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 Trade Name: Humira Pharmaceutical Form: Solution for injection INN or Proposed

INN:

ADALIMUMAB CAS Number: 331731‐18‐1 Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 40/0.8‐ Pharmaceutical form of the placebo: Solution for injection Route of administration of the placebo: Subcutaneous 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 is superior to placebo in the treatment of patients with moderately to severely active RA despite MTX treatment (i.e., MTX IR), as assessed by the proportion of patients achieving ACR20 at Week 12. Primary end point(s): Proportion of patients achieving ACR20 response compared to placebo . Secondary Objective: • change from baseline to Week 24 in structural joint damage as measured by modified Total Sharp Score (mTSS [van der Heijde method]) compared to placebo; • change from baseline to Week 12 in Health Assessment Questionnaire‐Disability Index (HAQ‐DI) score compared to placebo; • change from baseline to Week 12 in DAS28‐high‐sensitivity C‐reactive protein (hsCRP) compared to placebo; • proportion of patients achieving an SDAI score =3.3 at week 12; • proportion of patients achieving ACR20 response at Week 12 compared to adalimumab ; • proportion of patients achieving DAS28‐hsCRP =3.2 and DAS28‐hsCRP <2.6 at Week 12, Week 24, and Week 52; • change from baseline to Week 16 and Week 52 in structural joint damage as measured by mTSS; • proportion of patients achieving DAS28‐ESR =3.2 and DAS28‐ESR <2.6 at Week 12, Week 24, and Week 52; Timepoint(s) of evaluation of this end point: Change from baseline to Week 12.

SECONDARY OUTCOME:

Secondary end point(s): ‐ Modified Total Sharp Score (mTSS [van der Heijde method]) ; ‐ Health Assessment Questionnaire Disability Index (HAQ‐DI) ; ‐ DAS28‐high‐sensitivity C‐reactive protein (hsCRP) ; ‐ 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 ACR20 response compared to adalimumab ; ‐ proportion of patients achieving DAS28‐ESR =3.2; proportion of patients achieving DAS28‐ESR <2.6 Timepoint(s) of evaluation of this end point: ‐ Modified Total Sharp Score (mTSS [van der Heijde method]): Change from baseline to Week 24 and 52 ; ‐ Health Assessment Questionnaire Disability Index (HAQ‐DI): Change from baseline to Week 12 ; ‐ DAS28‐high‐sensitivity C‐reactive protein (hsCRP): Change from baseline to Week 12 ; ‐ Proportion of patients achieving ACR50 and ACR70 response: Change from baseline to Week 12, 24 and 52 ; ‐ proportion of patients achieving DAS28‐hsCRP =3.2; proportion of patients achieving DAS28‐ hsCRP <2.6: Weeks 12, 24 and 52 ; ‐ proportion of patients achieving ACR20 response compared to adalimumab: Weeks 12 ; ‐ proportion of patients achieving DAS28‐ESR =3.2; proportion of patients achieving DAS28‐ESR <2.6: Weeks 12, 24 and 52

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 (CRP) (or hsCRP) measurement =6 mg/L • have had regular use of MTX for at least the 12 weeks prior to study entry at a dose that is considered acceptable to adequately assess clinical response. • have at least 1 joint erosion in hand, wrist, or foot joints based on radiographic interpretation by the central reader and be rheumatoid factor or anticyclic citrullinated peptide (anti‐CCP) antibody positive; or have at least 3 joint erosions in hand, wrist, or foot joints based on radiographic interpretation by the central reader regardless of rheumatoid factor or anti‐CCP antibody status Are the trial subjects under 18? no Number of subjects