Impact of Annual Versus Biannual Infusions of Ocrelizumab in Patients With Active MS,After 2 Years of Initial Treatment, on Freedom From Radiological Disease Activity at Two Years: a Multicenter Randomized Controlled Non-inferiority Trial

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system and the leading cause of severe non-traumatic disability in young people, affecting 110,000 people in France. Ocrelizumab, a humanized anti-CD20 monoclonal antibody, has shown remarkable efficacy in Phase III trials on the inflammatory component of the disease, reducing the annualized relapse rate by 46% and the rate of new T2 lesions by 80% compared with interferon-β 1a. The use of anti-CD20 agents, including ocrelizumab, is associated with an infectious risk that increases with duration of exposure, part of which is due to the development of hypo-gammaglobulinemia in relation to cumulative dose. Several reports suggest a persistent effect of anti-CD20 drugs in MS, with no resumption of inflammatory activity after discontinuation: * During the development of ocrelizumab, at the end of phase 2, after having received 3 or 4 semi-annual cycles of ocrelizumab, a safety period with a therapeutic window of 18 months was planned, before re-administration in the extension study. During this therapeutic window, the annualized relapse rate remained stable, and patients showed no radiological disease activity. * Scandinavian observational studies of "off-label" use of anti-CD20 in MS provide real-life evidence of the absence of recovery of clinical and radiological activity after prolonged interruption of treatment. After 2 years of treatment, and with disease activity under control, spacing administration intervals could reduce the risk of infection without reducing treatment efficacy. This would facilitate the decision to maintain highly active immunotherapy over the long term. In addition, this therapeutic de-escalation, by reducing the frequency of infusions and associated day hospitalizations, would help to reduce treatment management costs. Our aim is to evaluate the non-inferiority of 12-monthly spacing of ocrelizumab infusions versus the conventional 6-monthly regimen, in a population of active MS patients over 18 years of age who have already received 4 or more semi-annual cycles of treatment for 2 years.

NCT Number	NCT05999604
Lead Sponsor	Fondation Ophtalmologique Adolphe de Rothschild
Conditions	Multiple Sclerosis
Enrollment	244 participants
Start Date	2023-11-09
Primary Completion	2029-11 (estimated)
Study Completion	2029-11 (estimated)
Updated on ClinicalTrials.gov	2026-01-21