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)

NCT ID: NCT01768572

Last Updated: 2017-06-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 202 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-03-31
• Study Completion Date: 2014-10-31

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.

Detailed Description

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, participants were eligible to enter a long term safety study (LTS11210) for active treatment with SAR153191 (REGN88).

Conditions

Rheumatoid Arthritis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Sarilumab 150 mg q2w

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.

Group Type: EXPERIMENTAL

sarilumab SAR153191 (REGN88)

Intervention Type: DRUG

Pharmaceutical form: solution Route of administration: subcutaneous

hydroxychloroquine

Intervention Type: DRUG

Dispensed according to local practice.

methotrexate

Intervention Type: DRUG

Dispensed according to local practice.

sulfasalazine

Intervention Type: DRUG

Dispensed according to local practice.

leflunomide

Intervention Type: DRUG

Dispensed according to local practice.

intravenous placebo

Intervention Type: DRUG

Pharmaceutical form: solution Route of administration: intravenous

Sarilumab 200 mg q2w

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.

Group Type: EXPERIMENTAL

sarilumab SAR153191 (REGN88)

Intervention Type: DRUG

Pharmaceutical form: solution Route of administration: subcutaneous

hydroxychloroquine

Intervention Type: DRUG

Dispensed according to local practice.

methotrexate

Intervention Type: DRUG

Dispensed according to local practice.

sulfasalazine

Intervention Type: DRUG

Dispensed according to local practice.

leflunomide

Intervention Type: DRUG

Dispensed according to local practice.

intravenous placebo

Intervention Type: DRUG

Pharmaceutical form: solution Route of administration: intravenous

Tocilizumab q4w

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.

Group Type: ACTIVE_COMPARATOR

tocilizumab

Intervention Type: DRUG

Pharmaceutical form: solution Route of administration: intravenous

hydroxychloroquine

Intervention Type: DRUG

Dispensed according to local practice.

methotrexate

Intervention Type: DRUG

Dispensed according to local practice.

sulfasalazine

Intervention Type: DRUG

Dispensed according to local practice.

leflunomide

Intervention Type: DRUG

Dispensed according to local practice.

subcutaneous placebo

Intervention Type: DRUG

Pharmaceutical form: solution Route of administration: subcutaneous

Interventions

sarilumab SAR153191 (REGN88)

Pharmaceutical form: solution Route of administration: subcutaneous

Intervention Type: DRUG

tocilizumab

Pharmaceutical form: solution Route of administration: intravenous

Intervention Type: DRUG

hydroxychloroquine

Dispensed according to local practice.

Intervention Type: DRUG

methotrexate

Dispensed according to local practice.

Intervention Type: DRUG

sulfasalazine

Dispensed according to local practice.

Intervention Type: DRUG

leflunomide

Dispensed according to local practice.

Intervention Type: DRUG

subcutaneous placebo

Pharmaceutical form: solution Route of administration: subcutaneous

Intervention Type: DRUG

intravenous placebo

Pharmaceutical form: solution Route of administration: intravenous

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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

Exclusion Criteria

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.

The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Regeneron Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Investigational Site Number 643030

