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)
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
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.
Studieoversigt
Status
Betingelser
Detaljeret beskrivelse
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).
Undersøgelsestype
Tilmelding (Faktiske)
Fase
- Fase 3
Kontakter og lokationer
Studiesteder
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Caba, Argentina, C1015ABO
- Investigational Site Number 032006
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Ramos Mejia, Argentina, B1704ETD
- Investigational Site Number 032010
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Rosario, Argentina, S200PBJ
- Investigational Site Number 032013
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San Fernando, Argentina
- Investigational Site Number 032015
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San Miguel De Tucuman, Argentina, 4000
- Investigational Site Number 032004
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Tucuman, Argentina, 4000
- Investigational Site Number 032005
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Leuven, Belgien, 3000
- Investigational Site Number 056010
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Curitiba, Brasilien, 80060-240
- Investigational Site Number 076001
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Sao Jose Do Rio Preto, Brasilien, 15090-000
- Investigational Site Number 076030
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Kemerovo, Den Russiske Føderation, 650066
- Investigational Site Number 643017
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Moscow, Den Russiske Føderation, 115404
- Investigational Site Number 643020
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Moscow, Den Russiske Føderation, 115522
- Investigational Site Number 643001
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Moscow, Den Russiske Føderation, 117997
- Investigational Site Number 643002
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Moscow, Den Russiske Føderation, 121374
- Investigational Site Number 643031
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Moscow, Den Russiske Føderation, 125284
- Investigational Site Number 643030
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St-Petersburg, Den Russiske Føderation, 191186
- Investigational Site Number 643032
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Doncaster, Det Forenede Kongerige, DN2 5LT
- Investigational Site Number 826004
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Edinburgh, Det Forenede Kongerige, EH4 2XU
- Investigational Site Number 826006
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Leeds, Det Forenede Kongerige, LS7 4SA
- Investigational Site Number 826001
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London, Det Forenede Kongerige, E11 1NR
- Investigational Site Number 826002
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Southampton, Det Forenede Kongerige, SO16 6YD
- Investigational Site Number 826005
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Wigan, Det Forenede Kongerige, WN6 9EP
- Investigational Site Number 826025
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Tallinn, Estland, 10138
- Investigational Site Number 233010
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Tallinn, Estland, 13419
- Investigational Site Number 233002
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Helsinki, Finland, 00290
- Investigational Site Number 246001
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Riihimäki, Finland, 11120
- Investigational Site Number 246010
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Alabama
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Huntsville, Alabama, Forenede Stater, 35801
- Investigational Site Number 840152
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Colorado
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Colorado Springs, Colorado, Forenede Stater, 80903
- Investigational Site Number 840151
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Florida
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Aventura, Florida, Forenede Stater, 33180
- Investigational Site Number 840153
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Fort Lauderdale, Florida, Forenede Stater, 33334
- Investigational Site Number 840033
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Miami, Florida, Forenede Stater, 33155
- Investigational Site Number 840048
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Palm Harbor, Florida, Forenede Stater, 34684
- Investigational Site Number 840155
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Maryland
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Wheaton, Maryland, Forenede Stater, 20902
- Investigational Site Number 840013
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Massachusetts
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Boston, Massachusetts, Forenede Stater, 02115
- Investigational Site Number 840154
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Michigan
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Lansing, Michigan, Forenede Stater, 48910
- Investigational Site Number 840150
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Pennsylvania
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Reading, Pennsylvania, Forenede Stater, 19611
- Investigational Site Number 840062
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Texas
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Austin, Texas, Forenede Stater, 78705
- Investigational Site Number 840038
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Dallas, Texas, Forenede Stater, 75235
- Investigational Site Number 840022
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Dallas, Texas, Forenede Stater, 75246
- Investigational Site Number 840156
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Mesquite, Texas, Forenede Stater, 75150
- Investigational Site Number 840074
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Amsterdam, Holland, 1056 AB
- Investigational Site Number 528010
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Leiden, Holland, 2333 ZA
- Investigational Site Number 528001
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Haifa, Israel, 31096
- Investigational Site Number 376010
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Tel Aviv, Israel, 64239
- Investigational Site Number 376011
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Firenze, Italien, 50141
- Investigational Site Number 380002
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Genova, Italien, 16132
- Investigational Site Number 380005
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Durango, Mexico, 34080
- Investigational Site Number 484008
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Leon, Mexico, 37000
- Investigational Site Number 484035
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Merida, Mexico, 97000
- Investigational Site Number 484009
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México, D.F., Mexico, 11850
- Investigational Site Number 484001
