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)

• Register: EUCTR
• Last refreshed on: 26 February 2018
• Main ID: EUCTR2012-003536-23-IT
• Date of registration: 05/02/2013
• Prospective Registration: Yes
• Primary sponsor: sanofi-aventis recherche & développement
• Public title: 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)
• Scientific title: A Randomized, Double-Blind, Double-Dummy Study Assessing The Safety and Tolerability of Sarilumab and Tocilizumab In Patients With Rheumatoid Arthritis Who Are Inadequate Responders to or Intolerant of TNF Antagonists - ASCERTAIN
• Date of first enrolment: 29/03/2013
• Target sample size: 200
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-003536-23
• 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: yes; Other trial design description: Double-dummy; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; 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, Belgium, Brazil, Colombia, Czech Republic, Estonia, Finland, Germany, Hungary, Israel, Italy, Mexico, Netherlands, Norway, Poland, Romania, Russian Federation, Spain, Sweden, United Kingdom, United States

Contacts

• Name: CONTACT POINT
• Affiliation: sanofi-aventis SpA

• Name: CONTACT POINT
• Affiliation: sanofi-aventis SpA

Key inclusion & exclusion criteria

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 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 pegol.
Continuous treatment with one or a combination of non-biologic disease modifying antirheumatic drugs (DMARDs) for at least 12 consecutive weeks and on a stable dose(s) for at least 6 consecutive weeks prior to randomization:
- Methotrexate – 10 to 25 mg/wk orally or intra muscular (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 antagonist 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.



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

Health Condition(s) or Problem(s) studied

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

Rheumatoid Arthritis
MedDRA version: 15.1 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Intervention(s)

Product Name: Sarilumab
Product Code: SAR153191 (REGN88)
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 (REGN88)
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

Trade Name: RoActemra 20 mg/ml concentrate for solution for infusion.
Product Name: RoActemra
Pharmaceutical Form: Solution for injection
INN or Proposed INN: tocilizumab
Other descriptive name: RoActemra
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 20-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Up to 24 weeks

Secondary Objective: Not applicable

Primary end point(s): Safety as measured by adverse events/serious adverse events, physical examinations, clinical laboratory, ECGs.

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 Outcome(s)

Timepoint(s) of evaluation of this end point: Not applicable

Secondary end point(s): Not applicable

Secondary ID(s)

2012-003536-23-CZ

SFY13370

Source(s) of Monetary Support

sanofi-aventis Recherche & Développement