Open Label Randomized Multicenter to Assess Efficacy & Tolerability of Ofatumumab 20mg vs. First Line DMT in RMS

NCT04788615 | Completed Phase 3

• 2 other identifiers: COMB157G33012020-004505-32
• Study Type: interventional
• Target: 185
• Locations: 4 countries
• Sites: 41

Brief Summary

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

Conditions

Multiple Sclerosis

Keywords

Ofatumumab; relapsing multiple sclerosis; relapsing-remitting MS; MS therapy; RMS; Relapsing MS; Glatiramer acetate; IFNβ-1b; IFNβ-1a; peg-IFNβ-1a; Teriflunomide; Dimethyl fumarate; Diroximel fumarate; OMB157; adult

Outcome Measures

Primary Outcomes (1)

• Number of participants with no evidence of disease activity (NEDA-3)

  NEDA-3 (yes/no) is defined as: 1. Absence of confirmed clinical relapse 2. Absence of new MRI activity (Gd+ T1 lesion or new/enlarged T2 lesion) with MRI re-baselined at Month 3 3. Absence of 3-month confirmed disability worsening

  Baseline to 15 month

Secondary Outcomes (17)

• Number of relapses

  Baseline to Month 15

• Annual relapse rate

  Baseline to Month 15

• Percentage of relapse-free patients and proportion of relapse free patients with MRI activity free

  Month 3, Month 9 and Month 15

• Time to 3 month Confirmed Disability Worsening (CDW) and time to 6-month Confirmed Disability Worsening (CDW)

  Baseline to Month 3 and to Month 6

• Change in expanded disability status scale (EDSS)

  Baseline to Month 15

Study Arms (2)

ofatumumab

EXPERIMENTAL

Oftatumumab 20mg auto injector syringes for subcutaneous injection on Day 1, Week 1 and 2, followed by subsequent monthly dosing, starting at Month 1.

Drug: Ofatumumab

First line DMT

ACTIVE COMPARATOR

1. Glatiramer acetate minimum dose 20mg or maximum dose 40mg twice a day or three times a week or 2. Interferon minimum dose 22µg or maximum dose of 0.25mg 3 times a week or once a week or Every second week depending on preparation or 3. Peg-Interferon beta-1a minimum dose of 63µg or maximum dose of 125µg every 2 weeks (14 days) or 4. Teriflunomide 14 mg once a day or 5. Dimethyl fumarate minimum dose of 120mg or maximum dose of 240mg twice a day 6. Diroximel fumarate minimum dose of 231mg or maximum dose of 462mg twice a day

Drug: First line DMT

Interventions

Ofatumumab DRUG

20mg Subcutaneous injection

Also known as: OMB157

ofatumumab

First line DMT DRUG

any one of these based on availability at country given as First line DMT Glatiramer acetate 20mg or 40mg or Interferon 22µg or 0.25mg or Peg-Interferon beta-1a 63µg or 125µg or Teriflunomide 14mg or Dimethyl fumarate 120mg or 240mg or Diroximel fumarate 231mg or 462mg

Also known as: Glatiramer acetate or Interferon or Peg-Interferon beta-1a or Teriflunomide or Dimethyl fumarate or Diroximel fumarate

First line DMT

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Written informed consent obtained before any assessment
• Male/female patients, 18 through 55 (inclusive) years of age.
• Diagnosis of MS according to the 2017 revised McDonald criteria (Thompson et al 2018).
• Relapsing MS: relapsing-course (RMS), as defined by Lublin et al 2014.
• Treatment Naïve patients, ≤ 5 years since first MS symptom.
• EDSS score 0-4.0 (inclusive).
• 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
• At least 1 relapse or 1 Gd+ enhanced lesion on T1 in 1 year prior to Screening.
• Able to obtain MRI assessment.

