An Open-label Study Evaluating Ofatumumab Treatment Effectiveness and PROs in Subjects With RMS Transitioning From Fumarate-based RMS Approved Therapies or Fingolimod to Ofatumumab

Study Overview
=================
Brief Summary
-----------------
Open-label study to evaluate the effectiveness of treatment with ofatumumab in subjects transitioning from any fumarate-based RMS approved therapy or fingolimod due to breakthrough disease.

Detailed Description
-----------------
This is a single arm, prospective, multicentre and open-label, 96-week study to evaluate the treatment effectiveness of ofatumumab (OMB) in subjects with relapsing multiple sclerosis (RMS) transitioning from fumarate-based RMS approved therapies, such as dimethyl fumarate (DMF), diroximel fumarate (DRF), and monomethyl fumarate (MMF), or fingolimod due to breakthrough disease activity.

Official Title
-----------------
A Single-arm, Prospective, Multicentre, Open-label Study to Evaluate Ofatumumab Treatment Effectiveness and Patient-reported Outcomes (PRO) in Patients With Relapsing Multiple Sclerosis (RMS) Transitioning From Fumarate-based RMS Approved Therapies or Fingolimod

Conditions
-----------------
Relapsing Multiple Sclerosis

Intervention / Treatment
-----------------
* Biological: Ofatumumab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of MS according to the 2017 Revised McDonald criteria Relapsing MS: relapsing forms of MS (RMS) including RMS and secondary progressive MS (SPMS) Disability status at screening defined by Expanded Disability Status Scale (EDSS) score of 0 to 4 (inclusive) MS treatment history with a maximum of 3 Disease Modifying Therapies (DMTs), where all fumarates are considered as one DMT Subject transitioning from either any fumarate-based RMS approved therapies, such as dimethyl fumarate (DMF) or diroximel fumarate (DRF), or fingolimod which was administered for a period of at least 6 months, as their last DMT before first study drug administration Breakthrough disease activity while the participant was adequately using fumarates or fingolimod prior to transitioning for a minimum of 6 months as evidenced by one or more clinically reported relapses or one or more signs of Magnetic Resonance Imaging (MRI) activity (e.g. Gd+ enhancement, new or enlarging T2 lesions) Neurologically stable within one month prior to first study drug administration Exclusion Criteria: Subjects with primary progressive MS or SPMS without disease activity Subjects meeting criteria for neuromyelitis optica Disease duration of more than 10 years since diagnosis Pregnant or nursing (lactating) women Women of child-bearing potential unless they are using highly effective forms of contraception during dosing and for at least 6 months after stopping study medication Subjects with active chronic disease of the immune system other than MS or with immunodeficiency syndrome Subjects with active systemic bacterial, fungal or viral infections (such as hepatitis, HIV, COVID-19), or known to have Acquired Immunodeficiency Syndrome (AIDS) Subjects with neurological symptoms consistent with Progressive Multifocal Leukoencephalopathy (PML) or with confirmed PML Subjects at risk of developing or having reactivation of syphilis or tuberculosis (e.g. subjects with known exposure to, or history of syphilis, or active or latent tuberculosis, even if previously treated), as confirmed by medical history or per local practice Subjects with active hepatitis B and C disease, assessed locally Have received any live or live-attenuated vaccines within 4 weeks prior to first study drug administration Have been treated with medications as specified or within timeframes specified (e.g. corticosteroids, ofatumumab, rituximab, ocrelizumab, alemtuzumab, natalizumab, daclizumab, cyclophosphamide, teriflunomide etc.) Subjects suspected of not being able or willing to cooperate or comply with study protocol requirements in the opinion of the investigator

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ofatumumab<br>Ofatumumab 20 mg subcutaneous injections every 4 weeks, following loading of 3 doses in the first 14 days | Biological: Ofatumumab<br>* Subjects will receive ofatumumab injections in an autoinjector (AI) for subcutaneous administration containing 20 mg ofatumumab (50 mg/ml, 0.4 ml content)<br>* Other names: OMB157;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annual Relapse Rate (ARR) | ARR is the number of confirmed relapses in a year calculated based on cumulative number of relapses by patient adjusted for time-in-study by patient | Up to 96 weeks from baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety evaluation | Proportion of patients with adverse events, including injection related reactions, abnormal laboratory results or vital signs, as well as proportion of patients discontinuing treatment due to insufficient effectiveness or tolerability/safety reasons | 96 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
RMS, MS, multiple sclerosis, relapsing multiple sclerosis, OMB157, adult, secondary progressive MS, SPMS