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    Summary
    EudraCT Number:2019-000797-39
    Sponsor's Protocol Code Number:201790
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2021-05-24
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2019-000797-39
    A.3Full title of the trial
    A 52-week, phase 3, multicentre, randomised, double blind, efficacy and safety study comparing GSK3196165 with placebo and with tofacitinib, in combination with methotrexate in participants with moderately to severely
    active rheumatoid arthritis who have an inadequate response to methotrexate.
    Studio di fase 3, multicentrico, randomizzato, in doppio cieco, della durata di 52 settimane volto a valutare l’efficacia e la sicurezza di GSK3196165 rispetto al placebo e a tofacitinib, in combinazione con metotrexato in partecipanti affetti da artrite reumatoide da moderatamente a gravemente attiva che presentano una risposta inadeguata al metotrexato
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Efficacy and safety of GSK3196165 versus placebo and tofacitinib in participants with moderately to severely active rheumatoid arthritis who have an inadequate response to methotrexate.
    L'efficacia e la sicurezza di GSK3196165 rispetto al placebo e a tofacitinib, in combinazione con metotrexato in partecipanti affetti da artrite reumatoide da moderatamente a gravemente attiva che presentano una risposta inadeguata al metotrexato
    A.3.2Name or abbreviated title of the trial where available
    contRAst-1
    contRAst-1
    A.4.1Sponsor's protocol code number201790
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorGLAXOSMITHKLINE RESEARCH AND DEVELOPMENT
    B.1.3.4CountryUnited Kingdom
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportGlaxoSmithKline LLC
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationGlaxoSmithKline Research & Development Ltd
    B.5.2Functional name of contact pointGSK Clinical Support HelpDesk
    B.5.3 Address:
    B.5.3.1Street AddressIron Bridge Road
    B.5.3.2Town/ cityStockley Park West, Uxbridge, Middlesex
    B.5.3.3Post codeUB11 1BU
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number02089904466
    B.5.5Fax number02089904968
    B.5.6E-mailGSKClinicalSupportHD@gsk.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Xeljanz
    D.2.1.1.2Name of the Marketing Authorisation holderPfizer Europe MA EEIG
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameTofacitinib
    D.3.2Product code [Tofacitinib]
    D.3.4Pharmaceutical form Capsule, hard
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNTofacitinib citrate
    D.3.9.1CAS number 540737-29-9
    D.3.9.2Current sponsor codeNA
    D.3.9.4EV Substance CodeSUB33105
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameGSK3196165
    D.3.2Product code [GSK3196165]
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNOtilimab
    D.3.9.1CAS number 1638332-55-4
    D.3.9.2Current sponsor codeGSK3196165
    D.3.9.4EV Substance CodeSUB177902
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number150
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboConcentrate for solution for injection
    D.8.4Route of administration of the placeboSubcutaneous use
    D.8 Placebo: 2
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboCapsule, hard
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Rheumatoid Arthritis
    Artrite reumatoide
    E.1.1.1Medical condition in easily understood language
    Rheumatoid Arthritis (RA) is a chronic, systemic inflammatory autoimmune disease, characterised by a symmetrical polyarthritis that is associated with substantial disability and morbidity
    L'artrite reumatoide (RA) è una malattia autoimmune infiammatoria sistemica cronica, caratterizzata da una poliartrite simmetrica associata a sostanziale disabilità e morbidità
    E.1.1.2Therapeutic area Diseases [C] - Musculoskeletal Diseases [C05]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 23.1
    E.1.2Level PT
    E.1.2Classification code 10039073
    E.1.2Term Rheumatoid arthritis
    E.1.2System Organ Class 10028395 - Musculoskeletal and connective tissue disorders
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To compare the efficacy of GSK3196165 at doses of 90 mg and 150 mg weekly versus placebo for the treatment of participants with moderately to severely active RA who are on a stable background of MTX and who
    have had an inadequate response to MTX.
    Per confrontare l’efficacia di GSK3196165 a dosi di 90 mg e 150 mg una volta alla settimana rispetto al placebo per il trattamento di partecipanti con AR da moderatamente a gravemente attiva che assumono una terapia di fondo stabile con MTX e che hanno manifestato una risposta inadeguata a MTX.
    E.2.2Secondary objectives of the trial
    To compare:
    - Efficacy of GSK3196165 at doses of 90 mg and 150 mg weekly versus tofacitinib for the treatment of participants with moderately to severely active RA who are on a stable background of MTX and who have had an inadequate response to MTX.