You may not qualify if:

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• Diseases other than multiple sclerosis responsible for the clinical or MRI presentation
• Progressive MS phenotypes: Patients with primary progressive MS (Polman et al 2011) or SPMS (Lublin et al 2014).
• 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
• Relapse between Screening and Baseline visits
• Pregnancy or breastfeeding
• Patients suspected of not being able or willing to cooperate or comply with study protocol requirements in the opinion of the Investigator
• 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.
• 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)
• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (41)

Novartis Investigative Site

Bayonne, Bayonne Cedex, 64109, France

Location

Novartis Investigative Site

Amiens, 80054, France

Location

Novartis Investigative Site

Bordeaux, 33076, France

Location

Novartis Investigative Site

Clermont-Ferrand, 63003, France

Location

Novartis Investigative Site

Créteil, 94010, France

Location

Novartis Investigative Site

Gonesse, 95500, France

Location

Novartis Investigative Site

Grenoble, 38043, France

Location

Novartis Investigative Site

Montpellier, 34090, France

Location

Novartis Investigative Site

Nice, 06202, France

Location

Novartis Investigative Site

Nîmes, 30029, France

Location

Novartis Investigative Site

Poissy, 78303, France

Location

Novartis Investigative Site

Rennes, 35033, France

Location

Novartis Investigative Site

Strasbourg, 67000, France

Location

Novartis Investigative Site

Frankfurt am Main, Hesse, 60590, Germany

Location

Novartis Investigative Site

Westerstede, Lower Saxony, 26655, Germany

Location

Novartis Investigative Site

Cologne, North Rhine-Westphalia, 50937, Germany

Location

Novartis Investigative Site

Bayreuth, 95445, Germany

Location

Novartis Investigative Site

Berlin, 12101, Germany

Location

Novartis Investigative Site

Berlin, 13353, Germany

Location

Novartis Investigative Site

Bielefeld, 33647, Germany

Location

Novartis Investigative Site

Dortmund, 44137, Germany

Location

Novartis Investigative Site

Heidelberg, 69120, Germany

Location

Novartis Investigative Site

Siegen, 57076, Germany

Location

Novartis Investigative Site

Ulm, 89073, Germany

Location

Novartis Investigative Site

Montichiari, BS, 25018, Italy

Location

Novartis Investigative Site

Milan, MI, 20132, Italy

Location

Novartis Investigative Site

Roma, RM, 00133, Italy

Location

Novartis Investigative Site

Roma, RM, 00189, Italy

Location

Novartis Investigative Site

Orbassano, TO, 10043, Italy

Location

Novartis Investigative Site

Naples, 80131, Italy

Location

Novartis Investigative Site

Santiago Compostela, A Coruna, 15706, Spain

Location

Novartis Investigative Site

Salt, Girona, 17190, Spain

Location

Novartis Investigative Site

El Palmar, Murcia, 30120, Spain

Location

Novartis Investigative Site

Barakaldo, Vizcaya, 48903, Spain

Location

Novartis Investigative Site

Barcelona, 08035, Spain

Location

Novartis Investigative Site

Madrid, 28009, Spain

Location

Novartis Investigative Site

Madrid, 28034, Spain

Location

Novartis Investigative Site

Madrid, 28040, Spain

Location

Novartis Investigative Site

Málaga, 29010, Spain

Location

Novartis Investigative Site

Seville, 41009, Spain

Location

Novartis Investigative Site

Valencia, 46026, Spain

Location

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

ofatumumab; Glatiramer Acetate; Interferons; teriflunomide; Dimethyl Fumarate; diroximel fumarate

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Peptides; Amino Acids, Peptides, and Proteins; Cytokines; Intercellular Signaling Peptides and Proteins; Proteins; Biological Factors; Fumarates; Dicarboxylic Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The independent EDSS (Expanded disability status scale) rater will be blind to the identity of the treatment throughout the study period. Patient MRI scans read by an independent central MRI reading center.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 8, 2021
• First Posted: March 9, 2021
• Study Start: July 23, 2021
• Primary Completion: November 4, 2025
• Study Completion: November 4, 2025
• Last Updated: March 3, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

ES (11); IT (6); FR (13); DE (11)