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)

Rheumatoid Arthritis Clinical Trial

Official 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-α Antagonists

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01709578
• Other study ID #: EFC10832
• Secondary ID: U1111-1115-8466
• Status: Completed
• Phase: Phase 3
• First received: October 15, 2012
• Last updated: November 16, 2015
• Start date: October 2012
• Est. completion date: March 2015

Study information

• Verified date: November 2015
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Primary 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-α) antagonists.

Secondary Objectives:

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-α 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.

• 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.

Description:

Total study duration is 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, patients are eligible to enter a long term safety study (LTS11210) for active treatment wit SAR153191 (REGN88).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 522
• Est. completion date: March 2015
• Est. primary completion date: March 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

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.

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• sarilumab SAR153191 (REGN88)
Pharmaceutical form:solution Route of administration: subcutaneous

Other:
• placebo
Pharmaceutical form:solution Route of administration: subcutaneous

Drug:
• hydroxychloroquine
Dispensed according to the local practice.
• methotrexate
Dispensed according to the local practice.
• sulfasalazine
Dispensed according to the local practice.
• leflunomide
Dispensed according to the local practice.

Locations

Country	Name	City	State
Argentina	Investigational Site Number 032008	Buenos Aires
Argentina	Investigational Site Number 032015	Buenos Aires
Argentina	Investigational Site Number 032006	Caba
Argentina	Investigational Site Number 032019	Caba
Argentina	Investigational Site Number 032016	Capital Federal
Argentina	Investigational Site Number 032020	Cordoba
Argentina	Investigational Site Number 032017	La Plata
Argentina	Investigational Site Number 032010	Ramos Mejia
Argentina	Investigational Site Number 032013	Rosario
Argentina	Investigational Site Number 032004	San Miguel De Tucuman
Argentina	Investigational Site Number 032009	Zarate
Australia	Investigational Site Number 036014	Victoria Park
Austria	Investigational Site Number 040004	Stockerau
Austria	Investigational Site Number 040003	Wien
Brazil	Investigational Site Number 076001	Curitiba
Brazil	Investigational Site Number 076016	Curitiba
Brazil	Investigational Site Number 076006	Goiania
Brazil	Investigational Site Number 076010	Juiz De Fora
Brazil	Investigational Site Number 076005	Rio De Janeiro
Brazil	Investigational Site Number 076015	Rio De Janeiro
Canada	Investigational Site Number 124005	Toronto
Canada	Investigational Site Number 124009	Trois-Rivières
Canada	Investigational Site Number 124104	Victoria
Chile	Investigational Site Number 152015	Temuco
Colombia	Investigational Site Number 170001	Bogota
Colombia	Investigational Site Number 170012	Bogota
Colombia	Investigational Site Number 170006	Bogotá
Colombia	Investigational Site Number 170007	Bucaramanga
Colombia	Investigational Site Number 170009	Bucaramanga
Colombia	Investigational Site Number 170014	Chia
Colombia	Investigational Site Number 170019	Medellin
Czech Republic	Investigational Site Number 203008	Hostivice
Czech Republic	Investigational Site Number 203004	Ostrava
Czech Republic	Investigational Site Number 203007	Praha 2
Czech Republic	Investigational Site Number 203002	Uherske Hradiste
Czech Republic	Investigational Site Number 203006	Zlin
Ecuador	Investigational Site Number 218003	Cuenca
Ecuador	Investigational Site Number 218001	Guayaquil
Ecuador	Investigational Site Number 218002	Quito
Germany	Investigational Site Number 276011	Bad Nauheim
Germany	Investigational Site Number 276001	Berlin
Germany	Investigational Site Number 276010	Berlin
Germany	Investigational Site Number 276014	Berlin
Germany	Investigational Site Number 276018	Deggingen
Germany	Investigational Site Number 276004	Erlangen
Germany	Investigational Site Number 276015	Halle/Saale
Germany	Investigational Site Number 276013	Hamburg
Germany	Investigational Site Number 276016	Leipzig
Germany	Investigational Site Number 276017	München
Germany	Investigational Site Number 276021	Osnabrück
Germany	Investigational Site Number 276020	Tübingen
Germany	Investigational Site Number 276019	Zerbst
Greece	Investigational Site Number 300002	Heraklion
Greece	Investigational Site Number 300005	Thessaloniki
Guatemala	Investigational Site Number 320001	Guatemala City
Guatemala	Investigational Site Number 320002	Guatemala City
Guatemala	Investigational Site Number 320003	Guatemala City
