A Phase 2b/3 Randomized, Double-blind, Placebo-Controlled, Parallel Group, Multicenter Protocol to Evaluate the Efficacy and Safety of Icotrokinra in Participants With Moderately to Severely Active Crohn's Disease
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 1,092
- 试验地点
- 373
- 主要终点
- Induction Study 1: Number of Participants with Clinical Response at Week 12
研究概览
简要总结
The purpose of this study is to evaluate how-well icotrokinra works (clinical efficacy) and how safe it is (safety) in participants with moderately to severely active Crohn's disease (CD; a long-term condition causing severe inflammation of the intestinal tract).
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of CD established at least 12 weeks before screening including both endoscopic evidence and a histopathology report consistent with a diagnosis of CD
- •Moderately to severely active CD based on CDAI criteria, defined as baseline (Week I-0) CDAI score >=220 but <=450 and either mean daily SF count >=4, or mean daily AP score >=2
- •Moderately to severely active CD based on SES-CD criteria assessed by baseline (Week I-0) endoscopic evidence of active ileal and/or colonic CD as assessed during central review of the screening video ileocolonoscopy defined as a SES-CD >= 6 for participants with colonic or ileocolonic disease, and SES-CD >= 4 for participants with isolated ileal disease, based on the presence of ulceration in any 1 of the 5 ileocolonic segments
- •A female participant of childbearing potential must have a negative highly sensitive serum pregnancy test (beta-hCG) at screening and a negative urine pregnancy test at Week I-0 prior to administration of study intervention and agree to further pregnancy tests
- •Demonstrated an inadequate response to, or failure to tolerate conventional therapy but naïve to advanced therapies (advanced drug therapy [ADT]-naïve) or inadequate response to (that is, primary or secondary nonresponse) or failure to tolerate advanced therapy defined as biologics and/or advanced oral agents for the treatment of CD- (ADT-inadequate responder [IR]) as defined in the protocol
排除标准
- •Has complications of CD, such as symptomatic strictures or stenoses, short gut syndrome, or any other manifestation, that may require surgery while enrolled in the study and/or could impair the use of instruments (such as CDAI) to assess response to study intervention
- •Presence of a stoma or ostomy
- •Participants with presence of active fistulas may be included if there is no surgery needed
- •Colonic resection within 24 weeks before baseline or any other major surgery performed within 12 weeks before baseline
- •Presence on screening colonoscopy of adenomatous colon polyps outside of an area of known colitis not removed before randomization
研究组 & 干预措施
Induction Study 2: Placebo
Participants will receive matching placebo for up to Week 12. Subsequent study treatment will be determined by the participant's response status at Week 12.
干预措施: Placebo (Drug)
Maintenance Study: Icotrokinra Dose 2
Participants who were receiving icotrokinra in either induction studies 1 or 2 and were in response at Week 12 of the induction study will be randomized to receive icotrokinra maintenance dose 2. Participants who were non-responders at Week 12 of the induction studies will also receive icotrokinra maintenance dose 2 but will not be randomized. After completion of the Maintenance Study through Week 40, eligible participants can participate in LTE.
干预措施: Icotrokinra (Drug)
Maintenance Study: Placebo
Participants who were receiving icotrokinra in either induction studies 1 or 2 and were in response at Week 12 will be randomized to receive placebo. Participants receiving placebo in induction studies 1 or 2 and in response at Week 12 of the induction study will continue to receive placebo during maintenance on non-randomized basis. Placebo non-responders from induction study will receive icotrokinra maintenance dose 2 on a non-randomized basis and will be assessed for response at Week 12.
Participants receiving placebo and meeting criteria for loss of response during the Maintenance Study will be eligible for a single blinded dose adjustment to icotrokinra dose 2. After completion of the Maintenance Study through Week 40, eligible participants can participate in LTE.
干预措施: Placebo (Drug)
Induction Study 1: Icotrokinra Dose 1
Participants will receive Icotrokinra dose 1 in Induction Study 1 up to Week 12. Subsequent treatment will be determined by the participant's response status at Week 12.
干预措施: Icotrokinra (Drug)
Maintenance Study: Placebo
Participants who were receiving icotrokinra in either induction studies 1 or 2 and were in response at Week 12 will be randomized to receive placebo. Participants receiving placebo in induction studies 1 or 2 and in response at Week 12 of the induction study will continue to receive placebo during maintenance on non-randomized basis. Placebo non-responders from induction study will receive icotrokinra maintenance dose 2 on a non-randomized basis and will be assessed for response at Week 12.
Participants receiving placebo and meeting criteria for loss of response during the Maintenance Study will be eligible for a single blinded dose adjustment to icotrokinra dose 2. After completion of the Maintenance Study through Week 40, eligible participants can participate in LTE.
