A Phase 2b Randomized, Double-blind, Multicenter, Placebo-controlled, Parallel Group, Dose Range Finding Study of JNJ-38518168 in Subjects With Active Rheumatoid Arthritis Despite Concomitant Methotrexate Therapy
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 272
- 主要终点
- Disease Activity Score 28 (DAS28) (C-reactive protein [CRP]) at Week 12
研究概览
简要总结
The purpose of this dose range finding study is to assess the effectiveness, safety and tolerability of JNJ-38518168 at doses of 3, 10, and 30 mg/d compared with placebo in patients with active rheumatoid arthritis (RA) despite concomitant methotrexate (MTX) therapy.
详细描述
This is a randomized (the study medication is assigned by chance), double-blind (neither physician nor patient knows the treatment that the patient receives), multicenter, placebo-controlled (an inactive substance that is compared with a drug to test whether the drug has a real effect in a clinical trial), parallel-group (each group of patients will be treated at the same time), dose range finding study of JNJ-38518168 in patients with active RA despite concomitant MTX therapy. The study will consist a screening period, a 24-week placebo-controlled period and a 4-week follow-up period between the last dose and the last visit. The duration of participation in the study for an individual patient will be up to 34 weeks (including screening). The patients will be assigned to 1 of 4 treatment groups in a 1:1:1:1 ratio to placebo and JNJ-38518168 (3 mg or 10 mg or 30 mg). Safety assessments and evaluations to determine the efficacy of JNJ-38518168 to reduce the signs and symptoms of RA will be performed at study visits. Safety will be monitored throughout the study.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Has had rheumatoid arthritis for at least 6 months prior to the date of signing the informed consent at screening
- •Must be positive for either anti-cyclic citrullinated peptide antibody or rheumatoid factor in serum at screening
- •Must have active rheumatoid arthritis (at least 6 swollen and 6 tender joints using a 66/68 joint count at the time of screening and at baseline and Serum C reactive protein greater than or equal to 0.80 mg/dL at the time of screening
- •Has been treated with and tolerated methotrexate treatment at dosages from 10 to 25 mg/week inclusive, for a minimum of 6 months with stable dose for at least 8 weeks prior to the date of signing the informed consent at screening
排除标准
- •Has inflammatory diseases other than rheumatoid arthritis, including but not limited to adult onset Still's disease, psoriatic arthritis, ankylosing spondylitis, systemic lupus erythematosus, and Lyme disease that might confound the evaluation of the benefit of study agent therapy
- •Has current signs or symptoms of liver or renal insufficiency or cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, psychiatric, or metabolic disturbances that are severe, progressive or uncontrolled
- •Has ever received any approved or investigational biologic agent for a rheumatoid indication
- •Has been treated with any nonbiologic disease modifying antirheumatic drugs within 4 weeks prior to the first administration of study agent
研究组 & 干预措施
Placebo
干预措施: Placebo (Drug)
Placebo
干预措施: Methotrexate (Drug)
JNJ-38518168 (3 mg/d)
干预措施: JNJ-38518168 (3 mg) (Drug)
JNJ-38518168 (3 mg/d)
干预措施: Methotrexate (Drug)
JNJ-38518168 (10 mg/d)
干预措施: JNJ-38518168 (10 mg) (Drug)
JNJ-38518168 (10 mg/d)
干预措施: Methotrexate (Drug)
JNJ-38518168 (30 mg/d)
干预措施: JNJ-38518168 (30 mg) (Drug)
JNJ-38518168 (30 mg/d)
干预措施: Methotrexate (Drug)
结局指标
主要结局
Disease Activity Score 28 (DAS28) (C-reactive protein [CRP]) at Week 12
时间窗: Baseline and Week 12
The DAS28 using CRP is a statistically derived index combining tender joints (28 joints), swollen joints (28 joints), CRP, and Patient's Global Assessment of Disease Activity. The set of 28 joint count is based on evaluation of the shoulder, elbow, wrist, metacarpophalangeal (MCP) MCP1 to MCP5, proximal interphalangeal (PIP) PIP1 to PIP5 joints of both the upper right extremity and the upper left extremity as well as the knee joints of lower right and lower left extremities. The values are 0=best to 10=worst.
次要结局
- DAS28 (ESR) response rates at Week 12 and Week 24(Week 12 and Week 24)
- DAS28 (CRP) remission rates at Week 12 and Week 24(Week 12 and Week 24)
- DAS28 (ESR) remission rates at Week 12 and Week 24(Week 12 and Week 24)
- ACR/European League Against Rheumatism (EULAR) remission rates at Week 12 and Week 24(Week 12 and Week 24)
- Change from baseline in DAS28 (CRP) at Week 24(Baseline and Week 24)
- Change from baseline in DAS28 (erythrocyte sedimentation rate [ESR]) at Week 12 and Week 24(Baseline, Week 12 and Week 24)
- DAS28 (CRP) response rates at Week 12 and Week 24(Week 12 and Week 24)
- American College of Rheumatology (ACR) 20/50/70 response rates at Week 12 and Week 24(Week 12 and Week 24)
- Hybrid ACR response at Week 12 and Week 24(Week 12 and Week 24)
- Change from baseline in Simplified Disease Activity Index (SDAI) at Week 12 and Week 24(Baseline, Week 12 and Week 24)
- Change from baseline in Clinical Disease Activity Index (CDAI) at Week 12 and Week 24(Baseline, Week 12 and Week 24)
- Health Assessment Questionnaire - Disability Index (HAQ-DI) response at Week 12 and Week 24(Week 12 and Week 24)
- Change from baseline in HAQ-DI score at Week 12 and Week 24(Baseline, Week 12 and Week 24)
- Percent change from baseline in ESR levels at Week 12 and Week 24(Baseline, Week 12 and Week 24)
- Percent change from baseline in ACR components at Week 12 and Week 24(Baseline, Week 12 and Week 24)
- Number of patients with adverse events(Up to Week 28)