A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multicenter, Dose-Ranging Study Evaluating the Efficacy and Safety of GS-1427 in Adult Participants With Moderately to Severely Active Ulcerative Colitis (UC)
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 228
- 试验地点
- 325
- 主要终点
- Proportion of Participants Achieving Clinical Response at Week 12
研究概览
简要总结
The goal of this study is to learn if emvistegrast (formerly GS-1427) is effective in treating participants with moderate to severe ulcerative colitis. The study will compare participants in different treatment groups treated with emvistegrast with participants treated with placebo.
The primary objective of this study is to assess the efficacy of emvistegrast, compared with placebo control, in achieving clinical response at Week 12.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Individuals have Ulcerative Colitis (UC) with symptoms of at least 90 days duration before randomization, with the diagnosis confirmed by endoscopy and histology at any time prior to randomization. Documentation of endoscopy and histology consistent with the diagnosis of UC must be available in the source documents.
- •Individuals have UC with minimum disease extent of 15 cm from the anal verge.
- •Individuals have moderately to severely active UC as determined by endoscopy occurring during screening with a total modified Mayo Clinic Score (mMCS) of 5 to 9 points, including a centrally read endoscopic subscore of at least
- •Individuals have an inadequate response or loss of response or are intolerant to at least 1 of the following UC treatments: corticosteroids, immunomodulators, or advanced therapy.
- •Individuals have an inadequate response or loss of response or are intolerant to < 3 AT mechanisms of action for UC (use of 2 or more AT with the same mechanism of action, eg, 2 TNF-α inhibitors, counts as 1 mechanism of action)
排除标准
- •Have a current diagnosis of Crohn's Disease (CD) or clinical findings suggestive of CD, diagnosis of indeterminate colitis due to etiologies such as an enteric pathogen, or lymphocytic or collagenous colitis.
- •Have a current diagnosis of toxic megacolon, symptomatic colonic stricture, acute severe colitis, fulminant colitis, or abdominal abscess at screening or randomization.
- •Have any history of exposure to vedolizumab or other integrin antagonists
- •Requirement for ongoing therapy with or use of any prohibited medication as specified in the protocol
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply
研究组 & 干预措施
Part A, Part B, Part C: Emvistegrast Dose A
Participants will receive emvistegrast Dose A Day 1 through Week 12 (Part A).
Participants who complete the 12-week Part A treatment period will be eligible to continue and remain on the same dose of emvistegrast through Week 52 (Part B).
Participants who complete Part B of the study will continue onto Part C: Blinded treatment extension for an additional 64 weeks (through Week 116).
干预措施: emvistegrast (Drug)
Part A, Part B, Part C: Emvistegrast Dose B
Participants will receive emvistegrast Dose B Day 1 through Week 12 (Part A).
Participants who complete the 12-week Part A treatment period will be eligible to continue and remain on the same dose of emvistegrast through Week 52 (Part B).
Participants who complete Part B of the study will continue onto Part C: Blinded treatment extension for an additional 64 weeks (through Week 116).
干预措施: emvistegrast (Drug)
Part A, Part B, Part C: Emvistegrast Dose C
Participants will receive emvistegrast Dose C Day 1 through Week 12 (Part A).
Participants who complete the 12-week Part A treatment period will be eligible to continue and remain on the same dose of emvistegrast through Week 52 (Part B).
Participants who complete Part B of the study will continue onto Part C: blinded treatment extension for an additional 64 weeks (through Week 116).
干预措施: emvistegrast (Drug)
Part A, Placebo; Part B, Part C: Emvistegrast
Participants will receive Placebo to match emvistegrast Day 1 through Week 12 (Part A). Part A placebo participants will be eligible to undergo re-randomization in a double-blind manner after endoscopy assessment at Week 12 to receive one of the emvistegrast dose A, B, or C treatments.
Participants will be eligible to continue and remain on the new dose through Week 52 (Part B). Participants who complete Part B of the study will continue onto Part C: blinded treatment extension for an additional 64 weeks (through Week 116).
干预措施: emvistegrast (Drug)
Part A, Placebo; Part B, Part C: Emvistegrast
Participants will receive Placebo to match emvistegrast Day 1 through Week 12 (Part A). Part A placebo participants will be eligible to undergo re-randomization in a double-blind manner after endoscopy assessment at Week 12 to receive one of the emvistegrast dose A, B, or C treatments.
Participants will be eligible to continue and remain on the new dose through Week 52 (Part B). Participants who complete Part B of the study will continue onto Part C: blinded treatment extension for an additional 64 weeks (through Week 116).
干预措施: Placebo-to-match emvistegrast (Drug)
结局指标
主要结局
Proportion of Participants Achieving Clinical Response at Week 12
时间窗: Week 12
Clinical response is defined as a decrease from baseline in the modified Mayo Clinic Score (mMCS) of ≥ 2 points and at least a 30% reduction from baseline, and a decrease in rectal bleeding subscore of ≥ 1 from baseline or an absolute rectal bleeding subscore of 0 or 1. The mMCS is a scoring system for assessment of Ulcerative Colitis (UC) activity and is composed of subscores from endoscopy (range: 0 to 3, where 0 = normal or inactive disease and 3 = severe disease (spontaneous bleeding, ulceration)), rectal bleeding (range: 0 to 3, where 0 = no blood seen and 3 = blood alone passes), and stool frequency (range: 0 to 3, where 0 = normal number of stools and 3 = at least 5 or more stools more than normal). Total score for mMCS ranges from 0 to 9 (sum of all subscores), with higher scores indicating higher disease activity.
次要结局
- To Assess the Efficacy of Emvistegrast in Achieving Partial Modified Mayo Clinic Score (mMCS) remission at Week 52(Week 52)
- Incidence of Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Deaths.(First dose date up to 116 weeks plus 28 days)
- Incidence of Treatment-emergent Lab Abnormalities(First dose date up to 116 weeks plus 28 days)
- Proportion of Participants Achieving Clinical Remission at Week 12(Week 12)
- Proportion of Participants Achieving Clinical Remission at Week 52(Week 52)
- Proportion of Participants Achieving Histologic-endoscopic Mucosal Improvement at Week 12(Week 12)
- Proportion of Participants Achieving Mucosal Healing at Week 12(Week 12)
- Proportion of Participants Achieving Endoscopic Improvement at Week 12(Week 12)
- To Assess the Efficacy of GS-1427 in Achieving Partial Modified Mayo Clinic Score (mMCS) remission at Week 52(Week 52)