NCT02165215已完成3 期
Phase III, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy (Maintenance of Remission) and Safety of Etrolizumab Compared With Placebo in Patients With Moderate to Severe Active Ulcerative Colitis Who Are Naive to TNF Inhibitors
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 359
- 试验地点
- 104
- 主要终点
- Maintenance Phase: Percentage of Participants in Remission at Week 62 Among Randomized Participants With a Clinical Response at Week 10, as Determined by the Mayo Clinic Score (MCS)
研究概览
简要总结
This Phase III, randomized, double-blind, parallel-grouped, placebo-controlled, multicenter study will investigate the efficacy and safety of etrolizumab in maintenance of remission in participants with moderately to severely active UC who are naive to TNF inhibitors and refractory to or intolerant of prior immunosuppressant and/or corticosteroid treatment.
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
- •Diagnosis of ulcerative colitis (UC) established at least 3 months prior to Day 1 by clinical and endoscopic evidence
- •Moderately to severely active UC as determined by an MCS of 6-12 with an endoscopic subscore greater than or equal to (≥)2 as determined by the central reading procedure (endoscopy to be performed 4-16 days prior to Day 1), a rectal bleeding subscore ≥1, and a stool frequency subscore ≥1 during the screening period (prior to Day 1)
- •Evidence of UC extending a minimum of 20 centimeters (cm) from the anal verge as determined by baseline endoscopy (flexible sigmoidoscopy or colonoscopy) performed during screening, 4-16 days prior to Day 1
- •Naive to treatment with any anti-TNF therapy
- •Participants must have had an inadequate response, loss of response, or intolerance to prior corticosteroid and/or immunosuppressant treatment
- •Background regimen for UC may include oral 5-aminosalicylate (5-ASA), oral corticosteroids, budesonide, probiotics, azathioprine (AZA), 6-mercaptopurine (6-MP), or methotrexate (MTX) if doses have been stable during the screening period
- •Use of highly effective contraception
- •Must have received a colonoscopy within the past year or be willing to undergo a colonoscopy in lieu of a flexible sigmoidoscopy at screening
排除标准
- •A history of or current conditions and diseases affecting the digestive tract, such as indeterminate colitis, suspicion of ischemic colitis, radiation colitis, 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
- •Any prior treatment with etrolizumab or other anti-integrin agents (including natalizumab, vedolizumab, and efalizumab) as stated in the protocol
- •Any prior treatment with anti-adhesion molecules (such as mucosal addressin cell adhesion molecule [MAdCAM-1])
- •Any prior treatment with rituximab
- •Any treatment with tofacitinib during screening
- •Cogenital or acquired immune deficiency, chronic hepatitis B or C infection, human immunodeficiency virus (HIV) positive, or history of tuberculosis (active or latent)
- •Evidence of or treatment for Clostridium difficile within 60 days prior to Day 1 or other intestinal pathogens within 30 days prior to Day 1
- •History of recurrent opportunistic infections and/or severe disseminated viral infections
- •History of organ transplant
- •Any major episode of infection requiring treatment with intravenous (IV) antibiotics within 8 weeks prior to screening or oral antibiotics within 4 weeks prior to screening
- •Received a live attenuated vaccine within 4 weeks prior to Day 1
研究组 & 干预措施
Open-Label Induction Phase: Etrolizumab
Experimental
All participants will receive treatment with open-label etrolizumab 105 milligrams (mg) subcutaneous (SC) injection once every 4 weeks (Q4W) up to Week 10.
干预措施: Etrolizumab (Drug)
Double-Blind Maintenance Phase: Etrolizumab
Experimental
Participants who achieved a clinical response at Week 10 during the induction phase and randomized to this arm for the double-blind maintenance phase will receive etrolizumab 105 mg SC injection Q4W from Week 12 up to Week 62.
干预措施: Etrolizumab (Drug)
Double-Blind Maintenance Phase: Placebo
Placebo Comparator
Participants who achieved a clinical response at Week 10 during the induction phase and randomized to this arm for the double-blind maintenance phase will receive placebo (matched to etrolizumab) SC injection Q4W from Week 12 up to Week 62.