Hungary	Investigational Site Number 348022	Budapest
Hungary	Investigational Site Number 348003	Debrecen
Hungary	Investigational Site Number 348004	Veszprém
Hungary	Investigational Site Number 348017	Veszprém
Israel	Investigational Site Number 376001	Haifa
Israel	Investigational Site Number 376003	Petach Tikva
Israel	Investigational Site Number 376002	Tel Hashomer
Italy	Investigational Site Number 380011	Catania
Italy	Investigational Site Number 380002	Firenze
Italy	Investigational Site Number 380005	Genova
Italy	Investigational Site Number 380014	Milano
Italy	Investigational Site Number 380013	Udine
Korea, Republic of	Investigational Site Number 410017	Daejeon
Korea, Republic of	Investigational Site Number 410016	Seoul
Lithuania	Investigational Site Number 440005	Kaunas
Lithuania	Investigational Site Number 440006	Klaipeda
Lithuania	Investigational Site Number 440007	Vilnius
Mexico	Investigational Site Number 484023	Chihuahua
Mexico	Investigational Site Number 484002	Guadalajara
Mexico	Investigational Site Number 484018	Guadalajara
Mexico	Investigational Site Number 484024	Guadalajara
Mexico	Investigational Site Number 484010	Mexicali
Mexico	Investigational Site Number 484017	México
Mexico	Investigational Site Number 484005	Monterrey
Mexico	Investigational Site Number 484019	Monterrey
Mexico	Investigational Site Number 484020	Monterrey
Mexico	Investigational Site Number 484021	Queretaro
New Zealand	Investigational Site Number 554005	Hamilton
New Zealand	Investigational Site Number 554011	Nelson
New Zealand	Investigational Site Number 554007	Otahuhu
New Zealand	Investigational Site Number 554001	Timaru
New Zealand	Investigational Site Number 554006	Wellington
Peru	Investigational Site Number 604001	Lima
Peru	Investigational Site Number 604005	Lima
Peru	Investigational Site Number 604006	Lima
Peru	Investigational Site Number 604007	Lima
Peru	Investigational Site Number 604008	Lima
Peru	Investigational Site Number 604009	Lima
Peru	Investigational Site Number 604010	Lima
Peru	Investigational Site Number 604012	Lima
Peru	Investigational Site Number 604013	Lima
Peru	Investigational Site Number 604014	Lima
Poland	Investigational Site Number 616014	Bialystok
Poland	Investigational Site Number 616019	Bydgoszcz
Poland	Investigational Site Number 616015	Elblag
Poland	Investigational Site Number 616018	Poznan
Poland	Investigational Site Number 616016	Szczecin
Poland	Investigational Site Number 616004	Warszawa
Poland	Investigational Site Number 616017	Warszawa
Poland	Investigational Site Number 616020	Wroclaw
Portugal	Investigational Site Number 620002	Lisboa
Portugal	Investigational Site Number 620004	Lisboa
Portugal	Investigational Site Number 620007	Ponte De Lima
Romania	Investigational Site Number 642001	Bucuresti
Romania	Investigational Site Number 642002	Bucuresti
Romania	Investigational Site Number 642012	Bucuresti
Romania	Investigational Site Number 642014	Iasi
Russian Federation	Investigational Site Number 643001	Moscow
Russian Federation	Investigational Site Number 643021	Moscow
Russian Federation	Investigational Site Number 643022	Novosibirsk
Russian Federation	Investigational Site Number 643008	Saint-Petersburg
Russian Federation	Investigational Site Number 643010	Samara
Slovakia	Investigational Site Number 703001	Kosice
Spain	Investigational Site Number 724016	Barakaldo
Spain	Investigational Site Number 724015	Barcelona
Spain	Investigational Site Number 724014	Cadiz
Spain	Investigational Site Number 724009	La Coruña
Spain	Investigational Site Number 724001	Málaga
Spain	Investigational Site Number 724011	Sabadell
Spain	Investigational Site Number 724013	Santiago De Compostela
Spain	Investigational Site Number 724017	Santiago De Compostela
Spain	Investigational Site Number 724007	Sevilla
Taiwan	Investigational Site Number 158005	Kaohsiung
Taiwan	Investigational Site Number 158006	Taipei
Taiwan	Investigational Site Number 158002	Taoyuan County
Turkey	Investigational Site Number 792007	Edirne
Turkey	Investigational Site Number 792008	Gaziantep
Turkey	Investigational Site Number 792009	Samsun
Ukraine	Investigational Site Number 804013	Kharkiv
Ukraine	Investigational Site Number 804014	Kyiv
Ukraine	Investigational Site Number 804027	Kyiv
Ukraine	Investigational Site Number 804011	Vinnytsia
Ukraine	Investigational Site Number 804009	Zaporizhzhya
United States	Investigational Site Number 840070	Anniston	Alabama
United States	Investigational Site Number 840132	Austin	Texas
United States	Investigational Site Number 840120	Baton Rouge	Louisiana
United States	Investigational Site Number 840138	Birmingham	Alabama
United States	Investigational Site Number 840123	Charlotte	North Carolina
United States	Investigational Site Number 840124	Clarksburg	West Virginia
United States	Investigational Site Number 840058	Columbia	South Carolina
United States	Investigational Site Number 840022	Dallas	Texas
