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)

NCT01768572 | Completed Phase 3 Results DMC

• 3 other identifiers: SFY133702012-003536-23U1111-1133-7839
• Study Type: interventional
• Target: 202
• Locations: 18 countries
• Sites: 75

Brief Summary

Primary Objective: To assess, in the same study, the safety of sarilumab and tocilizumab in participants with rheumatoid arthritis (RA) who were inadequate responders to or intolerant of tumor necrosis factor (TNF) antagonists.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Treatment Emergent Adverse Events (TEAEs)

  Adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug and does not necessary have to have a causal relationship with treatment. All adverse events that occurred from the first dose of the study drug administration up to 60 days after the end of treatment visit were considered as TEAEs. Serious AE (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly or a medically important event. A summary of SAEs, all other non-serious AEs, regardless of causality, are reported in AE section.

  Up to 211 days

Study Arms (3)

Sarilumab 150 mg q2w

EXPERIMENTAL

Sarilumab 150 mg subcutaneous (SC) injection once every 2 weeks (q2w) and placebo intravenous (IV) infusion once every 4 weeks (q4w) was added to one or a combination of the nonbiologic disease modifying antirheumatic drug (DMARD), hydroxychloroquine, methotrexate, sulfasalazine and/or leflunomide for 24 weeks, except for the simultaneous use of leflunomide and methotrexate.

Drug: sarilumab SAR153191 (REGN88); Drug: hydroxychloroquine; Drug: methotrexate; Drug: sulfasalazine; Drug: leflunomide; Drug: intravenous placebo

Sarilumab 200 mg q2w

EXPERIMENTAL

Sarilumab 200 mg SC injection q2w and placebo IV infusion q4w was added to one or a combination of the nonbiologic DMARD, hydroxychloroquine, methotrexate, sulfasalazine and/or leflunomide for 24 weeks, except for the simultaneous use of leflunomide and methotrexate.

Drug: sarilumab SAR153191 (REGN88); Drug: hydroxychloroquine; Drug: methotrexate; Drug: sulfasalazine; Drug: leflunomide; Drug: intravenous placebo

Tocilizumab q4w

ACTIVE COMPARATOR

Tocilizumab 4 mg/kg or 8 mg/kg IV infusion q4w and placebo SC injection q2w was added to one or a combination of the nonbiologic DMARD, hydroxychloroquine, methotrexate, sulfasalazine and/or leflunomide for 24 weeks, except for the simultaneous use of leflunomide and methotrexate.

Drug: tocilizumab; Drug: hydroxychloroquine; Drug: methotrexate; Drug: sulfasalazine; Drug: leflunomide; Drug: subcutaneous placebo

Interventions

sarilumab SAR153191 (REGN88) DRUG

Pharmaceutical form: solution Route of administration: subcutaneous

Sarilumab 150 mg q2w; Sarilumab 200 mg q2w

tocilizumab DRUG

Pharmaceutical form: solution Route of administration: intravenous

Tocilizumab q4w

hydroxychloroquine DRUG

Dispensed according to local practice.

Sarilumab 150 mg q2w; Sarilumab 200 mg q2w; Tocilizumab q4w

methotrexate DRUG

Dispensed according to local practice.

Sarilumab 150 mg q2w; Sarilumab 200 mg q2w; Tocilizumab q4w

sulfasalazine DRUG

Dispensed according to local practice.

Sarilumab 150 mg q2w; Sarilumab 200 mg q2w; Tocilizumab q4w

leflunomide DRUG

Dispensed according to local practice.

Sarilumab 150 mg q2w; Sarilumab 200 mg q2w; Tocilizumab q4w

subcutaneous placebo DRUG

Pharmaceutical form: solution Route of administration: subcutaneous

Tocilizumab q4w

intravenous placebo DRUG

Pharmaceutical form: solution Route of administration: intravenous

Sarilumab 150 mg q2w; Sarilumab 200 mg q2w

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of RA was, 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, was based on the 1991 revised criteria. Moderate-to-severely active RA. Anti-TNF therapy failures, was defined as participants with an inadequate clinical response was defined by the investigator, after being treated for at least 3 consecutive months, and/or intolerance to at least 1 TNF-antagonist, resulting in or requiring their discontinuation. TNF-antagonists were include, but were 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 prior to screening and on a stable dose(s) for at least 6 consecutive weeks prior to screening:
• Methotrexate - 10 to 25 milligram/week orally or parenteral (or per local labelling 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

You may not qualify if:

• Participants \<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 was longer
• Participants with active tuberculosis or latent tuberculosis infection. Prior or current history of interstitial lung disease. Prior treatment with anti-interleukin (IL) -6 or anti-IL-6R 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-α 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 were normalized, or whichever was longer
• Prior treatment with a janus kinase (JAK) inhibitor (eg, tofacitinib). Participants 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 judgement, was adversely affect the participant's participation in the study.