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Zapopan, Mexico, 44280
- Investigational Site Number 484036
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Kristiansand, Norge, 4604
- Investigational Site Number 578010
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Tønsberg, Norge, 3105
- Investigational Site Number 578006
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Bydgoszcz, Polen, 85-168
- Investigational Site Number 616019
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Bytom, Polen, 41-902
- Investigational Site Number 616054
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Lublin, Polen, 20-090
- Investigational Site Number 616030
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Warszawa, Polen, 01-518
- Investigational Site Number 616031
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Warszawa, Polen, 02-653
- Investigational Site Number 616017
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Braila, Rumænien, 810019
- Investigational Site Number 642006
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Bucharest, Rumænien
- Investigational Site Number 642010
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Bucharest, Rumænien, 020125
- Investigational Site Number 642020
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Bucuresti, Rumænien, 010584
- Investigational Site Number 642021
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Bucuresti, Rumænien, 010976
- Investigational Site Number 642001
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Targoviste, Rumænien, 130083
- Investigational Site Number 642022
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Barcelona, Spanien, 08035
- Investigational Site Number 724020
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Santander, Spanien, 39008
- Investigational Site Number 724021
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Sevilla, Spanien, 41010
- Investigational Site Number 724022
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Malmö, Sverige, 205 02
- Investigational Site Number 752004
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Uppsala, Sverige, 751 85
- Investigational Site Number 752002
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Liberec, Tjekkiet, 46063
- Investigational Site Number 203009
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Praha 2, Tjekkiet, 12850
- Investigational Site Number 203011
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Praha 4, Tjekkiet, 140 00
- Investigational Site Number 203010
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Budapest, Ungarn, 1027
- Investigational Site Number 348014
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Budapest, Ungarn, 1036
- Investigational Site Number 348022
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Esztergom, Ungarn, 2500
- Investigational Site Number 348021
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Kistarcsa, Ungarn, 2143
- Investigational Site Number 348016
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Szolnok, Ungarn, 5000
- Investigational Site Number 348009
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Szombathely, Ungarn, 9700
- Investigational Site Number 348015
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Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
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.
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Randomiseret
- Interventionel model: Parallel tildeling
- Maskning: Firedobbelt
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
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Eksperimentel: 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.
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Pharmaceutical form: solution Route of administration: subcutaneous
Dispensed according to local practice.
Dispensed according to local practice.
Dispensed according to local practice.
Dispensed according to local practice.
Pharmaceutical form: solution Route of administration: intravenous
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Eksperimentel: 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.
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Pharmaceutical form: solution Route of administration: subcutaneous
Dispensed according to local practice.
Dispensed according to local practice.
Dispensed according to local practice.
Dispensed according to local practice.
Pharmaceutical form: solution Route of administration: intravenous
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Aktiv komparator: 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.
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Dispensed according to local practice.
Dispensed according to local practice.
Dispensed according to local practice.
Dispensed according to local practice.
Pharmaceutical form: solution Route of administration: intravenous
Pharmaceutical form: solution Route of administration: subcutaneous
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Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
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Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Tidsramme: Up to 211 days
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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.
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Up to 211 days
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Samarbejdspartnere og efterforskere
Sponsor
Samarbejdspartnere
Publikationer og nyttige links
Generelle publikationer
- 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. Erratum In: Rheumatol Ther. 2021 Oct 29;:
- 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.
- 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.
Datoer for undersøgelser
Studer store datoer
Studiestart
Primær færdiggørelse (Faktiske)
Studieafslutning (Faktiske)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Skøn)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
- Sygdomme i immunsystemet
- Autoimmune sygdomme
- Ledsygdomme
- Muskuloskeletale sygdomme
- Reumatiske sygdomme
- Bindevævssygdomme
- Gigt
- Gigt, reumatoid
- Lægemidlers fysiologiske virkninger
- Molekylære mekanismer for farmakologisk virkning
- Anti-infektionsmidler
- Agenter fra det perifere nervesystem
- Nukleinsyresyntesehæmmere
- Enzymhæmmere
- Analgetika
- Sensoriske systemagenter
- Anti-inflammatoriske midler, ikke-steroide
- Analgetika, ikke-narkotisk
- Anti-inflammatoriske midler
- Antirheumatiske midler
- Antimetabolitter, Antineoplastisk
- Antimetabolitter
- Antineoplastiske midler
- Immunsuppressive midler
- Immunologiske faktorer
- Gastrointestinale midler
- Dermatologiske midler
- Reproduktive kontrolmidler
- Antiprotozoale midler
- Antiparasitære midler
- Antimalariamidler
- Abortfremkaldende midler, ikke-steroide
- Aborterende midler
- Folinsyreantagonister
- Methotrexat
- Leflunomid
- Hydroxychloroquin
- Sulfasalazin
Andre undersøgelses-id-numre
- SFY13370
- 2012-003536-23
- U1111-1133-7839 (Anden identifikator: UTN)
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