Evaluation of Personalized B Cell-Tailored Ocrelizumab Versus Standard Ocrelizumab in Relapsing-Remitting Multiple Sclerosis: A Randomized Controlled Trial

The primary objective of this study is to evaluate the **non-inferiority** of personalized B cell tailored ocrelizumab treatment compared to the standard fixed 24-week interval treatment in suppressing disease activity in patients with **relapsing-remitting multiple sclerosis**. This is clinically relevant as it may offer a more individualized treatment approach, potentially improving patient outcomes and optimizing resource utilization.

The clinical trial involves participants diagnosed with **Multiple Sclerosis**, specifically those with a current diagnosis of relapsing-remitting multiple sclerosis according to the 2017 McDonald criteria. The study population includes both male and female subjects aged 18 years and older, with an Expanded Disability Status Scale (EDSS) score ranging from 0 to 6.5. Participants must have been treated with ocrelizumab for a minimum of 48 weeks, including two 300 mg infusions and one 600 mg infusion, with the last infusion interval not exceeding 7.5 months. The trial does not specify the total number of participants, as this information was not provided by the sponsor. The selection process for the trial population includes individuals who are part of a vulnerable population, although specific lifestyle considerations such as diet or physical activity are not detailed. The trial aims to assess the efficacy of personalized B cell tailored ocrelizumab treatment in comparison to the standard fixed 24-week interval treatment in suppressing disease activity.

The clinical trial is designed to evaluate the **efficacy**, safety, and cost-effectiveness of personalized B cell tailored ocrelizumab treatment compared to the standard regimen in patients with **relapsing remitting multiple sclerosis**. This study is a randomized, controlled trial with an estimated duration extending until May 31, 2027. Participants will be randomly assigned to either the personalized dosing group or the standard treatment group, with the trial being conducted in a double-blind manner to ensure unbiased results.

The trial will commence with a screening visit to confirm eligibility based on criteria such as a current diagnosis of relapsing remitting multiple sclerosis according to the 2017 McDonald criteria, age of 18 or older, and an EDSS score between 0 and 6.5. Participants must have been treated with ocrelizumab for a minimum of 48 weeks prior to enrollment. The primary endpoints will assess the percentage of confirmed relapse-free patients and the percentage of patients without new or enlarging T2 MRI lesions after 96 weeks of follow-up.

Study visits will be scheduled at regular intervals throughout the trial to monitor patient progress and collect data. These visits will include assessments of disease activity, safety evaluations, and MRI scans. The end-of-study visit will occur at the conclusion of the 96-week follow-up period, where final assessments will be conducted to evaluate the primary and secondary endpoints.

Participant involvement is expected to last for the entire duration of the trial, approximately 96 weeks, unless early termination is warranted. Conditions that may lead to early termination include adverse events, withdrawal of consent, or non-compliance with the study protocol. The trial aims to provide valuable insights into the potential benefits of personalized dosing of ocrelizumab in managing multiple sclerosis.

The clinical trial involves the administration of **Ocrevus**, a 300 mg concentrate for solution for infusion, which is the experimental medication under investigation. The active substance in Ocrevus is **ocrelizumab**, a protein-based therapeutic agent. The pharmaceutical form of the medication is a solution for infusion, and it is administered via **intravenous infusion**. The dosing regimen for the trial includes a maximum daily dose of 600 mg, with a total maximum dose of 48,000 mg over the course of the study. The maximum treatment period is set at 480 days. The medication is not a pediatric formulation and is not classified as an orphan drug. The trial aims to evaluate the efficacy, safety, and cost-effectiveness of a B cell tailored ocrelizumab treatment compared to the standard fixed 24-week interval treatment in patients with relapsing-remitting multiple sclerosis.

In addition to the experimental treatment, the study may include the use of standard-of-care therapy as a comparator treatment. The standard treatment involves the administration of ocrelizumab at fixed intervals of 24 weeks. The trial is designed to assess whether the personalized B cell tailored approach is non-inferior to the standard treatment in terms of suppressing disease activity. Participant compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the treatment protocol. No placebo is used in this trial, and the focus is on comparing the tailored treatment approach to the established standard regimen.

Efficacy in the clinical trial titled "Efficacy, safety and cost-effectiveness of B cell tailored ocrelizumab versus standard ocrelizumab in relapsing remitting multiple sclerosis (BLOOMS)" will be assessed using two co-primary endpoints. These endpoints are the difference in the percentage of confirmed relapse-free patients between the two treatment groups after 96 weeks of follow-up, and the difference in the percentage of patients without new or enlarging T2 MRI lesions between the two treatment groups after the same period. The trial aims to demonstrate that personalized B cell tailored **ocrelizumab** treatment is non-inferior in suppressing multiple sclerosis disease activity compared to the standard treatment administered at fixed 24-week intervals. The efficacy parameters will be measured and collected at the 96-week mark, utilizing MRI scans to evaluate the presence of new or enlarging T2 lesions and clinical assessments to confirm relapse-free status. The analysis will focus on comparing these outcomes between the personalized dosing group and the standard treatment group to determine the efficacy of the tailored approach.