A Randomized, Double-blind, Parallel, Placebo-controlled Study Assessing the Efficacy and Safety of Sarilumab Added to Non-biologic DMARD Therapy in Patients With Rheumatoid Arthritis Who Are Inadequate Responders to or Intolerant of TNF-α Antagonists
A Randomized, Double-blind, Parallel, Placebo-controlled Study Assessing the Efficacy and Safety of Sarilumab Added to Non-biologic DMARD Therapy in Patients With Rheumatoid Arthritis Who Are Inadequate Responders to or Intolerant of TNF-α Antagonists
Primary Objective:
To demonstrate that sarilumab added to disease modifying anti-rheumatic drugs (DMARDs) were effective for:
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:
To assess the exposure of sarilumab added to DMARD therapy in this population.
To assess the safety of sarilumab in this population.
Total study duration was up to 34 weeks: screening up to 28 days, treatment phase of 24 weeks, and post-treatment follow-up of 6 weeks.
After completion of the treatment phase of this study, participant were eligible to enter a long term safety study (LTS11210) for active treatment with SAR153191 (REGN88).
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:
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:
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:
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
Caba, 1180, Argentina
Caba, C1015ABO, Argentina
Capital Federal, 1425, Argentina
Taoyuan County, 33305, Taiwan