A Two-part, Randomized, Double-blind, Multi-center, Placebo-controlled Study of the Dose-range, Safety and Efficacy of 4 and 12 Weeks of Treatment With AP1189 in Adult Rheumatoid Arthritis (RA) Patients With an Inadequate Response to Methotrexate (MTX) Alone - (RESOLVE)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 125
- 试验地点
- 1
- 主要终点
- Part A: Change in ACR20
研究概览
简要总结
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.
详细描述
In Part A approximately 120 randomized patients will be treated with either 60 mg AP1189, 80 mg AP1189, 100 mg AP1189 or placebo once daily for 4 weeks as add-on treatment to stable MTX treatment. Part A will conclude with an unblinded assessment for risk/benefit and a recommendation for dose selection for Part B.
In Part B patients will be randomized into groups of equal size evaluating 2-3 doses of AP1189 versus placebo. All doses will be administered once daily for 12 weeks as add-on treatment to stable MTX treatment. The proposed sample size per dose group/placebo group is 75 patients, by which the total study population of Part B may be either 225 or 300 patients, depending on the number of dose groups of AP1189 selected for evaluation based on Part A.
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
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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 value
- •Ongoing methotrexate therapy ≥12 weeks in a stable dose of 7.5 to 25 mg/week for at least 4 weeks prior to the baseline visit
- •Subject has an inadequate clinical response to maximally tolerated methotrexate therapy
- •Subjects 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 study
- •Negative QuantiFERON-in-Tube test (QFG-IT)
- •Females of child-bearing potential must use of highly effective birth control method
- •Male participant's partner must use highly effective birth control
排除标准
- •Use of all other biologic or nonbiologic DMARDs and immunosuppressive therapy within 4 weeks prior to administration of the first dose of study drug
- •Oral steroids at a dose >10 mg/day of prednisone or a prescription for oral steroids which has changed within 4 weeks of baseline
- •Receipt of an intra-articular or parenteral corticosteroid injection within 4 weeks prior to baseline
- •Major surgery (including joint operation) within 8 weeks prior to screening or planned surgery within the period of the study participation
- •Rheumatic autoimmune disease other than RA
- •Functional class IV as defined by the ACR Criteria for Classification of Functional Status in RA or wheelchair/bedbound
- •Prior history of or current inflammatory joint disease other than RA
- •Subjects with fibromyalgia
- •Initiation or change in dose for NSAIDs (including low-dose aspirin and Cyclooxygenase (COX-2) inhibitors) within 2 weeks prior to baseline
- •Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary, renal, hepatic, endocrine, or gastrointestinal disease
- •Serum 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 visit
- •Have prior renal transplant, current renal dialysis, or moderate to severe renal insufficiency
- •Uncontrolled disease states, such as asthma, psoriasis, or inflammatory bowel disease where flares are commonly treated with oral or parenteral corticosteroids
- •Evidence 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 screening
- •Neuropathy or other painful, chronic conditions that might interfere with pain evaluation
- •Body weight of >150 kg
- •HBsAg positive and/or Anti-HBc with sign of current infection.
研究组 & 干预措施
AP1189, 60 mg
Part A: (AP1189, 60 mg); Part B: (TBD)
干预措施: AP1189, 60 mg (Drug)
AP1189, 80 mg
Part A: (AP1189, 80 mg); Part B: (TBD)
干预措施: AP1189, 80 mg (Drug)
AP1189, 100 mg
Part A: (AP1189, 100 mg); Part B: (TBD)
干预措施: AP1189, 100 mg (Drug)
Placebo
Part A: (placebo); Part B: (placebo).
干预措施: Placebo (Drug)
结局指标
主要结局
Part A: Change in ACR20
时间窗: 4 weeks
The change in American College of Rheumatology 20% (ACR20) compared to baseline
Part B: Change in ACR20
时间窗: 12 weeks
The change in American College of Rheumatology 20% (ACR20) compared to baseline
Number of reported Adverse Events
时间窗: 12 weeks
Evaluation of the safety and tolerability of AP1189 on the number and severity of reported Adverse Events, compared with placebo
次要结局
- Part A: Change in ACR50(4 weeks)
- Part B: Change in ACR50(12 weeks)
- Part A: Change in ACR70(4 weeks)
- Part B: Change in ACR70(12 weeks)
- Part A: Change in CDAI(4 weeks)
- Part B: Change in CDAI(12 weeks)
- Part A: Change in DAS-28(4 weeks)
- Part B: Change in DAS-28(12 weeks)