A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of LY2127399 in Patients With Moderate to Severe Rheumatoid Arthritis (RA) Who Had an Inadequate Response to One or More TNF-α Inhibitors (FLEX V)
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 456
- 试验地点
- 1
- 主要终点
- Percentage of Participants With American College of Rheumatology 20% (ACR20) Response
研究概览
简要总结
The primary purpose of this study is to help answer if LY2127399 is safe and effective in the treatment of rheumatoid arthritis in participants with an inadequate response to one or more tumor necrosis factor-alpha (TNF-α) inhibitors.
This study is comprised of 2 periods:
Period 1: 24-week blinded treatment
Period 2: 48-week post-treatment follow-up
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of RA of more than 6 months and less than 15 years
- •At least 8 tender and swollen joints
- •An abnormally high C-reactive protein (CRP) level or erythrocyte sedimentation rate (ESR)
- •Positive for rheumatoid factor (RF) or anti-cyclic citrullinated peptide (CCP) antibody
- •Previously treated with biologic TNF-α inhibitor therapy (infliximab, certolizumab, golimumab, etanercept, adalimumab) and stopped treatment due to insufficient efficacy or intolerance
- •Regular use of at least 1 conventional disease-modifying anti-rheumatic drug (DMARD), with a stable dose for at least 8 weeks prior to study start
- •Woman must not be pregnant, breastfeeding, or become pregnant during the study
排除标准
- •Use of unstable doses of non-steroidal anti-inflammatory drugs (NSAIDS) in the past 6 weeks
- •Steroid injection or intravenous (IV) infusion in the last 6 weeks
- •Use of more than 10 milligrams/day (mg/day) of oral steroids in the last 6 weeks
- •History of a serious reaction to other biological DMARDs
- •Use of an oral calcineurin inhibitor (for example, cyclosporin or tacrolimus) in the last 8 weeks
- •Surgery on a joint or other major surgery less than 2 months ago, or plans to have joint surgery or major surgery during the study
- •Active fibromyalgia, juvenile chronic arthritis, spondyloarthropathy, Crohn's disease, ulcerative colitis, psoriatic arthritis, or other systemic inflammatory condition except RA
- •Cervical cancer or squamous skin cancer within the past 3 years, or other cancer within the past 5 years
- •Received a live vaccine received within the past 12 weeks (for example, vaccines for measles, mumps, rubella, and chicken pox, and nasal-spray flu vaccines)
- •Hepatitis or human immunodeficiency virus (HIV)
- •A serious bacterial infection (for example, pneumonia or cellulitis) within 3 months or a serious bone or joint infection within 6 months
- •Symptoms of herpes zoster or herpes simplex within the last month
- •Active or latent tuberculosis (TB)
- •Current symptoms of a serious disorder or illness
- •Use of an investigational drug within the last month
研究组 & 干预措施
120 milligrams (mg) LY2127399
Given every 4 weeks (Q4W) for 24 weeks. Participants receive a 240-mg loading dose when initiating treatment.
During the Treatment Period, for blinding purposes, participants will alternate injections of LY2127399 and injections of placebo every 2 weeks (Q2W).
At Week 16, responders will receive 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the 24-week treatment period.
At Week 16, non-responders (NR) will receive 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the 24-week treatment period.
干预措施: LY2127399 (Drug)
120 milligrams (mg) LY2127399
Given every 4 weeks (Q4W) for 24 weeks. Participants receive a 240-mg loading dose when initiating treatment.
During the Treatment Period, for blinding purposes, participants will alternate injections of LY2127399 and injections of placebo every 2 weeks (Q2W).
At Week 16, responders will receive 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the 24-week treatment period.
At Week 16, non-responders (NR) will receive 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the 24-week treatment period.
干预措施: Placebo Q4W (Drug)
90 mg LY2127399
Given Q2W for 24 weeks. Participants receive a 180-mg loading dose when initiating treatment.
At Week 16, both responders and NR will receive 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the 24-week treatment period.
