Clinical trial NCT01768572: 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)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2013-01-15
Enrollment: 202
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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.

Primary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
timeFrame: Up to 211 days
Secondary outcomes:
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Investigational Site Number 840152
state: Alabama
city: Colorado Springs
country: United States
facility: Investigational Site Number 840151
state: Colorado
city: Aventura
country: United States
facility: Investigational Site Number 840153
state: Florida
city: Fort Lauderdale
country: United States
facility: Investigational Site Number 840033
state: Florida
city: Miami
country: United States
facility: Investigational Site Number 840048
state: Florida
city: Palm Harbor
country: United States
facility: Investigational Site Number 840155
state: Florida
city: Wheaton
country: United States
facility: Investigational Site Number 840013
state: Maryland
city: Boston
country: United States
facility: Investigational Site Number 840154
state: Massachusetts
city: Lansing
country: United States
facility: Investigational Site Number 840150
state: Michigan
city: Reading
country: United States
facility: Investigational Site Number 840062
state: Pennsylvania
city: Austin
country: United States
facility: Investigational Site Number 840038
state: Texas
city: Dallas
country: United States
facility: Investigational Site Number 840022
state: Texas
city: Dallas
country: United States
facility: Investigational Site Number 840156
state: Texas
city: Mesquite
country: United States
facility: Investigational Site Number 840074
state: Texas
city: Caba
country: Argentina
facility: Investigational Site Number 032006
city: Ramos Mejia
country: Argentina
facility: Investigational Site Number 032010
city: Rosario
country: Argentina
facility: Investigational Site Number 032013
city: San Fernando
country: Argentina
facility: Investigational Site Number 032015
city: San Miguel De Tucuman
country: Argentina
facility: Investigational Site Number 032004
city: Tucuman
country: Argentina
facility: Investigational Site Number 032005
city: Leuven
country: Belgium
facility: Investigational Site Number 056010
city: Curitiba
country: Brazil
facility: Investigational Site Number 076001
city: Sao Jose Do Rio Preto
country: Brazil
facility: Investigational Site Number 076030
city: Liberec
country: Czechia
facility: Investigational Site Number 203009
city: Praha 2
country: Czechia
facility: Investigational Site Number 203011
city: Praha 4
country: Czechia
facility: Investigational Site Number 203010
city: Tallinn
country: Estonia
facility: Investigational Site Number 233010
city: Tallinn
country: Estonia
facility: Investigational Site Number 233002
city: Helsinki
country: Finland
facility: Investigational Site Number 246001
city: Riihimäki
country: Finland
facility: Investigational Site Number 246010
city: Budapest
country: Hungary
facility: Investigational Site Number 348014
city: Budapest
country: Hungary
facility: Investigational Site Number 348022
city: Esztergom
country: Hungary
facility: Investigational Site Number 348021
city: Kistarcsa
country: Hungary
facility: Investigational Site Number 348016
city: Szolnok
country: Hungary
facility: Investigational Site Number 348009
city: Szombathely
country: Hungary
facility: Investigational Site Number 348015
city: Haifa
country: Israel
facility: Investigational Site Number 376010
city: Tel Aviv
country: Israel
facility: Investigational Site Number 376011
city: Firenze
country: Italy
facility: Investigational Site Number 380002
city: Genova
country: Italy
facility: Investigational Site Number 380005
city: Durango
country: Mexico
facility: Investigational Site Number 484008
city: Leon
country: Mexico
facility: Investigational Site Number 484035
city: Merida
country: Mexico
facility: Investigational Site Number 484009
city: México, D.F.
country: Mexico
facility: Investigational Site Number 484001
city: Zapopan
country: Mexico
facility: Investigational Site Number 484036
city: Amsterdam
country: Netherlands
facility: Investigational Site Number 528010
city: Leiden
country: Netherlands
facility: Investigational Site Number 528001
city: Kristiansand
country: Norway
facility: Investigational Site Number 578010
city: Tønsberg
country: Norway
facility: Investigational Site Number 578006
city: Bydgoszcz
country: Poland
facility: Investigational Site Number 616019
city: Bytom
country: Poland
facility: Investigational Site Number 616054
city: Lublin
country: Poland
facility: Investigational Site Number 616030
city: Warszawa
country: Poland
facility: Investigational Site Number 616031
city: Warszawa
country: Poland
facility: Investigational Site Number 616017
city: Braila
country: Romania
facility: Investigational Site Number 642006
city: Bucharest
country: Romania
facility: Investigational Site Number 642020
city: Bucharest
country: Romania
facility: Investigational Site Number 642010
city: Bucuresti
country: Romania
facility: Investigational Site Number 642021
city: Bucuresti
country: Romania
facility: Investigational Site Number 642001
city: Targoviste
country: Romania
facility: Investigational Site Number 642022
city: Kemerovo
country: Russian Federation
facility: Investigational Site Number 643017
city: Moscow
country: Russian Federation
facility: Investigational Site Number 643020
city: Moscow
country: Russian Federation
facility: Investigational Site Number 643001
city: Moscow
country: Russian Federation
facility: Investigational Site Number 643002
city: Moscow
country: Russian Federation
facility: Investigational Site Number 643031
city: Moscow
country: Russian Federation
facility: Investigational Site Number 643030
city: St-Petersburg
country: Russian Federation
facility: Investigational Site Number 643032
city: Barcelona
country: Spain
facility: Investigational Site Number 724020
city: Santander
country: Spain
facility: Investigational Site Number 724021
city: Sevilla
country: Spain
facility: Investigational Site Number 724022
city: Malmö
country: Sweden
facility: Investigational Site Number 752004
city: Uppsala
country: Sweden
facility: Investigational Site Number 752002
city: Doncaster
country: United Kingdom
facility: Investigational Site Number 826004
city: Edinburgh
country: United Kingdom
facility: Investigational Site Number 826006
city: Leeds
country: United Kingdom
facility: Investigational Site Number 826001
city: London
country: United Kingdom
facility: Investigational Site Number 826002
city: Southampton
country: United Kingdom
facility: Investigational Site Number 826005
city: Wigan
country: United Kingdom
facility: Investigational Site Number 826025
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.