Effect of Sarilumab on Patient-reported Outcomes in Patients With Active Rheumatoid Arthritis
Condition: Rheumatoid Arthritis
MeSH terms: Arthritis; Arthritis, Rheumatoid
Intervention: SARILUMAB; Azathioprine; Chloroquine; Hydroxychloroquine; Leflunomide; Methotrexate; Sulfasalazine
Intervention description: Pharmaceutical form:Solution for injection in pre-filled syringe Route of administration: Subcutaneous; Pharmaceutical form:Tablet Route of administration: Oral; Pharmaceutical form:Tablet Route of administration: Oral; Pharmaceutical form:Tablet Route of administration: Oral; Pharmaceutical form:Tablet Route of administration: Oral; Pharmaceutical form:Solution for injection Route of administration: Subcutaneous / Intramuscular; Pharmaceutical form:Tablet Route of administration: Oral
Intervention MeSH terms: Hydroxychloroquine; Chloroquine; Sulfasalazine; Methotrexate; Azathioprine; Leflunomide
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 84.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Primary Objective:

      To assess the effect of sarilumab in combination with conventional synthetic
      Disease-Modifying Anti-Rheumatic Drug (csDMARD) and/or monotherapy on participant-reported
      impact of disease, using the rheumatoid arthritis impact of disease (RAID) questionnaire, in
      participants with moderately to severely active rheumatoid arthritis (RA) and inadequate
      response or intolerance to current csDMARD or tumor necrosis factor (TNF) inhibitors.

      Secondary Objectives:

        -  To assess the change of the RAID score from baseline (to Week 4, Week 12, and Week 24)
           in participants with moderately to severely active RA and inadequate response or
           intolerance to current csDMARD or TNF inhibitors, treated with sarilumab in combination
           with csDMARD and/or monotherapy.

        -  To assess the effect of sarilumab in combination with csDMARD and/or monotherapy on
           other participant-reported outcomes (global assessment of disease activity, disability,
           morning stiffness, fatigue, anxiety/depression, mood disorders, and physical activities)
           in participants with moderately to severely active RA and inadequate response or
           intolerance to current csDMARD or TNF inhibitors.

        -  To assess the efficacy of sarilumab in combination with csDMARD and/or monotherapy using
           disease activity score-28 for RA with erythrocyte sedimentation rate (DAS28-ESR) and
           clinical disease activity index in participants with moderately to severely active RA
           and inadequate response or intolerance to current csDMARD or TNF inhibitors.

        -  To assess the safety of sarilumab in combination with csDMARD and/or monotherapy in
           participants with moderately to severely active RA and inadequate response or
           intolerance to current csDMARD or TNF inhibitors.
    

Eligibility criteria:

        Inclusion criteria :

          -  Participants with moderately to severely active RA to European League against
             Rheumatology (EULAR)/American College of Rheumatology (ACR) Criteria.

          -  Participants with moderate to severe disease activity defined as a DAS28-ESR greater
             than (>) 3.2 at Screening.

          -  Participants with inadequate response within at least the last 3 months or intolerance
             to current csDMARD or to at least one anti-TNF therapy (as defined by the
             investigator).

          -  Oral corticosteroids (less than or equal to [<=] 15 mg/day prednisone or equivalent)
             and nonsteroidal anti-inflammatory drugs or cyclooxygenase-2 (up to the maximum
             recommended dose) were allowed if taken at a stable dose for at least 4 weeks prior to
             Baseline.

          -  Permitted csDMARDs were allowed if taken at a stable dose for at least 4 weeks prior
             to Baseline.

          -  Participants abled and given written informed consent and complied with the
             requirements of the study protocol.

        Exclusion criteria:

          -  Less than (<) 18 years of age.

          -  Participant unable to understand and write adequately to complete the study
             participant related outcome assessments.

          -  Exposure to sarilumab at any time prior to Baseline visit.

          -  Use of intra-articular or parenteral corticosteroids within 4 weeks prior to Baseline.

          -  Treatment with any investigational agent within the 4 weeks of Screening.

          -  Last RA treatment prior to inclusion with any anti-Janus kinase (JAK) or biologic
             DMARD other than anti-TNF.

          -  Participants treated with anti-TNF (i.e. adalimumab, infliximab, certolizumab,
             golimumab, etanercept) before the screening period, which are maintained within the 4
             weeks before the inclusion (i.e. the first injection of sarilumab).

          -  Rheumatic autoimmune disease other than RA or prior history or current inflammatory
             joint disease other than RA.

          -  Evidence of active malignant disease, malignancies diagnosed within the previous 10
             years (except basal and squamous cell carcinoma of the skin or carcinoma in situ of
             the cervix uteri previously excised and cured).

          -  Participant who was institutionalized due to regulatory or legal order or participant
             who was mentally disabled or educationally disadvantaged.

          -  Pregnant or breastfeeding woman.

          -  Women of childbearing potential not protected by highly-effective contraceptive
             method(s) of birth control (as defined in the informed consent form and/or in a local
             protocol addendum/amendment) over the study period and for at least 3 months following
             the last dose of sarilumab, and/or who are unwilling or unable to be tested for
             pregnancy.

          -  History of severe allergic or anaphylactic reactions to human, humanized, or murine
             monoclonal antibodies (or to any of the excipients associated to sarilumab).

          -  Immunization with a live/attenuated vaccine within 4 weeks prior to Baseline.

          -  Stage III or IV cardiac failure according to the New York Heart Association
             classification.

          -  History of previous gastrointestinal perforation or diverticulitis.

          -  Known active current/ recurrent infections (including but not limited to active
             tuberculosis [TB] or history of incompletely treated TB and atypical mycobacterial
             disease, hepatitis B and C, and herpes zoster). NOTE: in case of latent TB infection
             the participant might be included if a subsequent appropriate anti TB treatment is
             initiated since at least 3 weeks.

          -  Positive hepatitis B surface antigen, and/or positive total hepatitis B core antibody,
             and/or positive hepatitis C antibody at the Screening visit.

          -  Evidence of serious uncontrolled concomitant disease, including severe uncontrolled
             hypercholesterolemia or hypertriglyceridemia.

          -  Participants with any of the following laboratory abnormalities at the Screening or
             Baseline visit:

               -  Hemoglobin <8.5 grams per deciliter.

               -  White blood cells <3000/cubic millimeter (mm^3).

               -  Absolute neutrophil count <2000/mm^3

               -  Absolute lymphocyte count <500/mm^3

               -  Platelet count <150 000 cells/mm^3

               -  Creatinine clearance <30 milliliter per minute.

               -  Aspartate aminotransaminase or Alanine aminotransaminase >1.5 x upper limit of
                  normal (ULN).

               -  Bilirubin (total) >ULN, unless Gilbert's disease has been determined by genetic
                  testing and has been documented

               -  Total fasting cholesterol >3.50 gram per liter (g/L) [9.1 millimoles per liter
                  {mmol/L}]) or triglycerides >5.00 g/L [5.6 mmol/L]).

        The above information was not intended to contain all considerations relevant to a
        participant's potential participation in a clinical trial.