A Phase 3 Study in Moderate to Severe Rheumatoid Arthritis

INTERVENTION:

Product Name: BARICITINIB Product Code: LY3009104 Pharmaceutical Form: Tablet Current Sponsor code: LY3009104 Other descriptive name: Baricitinib Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 4‐ Pharmaceutical form of the placebo: Tablet Route of administration of the placebo: Oral use Product Name: BARICITINIB Product Code: LY3009104 Pharmaceutical Form: Tablet Current Sponsor code: LY3009104 Other descriptive name: Baricitinib Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 2‐ Pharmaceutical form of the placebo: Tablet Route of administration of the placebo: Oral use

CONDITION:

Moderately to severely active rheumatoid arthritis ; MedDRA version: 14.1 Level: SOC Classification code 10028395 Term: Musculoskeletal and connective tissue disorders System Organ Class: 10028395 ‐ Musculoskeletal and connective tissue disorders ; MedDRA version: 14.1 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 ‐ Musculoskeletal and connective tissue disorders Therapeutic area: Diseases [C] ‐ Musculoskeletal Diseases [C05]

PRIMARY OUTCOME:

Main Objective: Determine whether Baricitinib 4 mg QD is superior to placebo in the treatment of patients with moderately to severely active RA who have had inadequate response to or are intolerant to at least 1 cDMARD (cDMARD‐IR [inadequate response] patients) and who have not received a biologic DMARD, as assessed by the portion of patients achieving ACR20 at Week 12 ECG Addendum ‐ Approved: 22‐Aug‐2012 Primary objective is to compare the change from baseline in QTcF interval at approximately 90 minutes following first dose of investigational product (Week 0) and at week 1, Week 4, and week 12 between Baricitinib 4 mg QD and placebo. Primary end point(s): Proportion of patients achieving ACR20 response (baricitinib 4mg compared to placebo) Secondary Objective: ‐ change from baseline to Week 12 in Health Assessment Questionnaire‐Disability Index (HAQ‐DI) score ‐ change from baseline to week 12 in DAS28‐high‐sensitivity C‐reactive protein (hsCRP) ‐ proportion of patients achieving ACR20 at Week 12 (Baricitinib 2 mg compared to placebo) Timepoint(s) of evaluation of this end point: Week 12

SECONDARY OUTCOME:

Secondary end point(s): DAS28‐high‐sensitivity C‐reactive protein (hsCRP): ‐ Proportion of patients achieving ACR20 response (baricitinib 2mg compared to placebo) Timepoint(s) of evaluation of this end point: DAS28‐high‐sensitivity C‐reactive protein (hsCRP): Change from baseline to Weeks 12 and 24 ‐ Proportion of patients achieving ACR20 response (baricitinib 2mg compared to placebo) : Week 12

INCLUSION CRITERIA:

‐almeno 18 anni di età ‐diagnosi di Artrite Reumatoide iniziata in età adulta come definito dai criteri per la classificazione di AR ACR/EULAR 2010 ‐ AR da moderata a severa definita come almeno 6/68 articolazioni lasse e 6/66 tumefazioni delle articolazioni ‐ Valore della Proteina reattiva C > o uguale ad 1.2 ULN Risposta insufficiente o intolleranza ai cDMARDs o entrambe: uso regolare di un cDMARD per almeno 12 settimane prima di entrare in studio con un una dose continua e stabile per almeno le precedenti 8 settimane; Pe i pazienti che non in trattamento con cDMARD al momento dell'entrata in studio, l'investigatore dovrà documentare in cartella che il paziente ha fallito, non era in grado di tollerare o aveva qualche cntroindicazone per il trattamento con cDMARDs Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range 600 F.1.3 Elderly (>=65 y