Safety and Efficacy Study of M2951 in Participants With Rheumatoid Arthritis

Inclusion Criteria

• Men or women 18 to 75 years of age at the time of informed consent signature
• Confirmed diagnosis of RA according to 2010 American College of Rheumatology (ACR)/The European League Against Rheumatism (EULAR) RA classification criteria of at least 6 months duration
• Positive RF and/or anti-CCP (anti-cyclic citrullinated peptide)
• Persistently active disease defined as greater than equal to (>=) 6 swollen joints (of 66 counted) and >= 6 tender joints (of 68 counted)
• High-sensitivity C-reactive protein (hsCRP) >= 3.6 milligram per liter (mg/L)
• Treatment for >= 12 weeks with 10 to 25 mg/week MTX at a stable dose for at least 4 weeks prior to dosing with the investigational medicinal product (IMP) and maintained throughout the trial
• Women of childbearing potential must use acceptable methods of contraception for 4 weeks prior to randomization, throughout the trial, and for 90 days after the last dose of IMP. For the purposes of this trial
• Females who are postmenopausal (age-related amenorrhea >= 12 consecutive months and increased follicle-stimulating hormone [FSH] greater than (>) 40 milli international units per milliliter [mIU/mL]), or who have undergone hysterectomy or bilateral oophorectomy are exempt from pregnancy testing. If necessary to confirm postmenopausal status, an FSH will be drawn at Screening
• Acceptable contraception is defined as use of either 2 barrier methods (eg, female diaphragm and male condom), or 1 barrier method in conjunction with one of the following: spermicide, an intrauterine device, or hormonal contraceptives (implant or oral)
• Women of childbearing potential must have a negative serum pregnancy test at the Screening Visit and a negative urine pregnancy test at Day 1/randomization before dosing.

Exclusion Criteria

• Use of oral corticosteroids > 10 mg daily prednisone equivalent, use of injectable corticosteroids, or change in dose of corticosteroids within 2 weeks prior to Screening or during Screening
• Initiation or change in dose for nonsteroidal anti-inflammatory drugs (NSAIDs) within 2 weeks prior to Screening
• Treatment with tofacitinib, other Bruton's Tyrosine Kinase (BTK) inhibitors, or a biologic disease-modifying antirheumatic drug (DMARD; eg, anti-tumor necrosis factor alpha [anti-TNF-α], tocilizumab [anti-interleukin-6 receptor], abatacept [CTLA4-Fc]), or other immunosuppressive drugs(sulfasalazine would be acceptable at a stable dose) other than methotrexate within 3 months prior to Screening or during Screening
• Treatment with anti-CD20 therapy (eg, rituximab) within 12 months prior to Screening or during Screening
• Immunologic disorder other than Rheumatoid Arthritis (RA), with the exception of secondary Sjogren's syndrome associated with RA, and well-controlled diabetes or thyroid disorder, or any other condition requiring oral, intravenous, intramuscular, or intra-articular corticosteroid therapy
• Vaccination with live or live-attenuated virus vaccine within 1 month prior to Screening
• Active, clinically significant, viral, bacterial, or fungal infection, or any major episode of infection requiring hospitalization or treatment with parenteral anti-infectives within 4 weeks of Screening or during Screening, or completion of oral anti-infectives within 2 weeks before or during Screening, or a history of recurrent infections (ie, 3 or more of the same type of infection in a 12-month rolling period). Vaginal candidiasis, onychomycosis, and genital or oral herpes simplex virus considered by the Investigator to be sufficiently controlled would not be exclusionary
• History of or positive testing for human immunodeficiency virus (HIV), hepatitis C antibody and/or polymerase chain reaction, hepatitis B surface antigen (HBsAg) (+) and/or hepatitis B core total, and/or IgM antibody (+) at Screening
• History of or current diagnosis of active tuberculosis (TB); undergoing treatment for latent TB infection (LTBI); untreated LTBI (as determined by doc