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)

• Status: Completed
• Trial end date: 2015-03-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Sanofi
• Collaborator: Regeneron Pharmaceuticals
• Treatments: Hydroxychloroquine; Leflunomide; Methotrexate; Sulfasalazine

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