A Phase 2 Study of Multiple Intravenous Doses of LY2127399 in Patients With Rheumatoid Arthritis on Concomitant Methotrexate and an Inadequate Response to TNFα Inhibitor Therapy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Percentage of Participants Achieving American College of Rheumatology (ACR)50 Response at Week 16
研究概览
简要总结
The purpose of this study is to explore whether LY2127399 is effective in relieving signs and symptoms of rheumatoid arthritis (RA) in patients with a history of inadequate response or intolerance to at least 1 Tumor Necrosis Factor-Alpha (TNFα) inhibitor therapy. Examples of these TNFα inhibitor therapies that are currently on the market include Enbrel® (etanercept), Remicade® (infliximab), and Humira® (adalimumab).
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, Care Provider, Investigator)
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
- •Have given written informed consent approval
- •Women must not be at risk to become pregnant during study participation
- •Diagnosis of Rheumatoid Arthritis
- •Active Rheumatoid Arthritis
- •Current, regular use of Methotrexate, at a stable dose
- •Have been on at least 1 biologic tumor necrosis factor-alpha (TNFα) inhibitor therapy and either failed or were intolerant to treatment
- •Other criteria to be reviewed by study doctor
排除标准
- •Use of excluded medications (reviewed by study doctor)
- •Have medical findings which, in the opinion of the study doctor, put patient at an unacceptable risk for participation in the study
- •Have had recent or ongoing infection which, in the opinion of the study doctor put patient at an unacceptable risk for participation
- •Evidence of tuberculosis
- •Have systemic inflammatory condition other than rheumatoid arthritis (RA), such as juvenile RA, seronegative spondyloarthropathy, Crohn's disease, ulcerative colitis, or psoriatic arthritis.
- •Other criteria to be reviewed by study doctor
研究组 & 干预措施
30 milligram (mg) LY2127399
Double-blind Treatment: 30 mg LY2127399 administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks.
Rescue: At Week 16 primary endpoint, participants without at least 20% improvement in either tender or swollen joint counts based on 28 joints, could receive an additional (unblinded) 30 minute infusion of LY2127399 80 mg or remain on initial randomized treatment up to Week 24.
Follow-up: Optional visits beyond Week 24, if needed, to assess safety including B cell count recovery.
干预措施: LY2127399 (Biological)
80 mg LY2127399
Double-blind Treatment: 80 mg LY2127399 administered as a single IV infusion over 30 minutes at 0, 3, and 6 weeks.
Rescue: At Week 16 primary endpoint, participants without at least 20% improvement in either tender or swollen joint counts based on 28 joints, could receive an additional (unblinded) 30 minute infusion of LY2127399 80 mg or remain on initial randomized treatment up to Week 24.
Follow-up: Optional visits beyond Week 24, if needed, to assess safety including B cell count recovery.
干预措施: LY2127399 (Biological)
Placebo
Double-blind Treatment: Placebo comparator administered as a single IV infusion over 30 minutes at 0, 3, and 6 weeks.
Rescue: At Week 16 primary endpoint, participants without at least 20% improvement in either tender or swollen joint counts based on 28 joints could receive an additional (unblinded) 30 minute infusion of LY2127399 80 mg or remain on same initial randomized treatment up to Week 24.
Follow-Up: Optional visits beyond Week 24, if needed, to assess safety including B cell count recovery.
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage of Participants Achieving American College of Rheumatology (ACR)50 Response at Week 16
时间窗: 16 weeks
ACR50 Responder Index is a composite of clinical, laboratory, and functional measures in rheumatoid arthritis. ACR50 Responder is defined as a participant with greater than 50% improvement from baseline in both tender and swollen joint counts and in at least 3 of the following 5 criteria: physician global assessment, patient global assessment, functional ability measure (Health Assessment Questionnaire-Disability Index which measures participants' perceived degree of difficulty when performing various daily activities), visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein.
次要结局
- Number of Participants Experiencing An Adverse Event(Baseline up to 68 weeks)
- Change From Baseline in Medical Outcome Study 36-Item Short Form Health Survey (SF-36) at Week 16(Baseline, 16 weeks)
- Percentage of Participants Achieving American College of Rheumatology (ACR) 20 Response at Week 16(16 weeks)
- Percentage of Participants Achieving American College of Rheumatology (ACR)70 Response at Week 16(16 weeks)
- Change From Baseline in Tender Joint Count at Week 16(Baseline, 16 weeks)
- Change From Baseline in Participant's Assessment of Joint Pain at Week 16(Baseline, 16 weeks)
- Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 16(Baseline, 16 weeks)
- Change From Baseline in Swollen Joint Count at Week 16(Baseline, 16 weeks)
- Change From Baseline in Participant's Assessment of Disease Activity at Week 16(Baseline, 16 weeks)
- Percent Change From Baseline in C-reactive Protein (CRP) at Week 16(Baseline, 16 weeks)
- Change From Baseline in Physician's Global Assessment of Disease Activity at Week 16(Baseline, 16 weeks)
- Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Score at Week 16(Baseline, 16 weeks)
- Pharmacodynamics: Change From Baseline in Absolute CD20 + B Cell Count at Week 16(Baseline, 16 weeks)
- Pharmacodynamics: Change From Baseline in Total B Cells (CD20 + CD3-) as a Percentage of Total Lymphocytes(Baseline, 16 weeks)
- Pharmacokinetics: Predicted Population Mean Parameter: T-half Life (t1/2, Tau)(Pre-dose, Day 1 through Week 24)
- Change From Baseline in Disease Activity Score (DAS28) at Week 16(Baseline, 16 weeks)
- Number of Participants With Response (Response Rate) Based Upon European League Against Rheumatism Responder Index, 28 Joint Count (EULAR28) at Week 16(16 weeks)
- Pharmacodynamics: Change From Baseline in Serum Immunoglobulins at Week 16(Baseline, 16 weeks)
- Pharmacokinetics: Predicted Population Mean Parameter: C-trough Steady-state(Pre-dose, Day 1 through Week 24)