Phase IIa Randomized, Double Blind, Placebo Controlled, Multiple Dose Study on ABX464 in Combination With Methotrexate (MTX), in Patients With Moderate to Severe Active Rheumatoid Arthritis Who Have Inadequate Response to MTX or/and to Anti-Tnfα, or Intolerance to Anti-Tnfα
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Abivax S.A.
- 入组人数
- 60
- 试验地点
- 24
- 主要终点
- Number of Treatment-emergent Adverse Events in the ABX464 Treated Patients Versus Placebo
研究概览
简要总结
This Phase IIa study aims at investigating the safety and tolerability of 2 dose-levels of ABX464 administered daily in combination with methotrexate (MTX) in patients with moderate to severe active Rheumatoid Arthritis (RA) who had an inadequate response to MTX or/and to one or more anti- tumor necrosis factor alpha (TNFα) therapies.
详细描述
This is a randomized, double-blind, placebo-controlled, multicenter study. The study will consist of 3 phases: a screening phase, a treatment phase, and a follow-up phase.
Approximately 60 participants with active Rheumatoid Arthritis will be randomly assigned to receive placebo, 50mg ABX464 or 100mg ABX464 during the treatment phase.
The maximum period of active treatment will be 12 weeks. The maximum duration of study participation will be 17 weeks.
Participant safety will be monitored throughout the study. In addition, several experimental and clinical endpoints will be assessed to obtain information on preliminary efficacy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient with a confirmed and documented diagnosis of adult-onset rheumatoid arthritis, for at least 12 weeks, according to the revised 2010 American College of Rheumatology- European League Against Rheumatism (ACR-EULAR) classification criteria, including at least one positive criteria among the following: Rheumatoid Factor (RF), Anti-Citrullinated Peptide Antibody (ACPA) or bone erosion;
- •Swollen joint count (SJC) of ≥ 4 (28-joint count) and tender joint count (TJC) ≥4 (28-joint count) at screening;
- •Patient with a moderate to severe disease activity score Disease Activity Score (28 joints) C-Reactive Protein [DAS28 CRP] ≥ 3.2 and C-reactive Protein (CRP) ≥ 5 mg/L (≥ 4.76 nmol)/L) at screening;
- •Patient who had an inadequate response (IR), or failed either methotrexate (MTX) or/and anti- Tumor Necrosis Factor alpha (TNFα) therapy (both administered for at least 12 weeks before IR) or were intolerant to anti- TNFα therapy.
排除标准
- •Patient with a known positive anti-double stranded deoxyribonucleic acid (DNA [anti-dsDNA]) and confirmed diagnosis of systemic lupus erythematosus (SLE);
- •Patient with known active infections at screening such as CytoMegaloVirus (CMV), herpes virus and/or recent infectious hospitalization;
- •Acute, chronic or history of clinically relevant pulmonary, cardiovascular, hepatic, pancreatic or renal functional abnormality, encephalopathy, neuropathy or unstable Central Nervous System (CNS) pathology such as seizure disorder, angina or cardiac arrhythmias, active malignancy or any other clinically significant medical problems as determined by physical examination and/or laboratory screening tests and/or medical history;
- •Acute, chronic or history of immunodeficiency or other autoimmune disease;
- •Patient previously treated with any non-anti-TNF biological Disease-Modifying AntiRheumatic Drugs (bDMARDs), and targeted DMARDs (tDMARDS) prior to baseline.
研究组 & 干预措施
ABX464 50mg + methotrexate
Participants will receive one capsule of 50mg ABX464 plus one capsule of matching placebo once daily for 12 weeks
- methotrexate
干预措施: ABX464 50mg (Drug)
ABX464 50mg + methotrexate
Participants will receive one capsule of 50mg ABX464 plus one capsule of matching placebo once daily for 12 weeks
- methotrexate
干预措施: Matching Placebo (Drug)
ABX464 50mg + methotrexate
Participants will receive one capsule of 50mg ABX464 plus one capsule of matching placebo once daily for 12 weeks
- methotrexate
干预措施: Methotrexate (Drug)
ABX464 100mg + methotrexate
Participants will receive two capsules of 50mg ABX464 once daily for 12 weeks
- methotrexate
干预措施: ABX464 100mg (Drug)
ABX464 100mg + methotrexate
Participants will receive two capsules of 50mg ABX464 once daily for 12 weeks
- methotrexate
干预措施: Methotrexate (Drug)
Placebo + methotrexate
Participants will receive two capsules of matching placebo once daily for 12 weeks
- methotrexate
干预措施: Matching Placebo (Drug)
Placebo + methotrexate
Participants will receive two capsules of matching placebo once daily for 12 weeks
- methotrexate
干预措施: Methotrexate (Drug)
结局指标
主要结局
Number of Treatment-emergent Adverse Events in the ABX464 Treated Patients Versus Placebo
时间窗: through study completion, an average of 15 weeks
TEAE definition is undesirable events not present prior to medical treatment, or an already present event that worsens either in intensity or frequency following the treatment
次要结局
- Number of Patients Achieving ACR20/50/70 Response(Week 12)
- Change From Baseline in C-reactive Protein (CRP)(Week 12)
- Change From Baseline in Erythrocyte Sedimentation Rate (ESR)(Week 12)
- Number of Patients Achieving Low Disease Activity (LDA)(Week 12)
- Change From Baseline in Disease Activity Scores (DAS-CRP) (28 Joints) [DAS28](Week 12)
- Change From Baseline in Tender/Painful Joint Count (TJC28)(12 weeks)
- Number of Patients Achieving DAS28-CRP Response(Week 12)
- Number of Patients Achieving Disease Activity Score (DAS) DAS28-Erythrocyte Sedimentation Rate (ESR) [DAS28-ESR] Remission(Week 12)
- Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI)(12 weeks)
- Number of Patients Achieving ACR20 Response(at Week 12)
- Change From Baseline in Clinical Disease Activity Index Score (CDAI)(Week 12)
- Number of Patients Achieving Simplified Disease Activity Score (SDAI) Remission(Week 12)
- Change From Baseline in Pain Visual Analog Scale(12 weeks)
- Change From Baseline in Investigator Global Assessment of Disease (PrGA)(12 weeks)
- Change From Baseline in Disease Activtiy Score (DAS)28-Erythrocyte Sedimentation Rate (ESR)(12 weeks)
- Change From Baseline in Simplified Disease Activity Index Score (SDAI)(Week 12)
- Number of Patients Achieving Clinical Disease Activity (CDAI) Remission(Week 12)
- Number of Patients Achieving American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean Remission(Week 12)
- Change From Baseline in Swollen Joint Count (SJC)(12 weeks)
- Change From Baseline in Patient Global Assessment of Disease (PtGA)(12 weeks)