A Dose Response Study to Evaluate the Efficacy and Safety of Oral AP1189 Administered in Disease-Modifying Anti-Rheumatic Drug (DMARD) naïve Participants Participants With Early Rheumatoid Arthritis

Inclusion Criteria:

• Signed and dated informed consent obtained before undergoing any trial-specificprocedure.

• Participants with definite RA diagnosis according to the 2010 American College ofRheumatology (ACR)/European League Against Rheumatism (EULAR) classificationcriteria.

• Disease duration no longer than 6 months from diagnosis at the time of BaselineVisit and with a history of RA symptoms which does not exceed 18 months.

• Participants must be naïve to any Disease-modifying anti-rheumatic drugs (DMARDs)

• Participants with at least 6/68 tender and 6/66 swollen joints at Screening Visitand Baseline.

• Participants with "high" disease activity as documented by a Disease Activity Score 28 (DAS28) (C-Reactive Protein - CRP) index score > 5.1 at screening, and Clinicaldisease activity index (CDAI) >22 at Screening Visit and Baseline.

• Participants with serum high sensitive C-Reactive Protein (hsCRP) ≥3 mg/L at thetime of screening.

• Participants positive for serum rheumatoid factor (RF), AND/OR anti-cycliccitrullinated peptide antibodies (anti-CCP). If seronegative RA, hsCRP ≥6 mg/L atthe time of screening.

• Willing and able to comply with the scheduled study visits, the treatment plan, andall study procedures.

• Females of childbearing potential must have a negative pregnancy test at screeningand again at baseline.

• Sexually active female participants of childbearing potential and male participantsare excluded if not practicing two different methods of birth control with theirpartner during the study and for 90 days after the last dose of study drug or whowill not remain abstinent during the study and for 90 days after the last dose.

Exclusion Criteria:

• Functional class IV of Global Functional Status in RA, as defined by the ACRClassification.

• Rheumatic autoimmune disease other than RA, i.e. systemic lupus erythematosus, mixedconnective tissue disease, scleroderma, polymyositis, or significant systemicinvolvement secondary to RA.

• Current inflammatory joint disease other than RA.

• Non-inflammatory type of musculoskeletal condition that in the Investigator'sopinion is symptomatic and/or severe enough to interfere with the subject's primarydiagnosis of RA or the evaluation of the effect of the study drug.

• Gastrointestinal diseases known to interfere with the absorption or excretion ofmedications.

• Severe, progressive, or uncontrolled renal, hepatic, hematologic, gastrointestinal,metabolic, endocrine, pulmonary, cardiac or neurologic disease.

• Malignancy active during the 12 months preceding the Screening Visit.

• Acute hepatitis, chronic hepatitis, or detection of any unexplained elevation ofserum ALT or AST greater than 1.5-fold ULN, at least twice in the 6 months beforethe Screening Visit) or HIV infection.

• History of alcohol or drug abuse during the 12 months preceding the Screening Visit.

• Vaccination with live vaccines during the 6 weeks preceding the Screening Visit.

• Haemoglobin <9 g/dL or Haematocrit <30% at the Screening Visit

• White blood cell (WBC) count <3.0 x 109/L at the Screening Visit.

• Absolute neutrophil count <1.2 x 109/L at the Screening Visit.

• Platelet count <100 x 109/L at the Screening Visit.

• Serum alkaline-phosphatase, or gamma-glutamyl-transferase greater than 3-fold ULN;alanine aminotransferase, or aspartate aminotransferase, or total bilirubin greaterthan 2-fold ULN At the Screening Visit.

• Estimated creatinine clearance less than 45 mL/min/1.73 m2 (MDRD) at the ScreeningVisit.

• 12-lead electrocardiogram (ECG) with abnormal clinically significant findings, asjudged by the Investigator, at the Screening Visit.

• Positive QuantiFERON-in-Tube test (QFG-IT).

• Use of hydroxychloroquine during the 30 weeks preceding the Screening Visit.

• Treatment with any systemic or intraarticular corticosteroid within 6 weeks beforethe Screening Visit.

• Intermittent use of nonsteroidal anti-inflammatory drugs (NSAIDs). Use of NSAIDs isallowed if used in a stable dose regimen for at least 4 weeks prior to the ScreeningVisit.

• Use of other investigational drugs/treatments, or enrolment in a clinical trialduring the 6 months preceding the Screening Visit.

• Any other clinically relevant disease and condition that, in the opinion of theInvestigator, may jeopardize efficacy or safety assessments or may compromise thesubject's safety during trial participation.