Study to Assess the Short- and Long-term Efficacy of Certolizumab Pegol Plus Methotrexate Compared to Adalimumab Plus Methotrexate in Subjects With Moderate to Severe Rheumatoid Arthritis (RA) Inadequately Responding to Methotrexate
Condition: Rheumatoid Arthritis
MeSH terms: Arthritis; Arthritis, Rheumatoid
Intervention: Certolizumab Pegol (CZP); Adalimumab (ADA); Methotrexate (MTX)
Intervention description: Active substance: an injectable volume of 1 ml solution for injection CZP
Pharmaceutical form: prefilled syringes CZP
Concentration: 200 mg/ml CZP
Route of Administration: injections will be given subcutaneously: loading dose of CZP 400 mg at Baseline, and Weeks 2 and 4, followed by a maintenance dose of 200 mg every 2 weeks through Week 102 or withdrawal.; Active substance: an injectable volume of 0.8 ml solution for injection ADA
Pharmaceutical form: prefilled syringes ADA
Concentration: 40 mg/0.8 ml ADA
Route of Administration: injections will be given subcutaneously. ADA 40 mg plus an injection with Placebo (to preserve blind) at Baseline, and Weeks 2 and 4, followed by ADA 40 mg every 2 weeks through Week 102 or withdrawal.; Active substance: Methotrexate
Pharmaceutical form: oral tablet
Concentration: 15-25 mg/week
Route of Administration: MTX orally
Intervention MeSH terms: Adalimumab; Certolizumab Pegol; Methotrexate
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Enrollment: 915.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Certolizumab Pegol; Cimzia; Adalimumab; Humira; Rheumatoid Arthritis

Summary:

      This study is conducted to evaluate the short (12 Weeks) and long term (104 Weeks) efficacy
      of Certolizumab Pegol compared with Adalimumab both in combination with Methotrexate (MTX) in
      the treatment of moderate to severe Rheumatoid Arthritis (RA) that is not responding
      adequately to MTX.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subject must have a diagnosis of Rheumatoid Arthritis (RA) at Screening, as defined by
             the 2010 European League Against Rheumatism (EULAR)/American College of Rheumatology
             (ACR) classification criteria (Aletaha D et al, 2010)

          -  Subject must have a positive Rheumatoid Factor (RF) and/or a positive anti-Cyclic
             Citrullinated Peptide antibody (anti-CCP) as determined by the central laboratory at
             Screening

          -  Subject must have moderate to severe RA disease at Screening and Baseline defined as:

               1. Screening (all criteria required)

                    -  ≥ 4 swollen joints (of 28 prespecified joints)

                    -  Disease Activity Score [Erythrocyte Sedimentation Rate] (DAS28[ESR]) > 3.2

                    -  C-Reactive Protein (CRP) concentration ≥ 10 mg/L (or 1.0 mg/dL) or
                       Erythrocyte Sedimentation Rate (ESR) (Westergren) ≥ 28 mm/hr

               2. Baseline (both criteria required)

                    -  ≥ 4 swollen joints (of 28 prespecified joints)

                    -  Disease Activity Score [Erythrocyte Sedimentation Rate] (DAS28[ESR]) > 3.2

          -  Subject must have inadequately responded previously to Methotrexate (MTX)

          -  Subject is using MTX 15 to 25 mg/week orally or subcutaneously at Screening and has
             used the same MTX regimen for a minimum of 28 days prior to Baseline

        Exclusion Criteria:

          -  Subject has previously received any biological Disease Modifying Antirheumatic Drug
             (DMARD) or has received treatment with cyclophosphamide, chlorambucil, Janus Kinase,
             phosphodiesterase 4 inhibitors or investigational agents such as spleen tyrosine
             kinase

          -  Diagnosis of any other inflammatory arthritis

          -  Infected with Tuberculosis (TB) or high risk of acquiring TB infection

          -  Subjects with concurrent acute or chronic viral hepatitis B or C infection

          -  Subjects with a history of chronic or recurrent infections or subjects at high risk of
             infection

          -  Use of prohibited medications like nonbiological DMARDs (excluding MTX), biological
             DMARDs excluding study medications, experimental therapy, IA hyaluronic acid