STHENOS

Treatment tested

• Ofatumumab

  B-lymphocyte antigen CD20 binding agent

Compared with

• Glatiramer acetate

  Unknown

• Interferon β-1b
• Interferon beta-1a

  Interferon alpha/beta receptor agonist

• Peginterferon β-1a
• Teriflunomide

  Dihydroorotate dehydrogenase inhibitor

• Dimethyl fumarate

  Kelch-like ECH-associated protein 1 inhibitor

• Diroximel fumarate

  Kelch-like ECH-associated protein 1 inhibitor

• Interferon beta-1b

  Interferon alpha/beta receptor agonist

• Peginterferon beta-1a

  Interferon alpha/beta receptor agonist

Other measures (32)

Inclusion Criteria 1. Written informed consent obtained before any assessment 2. Male/female patients, 18 through 55 (inclusive) years of age. 3. Diagnosis of MS according to the 2017 revised McDonald criteria (Thompson et al 2018). 4. Relapsing MS: relapsing-course (RMS), as defined by Lublin et al 2014. 5. Treatment Naïve patients, ≤ 5 years since first MS symptom. 6. EDSS score 0-4.0 (inclusive). 7. Patient must be suitable to be treated with one of first line self-administered DMT-physician's choice (glatiramer acetate, IFNs, teriflunomide, DMF, diroximel fumarate according to EMA SmPC) or ofatumumab depending on randomization and physician's choice 8. At least 1 relapse or 1 Gd+ enhanced lesion on T1 in 1 year prior to Screening. 9. Able to obtain MRI assessment. 10. Neurologically stable within 1 month prior to first study drug administration Exclusion Criteria <!-- --> 1. Diseases other than multiple sclerosis responsible for the clinical or MRI presentation 2. Progressive MS phenotypes: Patients with primary progressive MS (Polman et al 2011) or SPMS (Lublin et al 2014). 3. Use of other experimental or investigational drugs at the time of enrollment (Screening) or within the prior 30 days, or 5 elimination half-lives, or until the expected pharmacodynamics effect has returned to baseline, whichever is longer 4. Relapse between Screening and Baseline visits 5. Pregnancy or breastfeeding 6. Patients suspected of not being able or willing to cooperate or comply with study protocol requirements in the opinion of the Investigator 7. Women of childbearing potential defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception (methods that result in less than 1% pregnancy rates) while receiving ofatumumab and for 6 months after the last administration. The requirements for contraception for the comparators should also be taken into consideration according to their SmPC. Highly effective methods of contraception include: * Total abstinence (when this is in line with the preferred and usual lifestyle of the participant). Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the participant. Periodic abstinence (e.g. calendar, ovulation, symptothermal, postovulation methods) and withdrawal are not acceptable methods of contraception. * Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or bilateral tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment. * Male sterilization (at least 6 months prior to screening). For female participants on the study, the vasectomized male partner should be the sole partner for that participant. (Vasectomized partner is a highly effective birth control method provided that partner is the sole sexual partner of the WOCBP trial participant and that the vasectomized partner has received medical assessment of the surgical success.) - Use of combined, estrogen and progesterone containing (oral, intravaginal, transdermal), hormonal methods of contraception or use of progesterone-only (oral, injectable, implantable) hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS), or other forms of hormonal contraception that have comparable efficacy (failure rate \<1%), for example hormone vaginal ring or transdermal hormone contraception. In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment. Women are considered post-menopausal if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate history of vasomotor symptoms). Women are considered not of childbearing potential if they are post-menopausal or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or bilateral tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of childbearing potential. If local regulations deviate from the contraception methods listed above to prevent pregnancy, local regulations apply and will be described in the ICF. 8. Patients with an active chronic disease (or stable but treated with immune therapy) of the immune system other than MS (e.g. rheumatoid arthritis, scleroderma, Sjögren's syndrome, Crohn's disease, ulcerative colitis, etc.) or with immunodeficiency syndrome (hereditary immune deficiency, drug-induced immune deficiency) 9. Patients with an active infection (bacterial, fungal, or viral like hepatitis, HIV or COVID), until the infection is resolved. Where local regulation requires it, Sars-Cov-19 must be ruled out by the PCR test. 10. Patients with neurological findings consistent with Progressive Multifocal Leukoencephalopathy (PML), or confirmed PML 11. Positive results at Screening for serological markers for hepatitis (H) B and C indicating acute or chronic infection: - Hepatitis B virus (HBV) screening should be performed before initiation of treatment. At a minimum, screening should include hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (HBcAb) testing. These can be complemented with other appropriate markers as per local guidelines. Patients with positive hepatitis B serology (either HBsAg or HBcAb) should consult a liver disease expert before the start of treatment and should be monitored and managed following local medical standards to prevent hepatitis B reactivation. - Hepatitis C risk must be ruled out via anti-HC IgG (if positive IgG, HCV-RNA PCR will be performed and if negative, patient can be enrolled) NOTE: If the Investigator suspects false positive hepatitis serology results such as an antibody pattern indicating acute hepatitis infection but no corresponding elevated liver enzymes and no signs or symptoms of liver disease, an infectious disease expert may be consulted. In the case the patient has a record of vaccination including HB, and there is no evidence of acute or chronic hepatitis infection (confirmed by an infectious disease expert), the Investigator must document (in source data and as a comment in the electronic Case Report Form (eCRF) that the serology results are considered false positive and may then enroll the subject. 12. Have received any live or live-attenuated vaccines within 4 weeks prior to first study drug administration 13. Any other disease or condition that could interfere with participation in the study according to the study protocol, or with the ability of the patients to cooperate or comply with the study procedures 14. Any of the following conditions or treatments that may impact the safety of the patient: - History of, or current, significant cardiac disease including cardiac failure (NYHA functional class II-IV), myocardial infarction (within 6 months prior to screening), unstable angina (within 6 months prior to screening), transient ischemic attack (within 6 months prior to screening), stroke, cardiac arrhythmias requiring treatment or uncontrolled arterial hypertension - Concomitant clinically significant cardiac arrhythmias, e.g. sustained ventricular tachycardia and clinically significant second or third degree AV block without a pacemaker on screening electrocardiogram (ECG) * History of or active severe respiratory disease, including Chronic Obstructive Pulmonary Disease, interstitial l

This study will compare ofatumumab vs. European approved platform first line self-administered disease modifying therapy (DMT) in newly diagnosed MS patients