A Phase 3 Study in Rheumatoid Arthritis

INTERVENTION:

Trade Name: Olumiant Product Name: Olumiant Product Code: LY3009104 Pharmaceutical Form: Tablet INN or Proposed

INN:

baricitinib Current Sponsor code: LY3009104 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 Trade Name: Olumiant Product Name: Olumiant Product Code: LY3009104 Pharmaceutical Form: Tablet INN or Proposed

INN:

baricitinib Current Sponsor code: LY3009104 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:

Rheumatoid arthritis ; MedDRA version: 20.0 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: The primary objective of the study is to evaluate the long‐term safety and tolerability of baricitinib.; Primary end point(s): a) Proportion of patients experiencing Treatment emergent adverse events (TEAEs), adverse events of special interest, and serious adverse; events (SAEs) over long term follow‐up.; b) Temporary study drug interruptions and/or permanent study drug discontinuations over the long term follow‐up; c) Vital signs and laboratory evaluations (including chemistry and hematology) Secondary Objective: To evaluate in patients initially randomized to receive baricitinib in the originating study, the effect of long‐term administration of baricitinib on the progression of structural joint damage, joint space narrowing and bone erosion. score, duration of morning stiffness, and changes in the European Quality of Life‐5 Dimensions‐5 Level (EQ‐5D‐5L) scores and in healthcare resource utilization.; Timepoint(s) of evaluation of this end point: a) All study visits.; b) All study visits except Visits 1, 2, 5 and 801.; c) All study visits.

SECONDARY OUTCOME:

Secondary end point(s): a) Proportion of patients who maintain an improvement of 20, 50, or 70 percent, respectively, in the American College of Rheumatology criteria ; (ACR20, ACR50 and ACR70) ; b) Proportion of patients who maintain a ; • Disease Activity Score modified to include the 28 diathrodial joint count (DAS28)‐high sensitivity C‐reactive protein (hsCRP)/DAS28 erythrocyte sedimentation rate (ESR)=3.2, DAS28‐hsCRP <2.6, and DAS28‐ESR <2.6 ; • Clinical Disease Activity Index (CDAI) =10, and CDAI =2.8; ; • Simplified Disease Activity Index (SDAI) =11 and SDAI =3.3 ; • ACR/EULAR remission according to the Boolean‐based definition ; • Health Assessment Questionnaire Disability Index (HAQ‐DI) improvement =0.22 and =0.3 ; c)Structural joint damage as measured by modified Total Sharp Score (mTSS) [van der Heijde method]) ; d) Proportion of patients with mTSS change =0 ; e) Joint space narrowing and bone erosion score ; f) Duration of morning stiffness ; g) European Quality of Life‐5 Dimensions‐5 Level (EQ‐5D‐5L) scores and healthcare resource utilization ; b) same as a) ; c) Change from baseline of originating study through each 12 months of treatment ; d) same as c) ; e) same as c) ; f) Change from baseline in duration of morning stiffness through each 12 months of treatment ; g) Change from baseline through each 12 months of treatment ; h) All study visits ; I) All study visits

INCLUSION CRITERIA:

Have completed the final active treatment study visit in Study I4V‐MC‐JADV, I4V‐MC‐JADZ, I4V‐MC‐JADX, JADW, or I4V‐MC‐JADA, or I4V‐MC‐JAGS. ; h) Proportion of patients who maintain a CDAI score of =10 from Studies JADV, JADW, and JADX after 3 months of treatment with baricitinib 2 mg QD and with patients continuing treatment with the 4‐mg QD dose ; I) Time to relapse (CDAI score >10 from Studies JADV, JADW, and JADX) after randomization to the baricitinib 2‐mg and 4‐mg QD doses Timepoint(s) of evaluation of this end point: a) Change from Month 6 (of the originating study) through each 12 months of treatment 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 3000 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 350