    - Effect of GSK3196165 on Patient Reported Outcomes (PROs) versus placebo and the active comparator tofacitinib
    - Safety and tolerability of GSK3196165 versus placebo and the active comparator tofacitinib
    - To determine the immunogenic potential of GSK3196165
    Per confrontare:

    - Efficacia di GSK3196165 a dosi di 90 mg e 150 mg una volta alla settimana rispetto a tofacitinib per il trattamento di partecipanti con AR da moderatamente a gravemente attiva che assumono una terapia di fondo stabile con MTX e che hanno manifestato una risposta inadeguata a MTX.
    - Effetto di GSK3196165 sugli esiti segnalati dal paziente (PRO) contro placebo e il comparatore attivo tofacitinib
    - Sicurezza e tollerabilità di GSK3196165 rispetto al placebo e al principio attivo comparatore tofacitinib
    - Determinare il potenziale immunogenico di GSK3196165
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Age =18 years at the time of signing informed consent.
    2. Meets ACR/EULAR 2010 RA Classification Criteria (see study reference manual [SRM]) with a duration of RA disease of =6 months at time of screening and participant not diagnosed before 16 years of age.
    3. Must have active disease at both screening and baseline, as defined by having both: a. =6/68 tender/painful joints (TJC), and b. =6/66 swollen joints (SJC).
    If surgical treatment of a joint has been performed, that joint cannot be counted in the TJC or SJC for enrolment purposes
    4. Must have a high sensitivity C-reactive protein (hsCRP)measurement =3 mg/L at screening.
    5. Must meet Class I, II or III of the ACR 1991 Revised Criteria for Global Functional Status in RA (see SRM).
    6. Must have at least 1 bone erosion present on hand/wrist or foot radiographs confirmed by central reading at screening.
    7. Must have inadequate response, despite currently taking Methotrexate (MTX): weekly 15-25 mg oral or injected, for at least 12 weeks at the
    maximum tolerated dose prior to Day 1, with no change in route of administration in this time. MTX dose must be stable and tolerated for at
    least 8 weeks prior to Day 1. A lower dose of =7.5 mg/week is acceptable if reduced for reasons of intolerance to MTX, e.g. nausea/vomiting, hepatic or hematologic toxicity, or per local
    requirement (there must be clear documentation in the medical record).
    8. Body weight =40 kg
    9. Male or female participants are eligible to participate so long as they meet and agree to abide by the contraceptive criteria detailed in Appendix 4 of protocol.
    10. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
    11. Willing to continue or initiate treatment with oral folic acid (at least 5 mg/week) or equivalent and be treated during the entire study (mandatory co-medication for MTX treatment).
    1. Età =18 anni al momento della firma del consenso informato.
    2. Soddisfa i criteri di classificazione ACR / EULAR 2010 RA (vedere il manuale di riferimento dello studio [SRM]) con una durata della malattia RA di =6 mesi al momento dello screening e il partecipante non diagnosticato prima dei 16 anni di età.
    3. Deve avere una malattia attiva sia allo screening che al basale, come definito dall'avere entrambi:
    a. =6 / 68 articolazioni tenere / dolorose (TJC) e
    b. =6 / 66 articolazioni gonfie (SJC).
    Se il trattamento chirurgico di un giunto è stato eseguito, tale articolazione non può essere conteggiata nel TJC o SJC ai fini dell'arruolamento
    4. Deve avere una misurazione della proteina C-reattiva (hsCRP) ad alta sensibilità =3 mg / L allo screening.
    5. Deve soddisfare i criteri I, II o III dei Criteri Revisionati ACR 1991 per lo stato funzionale globale in RA (vedere SRM).
    6. Deve avere almeno 1 erosione ossea presente sulla mano / polso o radiografie del piede confermate dalla lettura centrale allo screening.
    7. Deve avere una risposta inadeguata, nonostante stia attualmente assumendo Metotrexato (MTX): 15-25 mg per via orale o iniettati settimanalmente, per almeno 12 settimane alla dose massima tollerata prima del Giorno 1, senza cambiamenti nella via di somministrazione in questo momento. La dose di MTX deve essere stabile e tollerata per almeno 8 settimane prima del primo giorno. Una dose inferiore di 7,5 mg / settimana è accettabile se ridotta per motivi di intolleranza al MTX, ad es nausea / vomito, tossicità epatica o ematologica, o per esigenza locale (nella cartella clinica deve essere presente una documentazione chiara).
