Combined Phase 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 Crohn's Disease
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Galapagos NV
- 入组人数
- 1,372
- 试验地点
- 512
- 主要终点
- Induction Study: Percentage of Participants Who Achieved Clinical Remission by Crohn's Disease Activity Index (CDAI) at Week 10
研究概览
简要总结
The primary objectives of this study are to evaluate the safety and efficacy of filgotinib during induction and maintenance treatment of moderately to severely active Crohn's disease (CD) in participants who are biologic-naive and biologic-experienced.
Participants who complete the study, or do not meet protocol response or remission criteria at Week 10 will have the option to enter a separate long-term extension (LTE) study (Study GS-US-419-3896).
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
- •Documented diagnosis of CD with a minimum disease duration of 3 months with involvement of the ileum and/or colon at a minimum, as determined by histopathology and endoscopic assessment
- •Moderately to severely active CD
- •Cohort A (Biologic Naïve): 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 and immunomodulators
- •Cohort A (Biologic Experienced): 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) or discontinuation of use of at least one of the following agents for reasons other than inadequate clinical response, loss of response or intolerance: tumor necrosis factor alpha (TNFa) antagonists, vedolizumab, and ustekinumab
- •Cohort B (Biologic Experienced): 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): TNFa antagonists, vedolizumab, and ustekinumab
排除标准
- •Current complications of CD such as symptomatic strictures, severe rectal/anal stenosis, fistulae other than perianal fistulae, short bowel syndrome, etc.
- •Presence of ulcerative colitis, indeterminate colitis, ischemic colitis, fulminant colitis, or toxic mega-colon
- •Active tuberculosis (TB) or history of latent TB that has not been treated
- •Use of any prohibited concomitant medications as described in the study protocol
- •NOTE: Other protocol defined Inclusion/ Exclusion criteria may apply.
研究组 & 干预措施
Cohort A: Filgotinib 200 (mg) (Induction Study)
Biologic naïve and biologic experienced participants received filgotinib 200 milligram (mg) with placebo-to-match (PTM) filgotinib 100 mg tablet orally once daily, for a period of 10 weeks.
干预措施: Filgotinib (Drug)
Cohort A: Filgotinib 200 (mg) (Induction Study)
Biologic naïve and biologic experienced participants received filgotinib 200 milligram (mg) with placebo-to-match (PTM) filgotinib 100 mg tablet orally once daily, for a period of 10 weeks.
干预措施: Placebo (Other)
Cohort A: Filgotinib 100 mg (Induction Study)
Biologic naïve and biologic experienced participants received filgotinib 100 mg with PTM filgotinib 200 mg tablet orally once daily, for a period of 10 weeks.
干预措施: Filgotinib (Drug)
Cohort A: Filgotinib 100 mg (Induction Study)
Biologic naïve and biologic experienced participants received filgotinib 100 mg with PTM filgotinib 200 mg tablet orally once daily, for a period of 10 weeks.
干预措施: Placebo (Other)
Cohort A: Placebo (Induction Study)
Biologic naïve and biologic experienced participants received PTM filgotinib 200 mg and PTM filgotinib 100 mg tablet orally once daily, for a period of 10 weeks.
干预措施: Filgotinib (Drug)
Cohort A: Placebo (Induction Study)
Biologic naïve and biologic experienced participants received PTM filgotinib 200 mg and PTM filgotinib 100 mg tablet orally once daily, for a period of 10 weeks.
干预措施: Placebo (Other)
Cohort B: Filgotinib 200 mg (Induction Study)
Biologic experienced participants received filgotinib 200 mg with PTM filgotinib 100 mg tablet orally once daily, for a period of 10 weeks.
干预措施: Filgotinib (Drug)
Cohort B: Filgotinib 200 mg (Induction Study)
Biologic experienced participants received filgotinib 200 mg with PTM filgotinib 100 mg tablet orally once daily, for a period of 10 weeks.
干预措施: Placebo (Other)
Cohort B: Filgotinib 100 mg (Induction Study)
Biologic experienced participants received filgotinib 100 mg with PTM filgotinib 200 mg tablet orally once daily, for a period of 10 weeks.
干预措施: Filgotinib (Drug)
Cohort B: Filgotinib 100 mg (Induction Study)
Biologic experienced participants received filgotinib 100 mg with PTM filgotinib 200 mg tablet orally once daily, for a period of 10 weeks.
