To Evaluate The Effect Of SAR153191 (REGN88) Added To Other RA Drugs In Patients With RA Who Are Not Responding To Or Intolerant Of Anti-TNF Therapy (SARIL-RA-TARGET)
Condition: Rheumatoid Arthritis
MeSH terms: Arthritis; Arthritis, Rheumatoid
Intervention: Sarilumab; placebo; hydroxychloroquine; methotrexate; sulfasalazine; leflunomide
Intervention description: Pharmaceutical form:solution Route of administration: subcutaneous; Pharmaceutical form:solution Route of administration: subcutaneous; Dispensed according to the local practice.; Dispensed according to the local practice.; Dispensed according to the local practice.; Dispensed according to the local practice.
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: 546.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Primary Objective:

      To demonstrate that sarilumab added to disease modifying anti-rheumatic drugs (DMARDs) were
      effective for:

        -  reduction of signs and symptoms at Week 24 and

        -  improvement of physical function at Week 12

      in participants with active rheumatoid arthritis (RA) who were inadequate responders or
      intolerant to tumor necrosis factor alpha (TNF-α) antagonists.

      Secondary Objectives:

      The secondary objectives were to investigate the effects of SAR153191 (REGN88) when added to
      DMARD therapy, in participants with active RA who were inadequate responders or intolerant to
      TNF-α antagonists, for:

        -  Reduction of signs and symptoms at Week 12;

        -  Improvement in physical function at Week 24;

        -  Improvement in disease activity score as measured by other American College of
           Rheumatology (ACR) derived components at Weeks 12 and 24;

        -  Improvement in quality of life as measured by participant reported outcomes (PROs) at
           intermediate visits and Week 24.

      To assess the exposure of sarilumab added to DMARD therapy in this population.

      To assess the safety of sarilumab in this population.
    

Eligibility criteria:

        Inclusion criteria:

        Diagnosis of RA ≥6 months duration, according to the ACR /European League against
        Rheumatism (EULAR) 2010 RA Classification Criteria

        ACR Class I-III functional status, based on 1991 revised criteria

        Anti-TNF therapy failures, defined by the investigator as participants with an inadequate
        clinical response, after being treated for at least 3 consecutive months, and/or
        intolerance to at least 1 anti-TNF blocker(s), resulting in or requiring their
        discontinuation:

          -  TNF-blockers included, but were not limited to, etanercept, infliximab, adalimumab,
             golimumab and/or certolizumab

        Moderate-to-severely active RA

        Continuous treatment with one or a combination of DMARDs (except for simultaneous
        combination use of leflunomide and methotrexate) for at least 12 weeks prior to baseline
        and on a stable dose(s) for at least 6 weeks prior to screening:

          -  Methotrexate - 6 to 25 mg/week orally or parenterally

          -  Leflunomide - 10 to 20 mg orally daily

          -  Sulfasalazine - 1000 to 3000 mg orally daily

          -  Hydroxychloroquine - 200 to 400 mg orally daily

        Exclusion criteria:

        Participants <18 years of age or legal adult age

        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 active systemic RA, including but not limited to vasculitis, pulmonary fibrosis,
        and/or Felty's syndrome.

        Treatment with anti-TNF agents, as follows:

          -  Within 28 days prior to the baseline visit - etanercept

          -  Within 42 days prior to the baseline visit - infliximab, adalimumab, golimumab,
             certolizumab pegol

        Treatment with previous RA-directed biologic agents with other than TNF antagonist
        mechanisms:

        Within 28 days prior to the randomization (baseline) visit - anakinra Within 42 days prior
        to the randomization (baseline) visit - abatacept

        Within 6 months prior to the randomization (baseline) visit - any cell depleting agents
        including but not limited to rituximab without a normal lymphocyte and cluster of
        differentiation (CD) 19+ lymphocyte count

        Treatment with any DMARD other than those allowed per protocol and limited to the maximum
        specified dosage within 12 weeks prior to baseline

        Treatment with prednisone >10 mg or equivalent per day, or change in dosage within 4 weeks
        prior to baseline visit

        Any parenteral or intra-articular glucocorticoid injection within 4 weeks prior to baseline

        Prior treatment with anti-interleukin (IL) -6 or IL-6 receptor antagonist therapies,
        including tocilizumab or sarilumab, participation in a prior study of sarilumab,
        irrespective of treatment arm

        Prior treatment with a Janus kinase inhibitor (such as tofacitinib)

        New treatment or dose-adjustment to ongoing medication for dyslipidemia within 6 weeks
        prior to randomization, ie, stable dose for at least 6 weeks prior to randomization

        Participation in any clinical research study evaluating another investigational drug or
        therapy within 5 half-lives or 60 days of first investigational medicinal product (IMP)
        administration, whichever was longer

        History of alcohol or drug abuse within 5 years prior to the screening visit

        Participants with a history of malignancy 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. Nonmalignant lymphoproliferative
        disorders were also excluded

        Participants with active tuberculosis or latent tuberculosis infection

        The above information was not intended to contain all considerations relevant to a
        participant's potential participation in a clinical trial