Sponsors & Collaborators

• Sanofi: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (78)

Investigational Site Number 840152

Huntsville, Alabama, 35801, United States

Location

Investigational Site Number 840151

Colorado Springs, Colorado, 80903, United States

Location

Investigational Site Number 840153

Aventura, Florida, 33180, United States

Location

Investigational Site Number 840033

Fort Lauderdale, Florida, 33334, United States

Location

Investigational Site Number 840048

Miami, Florida, 33155, United States

Location

Investigational Site Number 840155

Palm Harbor, Florida, 34684, United States

Location

Investigational Site Number 840013

Wheaton, Maryland, 20902, United States

Location

Investigational Site Number 840154

Boston, Massachusetts, 02115, United States

Location

Investigational Site Number 840150

Lansing, Michigan, 48910, United States

Location

Investigational Site Number 840062

Reading, Pennsylvania, 19611, United States

Location

Investigational Site Number 840038

Austin, Texas, 78705, United States

Location

Investigational Site Number 840022

Dallas, Texas, 75235, United States

Location

Investigational Site Number 840156

Dallas, Texas, 75246, United States

Location

Investigational Site Number 840074

Mesquite, Texas, 75150, United States

Location

Investigational Site Number 032006

Caba, C1015ABO, Argentina

Location

Investigational Site Number 032010

Ramos Mejía, B1704ETD, Argentina

Location

Investigational Site Number 032013

Rosario, S200PBJ, Argentina

Location

Investigational Site Number 032015

San Fernando, Argentina

Location

Investigational Site Number 032004

San Miguel de Tucumán, 4000, Argentina

Location

Investigational Site Number 032005

San Miguel de Tucumán, 4000, Argentina

Location

Investigational Site Number 056010

Leuven, 3000, Belgium

Location

Investigational Site Number 076001

Curitiba, 80060-240, Brazil

Location

Investigational Site Number 076030

São José do Rio Preto, 15090-000, Brazil

Location

Investigational Site Number 203009

Liberec, 46063, Czechia

Location

Investigational Site Number 203011

Prague, 12850, Czechia

Location

Investigational Site Number 203010

Prague, 140 00, Czechia

Location

Investigational Site Number 233010

Tallinn, 10138, Estonia

Location

Investigational Site Number 233002

Tallinn, 13419, Estonia

Location

Investigational Site Number 246001

Helsinki, 00290, Finland

Location

Investigational Site Number 246010

Riihimäki, 11120, Finland

Location

Investigational Site Number 348014

Budapest, 1027, Hungary

Location

Investigational Site Number 348022

Budapest, 1036, Hungary

Location

Investigational Site Number 348021

Esztergom, 2500, Hungary

Location

Investigational Site Number 348016

Kistarcsa, 2143, Hungary

Location

Investigational Site Number 348009

Szolnok, 5000, Hungary

Location

Investigational Site Number 348015

Szombathely, 9700, Hungary

Location

Investigational Site Number 376010

Haifa, 31096, Israel

Location

Investigational Site Number 376011

Tel Aviv, 64239, Israel

Location

Investigational Site Number 380002

Florence, 50141, Italy

Location

Investigational Site Number 380005

Genova, 16132, Italy

Location

Investigational Site Number 484008

Durango, 34080, Mexico

Location

Investigational Site Number 484035

León, 37000, Mexico

Location

Investigational Site Number 484009

Mérida, 97000, Mexico

Location

Investigational Site Number 484001

México, D.F., 11850, Mexico

Location

Investigational Site Number 484036

Zapopan, 44280, Mexico

Location

Investigational Site Number 528010

Amsterdam, 1056 AB, Netherlands

Location

Investigational Site Number 528001

Leiden, 2333 ZA, Netherlands

Location

Investigational Site Number 578010

Kristiansand, 4604, Norway

Location

Investigational Site Number 578006

Tønsberg, 3105, Norway

Location

Investigational Site Number 616019

Bydgoszcz, 85-168, Poland

Location

Investigational Site Number 616054

Bytom, 41-902, Poland

Location

