A Multicenter, Randomized, Double-blind, PlacebO-controlled, Parallel-group Study to EValuate the Efficacy and Safety of JTE-051 Administered for 12 Weeks to Subjects with Active Rheumatoid Arthritis (MOVE-RA)

INTERVENTION: Product Name: JTE‐051 Product Code: JTE‐051 Pharmaceutical Form: Tablet INN or Proposed INN: No proposed INN available CAS Number: 1309784‐13‐1 Current Sponsor code: JTE‐051 Other descriptive name: JTE‐051 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 50‐ Pharmaceutical form of the placebo: Tablet Route of administration of the placebo: Oral use CONDITION: Rheumatoid Arthritis (RA) ; MedDRA version: 20.0 Level: LLT Classification code 10040107 Term: Seropositive rheumatoid arthritis System Organ Class: 100000004859 Therapeutic area: Diseases [C] ‐ Immune System Diseases [C20] PRIMARY OUTCOME: Main Objective: • To evaluate the clinical efficacy of JTE‐051 in subjects with active rheumatoid arthritis receiving background non‐biologic disease‐modifying anti‐rheumatic drug therapy; • To evaluate the safety and tolerability of JTE‐051 administered for 12 weeks to subjects with active rheumatoid arthritis receiving background non‐biologic disease‐modifying anti‐rheumatic drug therapy; • To evaluate the pharmacokinetics of JTE‐051 in plasma of subjects with active rheumatoid arthritis; Primary end point(s): Efficacy: Percentage of subjects achieving at least 20% improvement from baseline in tender and swollen joint counts and at least 20% improvement from baseline in the 3 of the 5 remaining American College of Rheumatology; (ACR) core set measures (ACR20 response rate) at end of treatment (EOT). ; ; Safety Parameters: Number of subjects with adverse events (AEs), type and severity of AEs, change from baseline in the safety laboratory, vital sign and electrocardiogram (ECG) parameters.; ; Pharmacokinetic (PK) Parameters: Trough plasma levels of JTE‐051 ; Secondary Objective: Not applicable. Timepoint(s) of evaluation of this end point: Efficacy: Tender and Swollen Joint Counts will be performed in all visits until the end of treatment (EOT). The measure of the improvement percentage will be performed at the end of treatment.; ; Safety: Safety information will be collected through the study. ; ; Pharmacokinetic: Trough concentrations of JTE‐051 will be measured at each visit during the Treatment Period; SECONDARY OUTCOME: Secondary end point(s): Secondary Efficacy: ; • Percentage of subjects achieving at least 20, 50 and 70% improvement from baseline in tender and swollen joint counts and at least 20, 50 and 70% improvement from baseline in 3 of the 5 remaining ACR‐core set measures, respectively (i.e., ACR20/50/70 response rate) ; • Change from baseline in Simplified Disease Activity Index (SDAI) ; • Percentage of subjects who achieved remission based on SDAI (=3.3) ; • Percentage of subjects who achieved low disease activity based on SDAI (=11) ; • Change from baseline in Clinical Disease Activity Index (CDAI) ; • Percentage of subjects who achieved remission based on CDAI (=2.8) ; • Percentage of subjects who achieved low disease activity based on CDAI (=10) ; • Percentage of subjects in Boolean Remission ; • Change from baseline in Disease Activity Score (DAS) based on hs‐CRP (DAS28‐CRP) ; • Percentage of subjects with DAS28‐CRP of <2.6 ; • Percentage of subjects with DAS28‐CRP of <3.2 ; • Percentage of subjects with good EULAR response at Week 12 ; • Percentage of subjects with moderate EULAR response at Week 12 ; • The lowest percentage change from baseline of 3 measures: tender joint count, swollen joint count and median change of the remaining 5 core measures (numeric ACR [ACR‐N] index) ; • Change from baseline in the Health Assessment Questionnaire Disability Index (HAQ‐DI) ; • Change from baseline in the number of tender and swollen joint counts (68/66 joints will be counted) ; • Change from baseline in subject pain score by numeric rating scale (NRS) ; • Change from baseline in subject global assessment (SGA) of disease activity by NRS ; • Change from baseline in physician global assessment (PGA) of disease activity by NRS ; • Change from baseline in hs‐CRP ; ; Supportive Efficacy: Non‐hs CRP will be evaluated at Weeks 2 and 12 for the following secondary efficacy counterparts: ACR20/50/70, SDAI, Boolean remission, DAS28‐CRP, EULAR response, ACR‐N and CRP. ; ; Exploratory Efficacy: Change from baseline in Vectra® DA score. ; ; Pharmacokinetic (PK) ‐ Exploratory: Relationship between the JTE‐051 dose (exposure) and response. Timepoint(s) of evaluation of this end point: • Secondary Efficacy: To be evaluated at weeks 2, 4, 8, 12 and 16; ; • Exploratory Efficacy Parameters: To be evaluated at weeks 2, 4, 8, 12 and 16; ; • Exploratory Pharmacokinetic (PK) Parameters: To be evaluated at weeks 2, 4, 18 and 12 INCLUSION CRITERIA: 1. Males and females, 18 to 75 years of age (inclusive) at the Screening Visit (Visit 1); 2. A diagnosis of Rheumatoid Arthritis prior to the Screening Visit, based on the ACR/EULAR 2010 Classification Criteria (ACR: American College of Rheumatology, EULAR: European League Against Rheumatism). Refer to Appendix 1 of the protocol for further reference; 3. Active disease despite ongoing therapy with up to 2 non‐biologic Disease Modifying Anti‐Rheumatic Drugs (DMARDs), including methotrexate (MTX) at both the Screening and Baseline Visits (Visit 1 and Visit 2), as defined by both: =6 out of 68 tender joints AND =6 out of 66 swollen joints; 4. Screening hs‐CRP =1.2 x ULN, based on the central laboratory values (hs‐CRP: high‐sensitivity C‐reactive protein, ULN: Upper limit of normal); 5. Background treatment with up to 2 non‐biologic DMARDs (Disease‐modifying anti‐rheumatic drugs), including MTX (mandatory) and one of the foll