To Evaluate The Safety of SAR153191 (REGN88) and Tocilizumab Added to Other RA Drugs in Patients With RA Who Are Not Responding to or Intolerant of Anti-TNF Therapy (SARIL-RA-ASCERTAIN)
Condition: Rheumatoid Arthritis
MeSH terms: Arthritis; Arthritis, Rheumatoid
Intervention: sarilumab SAR153191 (REGN88); tocilizumab; hydroxychloroquine; methotrexate; sulfasalazine; leflunomide; subcutaneous placebo; intravenous placebo
Intervention description: Pharmaceutical form: solution Route of administration: subcutaneous; Pharmaceutical form: solution Route of administration: intravenous; Dispensed according to local practice.; Dispensed according to local practice.; Dispensed according to local practice.; Dispensed according to local practice.; Pharmaceutical form: solution Route of administration: subcutaneous; Pharmaceutical form: solution Route of administration: intravenous
Intervention MeSH terms: Hydroxychloroquine; Sulfasalazine; Methotrexate; Leflunomide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 202.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Primary Objective:

      To assess, in the same study, the safety of sarilumab and tocilizumab in participants with
      rheumatoid arthritis (RA) who were inadequate responders to or intolerant of tumor necrosis
      factor (TNF) antagonists.
    

Eligibility criteria:

        Inclusion criteria:

        Diagnosis of RA was, according to the American College of Rheumatology (ACR)/European
        League against Rheumatism (EULAR) 2010 Rheumatoid Arthritis Classification Criteria with ≥
        3 months disease duration

        ACR Class I-III functional status, was based on the 1991 revised criteria.
        Moderate-to-severely active RA. Anti-TNF therapy failures, was defined as participants with
        an inadequate clinical response was defined by the investigator, after being treated for at
        least 3 consecutive months, and/or intolerance to at least 1 TNF-antagonist, resulting in
        or requiring their discontinuation. TNF-antagonists were include, but were not limited to,
        etanercept, infliximab, adalimumab, golimumab and/or certolizumab pegol

        Continuous treatment with one or a combination of non-biologic disease modifying
        antirheumatic drugs (DMARDs) for at least 12 consecutive weeks prior to screening and on a
        stable dose(s) for at least 6 consecutive weeks prior to screening:

          -  Methotrexate - 10 to 25 milligram/week orally or parenteral (or per local labelling
             requirements if the dose range differs)

          -  Leflunomide - 10 to 20 mg orally daily

          -  Sulfasalazine (SSZ) - 1000 to 3000 mg orally daily

          -  Hydroxychloroquine (HCQ) - 200 to 400 mg orally daily

        Exclusion criteria:

        Participants <18 years of age. Use of parenteral corticosteroids or intra-articular
        corticosteroids within 4 weeks prior to screening

        Use of oral corticosteroids in a dose higher than prednisone 10 mg or equivalent per day,
        or a change in dosage within 4 weeks prior to screening

        Past history of, or current, autoimmune or inflammatory systemic or localized joint
        disease(s) other than RA

        History of juvenile idiopathic arthritis or arthritis onset prior to age 16. Severe
        systemic RA, including but not limited to vasculitis, pulmonary fibrosis, and/or Felty's
        syndrome

        Participation in any clinical research study that evaluated an investigational drug or
        therapy within 5 half-lives or 60 days of the Screening Visit, whichever was longer

        Participants with active tuberculosis or latent tuberculosis infection. Prior or current
        history of interstitial lung disease. Prior treatment with anti-interleukin (IL) -6 or
        anti-IL-6R therapies, including but not limited to tocilizumab or sarilumab

        Treatment with anti-TNF agents, as follows:

          -  Etanercept: within 28 days prior to randomization

          -  Infliximab, adalimumab, golimumab, certolizumab pegol: within 42 days prior to
             randomization

        Treatment with RA-directed biologic agents with non- TNF-α antagonist mechanisms without
        adequate washout as follows:

          -  Anakinra: within 28 days prior to randomization

          -  Abatacept: within 42 days prior to randomization

          -  Rituximab or other cell depleting agent: Within 6 months prior to randomization or
             until total lymphocyte count and CD 19+ lymphocyte count were normalized, or whichever
             was longer

        Prior treatment with a janus kinase (JAK) inhibitor (eg, tofacitinib). Participants with a
        history of invasive opportunistic infection. Prior or current history of malignancy,
        including lymphoproliferative diseases, other than adequately-treated carcinoma in-situ of
        the cervix, nonmetastatic squamous cell or basal cell carcinoma of the skin, within 5 years
        prior to the randomization (baseline) visit

        Prior or current history of other significant concomitant illness(es) that, according to
        Investigator's judgement, was adversely affect the participant's participation in the
        study.

        The above information was not intended to contain all considerations relevant to a
        participant's potential participation in a clinical trial.