A Study in Moderate to Severe Rheumatoid Arthritis
Condition: Rheumatoid Arthritis
MeSH terms: Arthritis; Arthritis, Rheumatoid
Intervention: Adalimumab; Baricitinib; Methotrexate; Adalimumab Placebo; Baricitinib Placebo
Intervention description: Administered SC; Administered orally; Administered orally; Adalimumab placebo administered SC.; Baricitinib placebo administered orally.
Intervention MeSH terms: Adalimumab; Methotrexate
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 1307.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to determine whether baricitinib is superior to placebo in the
      treatment of participants with moderately to severely active Rheumatoid Arthritis (RA) who
      have had an inadequate response to methotrexate (MTX) treatment.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Have a diagnosis of adult-onset Rheumatoid Arthritis (RA) as defined by the American
             College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) 2010 Criteria
             for the Classification of RA

          -  Have moderately to severely active RA defined as the presence of at least 6/68 tender
             joints and at least 6/66 swollen joints

          -  Have a C-reactive protein (CRP) or high-sensitivity C-reactive protein (hsCRP)
             measurement ≥6 milligram per Liter (mg/L)

          -  Have had regular use of methotrexate (MTX) for at least the 12 weeks prior to study
             entry at a dose that is considered acceptable to adequately assess clinical response.

          -  Have at least 1 joint erosion in hand, wrist, or foot joints based on radiographic
             interpretation by the central reader and be rheumatoid factor or anticyclic
             citrullinated peptide (anti-CCP) antibody positive; or have at least 3 joint erosions
             in hand, wrist, or foot joints based on radiographic interpretation by the central
             reader regardless of rheumatoid factor or anti-CCP antibody status

        Exclusion Criteria:

          -  Are currently receiving corticosteroids at doses >10 mg of prednisone per day (or
             equivalent) or have been receiving an unstable dosing regimen of corticosteroids
             within 2 weeks of study entry or within 6 weeks of planned randomization

          -  Have started treatment with non-steroidal anti-inflammatory drugs (NSAIDs) or have
             been receiving an unstable dosing regimen of NSAIDs within 2 weeks of study entry or
             within 6 weeks of planned randomization

          -  Are currently receiving concomitant treatment with MTX, hydroxychloroquine, and
             sulfasalazine or combination of any 3 conventional disease-modifying antirheumatic
             drugs (cDMARDs)

          -  Are currently receiving or have received cDMARDs (eg, gold salts, cyclosporine,
             azathioprine, or any other immunosuppressives) other than MTX, hydroxychloroquine (up
             to 400 mg/day), or sulfasalazine (up to 3000 mg/day) within 4 weeks prior to study
             entry

          -  Have received leflunomide in the 12 weeks prior to study entry

          -  Have started a new physiotherapy treatment for RA in the 2 weeks prior to study entry

          -  Have ever received any biologic disease-modifying antirheumatic drugs (DMARD)

          -  Have received interferon therapy within 4 weeks prior to study entry or are
             anticipated to require interferon therapy during the study

          -  Have received any parenteral corticosteroid administered by intramuscular or
             intravenous injection within 2 weeks prior to study entry or within 6 weeks prior to
             planned randomization or are anticipated to require parenteral injection of
             corticosteroids during the study

          -  Have had 3 or more joints injected with intraarticular corticosteroids or hyaluronic
             acid within 2 weeks prior to study entry or within 6 weeks prior to planned
             randomization

          -  Have any condition or contraindication for adalimumab that would preclude the
             participant from participating in this protocol

          -  Have active fibromyalgia that would make it difficult to appropriately assess RA
             activity for the purposes of this study

          -  Have a diagnosis of any systemic inflammatory condition other than RA such as, but not
             limited to, juvenile chronic arthritis, spondyloarthropathy, Crohn's disease,
             ulcerative colitis, psoriatic arthritis, active vasculitis or gout(participants with
             secondary Sjögren's syndrome are not excluded)

          -  Have a diagnosis of Felty's syndrome

          -  Have had any major surgery within 8 weeks prior to study entry or will require major
             surgery during the study that, in the opinion of the investigator in consultation with
             Lilly or its designee, would pose an unacceptable risk to the participant

          -  Have experienced any of the following within 12 weeks of study entry: myocardial
             infarction, unstable ischemic heart disease, stroke, or New York Heart Association
             Stage IV heart failure

          -  Have a history or presence of cardiovascular, respiratory, hepatic, gastrointestinal,
             endocrine, hematological, neurological, or neuropsychiatric disorders or any other
             serious and/or unstable illness that, in the opinion of the investigator, could
             constitute a risk when taking investigational product or could interfere with the
             interpretation of data

          -  Are largely or wholly incapacitated permitting little or no self-care, such as being
             bedridden or confined to a wheelchair

          -  have a history of, lymphoproliferative disease; or have signs or symptoms suggestive
             of possible lymphoproliferative disease, including lymphadenopathy or splenomegaly; or
             have active primary or recurrent malignant disease; or have been in remission from
             clinically significant malignancy for <5 years

          -  Have been exposed to a live vaccine within 12 weeks prior to planned randomization or
             are expected to need/receive a live vaccine during the course of the study (with the
             exception of herpes zoster vaccination)

          -  Have a current or recent clinically serious viral, bacterial, fungal, or parasitic
             infection

          -  Have had symptomatic herpes zoster infection within 12 weeks prior to study entry

          -  Have a history of disseminated/complicated herpes zoster (eg, multidermatomal
             involvement, ophthalmic zoster, central nervous system involvement, or postherpetic
             neuralgia)

          -  Are immunocompromised and, in the opinion of the investigator, are at an unacceptable
             risk for participating in the study

          -  Have a history of active hepatitis B virus (HBV), hepatitis C virus (HCV), or human
             immunodeficiency virus (HIV)

          -  Have screening laboratory test values, including thyroid-stimulating hormone (TSH),
             outside the reference range for the population or investigative site that, in the
             opinion of the investigator, pose an unacceptable risk for the participant's
             participation in the study

          -  Have screening electrocardiogram (ECG) abnormalities that, in the opinion of the
             investigator or the sponsor, are clinically significant and indicate an unacceptable
             risk for the participant's participation in the study

          -  Have symptomatic herpes simplex at the time of study enrollment

          -  Have evidence of active or latent tuberculosis (TB)