Moscow, , Russia

Investigational Site Number 840152

Huntsville, Alabama, United States

Investigational Site Number 840151

Colorado Springs, Colorado, United States

Investigational Site Number 840153

Aventura, Florida, United States

Investigational Site Number 840033

Fort Lauderdale, Florida, United States

Investigational Site Number 840048

Miami, Florida, United States

Investigational Site Number 840155

Palm Harbor, Florida, United States

Investigational Site Number 840013

Wheaton, Maryland, United States

Investigational Site Number 840154

Boston, Massachusetts, United States

Investigational Site Number 840150

Lansing, Michigan, United States

Investigational Site Number 840062

Reading, Pennsylvania, United States

Investigational Site Number 840038

Austin, Texas, United States

Investigational Site Number 643032

Saint Petersburg, , Russia

Investigational Site Number 840022

Dallas, Texas, United States

Investigational Site Number 840156

Dallas, Texas, United States

Investigational Site Number 840074

Mesquite, Texas, United States

Investigational Site Number 032006

Caba, , Argentina

Investigational Site Number 032010

Ramos Mejía, , Argentina

Investigational Site Number 032013

Rosario, , Argentina

Investigational Site Number 032015

San Fernando, , Argentina

Investigational Site Number 032004

San Miguel de Tucumán, , Argentina

Investigational Site Number 032005

San Miguel de Tucumán, , Argentina

Investigational Site Number 056010

Leuven, , Belgium

Investigational Site Number 076001

Curitiba, , Brazil

Investigational Site Number 076030

São José do Rio Preto, , Brazil

Investigational Site Number 203009

Liberec, , Czechia

Investigational Site Number 203011

Prague, , Czechia

Investigational Site Number 203010

Prague, , Czechia

Investigational Site Number 233010

Tallinn, , Estonia

Investigational Site Number 233002

Tallinn, , Estonia

Investigational Site Number 246001

Helsinki, , Finland

Investigational Site Number 246010

Riihimäki, , Finland

Investigational Site Number 348014

Budapest, , Hungary

Investigational Site Number 348022

Budapest, , Hungary

Investigational Site Number 348021

Esztergom, , Hungary

Investigational Site Number 348016

Kistarcsa, , Hungary

Investigational Site Number 348009

Szolnok, , Hungary

Investigational Site Number 348015

Szombathely, , Hungary

Investigational Site Number 376010

Haifa, , Israel

Investigational Site Number 376011

Tel Aviv, , Israel

Investigational Site Number 380002

Florence, , Italy

Investigational Site Number 380005

Genova, , Italy

Investigational Site Number 484008

Durango, , Mexico

Investigational Site Number 484035

León, , Mexico

Investigational Site Number 484009

Mérida, , Mexico

Investigational Site Number 484001

México, D.F., , Mexico

Investigational Site Number 484036

Zapopan, , Mexico

Investigational Site Number 528010

Amsterdam, , Netherlands

Investigational Site Number 528001

Leiden, , Netherlands

Investigational Site Number 578010

Kristiansand, , Norway

Investigational Site Number 578006

Tønsberg, , Norway

Investigational Site Number 616019

Bydgoszcz, , Poland

Investigational Site Number 616054

Bytom, , Poland

Investigational Site Number 616030

Lublin, , Poland

Investigational Site Number 616031

Warsaw, , Poland

Investigational Site Number 616017

Warsaw, , Poland

Investigational Site Number 642006

Brăila, , Romania

Investigational Site Number 642021

Bucharest, , Romania

Investigational Site Number 642001

Bucharest, , Romania

Investigational Site Number 642020

Bucharest, , Romania

Investigational Site Number 642010

Bucharest, , Romania

Investigational Site Number 642022

Târgovişte, , Romania

Investigational Site Number 643017

Kemerovo, , Russia

Investigational Site Number 643020

Moscow, , Russia

Investigational Site Number 643001

Moscow, , Russia

Investigational Site Number 643002

Moscow, , Russia

Investigational Site Number 643031

Moscow, , Russia

Investigational Site Number 724020

Barcelona, , Spain

Investigational Site Number 724021

Santander, , Spain

Investigational Site Number 724022

Seville, , Spain

Investigational Site Number 752004

Malmo, , Sweden

Investigational Site Number 752002

Uppsala, , Sweden

Investigational Site Number 826004

Doncaster, , United Kingdom

Investigational Site Number 826006

Edinburgh, , United Kingdom

Investigational Site Number 826001

Leeds, , United Kingdom

Investigational Site Number 826002

London, , United Kingdom

Investigational Site Number 826005

Southampton, , United Kingdom

Investigational Site Number 826025

Wigan, , United Kingdom

Countries

United States; Argentina; Belgium; Brazil; Czechia; Estonia; Finland; Hungary; Israel; Italy; Mexico; Netherlands; Norway; Poland; Romania; Russia; Spain; Sweden; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 34519964 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32453485 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30590833 (View on PubMed)

Other Identifiers

2012-003536-23

Identifier Type: -

Identifier Source: secondary_id

U1111-1133-7839

Identifier Type: OTHER

Identifier Source: secondary_id

SFY13370

Identifier Type: -

Identifier Source: org_study_id