A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety and Efficacy of LY2127399 in Patients With Rheumatoid Arthritis (RA) With or Without Background Disease-Modifying Anti-rheumatic Drug (DMARD) Therapy (FLEX O)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,004
- 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 with or without background disease-modifying anti-rheumatic drug (DMARD) therapy.
This study is comprised of 2 periods:
Period 1 - 24-week blinded treatment
Period 2 - 48-week post-treatment follow-up
详细描述
In consideration of disease severity, all participants were assessed for non-response at Week 16. A total of 66 joints were examined for swelling, and a total of 66 joint were examined for tenderness. For participants who had at least 5 swollen and 5 tender joints at baseline, Week 16 non-responders (NRs) were defined as participants with <20% improvement from baseline in both tender joint counts and swollen joint counts. For participants who did not have at least 5 swollen and 5 tender joints at baseline, Week 16 NRs were defined as participants who had at least 2 additional tender and 2 additional swollen joints from baseline. All Week 16 NRs and all participants who discontinued study treatment at any time, for any reason, were defined as NRs starting at that timepoint and going forward for all American College of Rheumatology (ACR) imputed analyses, including the Week 24 endpoint.
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 Rheumatoid Arthritis (RA) of more than 6 months and less than 15 years
- •Global Assessment of Disease Activity visual analog scale (VAS) greater than or equal to 20/100 millimeters (mm)
- •If on one or more conventional disease-modifying anti-rheumatic Drugs (DMARDs) at randomization, must have been on a stable dose for at least 8 weeks prior to study start.
- •Women must not be pregnant, breastfeeding, or become pregnant during the study
排除标准
- •Use of unstable doses of non-steroidal 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 per day (mg/day) of oral steroids in the last 6 weeks
- •Use of biologic DMARD concurrently or recently
- •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 prior to study start, 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 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 mg LY2127399
LY2127399: 120 milligrams (mg), subcutaneous (SC) injection, every 4 weeks for 24 weeks. Participants received a 240-mg (2 SC injections of 120 mg each) loading dose of LY2127399 when initiating treatment.
During the Treatment Period, for blinding purposes, participants alternated injections of LY2127399 and injections of Placebo every 2 weeks.
After 16 weeks, non-responders received 90 mg of LY2127399 every 2 weeks for the rest of the 24-week Treatment Period.
干预措施: LY2127399 (Drug)
120 mg LY2127399
LY2127399: 120 milligrams (mg), subcutaneous (SC) injection, every 4 weeks for 24 weeks. Participants received a 240-mg (2 SC injections of 120 mg each) loading dose of LY2127399 when initiating treatment.
During the Treatment Period, for blinding purposes, participants alternated injections of LY2127399 and injections of Placebo every 2 weeks.
After 16 weeks, non-responders received 90 mg of LY2127399 every 2 weeks for the rest of the 24-week Treatment Period.
干预措施: Placebo (Drug)
90 mg LY2127399
LY2127399: 90 milligrams (mg), subcutaneous (SC) injection, every 2 weeks for 24 weeks. Participants received a 180-mg (2 SC injections of 90 mg each) loading dose of LY2127399 when initiating treatment.
After 16 weeks, non-responders continued to receive 90 mg of LY2127399 every 2 weeks for the rest of the 24-week Treatment Period.
干预措施: LY2127399 (Drug)
Placebo
Placebo: subcutaneous (SC) injection, every 2 weeks for 24 weeks. Participants received a loading dose of 2 SC injections of Placebo when initiating treatment.
After 16 weeks, non-responders received 90 milligrams (mg) of LY2127399 every 2 weeks for the rest of the 24-week Treatment Period.
干预措施: LY2127399 (Drug)
Placebo
Placebo: subcutaneous (SC) injection, every 2 weeks for 24 weeks. Participants received a loading dose of 2 SC injections of Placebo when initiating treatment.
After 16 weeks, non-responders received 90 milligrams (mg) of LY2127399 every 2 weeks for the rest of the 24-week Treatment Period.
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage of Participants With American College of Rheumatology 20% (ACR20) Response
时间窗: Up to 24 weeks
ACR20 Responder Index: Composite of clinical, laboratory, and functional measures of rheumatoid arthritis. ACR20 Responder: had \>=20% improvement from baseline in both 68 tender and 66 swollen joint counts and \>=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 non-responders at Week 16 as well as all participants who discontinued study treatment at any time, for any reason, were defined as non-responders starting at that timepoint and going forward, including Week 24 endpoint.
次要结局
- Percentage of Participants With American College of Rheumatology 50% (ACR50) and 70% (ACR70) Responses(Up to 24 weeks)
- Mean Percent Improvement in American College of Rheumatology Percent Improvement (ACR-N)(Up to 24 weeks)
- Change From Baseline to 24 Weeks in Tender Joint Count (68 Joint Count)(Baseline, up to 24 weeks)
- Change From Baseline to 24 Weeks in Swollen Joint Count (66 Joint Count)(Baseline, up to 24 weeks)
- Change From Baseline to 24 Weeks in Disease Activity Score (Based on 28 Joint Count)-C-Reactive Protein (DAS28-CRP)(Baseline, up to 24 weeks)
- Change From Baseline to 24 Weeks in Participant's Assessment of Pain (Visual Analog Scale)(Baseline, up to 24 weeks)
- Change From Baseline to 24 Weeks in Participant's Global Assessment of Disease Activity (Visual Analog Scale)(Baseline, up to 24 weeks)
- Change From Baseline to 24 Weeks in Health Assessment Questionnaire-Disability Index (HAQ-DI)(Baseline, up to 24 weeks)
- Time to American College of Rheumatology 20% (ACR20) Response(Baseline through 24 weeks)
- Change From Baseline to 24 Weeks in Physician's Global Assessment of Disease Activity (Visual Analog Scale)(Baseline, up to 24 weeks)
- Probability of an ACR20 Response by 24 Weeks(Baseline through 24 weeks)
- Percentage of Participants With DAS28-Based European League Against Rheumatism (EULAR) Response(Up to 24 weeks)
- Change From Baseline to 24 Weeks in Medical Outcomes Study 36-Item Short Form (SF-36) Health Status Survey Domain and Summary Scores(Baseline, up to 24 weeks)
- Change From Baseline in C-reactive Protein (CRP) up to Week 24 Endpoint(Baseline, up to 24 weeks)
- Change From Baseline to 24 Weeks in Absolute CD3-CD20+ B-cell Counts(Baseline, up to 24 weeks)
- Change From Baseline to 24 Weeks in Serum Immunoglobulin (Ig) Levels(Baseline, up to 24 weeks)
- Population Pharmacokinetics (PK)(Baseline through 24 weeks)
- Percentage of Participants Developing Anti-LY2127399 Antibodies(Baseline through 24 weeks)