrini M, Belachew S, Hauser SL. Contribution of Relapse-Independent Progression vs Relapse-Associated Worsening to Overall Confirmed Disability Accumulation in Typical Relapsing Multiple Sclerosis in a Pooled Analysis of 2 Randomized Clinical Trials. JAMA Neurol. 2020 Sep 1;77(9):1132-1140. doi: 10.1001/jamaneurol.2020.1568.
• Hauser SL, Bar-Or A, Comi G, Giovannoni G, Hartung HP, Hemmer B, Lublin F, Montalban X, Rammohan KW, Selmaj K, Traboulsee A, Wolinsky JS, Arnold DL, Klingelschmitt G, Masterman D, Fontoura P, Belachew S, Chin P, Mairon N, Garren H, Kappos L; OPERA I and OPERA II Clinical Investigators. Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis. N Engl J Med. 2017 Jan 19;376(3):221-234. doi: 10.1056/NEJMoa1601277. Epub 2016 Dec 21.

Drugs

Indications