A Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging, Parallel-Group, Phase 2b Study of LY3009104 in Patients with Active Rheumatoid Arthritis on background Methotrexate Therapy

INTERVENTION: Product Name: LY3009104 Product Code: LY3009104 Pharmaceutical Form: Capsule* INN or Proposed INN: Not available CAS Number: 1187595‐84‐1 Current Sponsor code: LY3009104 phosphate Other descriptive name: JAK1 / JAK2 Inhibtor Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 1‐ Pharmaceutical form of the placebo: Capsule* Route of administration of the placebo: Oral use Product Name: LY3009104 Product Code: LY3009104 Pharmaceutical Form: Capsule* INN or Proposed INN: Not available CAS Number: 1187595‐84‐1 Current Sponsor code: LY3009104 phosphate Other descriptive name: JAK1 / JAK2 Inhibtor Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 4‐ Pharmaceutical form of the placebo: Capsule* Route of administration of the placebo: Oral use CONDITION: Rheumatoid Arthritis ; MedDRA version: 12.1 Level: LLT Classification code 10039073 Term: Rheumatoid arthritis PRIMARY OUTCOME: Main Objective: To evaluate the efficacy of LY3009104 as assessed by the aggregate proportion of patients in the 4 mg and 8 mg dose groups who achieve an ACR20 response compared to placebo over 12 weeks in patients with active RA despite ongoing MTX; therapy. Primary end point(s): The primary analysis will be a comparison of the combined 4 mg and 8 mg dose groups with placebo on the ACR20 response rate at 12 weeks. Secondary Objective: 1 ‐ To characterize the dose‐response relationship of LY3009104 on ACR (20/50/N); response rates over 12 weeks and to evaluate model‐predicted responses for each dose versus placebo to identify one or more efficacious doses.; 2 ‐ To evaluate the efficacy of each dose of LY3009104 compared to placebo over 12 weeks. ; 3 ‐ To evaluate the relative efficacy of each dose of LY3009104 over 24 weeks.; 4 ‐ To evaluate the safety and tolerability of LY3009104 compared to placebo.; 5 ‐ To evaluate the efficacy of twice‐daily dosing of 2 mg of LY3009104 as compared to once‐daily dosing of 4 mg of LY3009104.; 6 ‐ To evaluate the safety of twice‐daily dosing of 2 mg of LY3009104 as compared to once daily dosing of 4 mg of LY3009104 as assessed by standard safety measures.; 7 ‐ To characterize the pharmacokinetics of LY3009104 and explore dose/PK relationships.; 8 ‐ To evaluate the impact of LY3009104 compared to placebo over the 12‐week study period with regard to patient‐reported outcomes. INCLUSION CRITERIA: [1] Ambulatory males or females between the ages of 18 and 75 years, inclusive. [1a] Male patients: Agree to use a reliable method of birth control during the study. [1b] Female patients: Females must not be pregnant, breastfeeding, or at risk to become pregnant during study participation. Female patients of childbearing potential, must test negative for pregnancy at the time of enrollment and agree to use a reliable method of birth control or remain abstinent during the study or for at least 30 days following the last dose of study drug, whichever is longer, or, must be a female of non‐childbearing potential, defined as: ‐ women who have had surgical sterilization (hysterectomy or bilateral oophorectomy or tubal ligation), ‐ women =60 years of age, or ‐ women =40 and <60 years of age who have had a cessation of menses for at least 12 months and a follicle‐stimulating hormone (FSH) test confirming non‐childbearing