Efficacy at 24 Weeks and Safety, Tolerability and Long Term Efficacy of Secukinumab (AIN457) in Patients With Active Rheumatoid Arthritis (RA) and an Inadequate Response to Anti-Tumor Necrosis Factor α (Anti-TNFα) Agents (CAIN457F2309 and CAIN457F2309E1)
Condition: Rheumatoid Arthritis
MeSH terms: Arthritis; Arthritis, Rheumatoid
Intervention: AIN457; Placebo; Abatacept
Intervention description: AIN457 (Secukinumab) is a human monoclonal antibody. Secukinumab binds and reduces the activity of Interleukin 17 (IL-17). AIN457 was given as i.v. (10mg/kg) at baseline, week 2 and week 4, and then s.c. (75 or 150mg) every 4 weeks starting at week 8.; Placebo was given as i.v. at baseline, week 2 and week 4, and then s.c. every 4 weeks starting at week 8.; Abatacept (from 500 to 1000 mg i.v. based on weight) was given as i.v. at baseline, weeks 2 and 4, and then every 4 weeks starting at week 8.
Intervention MeSH terms: Abatacept
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 551.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Rheumatoid Arthritis; RA; ACR; inflammatory joints

Summary:

      The core and extension studies assessed the safety and efficacy of secukinumab when added to
      a background therapy in patients with active rheumatoid arthritis who are intolerant to or
      have had an inadequate response to anti-TNF-α agents. Patients received either secukinumab,
      placebo or abatacept (active comparator). The core study was completed. However, the
      extension study was prematurely terminated after the primary endpoint analysis of the core
      study at week 24 had demonstrated numerically higher efficacy for the active comparator
      abatacept compared to secukinumab.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or non-pregnant, non-lactating female patients

          -  Presence of RA classified by ACR 2010 revised criteria for at least 3 months before
             screening

          -  At Baseline: Disease activity criteria defined by >= 6 tender joints out of 68 and >=
             6 swollen joints out of 66

        WITH at least 1 of the following at screening:

          -  Anti-Cyclic Citrullinated Peptide (Anti-CCP) antibodies positive OR

          -  Rheumatoid Factor positive

        AND WITH at least 1 of the following at screening:

          -  High sensitivity C-Reactive Protein (hsCRP) >= 10 mg/L OR

          -  Erythrocyte Sedimentation Rate (ESR) >= 28 millimeter (mm)/1st hour

          -  Patients must have been taking at least one anti-TNF-α agent given at an approved dose
             for at least 3 months before randomization and have experienced an inadequate response
             to treatment or have been intolerant to at least one administration of an anti-TNF-α
             agent

          -  Patients must be taking MTX or any other DMARD (but not more than 1 DMARD) for at
             least 3 months before randomization and have to be on a stable dose at least 4 weeks
             before randomization (7.5 to 25 mg/week for MTX or other DMARD at maximum tolerated
             dose)

        Exclusion Criteria:

          -  Chest x-ray with evidence of ongoing infectious or malignant process, obtained within
             3 months prior to screening and evaluated by a qualified physician

          -  RA patients functional status class IV according to the ACR 1991 revised criteria

          -  Patients who have ever received biologic immunomodulating agents except for those
             targeting TNFα

          -  Previous treatment with any cell-depleting therapies

        Other protocol-defined inclusion/exclusion criteria may apply.