Phase III, Randomized, Multicenter Double-Blind, Double Dummy Study to Evaluate the Efficacy and Safety of Etrolizumab Compared With Infliximab in Patients With Moderate to Severe Active Ulcerative Colitis Who Are Naive to TNF Inhibitors
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 397
- 试验地点
- 119
- 主要终点
- Percentage of Participants With Both Clinical Response at Week 10 and Clinical Remission at Week 54, as Determined by the Mayo Clinic Score (MCS)
研究概览
简要总结
This is a multicenter, Phase III, randomized, double-blind, double-dummy, parallel-group study to evaluate the safety, efficacy, and tolerability of etrolizumab compared with infliximab in treating participants with moderate to severe ulcerative colitis (UC) who are naive to tumor necrosis factor (TNF) inhibitors. Participants will be randomized in a 1:1 ratio to receive either etrolizumab 105 milligrams (mg) by subcutaneous (SC) injection once every 4 weeks (Q4W) + placebo (intravenous [IV] infusion at Weeks 0, 2, and 6, then once every 8 weeks [Q8W]) or infliximab 5 milligrams/kilogram (mg/kg) IV at Weeks 0, 2, and 6, then Q8W) + placebo (SC Q4W). Time on treatment is 54 weeks.
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
- •Moderately to severely active UC as determined by the Mayo Clinic Score assessment (MCS)
- •Naive to treatment with any anti-TNF inhibitor therapy (including TNF inhibitor biosimilars)
- •An inadequate response to or intolerance of prior corticosteroid and/or immunosuppressant treatment
- •Background regimen for UC may include oral 5-aminosalicylate (5-ASA), oral corticosteroids, budenoside multi-matrix system (MMX), probiotics, azathioprine (AZA), 6-mercaptopurine (6-MP), or methotrexate (MTX) if doses have been stable during the screening period
- •Use of highly effective contraception during and at least 24 weeks after the last dose of study drug
排除标准
- •A history of or current conditions and diseases affecting the digestive tract, such as indeterminate colitis, suspicion of ischemic, radiation or microscopic colitis, Crohn's disease, fistulas or abdominal abscesses, colonic mucosal dysplasia, intestinal obstruction, toxic megacolon, or unremoved adenomatous colonic polyps
- •Prior or planned surgery for UC
- •Past or present ileostomy or colostomy
- •Have received non-permitted inflammatory bowel disease (IBD) therapies (including natalizumab, vedolizumab, efalizumab, and tofactinib)
- •History of moderate or severe allergic or anaphylactic/anaphylactoid reactions to chimeric, human, or humanized antibodies; fusion proteins, or murine proteins; hypersensitivity to etrolizumab or any of its excipients
- •Chronic hepatitis B or C infection, Human deficiency virus (HIV) or tuberculosis (active or latent)
研究组 & 干预措施
Etrolizumab + Placebo (IV)
Participants will receive ertolizumab (SC) Q4W until Week 52 along with placebo matched to infliximab as IV infusion until Week 46.
干预措施: Etrolizumab (Drug)
Etrolizumab + Placebo (IV)
Participants will receive ertolizumab (SC) Q4W until Week 52 along with placebo matched to infliximab as IV infusion until Week 46.
干预措施: Placebo (IV) (Other)
Infliximab + Placebo (Injection)
Participants will receive IV infusion of infliximab at Weeks 0,2, and 6, then every 8 weeks until Week 46 partnered with placebo matched to etrolizumab by SC injection Q4W until Week 52.
干预措施: Infliximab (Drug)
Infliximab + Placebo (Injection)
Participants will receive IV infusion of infliximab at Weeks 0,2, and 6, then every 8 weeks until Week 46 partnered with placebo matched to etrolizumab by SC injection Q4W until Week 52.
干预措施: Placebo (Injection) (Other)
结局指标
主要结局
Percentage of Participants With Both Clinical Response at Week 10 and Clinical Remission at Week 54, as Determined by the Mayo Clinic Score (MCS)
时间窗: Week 10, Week 54
Mayo Clinic Score (MCS) is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease. Clinical Response is MCS with ≥3-point decrease and 30% reduction from baseline as well as ≥1-point decrease in rectal bleeding subscore or an absolute rectal bleeding score of 0 or 1. Clinical Remission is MCS ≤2 with individual subscores ≤1.
次要结局
- Percentage of Participants Achieving Clinical Remission at Week 54, as Determined by the MCS(Week 54)
- Percentage of Participants Achieving Clinical Remission at Both Week 10 and Week 54, as Determined by the MCS(Week 10 and Week 54)
- Percentage of Participants Achieving Clinical Remission at Week 54 Among Those With a Clinical Response at Week 10, as Determined by the MCS(Week 10 and Week 54)
- Pharmacokinetics: Etrolizumab Serum Concentration(Weeks 2, 10, 12, 30, and 54)
- Percentage of Participants Achieving Clinical Remission at Week 10, Defined as MCS ≤2 With Individual Subscores ≤1(Week 10)
- Percentage of Participants With Endoscopic Remission at Week 54, as Determined by the MCS(Week 54)
- Percentage of Participants Achieving Clinical Response at Week 10, as Determined by the MCS(Week 10)
- Percentage of Participants With Improvement in Endoscopic Appearance of the Mucosa at Week 10, Determined by the MCS(Baseline to Week 10)
- Percentage of Participants With Improvement in Endoscopic Appearance of the Mucosa at Week 54, as Determined by the MCS(Baseline to Week 54)
- Percentage of Participants With Improvement in Endoscopic Appearance of the Mucosa at Both Week 10 and Week 54, as Determined by the MCS(Baseline to Week 10, Week 54)
- Percentage of Participants Achieving Clinical Response at Both Weeks 10 and 54, as Determined by the MCS(Week 10, Week 54)
- Percentage of Participants That Achieve Clinical Remission Corticosteroid-Free at Week 54 (Off Corticosteroid for at Least 24 Weeks Prior to Week 54) Among Those Who Were Receiving Corticosteroids at Baseline, as Determined by the MCS(Week 54)
- Number of Participants With Adverse Events Leading to Study Drug Discontinuation(Baseline until the end of study (up to 66 weeks))
- Number of Participants With Infection-Related Adverse Events, Severity Determined According to the NCI CTCAE v4.0(Baseline until the end of study (up to 66 weeks))
- Number of Participants With Serious Infection-Related Adverse Events(Baseline until the end of study (up to 66 weeks))
- Number of Participants With Injection-Site Reactions, Severity Determined According to the NCI CTCAE v4.0(Baseline until the end of study (up to 66 weeks))
- Number of Participants With Adverse Events, Severity Determined According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0)(Baseline until the end of study (up to 66 weeks))
- Number of Participants With Malignancies(Baseline until the end of study (up to 66 weeks))
- Number of Participants With Hypersensitivity Reaction Events, Severity Determined According to the NCI CTCAE v4.0(Baseline until the end of study (up to 66 weeks))
- Number of Participants With Anti-Therapeutic Antibodies (ATAs) to Etrolizumab(Weeks 0, 4, 10, 12, 30, and 54)
- Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Overall Score at Weeks 10, 30, and 54(Weeks 10, 30, and 54)