Study to Determine the Effects of Different Doses of Methotrexate (MTX) When Taken With Adalimumab in Subjects With Early Rheumatoid Arthritis (RA)

A Double-Blind, Randomized, Parallel-Arm, Multicenter Study to Determine the Dose Response of Methotrexate (MTX) in Combination Therapy With Adalimumab in Subjects With Early Rheumatoid Arthritis (CONCERTO)

The purpose of this study is to determine the effects of different doses of methotrexate (MTX) when taken with adalimumab in subjects with early rheumatoid arthritis (RA).

Inclusion Criteria:

• Male and female subjects at least 18 years of age

• Subject has a diagnosis of Rheumatoid Arthritis (RA) as defined by either the 1987-revised American College of Rheumatology (ACR) classification criteria or the new ACR/ European League Against Rheumatism (EULAR) diagnostic criteria for RA 2010 and has a disease duration of less than 1 year from diagnosis by a licensed health care provider

• Subject must meet the following criteria:

  1. Disease Activity Score of C-reactive Protein (DAS28[CRP]) ≥ 3.2 (at the Baseline visit only)
  2. At least 6 swollen joints out of 66 assessed (at the Screening and Baseline visits)
  3. At least 8 tender joints out of 68 assessed (at the Screening and Baseline visits)
  4. C-reactive protein (CRP) ≥ 1.5 mg/dL (at the Screening visit only), or erythrocyte sedimentation rate (ESR) ≥ 28 mm/1h (at the Screening and Baseline visits)
  5. Fulfill at least one of the following three criteria: Rheumatoid Factor (RF) positive, have at least 1 bony erosion, anti-cyclic citrullinated peptide (anti-CCP) antibody positive

• Subject is judged to be in good health as determined by the Principal Investigator based upon the results of medical history, laboratory profile, physical examination, chest x-ray (CXR), and a 12-lead electrocardiogram (ECG) performed during Screening

Exclusion Criteria:

• Subject has previous exposure to any systemic biologic therapy including adalimumab
• Subject has been previously treated with greater than 1 disease modifying antirheumatic drugs (DMARDs) or with methotrexate (MTX)
• Subject has undergone joint surgery within the preceding two months (at joints to be assessed within the study)
• Subject has chronic arthritis diagnosed before age 17 years
• History of invasive infection (e.g., listeriosis and histoplasmosis), chronic or active Hepatitis C infection, human immunodeficiency virus (HIV) infection, immunodeficiency syndrome, chronic recurring infections or active tuberculosis (TB)
• Hepatitis B virus: hepatitis B surface antigen (HBs Ag) positive (+) or detected sensitivity on the hepatitis B virus DNA (HBV DNA) polymerase chain reaction (PCR) qualitative test
• Infection(s) requiring treatment with intravenous (IV) anti-infectives within 30 days prior to the Baseline Visit or oral anti-infectives within 14 days prior to the Baseline visit
• Female subject who is pregnant or breast-feeding or considering becoming pregnant