干预措施: Placebo (Other)
Cohort B: Placebo (Induction Study)
Biologic experienced participants received PTM filgotinib 200 mg with PTM filgotinib 100 mg tablet orally once daily, for a period of 10 weeks.
干预措施: Filgotinib (Drug)
Cohort B: Placebo (Induction Study)
Biologic experienced participants received PTM filgotinib 200 mg with PTM filgotinib 100 mg tablet orally once daily, for a period of 10 weeks.
干预措施: Placebo (Other)
Filgotinib 200 mg to Filgotinib 200 mg (Maintenance Study)
Participants who received filgotinib 200 mg in induction study and who achieved either clinical remission by PRO2 or endoscopic response at Week 10 were re-randomized to the maintenance study and received filgotinib 200 mg and PTM filgotinib 100 mg tablet orally once daily, up to Week 58.
干预措施: Filgotinib (Drug)
Filgotinib 200 mg to Placebo (Maintenance Study)
Participants who received filgotinib 200 mg in induction study and who achieved either clinical remission by PRO2 or endoscopic response at Week 10 were re-randomized to the maintenance study and received PTM filgotinib 100 mg and PTM filgotinib 200 mg tablet orally once daily, up to Week 58.
干预措施: Filgotinib (Drug)
Filgotinib 200 mg to Placebo (Maintenance Study)
Participants who received filgotinib 200 mg in induction study and who achieved either clinical remission by PRO2 or endoscopic response at Week 10 were re-randomized to the maintenance study and received PTM filgotinib 100 mg and PTM filgotinib 200 mg tablet orally once daily, up to Week 58.
干预措施: Placebo (Other)
Filgotinib 100 mg to Filgotinib 100 mg (Maintenance Study)
Participants who received filgotinib 100 mg in induction study and who achieved either clinical remission by PRO2 or endoscopic response at Week 10 were re-randomized to the maintenance study and received filgotinib 100 mg and PTM filgotinib 200 mg tablet orally once daily, up to Week 58.
干预措施: Filgotinib (Drug)
Filgotinib 100 mg to Placebo (Maintenance Study)
Participants who received filgotinib 100 mg in induction study and who achieved either clinical remission by PRO2 or endoscopic response at Week 10 were re-randomized to the maintenance study and received PTM filgotinib 200 mg and PTM filgotinib 100 mg tablet orally once daily, up to Week 58.
干预措施: Filgotinib (Drug)
Filgotinib 100 mg to Placebo (Maintenance Study)
Participants who received filgotinib 100 mg in induction study and who achieved either clinical remission by PRO2 or endoscopic response at Week 10 were re-randomized to the maintenance study and received PTM filgotinib 200 mg and PTM filgotinib 100 mg tablet orally once daily, up to Week 58.
干预措施: Placebo (Other)
Placebo to Placebo (Maintenance Study)
Participants who received placebo in induction study and who achieved either clinical remission by PRO2 or endoscopic response at Week 10 were re-randomized to the maintenance study and received PTM filgotinib 100 mg and PTM filgotinib 200 mg tablet orally once daily, up to Week 58.
干预措施: Placebo (Other)
结局指标
主要结局
Induction Study: Percentage of Participants Who Achieved Clinical Remission by Crohn's Disease Activity Index (CDAI) at Week 10
时间窗: Week 10
The CDAI system was a composite index of 8 disease activity variables: severity of abdominal pain, general well-being, very soft/liquid stool frequency, extra-intestinal symptoms, need for antidiarrheal drugs, presence of an abdominal mass, body weight and hematocrit. Participants reported information regarding symptoms using a diary. The subscores of abdominal pain (0-3), general well-being (0-4), and number of very soft or liquid stools were then summed over the 7 days prior to each visit. Additionally, the remaining predictors were also noted and weighted to create the total CDAI score which ranged from 0-600 with a higher score indicating a worse outcome. Clinical remission was defined as a CDAI of \< 150 points.
