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)

Rheumatoid Arthritis Clinical Trial

Official 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01768572
• Other study ID #: SFY13370
• Secondary ID: 2012-003536-23U1
• Status: Completed
• Phase: Phase 3
• First received: January 11, 2013
• Last updated: June 23, 2017
• Start date: March 2013
• Est. completion date: October 2014

Study information

• Verified date: June 2017
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 202
• Est. completion date: October 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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-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 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.

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• sarilumab SAR153191 (REGN88)
Pharmaceutical form: solution Route of administration: subcutaneous
• tocilizumab
Pharmaceutical form: solution Route of administration: intravenous
• hydroxychloroquine
Dispensed according to local practice.
• methotrexate
Dispensed according to local practice.
• sulfasalazine
Dispensed according to local practice.
• leflunomide
Dispensed according to local practice.
• subcutaneous placebo
Pharmaceutical form: solution Route of administration: subcutaneous
• intravenous placebo
Pharmaceutical form: solution Route of administration: intravenous

Locations

Country	Name	City	State
Argentina	Investigational Site Number 032006	Caba
Argentina	Investigational Site Number 032010	Ramos Mejia
Argentina	Investigational Site Number 032013	Rosario
Argentina	Investigational Site Number 032015	San Fernando
Argentina	Investigational Site Number 032004	San Miguel De Tucuman
Argentina	Investigational Site Number 032005	Tucuman
Belgium	Investigational Site Number 056010	Leuven
Brazil	Investigational Site Number 076001	Curitiba
Brazil	Investigational Site Number 076030	Sao Jose Do Rio Preto
Czechia	Investigational Site Number 203009	Liberec
Czechia	Investigational Site Number 203011	Praha 2
Czechia	Investigational Site Number 203010	Praha 4
Estonia	Investigational Site Number 233002	Tallinn
Estonia	Investigational Site Number 233010	Tallinn
Finland	Investigational Site Number 246001	Helsinki
Finland	Investigational Site Number 246010	Riihimäki
Hungary	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
Israel	Investigational Site Number 376010	Haifa
Israel	Investigational Site Number 376011	Tel Aviv
Italy	Investigational Site Number 380002	Firenze
Italy	Investigational Site Number 380005	Genova
Mexico	Investigational Site Number 484008	Durango
Mexico	Investigational Site Number 484035	Leon
Mexico	Investigational Site Number 484009	Merida
Mexico	Investigational Site Number 484001	México, D.F.
Mexico	Investigational Site Number 484036	Zapopan
Netherlands	Investigational Site Number 528010	Amsterdam
Netherlands	Investigational Site Number 528001	Leiden
Norway	Investigational Site Number 578010	Kristiansand
Norway	Investigational Site Number 578006	Tønsberg
Poland	Investigational Site Number 616019	Bydgoszcz
Poland	Investigational Site Number 616054	Bytom
Poland	Investigational Site Number 616030	Lublin
Poland	Investigational Site Number 616017	Warszawa
Poland	Investigational Site Number 616031	Warszawa
Romania	Investigational Site Number 642006	Braila
Romania	Investigational Site Number 642010	Bucharest
Romania	Investigational Site Number 642020	Bucharest
Romania	Investigational Site Number 642001	Bucuresti
Romania	Investigational Site Number 642021	Bucuresti
Romania	Investigational Site Number 642022	Targoviste
Russian Federation	Investigational Site Number 643017	Kemerovo
Russian Federation	Investigational Site Number 643001	Moscow
Russian Federation	Investigational Site Number 643002	Moscow
Russian Federation	Investigational Site Number 643020	Moscow
Russian Federation	Investigational Site Number 643030	Moscow
Russian Federation	Investigational Site Number 643031	Moscow
Russian Federation	Investigational Site Number 643032	St-Petersburg
Spain	Investigational Site Number 724020	Barcelona
Spain	Investigational Site Number 724021	Santander
Spain	Investigational Site Number 724022	Sevilla
Sweden	Investigational Site Number 752004	Malmö
Sweden	Investigational Site Number 752002	Uppsala
United Kingdom	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 States	Investigational Site Number 840038	Austin	Texas
United States	Investigational Site Number 840153	Aventura	Florida
United States	Investigational Site Number 840154	Boston	Massachusetts
United States	Investigational Site Number 840151	Colorado Springs	Colorado
United States	Investigational Site Number 840022	Dallas	Texas
United States	Investigational Site Number 840156	Dallas	Texas
United States	Investigational Site Number 840033	Fort Lauderdale	Florida
United States	Investigational Site Number 840152	Huntsville	Alabama
United States	Investigational Site Number 840150	Lansing	Michigan
United States	Investigational Site Number 840074	Mesquite	Texas
United States	Investigational Site Number 840048	Miami	Florida
United States	Investigational Site Number 840155	Palm Harbor	Florida
United States	Investigational Site Number 840062	Reading	Pennsylvania
United States	Investigational Site Number 840013	Wheaton	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
Sanofi	Regeneron Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  Brazil,  Czechia,  Estonia,  Finland,  Hungary,  Israel,  Italy,  Mexico,  Netherlands,  Norway,  Poland,  Romania,  Russian Federation,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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