    8. Peso corporeo =40 kg
    9. I partecipanti di sesso maschile o femminile possono partecipare purché s' incontrino e accettino di rispettare i criteri contraccettivi descritti nell'appendice 4 del protocollo.
    10. Capace di dare il consenso informato firmato che include la conformità con i requisiti e le restrizioni elencati nel modulo di consenso informato (ICF) e in questo protocollo.
    11. Disposto a continuare o iniziare il trattamento con acido folico orale (almeno 5 mg / settimana) o equivalente e essere trattato durante l'intero studio (co-medicazione obbligatoria per il trattamento MTX).
    E.4Principal exclusion criteria
    1. Active infections (including localised infections), or history of recurrent infections (excluding recurrent fungal infections of the nail bed), or has required management of acute or chronic infections, as
    described in the protocol.
    2. Symptomatic herpes zoster within 3 months prior to screening.
    3. Hereditary or acquired immunodeficiency disorder, including immunoglobulin deficiency.
    4. Known infection with human immunodeficiency virus (HIV) or positive test at screening.
    5. History of infected joint prosthesis at any time, with the prosthesis still in situ. History of chronic leg ulcers, permanent in-dwelling catheters,chronic sinusitis,recurrent chest infections or recurrent urinary
    tract infections.
    6. Any baseline symptomatology that in the investigator's opinion would confound the early detection of pulmonary alveolar proteinosis based upon clinical features, such as persistent cough (CTC Grade =2) or
    persistent dyspnoea (dyspnoea scale Grade =2).
    7. Current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, persistent jaundice, or cirrhosis.
    8. Current acute or chronic Hepatitis B and/or Hepatitis C.
    9. Current or history of renal disease or estimated glomerular filtration rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI) calculation <60 mL/min/1.73m2 at screening.
    10. Breast cancer within the past 10 years or lymphoma, leukaemia, or any other malignancy within the past 5 years except for cervical carcinoma in situ that has been resected with no evidence of recurrence
    or metastatic disease, or basal cell or squamous epithelial cancers of the skin that have been resected with no evidence of recurrence or metastatic disease for at least 3 years.
    11. History of any lymphoproliferative disorder, such as Epstein Barr Virus (EBV) related lymphoproliferative disorder, or signs and symptoms suggestive of current lymphatic disease.
    12. History or presence of significant other concomitant illness according to the Investigator judgment such as, but not limited to cardiovascular (including Stage III or IV cardiac failure according to New York Heart
    Association classification, myocardial infarction within 12 months, unstable angina pectoris, uncontrolled hypertension, uncontrolled hypercholesterolemia), neurological,
    endocrinological, gastrointestinal (including diverticulitis), hepatic disease, metabolic, lymphatic disease, or previous renal transplant that would adversely affect the participant's participation
    13. Any condition or contraindication as addressed in the local product information or local clinical practice for tofacitinib that would preclude the participant from participating in this protocol.
    14. History of other inflammatory rheumatologic or systemic autoimmune disorder, other than Sjögren's syndrome secondary to RA, that may confound the evaluation of the effect of the study intervention such as mixed connective tissue disease, psoriatic arthritis, juvenile chronic arthritis, spondyloarthritis, Felty's Syndrome, systemic lupus erythematosus, scleroderma, Crohn's disease, ulcerative colitis, or vasculitis.
    15. Presence of fibromyalgia that, in the investigator's opinion, would make it difficult to appropriately assess RA activity for the purposes of this study.
    16. Undergone any major surgery within 8 weeks prior to study entry or will require major surgery during the study that, in the opinion of the investigator would pose an unacceptable risk to the participant.
    17. Current or previous active Mycobacterium tuberculosis (TB) regardless of treatment.
    18-36 Other exclusion criteria as mentionned in the protocol.
    1. Infezioni attive (incluse infezioni localizzate) o anamnesi d' infezioni ricorrenti (escluse le infezioni ricorrenti da fungo del letto ungueale) o ha richiesto la gestione d' infezioni acute o croniche, come descritto nel protocollo.
    2. Herpes zoster sintomatico nei 3 mesi precedenti lo screening.
    3. Disturbo da immunodeficienza ereditaria o acquisita, inclusa la carenza di immunoglobulina.
    4. Infezione nota con virus dell'immunodeficienza umana (HIV) o test positivo allo screening.
    5. Storia della protesi articolare infetta in qualsiasi momento, con la protesi ancora in situ. Storia d' ulcere croniche alle gambe, cateteri permanenti permanenti, sinusite cronica, infezioni toraciche ricorrenti o infezioni ricorrenti del tratto urinario.
