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)

• Register: EUCTR
• Last refreshed on: 24 January 2022
• Main ID: EUCTR2011-003538-16-DE
• Date of registration: 10/12/2012
• Prospective Registration: Yes
• Primary sponsor: sanofi-aventis recherche & développement
• Public title: 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)
• Scientific title: 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-a Antagonists - SARIL-RA-TARGET
• Date of first enrolment: 26/03/2013
• Target sample size: 522
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-003538-16
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Austria, Brazil, Canada, Chile, Colombia, Czech Republic, Ecuador, Estonia, 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

• Affiliation: Sanofi-Aventis Deutschland GmbH

• Affiliation: Sanofi-Aventis Deutschland GmbH

Key inclusion & exclusion 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:
Patients <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 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-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.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Rheumatoid Arthritis
MedDRA version: 18.1 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Intervention(s)

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/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 131.6-
Pharmaceutical form of the placebo: Solution for injection in pre-filled syringe
Route of administration of the placebo: Subcutaneous use

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/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 175-
Pharmaceutical form of the placebo: Solution for injection in pre-filled syringe
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

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 at week 12
in patients with active rheumatoid arthritis (RA) who are inadequate responders or intolerant to tumor necrosis factor alpha (TNF-a) antagonists

Primary end point(s): 1 - The percentage of patients who achieved at least 20% improvement in the American College of Rheumatology (ACR) criteria
2 - Change in physical function as measured by the average of change from baseline in the health assessment questionnaire-disability index (HAQ-DI) at week 12

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 week 24,
• improvement in disease activity score as measured by other American College of Rheumatology 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.

Timepoint(s) of evaluation of this end point: 1 - At Week 24
2 - At Week 12

Secondary Outcome(s)

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

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

Secondary ID(s)

EFC10832

2011-003538-16-LT

Source(s) of Monetary Support

sanofi-aventis Recherche & Développement

Ethics review

Status: Approved
Approval date: 21/03/2013
Contact:

Results

• Results available: Yes
• Date Posted: 07/04/2016
• Date Completed: 23/03/2015
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2011-003538-16/results