Combined Phase 2b/3, Double-Blind, Randomized, Placebo-Controlled Studies Evaluating the Efficacy and Safety of Filgotinib in the Induction and Maintenance of Remission in Subjects With Moderately to Severely Active Ulcerative Colitis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,351
- 试验地点
- 342
- 主要终点
- Maintenance Study: Percentage of Participants Who Achieved EBS Remission at Week 58
研究概览
简要总结
The primary objectives of this study are to evaluate the efficacy of filgotinib in the induction and maintenance treatment of moderately to severely active ulcerative colitis (UC) in participants who are biologic-naive and biologic-experienced.
Participants who complete the study, or met protocol specified efficacy discontinuation criteria will have the option to enter a separate, long-term extension (LTE) study (Gilead Study GS-US-418-3899: NCT02914535).
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males or non-pregnant, non-lactating females, ages 18 to 75 years, inclusive based on the date of the screening visit
- •Documented diagnosis of UC of at least 6 months AND with a minimum disease extent of 15 cm from the anal verge. Documentation should include endoscopic and histopathologic evidence of UC.
- •A surveillance colonoscopy is required at screening in individuals with a history of UC for 8 or more years, if one was not performed in the prior 24 months
- •Moderately to severely active UC
- •Previously demonstrated an inadequate clinical response, loss of response to, or intolerance to at least 1 of the following agents (depending on current country treatment recommendations/guidelines): corticosteroids, immunomodulators, tumor necrosis factor alpha (TNFa) antagonists, or vedolizumab
排除标准
- •Presence of Crohn's disease, indeterminate colitis, ischemic colitis, fulminant colitis, ulcerative proctitis, or toxic mega-colon
- •Active tuberculosis (TB) or history of latent TB that has not been treated
- •Use of any concomitant prohibited medications as described in the protocol
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Induction Study (Cohort A): Filgotinib 200 mg
Participants in Cohort A (biologic-naive) received filgotinib 200 milligrams (mg) and placebo-to-match (PTM) filgotinib 100 mg orally once daily for 10 weeks.
干预措施: Filgotinib (Drug)
Induction Study (Cohort A): Filgotinib 200 mg
Participants in Cohort A (biologic-naive) received filgotinib 200 milligrams (mg) and placebo-to-match (PTM) filgotinib 100 mg orally once daily for 10 weeks.
干预措施: PTM filgotinib (Drug)
Induction Study (Cohort A): Filgotinib 100 mg
Participants in Cohort A (biologic-naive) received filgotinib 100 mg and PTM filgotinib 200 mg orally once daily for 10 weeks.
干预措施: Filgotinib (Drug)
Induction Study (Cohort A): Filgotinib 100 mg
Participants in Cohort A (biologic-naive) received filgotinib 100 mg and PTM filgotinib 200 mg orally once daily for 10 weeks.
干预措施: PTM filgotinib (Drug)
Induction Study (Cohort A): Placebo
Participants in Cohort A (biologic-naive) received PTM filgotinib 200 mg and PTM filgotinib 100 mg orally once daily for 10 weeks.
干预措施: PTM filgotinib (Drug)
Induction Study (Cohort B): Filgotinib 200 mg
Participants in Cohort B (biologic-experienced) received filgotinib 200 mg and PTM filgotinib 100 mg orally once daily for 10 weeks.
干预措施: Filgotinib (Drug)
Induction Study (Cohort B): Filgotinib 200 mg
Participants in Cohort B (biologic-experienced) received filgotinib 200 mg and PTM filgotinib 100 mg orally once daily for 10 weeks.
干预措施: PTM filgotinib (Drug)
Induction Study (Cohort B): Filgotinib 100 mg
Participants in Cohort B (biologic-experienced) received filgotinib 100 mg and PTM filgotinib 200 mg orally once daily for 10 weeks.
干预措施: Filgotinib (Drug)
Induction Study (Cohort B): Filgotinib 100 mg
Participants in Cohort B (biologic-experienced) received filgotinib 100 mg and PTM filgotinib 200 mg orally once daily for 10 weeks.
干预措施: PTM filgotinib (Drug)
Induction Study (Cohort B): Placebo
Participants in Cohort B (biologic-experienced) received PTM filgotinib 200 mg and PTM filgotinib 100 mg orally once daily for 10 weeks.
干预措施: PTM filgotinib (Drug)
Maintenance Study: Filgotinib 200 mg From Induction Filgotinib 200 mg
Participants in the Filgotinib 200 mg arm who completed the Induction Study and achieved either Endoscopy/Bleeding/Stool Frequency (EBS) remission or Mayo Clinic Score (MCS) response at Week 10 were re-randomized at Week 11 into the Maintenance Study to receive filgotinib 200 mg and PTM filgotinib 100 mg for an additional 47 weeks (up to Week 58).
干预措施: Filgotinib (Drug)
Maintenance Study: Filgotinib 200 mg From Induction Filgotinib 200 mg
Participants in the Filgotinib 200 mg arm who completed the Induction Study and achieved either Endoscopy/Bleeding/Stool Frequency (EBS) remission or Mayo Clinic Score (MCS) response at Week 10 were re-randomized at Week 11 into the Maintenance Study to receive filgotinib 200 mg and PTM filgotinib 100 mg for an additional 47 weeks (up to Week 58).
干预措施: PTM filgotinib (Drug)
Maintenance Study: Placebo From Induction Filgotinib 200 mg
Participants in the Filgotinib 200 mg arm who completed the Induction Study and achieved either EBS remission or MCS response at Week 10 were re-randomized at Week 11 into the Maintenance Study to receive PTM filgotinib orally once daily for an additional 47 weeks (up to Week 58).
