A Phase 2, Multicenter, Randomized, Parallel-Arm, Placebo-Controlled Study of LY3074828 in Subjects With Active Crohn's Disease (SERENITY)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 191
- 试验地点
- 108
- 主要终点
- Percentage of Participants Achieving Endoscopic Response at Week 12
研究概览
简要总结
The purpose of this study is to evaluate the safety and effectiveness of the study drug Mirikizumab in participants with active Crohn's Disease.
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
- •Active Crohn's Disease (CD) as determined by the SES-CD, and participant reported stool frequency and abdominal pain.
- •Inadequate response or failure to tolerate at least one of the following: aminosalicylates; budesonide; systemic corticosteroids; immunosuppressants (eg, azathioprine, 6-mercaptopurine, or methotrexate); or prior exposure to biologics for the treatment of CD.
排除标准
- •Have complications of CD such as strictures, stenoses, or any other manifestation for which surgery might be indicated, or that could confound the evaluation of efficacy.
- •Diagnosis of conditions affecting the digestive tract, such as ulcerative colitis, indeterminate colitis, fistulizing disease, abdominal or perianal abscess, adenomatous colonic polyps not excised, colonic mucosal dysplasia, and short bowel syndrome.
- •Have had any kind of bowel resection, diversion, or placement of a stoma within 6 months or any other intra-abdominal surgery within 3 months prior to screening.
- •Are unsuitable for inclusion in the study in the opinion of the investigator or sponsor for any reason that may compromise the subject's safety or confound data interpretation.
研究组 & 干预措施
Mirikizumab
Period 1 (Weeks 0 -12): 200 Milligram (mg), 600 mg, and 1000 mg mirikizumab administered intravenously (IV) every 4 Weeks (Q4W).
Period 2 (Weeks 12 - 52): 200 mg, 600 mg, and 1000 mg mirikizumab administered IV Q4W; 300 mg mirikizumab administered subcutaneously (SC) Q4W; 1000 mg mirikizumab administered IV Q4W for non-improvers in period 1; and 1000 mg mirikizumab administered IV Q4W for participants on placebo during period 1.
Period 3 (Weeks 52 - 208): 300 mg mirikizumab administered SC Q4W.
干预措施: Mirikizumab (Drug)
Placebo
Period 1 (Weeks 0 -12): Participants received placebo administered intravenously (IV) Q4W.
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage of Participants Achieving Endoscopic Response at Week 12
时间窗: Week 12
Endoscopic response defined as ≥ 50% reduction from baseline in Simple Endoscopic Score for Crohn's Disease (SES-CD) at Week 12. The SES-CD evaluates 4 endoscopic variables: presence and size of ulcers, proportion of surface covered by ulcers, proportion of surface affected by disease, and presence and severity of stenosis. The total SES-CD calculated as sum of 4 variables for 5 bowel segments: (ileum;right,transverse,and left colon;and rectum): presence and size of ulcers (none = score 0; diameter 0.1-0.5 cm = score 1; 0.5-2 cm = score 2; \>2 cm = score 3); extent of ulcerated surface (none = 0; \<10% = 1;10-30% = 2;\>30% = 3);extent of affected surface (none = 0; \<50% = 1;50-75% = 2;\>75% =3); and presence and type of narrowings (none=0; single, can be passed=1; multiple,can be passed=2; cannot be passed=3). Total SES-CD scores range from 0 to 56, with higher scores indicating more severe disease.
次要结局
- Percentage of Participants Achieving Endoscopic Remission at Week 12(Week 12)
- Percentage of Participants Achieving Patient Reported Outcome Remission at Week 12(Week 12)
- Mean Change From Baseline on the Patient Global Rating - Severity (PGRS) Crohn's Disease Score at Week 12(Baseline, Week 12)
- Mean of Patient Global Rating - Change (PGRC) Crohn's Disease Score at Week 12(Baseline, Week 12)
- Mean Change From Baseline on the Inflammatory Bowel Disease Questionnaire (IBDQ) Score at Week 12(Baseline, Week 12)
- Mean Change From Baseline on the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Week 12(Baseline, Week 12)
- Mean Change From Baseline on the 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores at Week 12(Baseline, Week 12)
- Population Pharmacokinetics (PopPK): Mean Population Clearance of Mirikizumab(Week 0, 4, 8: Predose, end of infusion; Week 2; 4; 6; 8, 11-12; 12-13; 16; 20; 24; 28; 36; 44; 52; 60; 68; 76; 84; 92; 104; 108; 112; 120; 128; 136; 144; 156; 164; 172; 180; 188; 196 and 208 weeks post infusion)
- Population Pharmacokinetics (PopPK): Mean Population Volume of Distribution of Mirikizumab(Week 0, 4, 8: Predose, end of infusion; Week 2; 4; 6; 8, 11-12; 12-13; 16; 20; 24; 28; 36; 44; 52; 60; 68; 76; 84; 92; 104; 108; 112; 120; 128; 136; 144; 156; 164; 172; 180; 188; 196 and 208 weeks post infusion)