Evaluation of Ofatumumab Efficacy and Patient-Reported Outcomes in Relapsing Multiple Sclerosis Patients Transitioning from Fumarate-Based Therapies or Fingolimod

The primary objective of this study is to **demonstrate the effectiveness** of ofatumumab 20 mg administered subcutaneously every 4 weeks in patients with **relapsing multiple sclerosis (RMS)** who have experienced breakthrough disease while on fumarate-based therapies or fingolimod. This is clinically relevant as it aims to provide an alternative treatment option for patients who do not respond adequately to current therapies, potentially improving disease management and patient outcomes.

Secondary objectives include evaluating the **safety** of ofatumumab 20 mg administered subcutaneously every 4 weeks in the same patient population. Assessing safety is crucial to ensure that the treatment is not only effective but also well-tolerated, minimizing adverse effects and enhancing patient adherence to the therapy.

The clinical trial involves a total of **160 participants** diagnosed with **relapsing multiple sclerosis (RMS)**. The study population includes both male and female subjects, with an age range of 18 to 65 years. Participants were selected based on specific criteria, including a diagnosis of multiple sclerosis according to the 2017 Revised McDonald criteria and a history of relapsing forms of MS, such as RMS and secondary progressive MS. The trial targets individuals who have experienced breakthrough disease activity while on fumarates or fingolimod for at least six months. Participants must have a disability status at screening defined by an Expanded Disability Status Scale (EDSS) score of 0 to 4, and they should be neurologically stable within one month prior to the first study drug administration. The trial includes individuals transitioning from fumarate-based therapies or fingolimod, with a maximum of three disease-modifying therapies in their treatment history. The study does not specify particular lifestyle considerations such as diet or physical activity. The trial population includes vulnerable groups, ensuring a comprehensive evaluation of the treatment's effectiveness across diverse demographics.

The clinical trial is designed as a **single-arm**, prospective, multicentre, open-label study to evaluate the effectiveness of **ofatumumab** treatment and patient-reported outcomes in patients with **relapsing multiple sclerosis (RMS)** transitioning from fumarate-based RMS approved therapies or fingolimod. The trial aims to demonstrate the effectiveness of ofatumumab 20 mg administered subcutaneously every four weeks in subjects who have experienced breakthrough disease on fumarates or fingolimod. The primary endpoint is the annual relapse rate measured over a period of 96 weeks, while secondary endpoints include the proportion of subjects experiencing adverse events, laboratory or vital signs abnormalities, and treatment discontinuation due to insufficient effectiveness or tolerability.

The trial duration is estimated to conclude by April 2025, with recruitment having commenced in August 2020. Participants will be involved in the study for a maximum treatment period of 96 weeks. The study visits are structured to include an initial screening visit to confirm eligibility based on criteria such as a diagnosis of MS according to the 2017 Revised McDonald criteria, a disability status defined by an Expanded Disability Status Scale score of 0 to 4, and a history of treatment with a maximum of three disease-modifying therapies. Follow-up visits will be conducted to monitor the participants' response to treatment and any adverse events. The end-of-study visit will assess the overall outcomes and safety of the treatment.

Participants may be subject to early termination from the study if they experience significant adverse events, fail to comply with the study protocol, or if the investigator deems it necessary for the participant's safety. The study is not categorized as low intervention and is classified as a phase 3 trial. The investigational product, Kesimpta 20 mg solution for injection in a pre-filled pen, is a clinical variant of an approved product, and the administration route is subcutaneous use. The trial does not include a pediatric formulation, and the maximum total dose amount is 540 mg over the treatment period.

The clinical trial involves the administration of **Kesimpta**, a 20 mg solution for injection in a pre-filled pen, containing the active substance **ofatumumab**. This medication is a protein-based therapeutic agent classified under the ATC code L04AG12. The pharmaceutical form is a solution for injection, specifically designed for subcutaneous use. The medication is administered using an autoinjector device, known as Delta-04, which is assembled with a pre-filled syringe to facilitate single-use administration. The dosing regimen involves a maximum daily dose of 20 mg, with a total maximum dose of 540 mg over the course of the treatment. The treatment period extends up to 96 weeks, with the medication being administered every four weeks.

In this study, **Kesimpta** is utilized as the experimental treatment to evaluate its effectiveness in patients with relapsing multiple sclerosis (RMS) who have experienced breakthrough disease on fumarate-based therapies or fingolimod. The trial is designed as a single-arm, prospective, multicentre, open-label study, focusing on patient-reported outcomes and the therapeutic impact of ofatumumab. No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are employed in this study. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the treatment protocol.

Efficacy in this clinical trial will be assessed primarily through the measurement of the **Annual Relapse Rate (ARR)**, based on confirmed relapses, over a period of 96 weeks. This endpoint is designed to evaluate the effectiveness of ofatumumab 20 mg administered subcutaneously every 4 weeks in patients with relapsing forms of multiple sclerosis (MS) who have experienced breakthrough disease on fumarate-based therapies or fingolimod. Secondary endpoints include the proportion of subjects experiencing adverse events, including injection-related reactions, and the proportion of patients with laboratory or vital signs results meeting abnormal criteria. Additionally, the trial will assess the proportion of subjects discontinuing treatment due to insufficient effectiveness or tolerability/safety reasons.