A Dose-range Study of the Safety and Efficacy of Treatment in Adult Rheumatoid Arthritis Patients With an Inadequate Response to Methotrexate

The RESOLVE study is a two-part, randomized, double-blind, multi-center, placebo-controlled study of the safety, dose-range finding confirmation, and efficacy of 4 (Part A) and 12 weeks (Part B) of treatment with AP1189 in adult RA patients with an inadequate response to MTX alone.

Inclusion Criteria:Confirmed diagnosis of RA according to the 2010 ACR/EULAR RA classification criteria and are ACR class I-III≥6 swollen joints (based on 66 joint counts) and ≥ 6 tender joints (based on 68 joint counts)Must meet at least one of the following parameters at Screening:A positive result for Anti-Cyclic Citrullinated Peptide (anti-CCP) or Rheumatoid Factor (RF),Serum CRP ≥ 6 mg/L based on central laboratory valueOngoing methotrexate therapy ≥12 weeks in a stable dose of 7.5 to 25 mg/week for at least 4 weeks prior to the baseline visitSubject has an inadequate clinical response to maximally tolerated methotrexate therapySubjects should be receiving an adequate and prescribed stable dose of folic acid (≥5 mg/week total dose or as per local clinical practice) which should be confirmed or initiated at screening and continued throughout the studyNegative QuantiFERON-in-Tube test (QFG-IT)Females of child-bearing potential must use of highly effective birth control methodMale participant's partner must use highly effective birth controlExclusion Criteria:Use of all other biologic or nonbiologic DMARDs and immunosuppressive therapy within 4 weeks prior to administration of the first dose of study drugOral steroids at a dose >10 mg/day of prednisone or a prescription for oral steroids which has changed within 4 weeks of baselineReceipt of an intra-articular or parenteral corticosteroid injection within 4 weeks prior to baselineMajor surgery (including joint operation) within 8 weeks prior to screening or planned surgery within the period of the study participationRheumatic autoimmune disease other than RAFunctional class IV as defined by the ACR Criteria for Classification of Functional Status in RA or wheelchair/bedboundPrior history of or current inflammatory joint disease other than RASubjects with fibromyalgiaInitiation or change in dose for NSAIDs (including low-dose aspirin and Cyclooxygenase (COX-2) inhibitors) within 2 weeks prior to baselineEvidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary, renal, hepatic, endocrine, or gastrointestinal diseaseSerum Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) higher than 1.5 x the upper limit of normal (ULN) and alkaline phosphatase (ALP) and/or bilirubin values above the ULN at the screening visitHave prior renal transplant, current renal dialysis, or moderate to severe renal insufficiencyUncontrolled disease states, such as asthma, psoriasis, or inflammatory bowel disease where flares are commonly treated with oral or parenteral corticosteroidsEvidence of active malignant disease (except basal cell carcinoma of the skin that has been excised and cured)History of alcohol, drug, or chemical abuse within the 6 months prior to screeningNeuropathy or other painful, chronic conditions that might interfere with pain evaluationBody weight of >150 kgHBsAg positive and/or Anti-HBc with sign of current infection.