A randomized, double blind, placebo-controlled, dose response, phase II, multicentre trial to evaluate the efficacy and safety of oral AP1189 administered at the doses of 40, 70, or 100 mg for 12 weeks in combination with methotrexate, in DMARD-naïve participants with early rheumatoid arthritis and active inflammation.

Trial details

Who runs it

Synact Pharma ApS

Trial code

EU 2024-514981-37-00

Record updated

2026. március 27.

Original description

To determine the efficacy of oral AP1189 in combination with oral Methotrexate (MTX) over a 12-week treatment period in Disease-Modifying Anti-Rheumatic Drug (DMARD)-naïve participants with newly diagnosed Rheumatoid Arthritis (RA), in comparison with oral MTX alone.Read full original descriptionShow less

To determine the efficacy of oral AP1189 in combination with oral Methotrexate (MTX) over a 12-week treatment period in Disease-Modifying Anti-Rheumatic Drug (DMARD)-naïve participants with newly diagnosed Rheumatoid Arthritis (RA), in comparison with oral MTX alone.

Inclusion: Signed and dated informed consent obtained before undergoing any trial-specific procedure; Willing and able to comply with the scheduled study visits, the treatment plan, and all study procedures; Females of childbearing potential must have a negative pregnancy test at screening and again at baseline; Sexually active female participants of childbearing potential and male participants must use a highly effective method of birth control (hormonal contraceptives, intrauterine device, vasectomy, bilateral tubal occlusion, sexual abstinence) with their partner during the study and for 90 days after the last dose of study drug or who will not remain abstinent during the study and for 90 days after the last dose. (See Appendix 1: Contraceptive Guidance and Woman of Childbearing Potential); Male or female aged ≥18 years; Participants with definite RA diagnosis according to the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria; Disease duration no longer than 6 months from diagnosis at the time of Baseline Visit (newly diagnosed) and with a history of RA symptoms which does not exceed 18 months. RA symptoms is defined as the participant self-reported duration of signs and symptoms of synovitis (e.g. pain, swelling, tenderness) of any joints; Participants must be naïve to any DMARDs (csDMARDs, or bDMARDs, or tsDMARDs); Participants with at least 6/68 tender and 6/66 swollen joints at Screening Visit and 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 Clinical disease activity index (CDAI) >22 at Screening Visit and Baseline; Participants with serum high sensitive C-Reactive Protein (hsCRP) ≥3 mg/L at the time of screening; Participants positive for serum rheumatoid factor (RF), AND/OR anti-cyclic citrullinated peptide antibodies (anti-CCP). If seronegative RA, hsCRP ≥6 mg/L at the time of screening.

Exclusion: Treatment with any systemic or intraarticular corticosteroid within 6 weeks before the Screening Visit (topical or inhaled corticosteroids are allowed); Intermittent use of nonsteroidal anti-inflammatory drugs (NSAIDs). Use of NSAIDs is allowed if used in a stable dose regimen for at least 4 weeks prior to the Screening Visit; Use of other investigational drugs/treatments, or enrolment in a clinical trial during the 6 months preceding the Screening Visit; Vaccination with live vaccines during the 6 weeks preceding the Screening Visit; Rheumatic autoimmune disease other than RA, i.e. systemic lupus erythematosus, mixed connective tissue disease, scleroderma, polymyositis, or significant systemic involvement secondary to RA (vasculitis, pulmonary fibrosis or Felty's syndrome); Any other clinically relevant disease and condition that, in the opinion of the Investigator, may jeopardize efficacy or safety assessments or may compromise the subject’s safety during trial participation; Current inflammatory joint disease other than RA; Non-inflammatory type of musculoskeletal condition (e.g., osteoarthritis or fibromyalgia) that in the Investigator's opinion is symptomatic and/or severe enough to interfere with the subject's primary diagnosis of RA or the evaluation of the effect of the study drug; Gastrointestinal diseases known to interfere with the absorption or excretion of medications; Severe, progressive, or uncontrolled renal, hepatic, hematologic, gastrointestinal, metabolic, endocrine, pulmonary, cardiac or neurologic disease; Malignancy (with the exception of adequately treated or excised non-metastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ) active during the 12 months preceding the Screening Visit; History of alcohol or drug abuse during the 12 months preceding the Screening Visit; Acute hepatitis (during the 6 months preceding the Screening Visit), chronic hepatitis (previous documented diagnosis of viral or autoimmune hepatitis, or detection of any unexplained elevation of serum ALT or AST greater than 1.5-fold ULN, at least twice in the 6 months before the Screening Visit) or HIV infection; 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 greater than 2-fold ULN at the Screening Visit; Estimated creatinine clearance less than 45 mL/min/1.73 m2 (CKD-EPI) at the Screening Visit; Functional class IV of Global Functional Status in RA, as defined by the ACR Classification; Positive or indeterminate QuantiFERON-in-Tube test (QFG-IT) (Mantoux test can be used if QFG-IT is not possible); Use of hydroxychloroquine during the 30 weeks preceding the Screening Visit; Females who are pregnant, lactating; 12-lead electrocardiogram (ECG) with abnormal clinically significant findings, as judged by the Investigator, at the Screening Visit.

EU CTIS 2024-514981-37-00