A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study Evaluating the Efficacy and Safety of Baricitinib (LY3009104) in Patients with Moderately to Severely Active Rheumatoid Arthritis Who Have Had an Inadequate Response to Tumor Necrosis Factor Inhibitors

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: 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 an inadequate response to a TNF inhibitor, despite ongoing treatment with cDMARDs, as assessed by the proportion of patients achieving ACR20 at Week 12. 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 (baricitinib 4mg compared to placebo); ‐ change from baseline to Week 12 in DAS28‐high‐sensitivity C‐reactive protein (hsCRP) (baricitinib 4mg compared to placebo); ‐ proportion of patients achieving ACR20 at Week 12 (baricitinib 2mg compared to placebo); ‐ change from baseline to Week 12 in HAQ‐DI score (baricitinib 2mg compared to placebo); ‐ change from baseline to Week 12 in DAS28‐hsCRP (baricitinib 2mg compared to placebo); Timepoint(s) of evaluation of this end point: Week 12

SECONDARY OUTCOME:

Secondary end point(s): ‐ Health Assessment Questionnaire‐Disability Index (HAQ‐DI) score ; ‐ DAS28‐high‐sensitivity C‐reactive protein (hsCRP) ; ‐ Proportion of patients achieving ACR20 response (baricitinib 2mg compared to placebo) ; ‐ Proportion of patients achieving ACR20 response ; ‐ Proportion of patients achieving ACR50 and ACR70 response ; ‐ proportion of patients achieving DAS28‐hsCRP =3.2; proportion of patients achieving DAS28‐ hsCRP <2.6 ; ‐ proportion of patients achieving DAS28‐ESR =3.2; proportion of patients achieving DAS28‐ ESR <2.6 ; Timepoint(s) of evaluation of this end point: ‐ Health Assessment Questionnaire‐Disability Index (HAQ‐DI) score: Change from baseline to Weeks 12 and 24 ; ‐ 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 ; ‐ Proportion of patients achieving ACR20 response: Week 24 ; ‐ Proportion of patients achieving ACR50 and ACR70 response: Weeks 12 and 24 ; ‐ proportion of patients achieving DAS28‐hsCRP =3.2; proportion of patients achieving DAS28‐ hsCRP <2.6: Weeks 12 and 24 ; ‐ proportion of patients achieving DAS28‐ESR =3.2; proportion of patients achieving DAS28‐ ESR <2.6: Weeks 12 and 24 ;

INCLUSION CRITERIA:

• are at least 18 years of age • have a diagnosis of adult‐onset RA as defined by the ACR/EULAR 2010 Criteria for the Classification of RA • have moderately to severely active RA defined as the presence of at least 6/68 tender joints and at least 6/66 swollen joints • have a C‐reactive protein (or hsCRP) measurement =1 times the upper limit of normal (ULN) • have been treated at approved doses with at least 1 biologic TNF‐ a inhibitor and either: ‐ experienced insufficient efficacy or loss of efficacy ‐ experienced intolerance of such treatment • have had regular use of at least 1 cDMARD for at least the 12 weeks prior to study entry with a continuous, nonchanging dose for at least 8 weeks prior to study entry Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 N