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 documented results within
3 months of the Screening Visit of a positive TB skin test with purified protein
derivative with induration >= 5 millimeter (mm), a positive QuantiFERON-TB test or
positive or borderline T-SPOT [Elispot] test); or positive QuantiFERON-TB test at
Screening. Participants with documented completed appropriate LTBI treatment would not
be excluded and are not required to be tested

- Participants with current household contacts with active TB will also be excluded

- Indeterminate QuantiFERON-TB or T-SPOT tests may be repeated once, and will be
considered positive if retest results are positive or indeterminate

- History of cancer, except adequately treated basal cell or squamous cell carcinomas of
the skin (no more than 3 lesions requiring treatment in lifetime) or carcinoma in
situ/cervical intraepithelial neoplasia of the uterine cervix, unless considered cured
> 5 years

- Clinically significant abnormality on electrocardiogram (ECG), or an active infective
process or any other clinically significant abnormality on Screening chest X-ray (CXR)
taken within 4 weeks of the first dose, per Investigator opinion. If a CXR has been
taken within the previous 3 months and results are available and normal, the CXR does
not need to be carried out

- B cell (CD19) count less than (<) 50% of the lower limit of normal at Screening

- Significant cytopenia including absolute neutrophil count < 1,500/ mm^3, platelet
count < 100,000/mm^3, or absolute lymphocyte count < 1,000/mm^3