Induction Study: Percentage of Participants Who Achieved Endoscopic Response at Week 10
时间窗: Week 10
The Simple Endoscopic Score for Crohn's Disease (SES-CD) assessed the degree of inflammation on the basis of 4 components: size of ulcers, ulcerated surface, affected surface, and presence of narrowing. Each of these components was scored on a scale of 0 to 3 (worst). In the SES-CD, each of these 4 components are assessed in the five segments: ileum, right colon, transverse colon, left colon, and rectum. The SES-CD was the sum of the individual scores of each of the components across the five segments. The range of SES-CD scores was 0 - 12 for each segment, and 0 - 60 for the overall SES-CD score, with larger scores indicating greater severity of disease. Endoscopic response was defined as ≥ 50% reduction from baseline in total SES-CD score.
Maintenance Study: Percentage of Participants Who Achieved Clinical Remission by CDAI at Week 58
时间窗: Week 58
The CDAI system was a composite index of 8 disease activity variables: severity of abdominal pain, general well-being, very soft/liquid stool frequency, extra-intestinal symptoms, need for antidiarrheal drugs, presence of an abdominal mass, body weight and hematocrit. Participants reported information regarding symptoms using a diary. The sub scores of abdominal pain (0-3), general well-being (0-4), and number of very soft or liquid stools were then summed over the 7 days prior to each visit. Additionally, the remaining predictors were also noted and weighted to create the total CDAI score which ranged from 0-600 with a higher score indicating a worse outcome. Clinical remission was defined as a CDAI of \< 150 points.
Maintenance Study: Percentage of Participants Who Achieved Endoscopic Response at Week 58
时间窗: Week 58
The SES-CD assessed the degree of inflammation on the basis of 4 components: size of ulcers, ulcerated surface, affected surface, and presence of narrowing. Each of these components was scored on a scale of 0 to 3 (worst). In the SES-CD, each of these 4 components are assessed in the five segments: ileum, right colon, transverse colon, left colon, and rectum. The SES-CD was the sum of the individual scores of each of the components across the five segments. The range of SES-CD scores was 0 - 12 for each segment, and 0 - 60 for the overall SES-CD score, with larger scores indicating greater severity of disease. Endoscopic response was defined as ≥ 50% reduction from baseline in total SES-CD score.
次要结局
- Maintenance Study: Percentage of Participants Who Achieved Sustained Clinical Remission by PRO2 at Both Weeks 10 and 58(Weeks 10 and 58)
- Induction Study: Percentage of Participants Who Achieved Clinical Remission by PRO2 at Week 10(Week 10)
- Induction Study: Percentage of Participants Who Achieved Clinical Response by CDAI at Week 10(Week 10)
- Maintenance Study: Percentage of Participants Who Achieved Clinical Remission by PRO2 at Week 58(Week 58)
- Maintenance Study: Percentage of Participants Who Achieved Clinical Response by CDAI at Week 58(Week 58)
- Maintenance Study: Percentage of Participants Who Achieved Sustained Clinical Remission by CDAI at Both Weeks 10 and 58(Weeks 10 and 58)
- Maintenance Study: Percentage of Participants Who Achieved 6 Month Corticosteroid-Free Remission by CDAI at Week 58(Week 58)
- Maintenance Study: Percentage of Participants Who Achieved 6 Month Corticosteroid-Free Remission by PRO2 at Week 58(Week 58)
- Induction Study:Pharmacokinetic Plasma Concentrations of Filgotinib at Week 4(Week 4: 0.5, 1, 2, and 3 hours (hrs) post dose)
- Induction Study: Pharmacokinetic Plasma Concentrations of Filgotinib at Week 10(Week 10: Predose)
- Maintenance Study: Pharmacokinetic Plasma Concentrations of Filgotinib at Week 26(Week 26: At any timepoint)
- Induction Study: Pharmacokinetic Plasma Concentrations of Filgotinib's Metabolite GS-829845 at Week 10(Week 10: Predose)
- Maintenance Study: Pharmacokinetic Plasma Concentrations of Filgotinib at Week 58(Week 58: Pre-dose)
- Induction Study: Pharmacokinetic Plasma Concentrations of Filgotinib's Metabolite GS-829845 at Week 4(Week 4: 0.5, 1, 2, and 3 hrs post dose)
- Maintenance Study: Pharmacokinetic Plasma Concentrations of Filgotinib's Metabolite GS-829845 at Week 26(Week 26: At any timepoint)
- Maintenance Study: Pharmacokinetic Plasma Concentrations of Filgotinib's Metabolite GS-829845 at Week 58(Week 58: Pre-dose)