Investigational Site Number 616030

Lublin, 20-090, Poland

Location

Investigational Site Number 616031

Warsaw, 01-518, Poland

Location

Investigational Site Number 616017

Warsaw, 02-653, Poland

Location

Investigational Site Number 642006

Brăila, 810019, Romania

Location

Investigational Site Number 642021

Bucharest, 010584, Romania

Location

Investigational Site Number 642001

Bucharest, 010976, Romania

Location

Investigational Site Number 642020

Bucharest, 020125, Romania

Location

Investigational Site Number 642010

Bucharest, Romania

Location

Investigational Site Number 642022

Târgovişte, 130083, Romania

Location

Investigational Site Number 643017

Kemerovo, 650066, Russia

Location

Investigational Site Number 643020

Moscow, 115404, Russia

Location

Investigational Site Number 643001

Moscow, 115522, Russia

Location

Investigational Site Number 643002

Moscow, 117997, Russia

Location

Investigational Site Number 643031

Moscow, 121374, Russia

Location

Investigational Site Number 643030

Moscow, 125284, Russia

Location

Investigational Site Number 643032

Saint Petersburg, 191186, Russia

Location

Investigational Site Number 724020

Barcelona, 08035, Spain

Location

Investigational Site Number 724021

Santander, 39008, Spain

Location

Investigational Site Number 724022

Seville, 41010, Spain

Location

Investigational Site Number 752004

Malmo, 205 02, Sweden

Location

Investigational Site Number 752002

Uppsala, 751 85, Sweden

Location

Investigational Site Number 826004

Doncaster, DN2 5LT, United Kingdom

Location

Investigational Site Number 826006

Edinburgh, EH4 2XU, United Kingdom

Location

Investigational Site Number 826001

Leeds, LS7 4SA, United Kingdom

Location

Investigational Site Number 826002

London, E11 1NR, United Kingdom

Location

Investigational Site Number 826005

Southampton, SO16 6YD, United Kingdom

Location

Investigational Site Number 826025

Wigan, WN6 9EP, United Kingdom

Location

Related Publications (3)

• Rehberg M, Giegerich C, Praestgaard A, van Hoogstraten H, Iglesias-Rodriguez M, Curtis JR, Gottenberg JE, Schwarting A, Castaneda S, Rubbert-Roth A, Choy EHS; MOBILITY, MONARCH, TARGET, and ASCERTAIN investigators. Identification of a Rule to Predict Response to Sarilumab in Patients with Rheumatoid Arthritis Using Machine Learning and Clinical Trial Data. Rheumatol Ther. 2021 Dec;8(4):1661-1675. doi: 10.1007/s40744-021-00361-5. Epub 2021 Sep 14.

  PMID: 34519964 DERIVED

• Kovalenko P, Paccaly A, Boyapati A, Xu C, St John G, Nivens MC, Davis JD, Rippley R, DiCioccio AT. Population Pharmacodynamic Model of Neutrophil Margination and Tolerance to Describe Effect of Sarilumab on Absolute Neutrophil Count in Patients with Rheumatoid Arthritis. CPT Pharmacometrics Syst Pharmacol. 2020 Jul;9(7):405-416. doi: 10.1002/psp4.12534. Epub 2020 Jun 20.

  PMID: 32453485 DERIVED

• Emery P, Rondon J, Parrino J, Lin Y, Pena-Rossi C, van Hoogstraten H, Graham NMH, Liu N, Paccaly A, Wu R, Spindler A. Safety and tolerability of subcutaneous sarilumab and intravenous tocilizumab in patients with rheumatoid arthritis. Rheumatology (Oxford). 2019 May 1;58(5):849-858. doi: 10.1093/rheumatology/key361.

  PMID: 30590833 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

sarilumab; tocilizumab; Hydroxychloroquine; Methotrexate; Sulfasalazine; Leflunomide

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Aminopterin; Pterins; Pteridines; Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Isoxazoles; Azoles; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi

Contact-US@sanofi.com

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 11, 2013
• First Posted: January 15, 2013
• Study Start: March 1, 2013
• Primary Completion: October 1, 2014
• Study Completion: October 1, 2014
• Last Updated: June 26, 2017
• Results First Posted: June 26, 2017

Record last verified: 2017-06

Locations

BE (1); NL (2); ES (2); GB (6); NO (2); FI (2); AR (6); ME (5); CZ (3); BR (2); HU (6); RU (7); US (14); PL (5); SE (2); IL (2); RO (6); IT (2)