干预措施: Placebo (Drug)
结局指标
主要结局
Maintenance Phase: Percentage of Participants in Remission at Week 62 Among Randomized Participants With a Clinical Response at Week 10, as Determined by the Mayo Clinic Score (MCS)
时间窗: Week 62
MCS is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. 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. Remission is MCS ≤2 with individual subscores ≤1 and a rectal bleeding subscore of 0.
次要结局
- Maintenance Phase: Change From Baseline to Week 62 in UC Bowel Movement Signs and Symptoms, as Assessed by the Ulcerative Colitis Patient-Reported Outcome Signs and Symptoms (UC-PRO/SS) Questionnaire(Baseline, Week 62)
- Maintenance Phase: Change From Baseline to Week 62 in UC Functional Symptoms, as Assessed by the UC-PRO/SS Questionnaire(Baseline, Week 62)
- Number of Participants With Serious Infection-Related Adverse Events(From Baseline up to Week 74)
- Number of Participants With Malignancies(From Baseline up to Week 74)
- Maintenance Phase: Percentage of Participants in Clinical Remission at Week 62, as Determined by the MCS(Week 62)
- Maintenance Phase: Percentage of Participants With Improvement From Baseline in Endoscopic Appearance of the Mucosa at Week 62, as Determined by the MCS Endoscopic Subscore(Baseline, Week 62)
- Maintenance Phase: Percentage of Participants in Remission at Week 62 Among Randomized Participants in Remission at Week 10, as Determined by the MCS(Week 62)
- Maintenance Phase: Percentage of Participants With Histologic Remission at Week 62, as Determined by the Nancy Histological Index(Week 62)
- Maintenance Phase: Percentage of Participants With Endoscopic Remission at Week 62, as Determined by the MCS Endoscopic Subscore(Week 62)
- Maintenance Phase: Percentage of Participants With Corticosteroid-Free Clinical Remission at Week 62 Among Participants Who Were Receiving Corticosteroids at Baseline, as Determined by the MCS(Baseline, Week 62)
- Number of Participants With Injection-Site Reactions by Severity, According to NCI-CTCAE v4.0(From Baseline up to Week 74)
- Maintenance Phase: Etrolizumab Serum Trough Concentration (for Arms/Timepoints Above LLOQ)(Pre-dose (0 hour) at Baseline and Weeks 12, 24, 44, and 62)
- Maintenance Phase: Percentage of Participants Who Maintained Clinical Remission at Week 62 Among Randomized Participants in Clinical Remission at Week 10, as Determined by the MCS(Week 62)
- Maintenance Phase: Percentage of Participants With Corticosteroid-Free Remission at Week 62 Among Participants Who Were Receiving Corticosteroids at Baseline, as Determined by the MCS(Baseline, Week 62)
- Number of Participants With at Least One Adverse Event by Severity, According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v4.0)(From Baseline up to Week 74)
- Number of Participants With Adverse Events Leading to Study Drug Discontinuation(From Baseline up to Week 74)
- Number of Participants With Infection-Related Adverse Events by Severity, According to NCI-CTCAE v4.0(From Baseline up to Week 74)
- Number of Participants With Hypersensitivity Reaction Events by Severity, According to NCI-CTCAE v4.0(From Baseline up to Week 74)
- Maintenance Phase: Change From Baseline to Week 62 in Health-Related Quality of Life, as Assessed by the Overall Score of the Inflammatory Bowel Disease Questionnaire (IBDQ)(Baseline, Week 62)
- Number of Participants With Anti-Therapeutic Antibodies (ATAs) to Etrolizumab(Baseline, Weeks 4, 12, 24, 44, and 62, and and Early Termination/End of Safety Follow-Up (up to Week 74))
- Maintenance Phase: Etrolizumab Serum Trough Concentration (for Arms/Timepoints Below LLOQ)(Pre-dose (0 hour) at Baseline and Weeks 12, 24, 44, and 62)
研究者
研究点 (104)
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