    6. Qualsiasi sintomatologia di base che secondo l'opinione dello sperimentatore confonderebbe la diagnosi precoce di proteinosi alveolare polmonare basata su caratteristiche cliniche, come tosse persistente (grado CT2 =2) o dispnea persistente (grado dispnea di grado =2).
    7. Insufficienza epatica o patologica biliare attuale per valutatore definita dalla presenza d' ascite, encefalopatia, coagulopatia, ipoalbuminemia, varici esofagee o gastriche, ittero persistente o cirrosi.
    8. Attuale epatite B acuta o cronica e / o epatite C.
    9. Corrente o storia di malattia renale o velocità di filtrazione glomerulare stimata (eGFR) mediante calcolo dell'epidemiologia cronica del rene nell'epidemia (CKD-EPI) <60 mL / min / 1,73m2 allo screening.
    10. Cancro al seno negli ultimi 10 anni o linfoma, leucemia o qualsiasi altra neoplasia negli ultimi 5 anni ad eccezione del carcinoma cervicale in situ che è stato asportato senza evidenza di recidiva o malattia metastatica, o tumori epiteliali a cellule basali o squamose di la pelle che è stata resecata senza evidenza di recidiva o malattia metastatica per almeno 3 anni.
    11. Storia di qualsiasi disturbo linfoproliferativo, come il disturbo linfoproliferativo di Epstein Barr Virus (EBV), o segni e sintomi che suggeriscono l'attuale malattia linfatica.
    12. Anamnesi o presenza d' altre malattie concomitanti significative secondo il giudizio dello sperimentatore come, ma non limitato a cardiovascolare (incluso insufficienza cardiaca di stadio III o IV secondo la classificazione della New York Heart Association, infarto del miocardio entro 12 mesi, angina pectoris instabile, ipertensione incontrollata, ipercolesterolemia incontrollata), neurologica, endocrinologica, gastrointestinale (compresa la diverticolite), malattia epatica, malattia metabolica, linfatica o precedente trapianto renale che influirebbe negativamente sulla partecipazione del partecipante
    13. Qualsiasi condizione o controindicazione, come indicato nelle informazioni sul prodotto locale o nella pratica clinica locale per il tofacitinib, che precluderebbe al partecipante la partecipazione a questo protocollo.
    14. Anamnesi d' altre patologie autoimmuni reumatologiche o sistemiche infiammatorie, diverse dalla sindrome di Sjögren secondaria a RA, che può confondere la valutazione dell'effetto dell'intervento dello studio come la malattia mista del tessuto connettivo, l'artrite psoriasica, l'artrite cronica giovanile, la spondiloartrite, la sindrome di Felty , lupus eritematoso sistemico, sclerodermia, morbo di Crohn, colite ulcerosa o vasculite.
    15. Presenza di fibromialgia che, secondo il parere dello sperimentatore, renderebbe difficile valutare in modo appropriato l'attività della RA ai fini di questo studio.
    16. Sottoposto a qualsiasi intervento chirurgico maggiore entro 8 settimane prima dell'ingresso nello studio o richiederà un intervento chirurgico maggiore durante lo studio che, secondo il parere dello sperimentatore, potrebbe comportare un rischio inaccettabile per il partecipante.
    17. Mycobacterium tuberculosis (TB) attuale o precedente attivo indipendentemente dal trattamento.
    18-36 altri criteri di esclusione sono menzionati nel protocollo.
    E.5 End points
    E.5.1Primary end point(s)
    Proportion of participants achieving ACR20
    Proporzione dei partecipanti che raggiungono l'ACR20
    E.5.1.1Timepoint(s) of evaluation of this end point
    At week 12
    Alla settimana 12
    E.5.2Secondary end point(s)
    1) Major Secondary Efficacy Endpoints Week 12 versus placebo:
    - Proportion of participants achieving CDAI total score =10 (CDAI LDA).
    - Change from baseline in HAQ-DI.
    Non-inferiority versus tofacitinib at Week 12:
    - Proportion of participants achieving ACR20.
    Other Secondary Efficacy Endpoints
    Week 12 (vs. placebo and vs. tofacitinib), Week 24 and Week 52 (vs. tofacitinib):
    Proportion of participants achieving:
    - CDAI total score =10 (CDAI LDA).
    - CDAI total score =2.8 (CDAI Remission).
    - ACR20/50/70.
    - DAS28-CRP <=3.2 and DAS28(ESR) <=3.2 (DAS28 LDA).
