A Phase 3, Randomized, Placebo-Controlled, Blinded, Multicenter Study of the Induction and Maintenance of Clinical Response and Remission by MLN0002 in Patients With Moderate to Severe Ulcerative Colitis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 895
- 试验地点
- 104
- 主要终点
- Induction Phase: Percentage of Participants With a Clinical Response at Week 6
研究概览
简要总结
The primary purpose of this study was to determine the effect of vedolizumab induction treatment on clinical response at 6 weeks and to determine the effect of vedolizumab maintenance treatment on clinical remission at 52 weeks.
详细描述
This multicenter, phase 3, randomized, blinded, placebo-controlled study in patients with moderately to severely active ulcerative colitis comprises two phases:
- The Induction Phase, designed to establish the efficacy and safety of vedolizumab for the induction of clinical response and remission.
- The Maintenance Phase, designed to establish the efficacy and safety of vedolizumab for the maintenance of clinical response and remission.
The 6-week Induction Phase contained 2 cohorts of participants: Cohort 1 participants were randomized and treated with double-blind study drug, and Cohort 2 participants were treated with open-label vedolizumab. The second cohort was enrolled to ensure that the sample size of Induction Phase responders randomized into the Maintenance Study provided sufficient power for the Maintenance Study primary efficacy analysis. These participants did not contribute to the efficacy analyses performed for the Induction Study. Participants in both cohorts were assessed for treatment response at Week 6.
In the Maintenance Phase vedolizumab-treated participants from both Cohort 1 and Cohort 2 who demonstrated a clinical response were randomized in a 1:1:1 ratio to double-blind treatment with vedolizumab administered every 4 weeks (Q4W), vedolizumab administered every 8 weeks (Q8W), or placebo. Vedolizumab-treated participants who did not demonstrate response at Week 6 continued treatment with open-label vedolizumab, administered Q4W. Participants treated with double-blind placebo in the Induction Phase continued on double-blind placebo during the Maintenance Phase, regardless of treatment response during induction. The Maintenance Phase began at Week 6 and concluded with Week 52 assessments.
After the Week 52 assessments, participants meeting protocol-defined criteria were eligible to enroll in Study C13008 (NCT00790933; Long-term Safety) to receive open-label vedolizumab treatment. Participants who withdrew early (prior to Week 52) due to sustained nonresponse, disease worsening, or the need for rescue medications may also have been eligible for Study C13008. Participants who did not enroll into Study C13008 were to complete a final on-study safety assessment at Week 66 (or final safety visit 16 weeks after the last dose) in the Maintenance Phase of Study C13006.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Each patient must meet all of the following inclusion criteria to be enrolled in the study:
- •Diagnosis of moderately to severely active ulcerative colitis
- •Demonstrated, over the previous 5 year period, an inadequate response to, loss of response to, or intolerance at least 1 of the following agents:
- •Immunomodulators
- •Tumor necrosis factor-alpha (TNFα) antagonists
- •Corticosteroids
- •May be receiving a therapeutic dose of conventional therapies for inflammatory bowel disease (IBD) as defined by the protocol
排除标准
- •Evidence of abdominal abscess at the initial screening visit
- •Extensive colonic resection, subtotal or total colectomy
- •Ileostomy, colostomy, or known fixed symptomatic stenosis of the intestine
- •Have received non permitted IBD therapies within either 30 or 60 days, depending on the medication, as stated in the protocol
- •Chronic hepatitis B or C infection
- •Active or latent tuberculosis
研究组 & 干预措施
Vedolizumab
In the Induction Phase participants received vedolizumab 300 mg, administered by intravenous infusion at Week 0 and Week 2 (Days 1 and 15).
In the Maintenance Phase, participants who demonstrated a clinical response at Week 6 according to protocol-specified criteria were randomized in a 1:1:1 ratio to double-blind treatment with vedolizumab administered every 4 weeks, vedolizumab administered every 8 weeks, or placebo for up to Week 50. Participants who did not demonstrate response at Week 6 of the Induction Phase continued treatment with vedolizumab, administered every 4 weeks during the Maintenance Phase.
干预措施: vedolizumab (Drug)
Placebo
In the Induction Phase participants received placebo intravenous infusion at Week 0 and Week 2 (Days 1 and 15). Participants continued to receive placebo during the Maintenance Phase, regardless of treatment response during Induction.
干预措施: Placebo (Other)
结局指标
主要结局
Induction Phase: Percentage of Participants With a Clinical Response at Week 6
时间窗: Baseline and Week 6
Clinical response is defined as a reduction in complete Mayo score of ≥ 3 points and ≥ 30% from Baseline with an accompanying decrease in rectal bleeding subscore of ≥ 1 point or absolute rectal bleeding subscore of ≤ 1 point. The Mayo Score is a standard assessment tool to measure ulcerative colitis disease activity in clinical trials. The index consists of 4 components: two that are patient reported (rectal bleeding and stool frequency), a global assessment by the physician, and an endoscopic subscore. Each component is scored on a scale from 0 to 3 and the complete score ranges from 1 to 12 (higher scores indicate greater disease activity). All participants who prematurely discontinued for any reason were considered as not achieving clinical response.
Maintenance Phase: Percentage of Participants in Clinical Remission at Week 52
时间窗: Week 52
Clinical Remission is defined as a complete Mayo score of ≤ 2 points and no individual subscore \> 1 point. The Mayo Score is a standard assessment tool to measure ulcerative colitis disease activity in clinical trials. The index consists of 4 components: two that are patient reported (rectal bleeding and stool frequency), a global assessment by the physician, and an endoscopic subscore. Each component is scored on a scale from 0 to 3 and the complete score ranges from 1 to 12 (higher scores indicate greater disease activity). All participants who prematurely discontinued for any reason were considered as not achieving clinical remission.
次要结局
- Induction Phase: Percentage of Participants in Clinical Remission at Week 6(Week 6)
- Induction Phase: Percentage of Participants With Mucosal Healing at Week 6(Week 6)
- Maintenance Phase: Percentage of Participants With Durable Clinical Response(Baseline, Week 6 and Week 52)
- Maintenance Phase: Percentage of Participants With Mucosal Healing at Week 52(Week 52)
- Maintenance Phase: Percentage of Participants With Durable Clinical Remission(Week 6 and Week 52)
- Maintenance Phase: Percentage of Participants With Corticosteroid-free Remission at Week 52(Week 52)