干预措施: LY2127399 (Drug)
Placebo
Given Q2W for 24 weeks. Participants receive 2 injections of placebo when initiating treatment.
At Week 16, responders will receive 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the 24-week treatment period.
At Week 16, NR will receive a 180-mg loading dose of LY2127399 (2 injections of 90 mg), followed by 90 mg of LY2127399 Q2W for the rest of the 24-week treatment period.
干预措施: LY2127399 (Drug)
Placebo
Given Q2W for 24 weeks. Participants receive 2 injections of placebo when initiating treatment.
At Week 16, responders will receive 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the 24-week treatment period.
At Week 16, NR will receive a 180-mg loading dose of LY2127399 (2 injections of 90 mg), followed by 90 mg of LY2127399 Q2W for the rest of the 24-week treatment period.
干预措施: Placebo Q2W (Drug)
结局指标
主要结局
Percentage of Participants With American College of Rheumatology 20% (ACR20) Response
时间窗: Baseline through Week 24
ACR Responder Index: composite of clinical, laboratory, and functional measures of rheumatoid arthritis (RA). ACR20 Responder: a ≥20% improvement from baseline in both 68 tender joint counts (TJC) and 66 swollen joint counts (SJC) and a ≥20% improvement in at least 3 of 5 criteria: participant's and physician's global assessment of disease activity, Health Assessment Questionnaire-Disability Index (HAQ-DI) (which measured participants' perceived degree of difficulty performing daily activities), joint pain, and C-reactive protein (CRP). Percentage of participants achieving ACR20 response = (number of ACR20 responders / number of participants treated) \* 100. All NR at Week 16, as well as all participants who discontinued study treatment at any time for any reason, were defined as NR starting at that time-point and going forward, including Week 24 endpoint.
次要结局
- Change From Baseline to Week 24 in Tender Joint Count (68 Joint Count)(Baseline, Week 24)
- Change From Baseline to Week 24 in Participant's Assessment of Pain [Visual Analog Scale (VAS)](Baseline, Week 24)
- Percentage of Participants With American College of Rheumatology 50% (ACR50) and 70% (ACR70) Response(Baseline through Week 24)
- American College of Rheumatology Percent Improvement (ACR-N)(Baseline through Week 24)
- Change From Baseline to Week 24 in Swollen Joint Count (66 Joint Count)(Baseline, Week 24)
- Change From Baseline to Week 24 in Brief Pain Inventory Short Form (BPI-SF) Individual Items and Interference Scores(Baseline, Week 24)
- Change From Baseline to Week 24 in Absolute B Cell Counts(Baseline, Week 24)
- Change From Baseline to Week 24 in Physician's Global Assessment of Disease Activity (VAS)(Baseline, Week 24)
- Time to ACR20 Response(Baseline through Week 24)
- Population Pharmacokinetics (PK): Constant Clearance(Baseline through Week 24)
- Change From Baseline to Week 24 in Participant's Global Assessment of Disease Activity (VAS)(Baseline, Week 24)
- Change From Baseline to Week 24 in Health Assessment Questionnaire-Disability Index (HAQ-DI)(Baseline, Week 24)
- Change From Baseline to Week 24 in Disease Activity Score Based on 28 Joint Count and C-Reactive Protein Level (DAS28-CRP)(Baseline, Week 24)
- Change From Baseline to Week 24 in Brief Fatigue Inventory (BFI) Individual Items and Impact Scores(Baseline, Week 24)
- Change From Baseline to Week 24 in Duration of Morning Stiffness (Minutes)(Baseline, Week 24)
- Percentage of Participants With DAS28-CRP Based European League Against Rheumatism (EULAR) Response(Baseline through Week 24)
- Change From Baseline to Week 24 in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Domain and Summary Scores(Baseline, Week 24)
- Percentage of Participants Developing Anti-LY2127399 Antibodies(Baseline through Week 24)
- Change From Baseline to Week 24 in Serum Immunoglobulin (Ig) Levels(Baseline, Week 24)
- Change From Baseline to Week 24 in CRP(Baseline, Week 24)