    - DAS28-CRP <2.6 and DAS28(ESR) <2.6 (DAS28 Remission).
    - A good/moderate EULAR response.
    - ACR/EULAR Remission.
    - No radiographic progression defined as a change from baseline in van der Heijde mTSS score of =0.5.
    Change from baseline in:
    - CDAI total score.
    - DAS28-CRP/DAS28-ESR.
    - van der Heijde mTSS.
    2) Change from baseline at Week 12 (vs. placebo and vs. tofacitinib),
    Week 24 and Week 52 (vs. tofacitinib) in:
    - HAQ-DI.
    - Arthritis pain VAS.
    - SF-36 physical and mental component scores, and domain scores.
    - FACIT-Fatigue.
    3) - Incidence of AEs, SAEs and AESIs.
    - Change from baseline in key laboratory parameters.
    - Proportion of participants with NCICTCAE =Grade 3 haematological/clinical chemistry abnormalities.
    4) Safety Biomarker Endpoints
    - GM-CSF autoantibody concentrations.
    - Anti-GSK3196165 antibodies.
    1) Endpoint secondari di Efficacia Secondaria Settimana 12 rispetto a placebo:
    - Proporzione dei partecipanti che raggiungono il CDAI punteggio totale =10 (CDAI LDA).
    - Cambia dalla linea di base in HAQ-DI.
    Non inferiorità rispetto a tofacitinib alla settimana 12:
    - Proporzione dei partecipanti che raggiungono l'ACR20.
    Altri endpoint secondari d' efficacia
    Settimana 12 (vs. placebo e vs. tofacitinib), Settimana 24 e Settimana 52 (vs.
    tofacitinib):
    Proporzione dei partecipanti che ottengono:
    - Punteggio totale CDAI =10 (CDAI LDA).
    - Punteggio totale CDAI =2,8 (Remissione CDAI).
    - ACR20/50/70.
    - DAS28-CRP <=3.2 e DAS28 (ESR) <=3.2 (DAS28 LDA).
    - DAS28-CRP <2.6 e DAS28 (ESR) <2.6 (Remissione DAS28).
    - Una risposta EULAR buona/moderata.
    - Remissione ACR / EULAR.
    - Nessuna progressione radiografica definita come variazione rispetto al basale in van der Heijde punteggio mTSS di =0.5.
    Cambia dalla baseline in:
    - Punteggio totale CDAI.
    - DAS28-CRP / DAS28-ESR.
    - van der Heijde me.
    2) Change from baseline at Week 12 (vs. placebo and vs. tofacitinib),
    Week 24 and Week 52 (vs. tofacitinib) in:
    - HAQ-DI.
    - Arthritis pain VAS.
    - SF-36 physical and mental component scores, and domain scores.
    - FACIT-Fatigue.
    3) - Incidence of AEs, SAEs and AESIs.
    - Change from baseline in key laboratory parameters.
    - Proportion of participants with NCICTCAE =Grade 3
    haematological/clinical chemistry abnormalities.
    4) Safety Biomarker Endpoints
    - GM-CSF autoantibody concentrations.
    - Anti-GSK3196165 antibodies.
    E.5.2.1Timepoint(s) of evaluation of this end point
    At various timepoint up to week 52 as defined in the protocol
    A vari tempi fino alla settimana 52 come definito nel protocollo
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    Immunogenicity
    immunogenecità
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Yes
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial6
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned4
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA75
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA Information not present in EudraCT
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Argentina
    Brazil
    Canada
    China
    Czechia
    Hungary
    India
    Italy
    Lithuania
    Malaysia
    Mexico
    Philippines
    Poland
    Russian Federation
    Serbia
    South Africa
    Spain
    Sweden
    Ukraine
    United States
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months9
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months9
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 1496
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 204
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state18
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 405
    F.4.2.2In the whole clinical trial 1700
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    Participants who complete the treatment visits to Week 52 may be eligible to transition into the long-term extension study 209564. Any participant who does not transition into Study 209564 will undergo a safety follow-up visit at 8 weeks post last dose of SC study intervention.
    I partecipanti che completano le visite di trattamento alla settimana 52 possono essere ammessi alla transizione nello studio di estensione a lungo termine 209564. Qualsiasi partecipante che non passi nello studio 209564 sarà sottoposto a una visita di follow-up di sicurezza a 8 settimane dopo l'ultima dose di intervento dello studio SC .
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2019-12-20
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2019-11-20
    P. End of Trial
    P.End of Trial StatusOngoing
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