Dose Finding Study of Namilumab in Combination With Methotrexate in Participants With Moderate to Severe Rheumatoid Arthritis (RA)

Inclusion Criteria

• In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.
• The participant or, when applicable, the participant's legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.
• Is male or female and aged 18 years (20 years in Japan) or older (65 years maximum in Czech Republic) at time of signing the informed consent form.
• Must have adult onset rheumatoid arthritis (RA) as defined by the 2010 American College of Rheumatology (ACR)/ European League against Rheumatism (EULAR) criteria for the classification of RA for at least 6 months prior to Screening Visit.
• Must have active disease defined as:

a. At least moderately active disease defined by Disease Activity Score 28 based on C-reactive protein [DAS28(CRP)] ≥3.2 at screening and Disease Activity Score 28 based on Erythrocyte Sedimentation Rate [DAS28(ESR)] ≥3.2 at baseline visit [Day 1] and Swollen joint count (SJC) ≥4 (within the 28 joints from DAS28) at both the Screening and baseline [Day 1] Visits.

• Visual analog scale (VAS) pain >40 mm as measured using the 100 mm study site electronic VAS scale at the Screening Visit and baseline [Day 1] Visits.
• Currently receiving treatment for Rheumatoid Arthritis (RA) with methotrexate (MTX), and:
• Has received MTX on a weekly basis for at least 3 months prior to the Baseline (Day 1) Visit AND;
• Has received treatment with 15 mg/week ≤MTX ≤25 mg/week (6 mg/week ≤MTX ≤16 mg/week in Japan) at a stable dose via the same route of administration and formulation for at least 8 weeks prior to Baseline [Day 1] Visit

OR:

For participants outside Japan, a stable dose for at least 8 weeks of MTX of ≥7.5 mg/week is acceptable, if the MTX dose has been reduced for reasons of documented intolerance to MTX, e.g. hepatic or hematological toxicity documented in Electronic case report form (eCRF), or per local requirement.

• Willing to continue or initiate treatment with oral folic acid (at least 5 mg/week) or equivalent and be treated during the entire study (mandatory co-medication for MTX treatment).
• Must have a posterior, anterior (PA) and lateral chest x-ray obtained within 3 months prior to Screening, or recorded during screening.
• A female participant of childbearing potential who is sexually active with a nonsterilized male partner agrees to routinely use adequate contraception from signing of the informed consent throughout the duration of the study until the end of the safety follow up (18 weeks after last dose).
• A male participant who is non-sterilized and sexually active with a female partner of childbearing potential agrees to use adequate contraception from signing of the informed consent throughout the duration of the study until the end of the safety follow up (18 weeks after last dose).
• Is able and willing to complete questionnaires at home using an electronic device in an approved language.
• Has either Inadequate response to methotrexate (MTX-IR) or Inadequate response to TNF-inhibitor (TNF-IR).

Exclusion Criteria

• Participants 65 years of age in Czech Republic.
• Has received any investigational compound within 30 days, or within 5 half lives (whichever is longer) prior to the Screening Visit, or is participating or plans to participate in any other clinical study during this study.
• Has a history of or currently has any inflammatory joint disease other than RA (eg, gout, reactive arthritis, psoriatic arthritis, seronegative spondyloarthropathy or Lyme disease) or other systemic autoimmune disorder (eg, systemic lupus erythematosus [SLE], inflammatory bowel disease, scleroderma, inflammatory myopathy, mixed connective tissue disease or other overlap syndrome).
• Has any major systemic features of RA, eg, Felty's syndrome, vasculitis or interstitial fibrosis of the lungs.
• Has a diagnosis of