United States	Investigational Site Number 840125	Debary	Florida
United States	Investigational Site Number 840201	Denver	Colorado
United States	Investigational Site Number 840009	Duncansville	Pennsylvania
United States	Investigational Site Number 840114	El Paso	Texas
United States	Investigational Site Number 840055	Frederick	Maryland
United States	Investigational Site Number 840134	Fullerton	California
United States	Investigational Site Number 840141	Glendale	California
United States	Investigational Site Number 840129	Houston	Texas
United States	Investigational Site Number 840133	Houston	Texas
United States	Investigational Site Number 840018	Idaho Falls	Idaho
United States	Investigational Site Number 840025	Jackson	Tennessee
United States	Investigational Site Number 840052	Kansas City	Kansas
United States	Investigational Site Number 840111	La Jolla	Florida
United States	Investigational Site Number 840109	Lake Charles	Louisiana
United States	Investigational Site Number 840150	Lansing	Michigan
United States	Investigational Site Number 840130	Lewes	Delaware
United States	Investigational Site Number 840015	Lexington	Kentucky
United States	Investigational Site Number 840112	Lincoln	Nebraska
United States	Investigational Site Number 840059	Memphis	Tennessee
United States	Investigational Site Number 840110	Meridian	Idaho
United States	Investigational Site Number 840074	Mesquite	Texas
United States	Investigational Site Number 840048	Miami	Florida
United States	Investigational Site Number 840024	Naples	Florida
United States	Investigational Site Number 840127	Oklahoma City	Oklahoma
United States	Investigational Site Number 840106	Orchard Park	New York
United States	Investigational Site Number 840006	Orlando	Florida
United States	Investigational Site Number 840128	Ormond Beach	Florida
United States	Investigational Site Number 840063	Palm Harbor	Florida
United States	Investigational Site Number 840142	Phoenix	Arizona
United States	Investigational Site Number 840117	Pittsburgh	Pennsylvania
United States	Investigational Site Number 840062	Reading	Pennsylvania
United States	Investigational Site Number 840121	Rochester	New York
United States	Investigational Site Number 840115	Roslyn	New York
United States	Investigational Site Number 840135	San Diego	California
United States	Investigational Site Number 840021	Santa Maria	California
United States	Investigational Site Number 840060	Sarasota	Florida
United States	Investigational Site Number 840118	Smithtown	New York
United States	Investigational Site Number 840036	Spokane	Washington
United States	Investigational Site Number 840137	St Clair Shores	Michigan
United States	Investigational Site Number 840100	Stanford	California
United States	Investigational Site Number 840139	Syracuse	New York
United States	Investigational Site Number 840140	Tampa	Florida
United States	Investigational Site Number 840011	Tulsa	Oklahoma
United States	Investigational Site Number 840037	Tupelo	Mississippi
United States	Investigational Site Number 840049	Upland	California
United States	Investigational Site Number 840126	Vero Beach	Florida
United States	Investigational Site Number 840131	Whittier	California
United States	Investigational Site Number 840116	Wilmington	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Brazil,  Canada,  Chile,  Colombia,  Czech Republic,  Ecuador,  Germany,  Greece,  Guatemala,  Hungary,  Israel,  Italy,  Korea, Republic of,  Lithuania,  Mexico,  New Zealand,  Peru,  Poland,  Portugal,  Romania,  Russian Federation,  Slovakia,  Spain,  Taiwan,  Turkey,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The percentage of patients who achieved at least 20% improvement in the American College of Rheumatology (ACR) criteria		At Week 24	No
Primary	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		At Week 12	No
Secondary	Percentage of patients achieving American College of Rheumatology (ACR) 20/50/70 criteria		At Week 12	No
Secondary	Percentage of patients achieving American College of Rheumatology (ACR) 50/70 criteria		At Week 24	No
Secondary	Changes from baseline in disease activity score (DAS) 28		At Week 12 and Week 24	No
Secondary	Disease activity score (DAS) 28 remission rate		At Week 12 and Week 24	No
Secondary	Change from baseline in short form (SF)-36 domains		At Week 12 and Week 24	No
Secondary	Change from baseline in the Rheumatoid Arthritis-Work Productivity Survey (WPS-RA) items		At Week 12 and Week 24	No
Secondary	Change from baseline in the Functional Assessment of Chronic Illness Therapy Fatigue scale (FACIT-fatigue)		At Week 12 and Week 24	No
Secondary	Change from baseline in European Quality of Life-5 dimension (EQ-5D)		At Week 12 and Week 24	No
Secondary	Change from baseline in rheumatoid arthritis impact of disease (RAID) scores		At Week 12 and Week 24	No
Secondary	Change from baseline in each individual ACR component		At Week 12 and Week 24	No