干预措施: PTM filgotinib (Drug)
Maintenance Study: Filgotinib 100 mg From Induction Filgotinib 100 mg
Participants in the Filgotinib 100 mg arm who completed the Induction Study and achieved either EBS remission or MCS response at Week 10 were re-randomized at Week 11 into the Maintenance Study to receive filgotinib 100 mg and PTM filgotinib 200 mg for an additional 47 weeks (up to Week 58).
干预措施: Filgotinib (Drug)
Maintenance Study: Filgotinib 100 mg From Induction Filgotinib 100 mg
Participants in the Filgotinib 100 mg arm who completed the Induction Study and achieved either EBS remission or MCS response at Week 10 were re-randomized at Week 11 into the Maintenance Study to receive filgotinib 100 mg and PTM filgotinib 200 mg for an additional 47 weeks (up to Week 58).
干预措施: PTM filgotinib (Drug)
Maintenance Study: Placebo From Induction Filgotinib 100 mg
Participants in the Filgotinib 100 mg arm who completed the Induction Study and achieved either EBS remission or MCS response at Week 10 were rerandomized at Week 11 into the Maintenance Study to receive PTM filgotinib orally once daily for an additional 47 weeks (up to Week 58).
干预措施: PTM filgotinib (Drug)
Maintenance Study: Placebo From Induction Placebo
Participants in the Placebo arm who completed the Induction Study and achieved either EBS remission or MCS response at Week 10 were re-randomized at Week 11 into the Maintenance Study to receive PTM filgotinib for an additional 47 weeks (up to Week 58).
干预措施: PTM filgotinib (Drug)
结局指标
主要结局
Maintenance Study: Percentage of Participants Who Achieved EBS Remission at Week 58
时间窗: Week 58
EBS remission was defined as an endoscopic subscore of 0 or 1; rectal bleeding subscore of 0; and at least a 1-point decrease in stool frequency from baseline to achieve a subscore of 0 or 1. Endoscopic subscore range: 0 to 3, where 0 = normal or inactive disease and 3 = severe disease (spontaneous bleeding, ulceration); rectal bleeding subscore range: 0 to 3, where 0 = no blood seen and 3 = blood alone passes; stool frequency subscore range: 0 to 3, where 0 = normal number of stools and 3 = at least 5 stools more than normal. Total score for EBS ranged from 0 to 9 (sum of all subscores), with higher scores indicating more severe disease.
Induction Study: Percentage of Participants Who Achieved Endoscopy/Bleeding/Stool Frequency (EBS) Remission at Week 10
时间窗: Week 10
EBS remission was defined as an endoscopic subscore of 0 or 1; rectal bleeding subscore of 0; and at least a 1-point decrease in stool frequency from baseline to achieve a subscore of 0 or 1. Endoscopic subscore range: 0 to 3, where 0 = normal or inactive disease and 3 = severe disease (spontaneous bleeding, ulceration); rectal bleeding subscore range: 0 to 3, where 0 = no blood seen and 3 = blood alone passes; stool frequency subscore range: 0 to 3, where 0 = normal number of stools and 3 = at least 5 stools more than normal. Total score for EBS ranged from 0 to 9 (sum of all subscores), with higher scores indicating more severe disease.
次要结局
- Induction Study: Percentage of Participants Who Achieved an Endoscopic Subscore of 0 at Week 10(Week 10)
- Maintenance Study: Percentage of Participants Who Achieved Endoscopic Subscore of 0 at Weeks 58(Week 58)
- Induction Study: Percentage of Participants Who Achieved Geboes Histologic Remission at Week 10(Week 10)
- Induction Study: PK Parameter: AUCtau of Filgotinib and Its Metabolite GS-82984(Predose and at 0.5, 1, 2, 3, 4 and 6 hours postdose at a single visit between Week 2 and Week 10)
- Induction Study: Pharmacokinetic (PK) Parameter: Cmax of Filgotinib and Its Metabolite GS-829845(Predose and at 0.5, 1, 2, 3, 4 and 6 hours postdose at a single visit between Week 2 and Week 10)
- Induction Study: PK Parameter: Tmax of Filgotinib and Its Metabolite GS-829845(Predose and at 0.5, 1, 2, 3, 4 and 6 hours postdose at a single visit between Week 2 and Week 10)
- Induction Study: PK Parameter: Ctau of Filgotinib and Its Metabolite GS-82984(Predose and at 0.5, 1, 2, 3, 4 and 6 hours postdose at a single visit between Week 2 and Week 10)
- Induction Study: Percentage of Participants Who Achieved MCS Remission at Week 10(Week 10)
- Maintenance Study: Percentage of Participants Who Achieved 6-Month Corticosteroid-Free EBS Remission at Week 58(Week 58)
- Maintenance Study: Percentage of Participants Who Achieved MCS Remission (Alternative Definition) at Week 58(Week 58)
- Induction Study: Percentage of Participants Who Achieved MCS Remission (Alternative Definition) at Week 10(Week 10)
- Maintenance Study: Percentage of Participants Who Achieved MCS Remission at Week 58(Week 58)
- Maintenance Study: Percentage of Participants Who Achieved Sustained EBS Remission at Week 58(Week 58)
- Maintenance Study: Plasma Concentration of Filgotinib and Its Metabolite GS-829845(Week 26 (any Time) and Week 58 (predose))
- Induction Study: PK Parameter: AUClast of Filgotinib and Its Metabolite GS-82984(Predose and at 0.5, 1, 2, 3, 4 and 6 hours postdose at a single visit between Week 2 and Week 10)
- Maintenance Study: Percentage of Participants Who Achieved Geboes Histologic Remission at Week 58(Week 58)