Efficacy of Annual vs. Semi-Annual Ocrelizumab Infusions on Radiological Disease Activity in Active Multiple Sclerosis: A Randomized Non-Inferiority Trial

The primary objective of this study is to compare the **efficacy** of a treatment regimen involving annual administrations of **ocrelizumab** versus a conventional regimen with semi-annual administrations. This comparison focuses on the absence of radiological disease activity at 2 years in patients with active **multiple sclerosis** who have been treated with ocrelizumab for at least 2 years. This objective is clinically relevant as it aims to determine if less frequent dosing can maintain disease control, potentially improving patient compliance and reducing healthcare costs.

Secondary objectives include: - No incidence of relapse over the 2 years. - The percentage of patients with no change in disability over the 2 years. - The percentage of patients maintaining no evidence of disease activity over the two years. - The percentage of patients with at least 3 new T2 lesions at 2 years. - The number of new T2 lesions at 24 months. - No radiological disease activity at 12 months. - The incidence of hypogammaglobulinemia over the two years. - The evolution of gamma globulin levels between inclusion and 2 years. - The evolution of the IgG, IgM, and IgA levels between inclusion and 2 years. - The evolution of CD19 lymphocyte repopulation over the 2 years. - The incidence of infectious events over the two years. - Cancer incidence over the two years.

The clinical trial focuses on patients diagnosed with **multiple sclerosis**, specifically those who have been treated with ocrelizumab for at least two years. The study population includes both male and female participants aged 18 years and older, with an **Expanded Disability Status Scale (EDSS)** score ranging from 0 to 6. Participants must have had relapsing-remitting or secondarily progressive multiple sclerosis at the initiation of anti-CD20 therapy, with no relapses for at least 18 months. The trial does not involve a vulnerable population. Participants are required to undergo follow-up cerebral-medullary MRI as part of their care. The sponsor has not provided the total number of participants involved in the study. Key lifestyle considerations such as diet, physical activity, or habits are not specified. The selection criteria include the ability to understand French and affiliation with a social security scheme. The trial aims to compare the efficacy of annual versus semi-annual administrations of ocrelizumab in maintaining the absence of radiological disease activity over two years.

The clinical trial is designed to evaluate the **efficacy** of annual versus semi-annual infusions of **ocrelizumab** in patients with active **multiple sclerosis** who have been treated for at least two years. This is a multicenter, randomized, controlled, non-inferiority trial. The trial will be conducted over a period of 24 months, with the primary endpoint being the percentage of patients with no new or enlarged T2 lesions greater than 3mm on cerebro-medullary MRI at 24 months compared to the inclusion MRI. Secondary endpoints include relapse rates, disability progression, and the incidence of hypogammaglobulinemia, among others.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, previous treatment history, and **Expanded Disability Status Scale (EDSS)** scores. Follow-up visits will occur at regular intervals to monitor the absence of radiological disease activity and assess secondary endpoints. The end-of-study visit will take place at 24 months, where final assessments will be conducted to evaluate the primary and secondary outcomes.

The expected length of participant involvement is approximately two years. Conditions that may lead to early termination from the study include the occurrence of significant adverse events, withdrawal of consent, or non-compliance with study procedures. The trial aims to provide valuable insights into the optimal dosing schedule of ocrelizumab for maintaining disease stability in patients with multiple sclerosis.

The clinical trial involves the administration of **Ocrevus**, a pharmaceutical product containing the active substance **ocrelizumab**. Ocrevus is formulated as a **concentrate for solution for infusion** and is intended for intravenous (IV) infusion. Each vial contains 300 mg of ocrelizumab, a protein-based therapeutic agent. The maximum total dose administered per treatment cycle is 600 mg. The trial aims to evaluate the efficacy of annual versus semi-annual infusions of ocrelizumab in patients with active multiple sclerosis (MS) who have been treated for at least two years. The administration schedule is designed to assess the absence of radiological disease activity over a two-year period.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The focus is solely on the administration of ocrelizumab to determine its effectiveness in managing active MS. The trial does not involve any pediatric formulations, and the product is not classified as an orphan drug. Participant compliance with the dosing schedule is monitored to ensure adherence to the treatment protocol. The trial is conducted under the authorization of the European Union, with the marketing authorization number EU/1/17/1231/001, and is sponsored by Roche Registration GmbH.

The efficacy of the clinical trial will be assessed by evaluating the primary and secondary endpoints related to the treatment of active multiple sclerosis with ocrelizumab. The primary endpoint is the percentage of patients with no new or enlarged T2 lesion greater than 3mm on cerebro-medullary MRI at 24 months compared to the inclusion MRI. This endpoint will be measured using MRI scans to detect changes in lesion size and number, providing a radiological assessment of disease activity.

Secondary endpoints include several measures of clinical and radiological outcomes. These include the incidence of relapses, defined as the onset or worsening of symptoms leading to an increase in the Expanded Disability Status Scale (EDSS) score, and disability progression, measured by changes in the Multiple Sclerosis Functional Composite (MSFC) score and EDSS score. Additional secondary endpoints involve the percentage of patients with No Evidence of Disease Activity (NEDA 3) at 24 months, the number of new T2 lesions on MRI, and the evolution of various immunological markers such as gamma globulin levels, IgG, IgM, IgA assays, and CD19 lymphocyte counts. The incidence of infectious events requiring treatment and cancer will also be monitored.

These efficacy parameters will be collected and analyzed at specified timepoints, including baseline, 12 months, and 24 months, using validated scales and laboratory tests. The trial aims to compare the efficacy of annual versus semi-annual administrations of ocrelizumab in maintaining the absence of radiological disease activity over a two-year period in patients who have been treated with ocrelizumab for at least two years.