A Phase 2, Multicenter, Randomized, Double-Blind, Parallel, Placebo-Controlled Study of LY3074828 in Subjects With Moderate to Severe Ulcerative Colitis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 249
- 试验地点
- 14
- 主要终点
- Induction Period: Percentage of Participants With Clinical Remission at Week 12
研究概览
简要总结
The main purpose of this study is to test the hypothesis that treatment with mirikizumab is superior to placebo in providing clinical benefit to participants with moderate to severe ulcerative colitis (UC). This study will also investigate how the body processes the drug.
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
- •Have moderate to severe active UC as defined by a Mayo score of 6 to 12 with an endoscopic subscore ≥2 within 14 days before the first dose of study treatment (note: a partial Mayo score of at least 4 and other eligibility criteria must have been met before endoscopy is performed as a study procedure)
- •Have evidence of UC extending proximal to the rectum (≥15 centimeters [cm] of involved colon)
- •Up-to-date colorectal cancer surveillance (performed according to local standard), for subjects with family history of colorectal cancer, personal history of increased colorectal cancer risk, age >50 years, or other known risk factor
- •Participants must either: be naive to biologic therapy (eg, tumor necrosis factor [TNF] antagonists or vedolizumab) and have at least 1 of the following: inadequate response or failure to tolerate current treatment with oral or intravenous corticosteroids or immunomodulators (6-mercaptopurine or azathioprine) or history of corticosteroid dependence (an inability to successfully taper corticosteroids without return of UC) OR have received treatment with 1 or more biologic agents (eg, TNF antagonists or vedolizumab) at doses approved for the treatment of UC with documented history of failure to respond to or tolerate such treatment
排除标准
- •Have been diagnosed with indeterminate colitis, proctitis (distal disease involving the rectum only; less than 15 cm from the anal verge) or Crohn's Disease
- •Have had surgery for treatment of UC or are likely to require surgery for UC during the study
- •Have received any of the following for treatment of UC: cyclosporine or thalidomide within 30 days of screening, corticosteroid enemas, corticosteroid suppositories, or topical treatment with 5-aminosalicyclic acid within 30 days of screening
研究组 & 干预措施
Placebo SC Q4W (Maintenance)
Induction placebo responders: Placebo administered subcutaneously (SC) Q4W during the maintenance period.
干预措施: Placebo (Drug)
Placebo IV Q4W (Induction)
Placebo administered every 4 weeks (Q4W) intravenously (IV) during the induction period.
干预措施: Placebo (Drug)
200mg Mirikizumab SC Q4W Extension Open-Label
Extension Induction responders: 200 mg mirikizumab administered subcutaneously (SC) once every 4 weeks (Q4W) during the Extension Open-Label
干预措施: Mirikizumab (Drug)
200 mg Mirikizumab IV Q4W (induction)
200 mg mirikizumab administered every 4 weeks (Q4W) intravenously (IV) during the induction period.
Participants who do not have a clinical response may choose to participate in the unblinded study extension period.
干预措施: Mirikizumab (Drug)
200 mg Mirikizumab SC Q12W (Maintenance)
Induction mirikizumab responders were re-randomized: 200 mg mirikizumab administered subcutaneously (SC) once every 12 weeks (Q12W) during the maintenance period.
干预措施: Mirikizumab (Drug)
1000mg Mirikizumab IV Q4W Extension Open-Label
Induction non-responders: 1000 mg mirikizumab administered intravenously (IV) once every 4 weeks (Q4W) during the Extension Open-Label.
干预措施: Mirikizumab (Drug)
600mg Mirikizumab IV Q4W Extension Open-Label
Induction non-responders: 600 mg mirikizumab administered intravenously (IV) once every 4 weeks (Q4W) during the Extension Open-Label.
干预措施: Mirikizumab (Drug)
200 mg Mirikizumab SC Q4W (Maintenance)
Induction mirikizumab responders were re-randomized: 200 mg mirikizumab administered subcutaneously (SC) Q4W during the maintenance period.
干预措施: Mirikizumab (Drug)
600 mg Mirikizumab IV Q4W (Induction)
600 mg mirikizumab administered every 4 weeks (Q4W) intravenously (IV) during the induction period.
Participants who do not have a clinical response may choose to participate in the unblinded study extension period.
干预措施: Mirikizumab (Drug)
50 mg Mirikizumab IV Q4W (Induction)
50 mg mirikizumab administered every 4 weeks (Q4W) intravenously (IV) during the induction period. Participants who do not have a clinical response may choose to participate in the unblinded study extension period.
干预措施: Mirikizumab (Drug)
结局指标
主要结局
Induction Period: Percentage of Participants With Clinical Remission at Week 12
时间窗: Week 12
Clinical remission at week 12 is a defined as achieving a 9-pt Mayo subscore for rectal bleeding=0, stool frequency=0 or 1 with ≥ 1 point decrease from baseline, and endoscopy=0 or 1, excluding Physician's Global Assessment (PGA). * Stool Frequency Subscore, based on the participant's diary and scored from 0 (normal number of stools) to 3 (5 or more stools than normal); * Rectal Bleeding Subscore, based on the participant's diary and scored from 0 (no blood) to 3 (blood only passed); * Endoscopy Subscore, based on colonoscopy or sigmoidoscopy and scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration); * Physician's Global Assessment subscore, based on the physician's overall assessment, and scored from 0 (normal) to 3 (severe disease). The total score ranges from 0 to 9 points, with higher scores representing more severe disease.
次要结局
- Induction Period: Change From Baseline to Week 12 in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score(Baseline, Week 12)
- Induction Period: Percentage of Participants With Endoscopic Improvement at Week 12(Week 12)
- Maintenance Period: Percentage of Participants With Endoscopic Improvement at Week 52(Week 52)
- Induction Period: Percentage of Participants With Clinical Response at Week 12(Week 12)
- Induction Period: Percentage of Participants With Endoscopic Remission at Week 12(Week 12)
- Maintenance Period: Percentage of Participants With Endoscopic Remission at Week 52(Week 52)
- Induction Period: Change From Baseline to Week 12 in 36-Item Short Form Health Survey (SF-36)(Baseline, Week 12)
- Induction Period: Change From Baseline to Week 12 in Patient's Global Impressions of Severity (PGI-S) Score(Baseline, Week 12)
- Induction Period: Patient's Global Impressions of Improvement (PGI-I) Score at Week 12(Week 12)
- Pharmacokinetics (PK): Area Under the Concentration-Time Curve During Dosing Interval at Steady State (AUCss, Tau) of Mirikizumab(Induction Period: Day (D) 1, D15 ± 2d, D29 ± 2d, D43 ± 2d, D57 ± 2d, D78-85; Maintenance Period: D85-92,D113± 7d,D141± 7d,D169± 7d,D225 ±7d,D281 ±7d,D337 ±7d,D393± 7d,D448± 7d,D504± 7d,D560± 7d,D616± 7d,D672± 7d,D728± 7d,D784± 7d,D840± 7d)
- Induction Period: Percentage of Participants With Symptomatic Remission at Week 12(Week 12)
- Maintenance Period: Percentage of Participants With Symptomatic Remission at Week 52(Week 52)