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: Methotrexat HEXAL® 2,5 mg Tabletten Pharmaceutical Form: Capsule INN or Proposed

INN:

METHOTREXATE CAS Number: 59‐05‐2 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 2.5‐ Pharmaceutical form of the placebo: Capsule Route of administration of the placebo: Oral use Trade Name: Methotrexate 2.5mg Tablets Pharmaceutical Form: Capsule INN or Proposed

INN:

METHOTREXATE CAS Number: 59‐05‐2 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 2.5‐ Pharmaceutical form of the placebo: Capsule Route of administration of the placebo: Oral use Trade Name: Methotrexate 2.5 mg tablets Pharmaceutical Form: Capsule INN or Proposed

INN:

METHOTREXATE CAS Number: 59‐05‐2 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 2.5‐ Pharmaceutical form of the placebo: Capsule Route of administration of the placebo: Oral use Trade Name: Methotrexat HEXAL® 2,5 mg Tabletten Pharmaceutical Form: Capsule INN or Proposed

INN:

METHOTREXATE CAS Number: 59‐05‐2 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 5‐ Trade Name: Methotrexate 2.5mg Tablets Pharmaceutical Form: Capsule INN or Proposed

INN:

METHOTREXATE CAS Number: 59‐05‐2 Concentration unit: mg milligram(s) Concentration type: equal Concentration numbe

CONDITION:

Moderately to severely active rheumatoid arthritis ; MedDRA version: 17.1 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 ‐ Musculoskeletal and connective tissue disorders Therapeutic area: Diseases [C] ‐ Musculoskeletal Diseases [C05]

SECONDARY OUTCOME:

Secondary end point(s): Endpoint 2 ‐ Proportion of patients achieving ACR20 (baricitinib plus MTX compared to MTX monotherapy) ; Endpoint 3 ‐ Change from baseline in Health Assessment Questionnaire Disability Index (HAQ‐DI) ; Endpoint 4 ‐ Change from baseline in DAS28‐high‐sensitivity C‐reactive protein (hsCRP) ; Endpoint 5 ‐ Change from baseline in Modified Total Sharp Score (mTSS [van der Heijde method]) ; Endpoint 6 ‐ AUC of HAQ‐DI (baricitinib monotherapy compared to MTX monotherapy) ; Endpoint 7 ‐ AUC of DAS28‐hsCRP (baricitinib monotherapy compared to MTX monotherapy) ; Endpoint 8 ‐Proportion of patients achieving ACR20 ; Endpoint 9 ‐ Proportion of patients achieving ACR50 ; Endpoint 10 ‐ Proportion of patients achieving ACR70 ; Endpoint 11 ‐ Proportion of patients achieving DAS28‐hsCRP =3.2 ; Endpoint 12 ‐ Proportion of patients achieving DAS28‐ hsCRP <2.6 ; Endpoint 13 ‐ Proportion of patients achieving DAS28‐ESR =3.2 ; Endpoint 14 ‐ Proportion of patients achieving DAS28‐ESR <2.6 ; ; ; Timepoint(s) of evaluation of this end point: Enpoints 2 to 7: Week 24 ; Enpoint 8: Weeks 12 and 52 ; Enpoints 9 to 14: Weeks 12, 24 and 52

INCLUSION CRITERIA:

• are at least 18 years of age • have a diagnosis of adult‐onset RA as defined by ACR/EULAR 2010 Criteria for the Classification of RA • have documented history of positive rheumatoid factor and/or cyclic citrullinated peptide (CCP) antibody test

PRIMARY OUTCOME:

Main Objective: Determine whether baricitinib monotherapy is noninferior to MTX monotherapy in the treatment of patients with moderate to severe active RA who have had limited or no treatment with MTX and are naive to other conventional or biologic DMARDs, as assessed by the proportion of patients achieving a 20% improvement in American College of Rheumatology criteria (ACR20) at Week 24. Primary end point(s): Endpoint 1: Proportion of patients achieving ACR20 (noninferiority of baricitinib monotherapy to MTX monotherapy); Secondary Objective: • proportion of patients achieving ACR20 at Week 24 for baricitinib plus MTX versus MTX monotherapy; • change from baseline to Week 24 in Health Assessment Questionnaire‐Disability Index (HAQ‐DI) score ; • change from baseline to Week 24 in DAS28–high‐sensitivity C reactive protein (hsCRP) ; • change from baseline to Week 24 in structural joint damage as measured by modified Total Sharp Score (mTSS [van der Heijde method]) for baricitinib plus MTX versus MTX monotherapy; • change from baseline up to Week 24 in HAQ‐DI score for baricitinib monotherapy versus MTX monotherapy; • change from baseline up to Week 24 in DAS28‐hsCRP score for baricitinib monotherapy versus MTX monotherapy; • proportion of patients achieving an SDAI score =3.3 at week 12 Timepoint(s) of evaluation of this end point: Enpoint 1: Week 24; • 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 =1.2 times the upper limit of normal (ULN) • have had limited or no treatment with MTX 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 Number of subjects for this age range