Rheumatoid Arthritis MedDRA version: 16.1 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Interventions
Product Name: Sarilumab
Product Code: SAR153191
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: Sarilumab
Current Sponsor code: SAR153191
Concentration unit: mg/
Sponsors
sanofi-aventis recherche & développement
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Diagnosis of rheumatoid arthritis =6 months duration, according to the American College of Rheumatology (ACR)/European League against Rheumatism (EULAR) 2010 Rheumatoid Arthritis Classification Criteria ACR Class I-III functional status, based on 1991 revised criteria Anti-TNF therapy failures, defined by the investigator as patients 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 may include, but are not limited to, etanercept, infliximab, adalimumab, golimumab and/or certolizumab. Moderate-to-severely active rheumatoid arthritis. 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/wk orally or parenterally Leflunomide – 10 to 20 mg orally daily Sulfasalazine – 1000 to 3000 mg orally daily. Hydroxychloroquine - 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 400 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 122
Exclusion criteria
Exclusion criteria: Patients 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-IL-6 or IL-6R 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 is longer. History of alcohol or drug abuse within 5 years prior to the screening visit. Patients 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 are also excluded. Patients with active tuberculosis or latent tuberculosis infection.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate that sarilumab added to disease modifying anti-rheumatic drugs (DMARDs) is effective for: • reduction of signs and symptoms at week 24 and • improvement of physical function over 24 weeks in patients with active rheumatoid arthritis (RA) who are inadequate responders or intolerant to tumor necrosis factor alpha (TNF-a) antagonists ;Secondary Objective: The secondary objectives are to investigate the effects of SAR153191 (REGN88) when added to DMARD therapy, in patients with active RA who are inadequate responders or intolerant to TNF-a antagonists, for: • reduction of signs and symptoms at 12 weeks, • improvement in physical function at 12 weeks, • improvement in disease activity as measured by other ACR derived components at Weeks 12 and 24, and • improvement in quality of life as measured by patient reported outcomes (PROs) at intermediate visits and Week 24. To assess the safety of sarilumab in this population. To assess the exposure of sarilumab added to DMARD therapy in this population. ;Primary end point(s): The percentage of patients who achieved at least 20% improvement in the American College of Rheumatology (ACR) criteria Change in physical function as measured by the average of change from baseline in the health assessment questionnaire-disability index (HAQ-DI) from Wk 8 to Wk 24;Timepoint(s) of evaluation of this end point: At Week 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1- Percentage of patients achieving American College of Rheumatology (ACR) 20/50/70 criteria 2- Percentage of patients achieving American College of Rheumatology (ACR) 50/70 criteria 3- Changes from baseline in disease activity score (DAS) 28 4- Disease activity score (DAS) 28 remission rate 5- Change from baseline in short form (SF)-36 domains 6- Change from baseline in the Rheumatoid Arthritis-Work Productivity Survey (WPS-RA) items 7- Change from baseline in the Functional Assessment of Chronic Illness Therapy Fatigue scale (FACIT-fatigue) 8- Change from baseline in European Qouality of Life-5 dimension (EQ-5D) 9- Change from baseline in rheumatoid arthritis impact of disease (RAID) scores 10- Change from baseline in each individual ACR component ;Timepoint(s) of evaluation of this end point: 1- At Week 12 2- At Week 24 3 to 10- At Week 12 and Week 24 | — |
Countries
Argentina, Australia, Austria, Brazil, Canada, Chile, Colombia, Czech Republic, Ecuador, Germany, Greece, Guatemala, Hong Kong, Hungary, India, Israel, Italy, Korea, Republic of, Lithuania, Mexico, New Zealand, Peru, Poland, Portugal, Romania, Russian Federation, Slovakia, Spain, Switzerland, Taiwan, Turkey, Ukraine, United States
Contacts
Public ContactClinical Study Unit
UAB Sanofi-Aventis Lietuva
Outcome results
None listed