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)

Conditions: Rheumatoid Arthritis
MedDRA version: 14.1Level: PTClassification code 10039073Term: Rheumatoid arthritisSystem Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Registration Number: EUCTR2012-003536-23-FI

Lead Sponsor: sanofi-aventis recherche & développement

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 200

Inclusion Criteria

Diagnosis of RA, 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, based on the 1991 revised criteria.
Moderate-to-severely active RA.
Anti-TNF therapy failures, defined as patients with an inadequate clinical response 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 may include, but are 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 mg/wk orally or parenteral (or per local labeling 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

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 170
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30

Exclusion Criteria

Patients <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 is longer.
Patients with active tuberculosis or latent tuberculosis infection.
Prior or current history of interstitial lung disease.
Prior treatment with anti-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-a 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 are normalized, or whichever is longer.
Prior treatment with a janus kinase (JAK) inhibitor (eg, tofacitinib).
Patients 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 judgment, would adversely affect the patient’s participation in the study.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess, in the same study, the safety of sarilumab and tocilizumab in patients with rheumatoid arthritis (RA) who are inadequate responders to or intolerant of tumor necrosis factor (TNF) antagonists.;Secondary Objective: Not applicable;Primary end point(s): Safety as measured by adverse events/serious adverse events, physical examinations, clinical laboratory, ECGs.;Timepoint(s) of evaluation of this end point: Up to 24 weeks

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Not applicable;Timepoint(s) of evaluation of this end point: Not applicable

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