干预措施: Icotrokinra (Drug)
Induction Study 1: Placebo
Participants will receive matching placebo in Induction Study 1 up to Week 12. Subsequent treatment will be determined by the participant's response status at Week 12.
干预措施: Placebo (Drug)
Induction Study 2: Icotrokinra
Participants will receive Icotrokinra at the dose regimen determined in Induction Study 1 up to Week 12. Subsequent study treatment will be determined by the participant's response status at Week 12.
干预措施: Icotrokinra (Drug)
Maintenance Study: Icotrokinra Dose 1
Participants who were receiving icotrokinra in either induction studies 1 or 2 and were in response at Week 12 of the induction study will be randomized to receive icotrokinra maintenance dose 1. Participants receiving Icotrokinra Dose 1 and meeting criteria for loss of response during the Maintenance Study will be eligibile for a single blinded dose adjustment to Icotrokinra Dose 2. After completion of the Maintenance Study through Week 40, eligible participants can participate in long-term extension (LTE).
干预措施: Icotrokinra (Drug)
Induction Study 1: Icotrokinra Dose 2
Participants will receive Icotrokinra dose 2 in Induction Study 1 up to Week 12. Subsequent treatment will be determined by the participant's response status at Week 12.
干预措施: Icotrokinra (Drug)
结局指标
主要结局
Induction Study 1: Number of Participants with Clinical Response at Week 12
时间窗: At Week 12
Clinical response is defined as a greater than or equal to (\>=) 100-point reduction from baseline in Crohn's Disease Activity Index (CDAI) score. CDAI scores range from 0 to approximately 600. Higher score indicates higher disease activity.
Induction Study 2: Number of Participants with Clinical Remission at Week 12 (Co-Primary Endpoint)
时间窗: At Week 12
Clinical remission is defined as CDAI score less than (\<) 150. CDAI scores range from 0 to approximately 600. Higher score indicates higher disease activity.
Induction Study 2: Number of Participants with Endoscopic Response at Week 12 (Co-Primary Endpoint)
时间窗: At Week 12
Endoscopic response is defined as greater than (\>) 50% improvement from baseline in Simple Endoscopic Score for Crohn's Disease (SES-CD) score or a decrease of at least 2 points in participants with a baseline score of 4 and isolated ileal disease. SES-CD score can range from 0 to 56. Higher scores indicating more severe disease.
Maintenance Study: Number of Participants with Clinical Remission at Week 40 (Co-Primary Endpoint)
时间窗: At Week 40
Clinical remission is defined as CDAI score \< 150. CDAI scores range from 0 to approximately 600. Higher score indicates higher disease activity.
Maintenance Study: Number of Participants with Endoscopic Response at Week 40 (Co-Primary Endpoint)
时间窗: At Week 40
Endoscopic response is defined as \> 50% improvement from baseline in SES-CD score or a decrease of at least 2 points in participants with a baseline score of 4 and isolated ileal disease. SES-CD score can range from 0 to 56. Higher scores indicating more severe disease.
Induction Study 1: Number of Participants with Clinical Response at Week 12
时间窗: At Week 12
Clinical response is defined as a greater than or equal to (\>=) 100-point reduction from baseline in Crohn's Disease Activity Index (CDAI) score. CDAI scores range from 0 to approximately 600. Higher score indicates higher disease activity.
Induction Study 2: Number of Participants with Clinical Remission at Week 12 (Co-Primary Endpoint)
时间窗: At Week 12
Clinical remission is defined as CDAI score less than (\<) 150. CDAI scores range from 0 to approximately 600. Higher score indicates higher disease activity.
Induction Study 2: Number of Participants with Endoscopic Response at Week 12 (Co-Primary Endpoint)
时间窗: At Week 12
Endoscopic response is defined as greater than (\>) 50% improvement from baseline in Simple Endoscopic Score for Crohn's Disease (SES-CD) score or a decrease of at least 2 points in participants with a baseline score of 4 and isolated ileal disease. SES-CD score can range from 0 to 56. Higher scores indicating more severe disease.
Maintenance Study: Number of Participants with Clinical Remission at Week 40 (Co-Primary Endpoint)
时间窗: At Week 40
Clinical remission is defined as CDAI score \< 150. CDAI scores range from 0 to approximately 600. Higher score indicates higher disease activity.
Maintenance Study: Number of Participants with Endoscopic Response at Week 40 (Co-Primary Endpoint)
时间窗: At Week 40
Endoscopic response is defined as \> 50% improvement from baseline in SES-CD score or a decrease of at least 2 points in participants with a baseline score of 4 and isolated ileal disease. SES-CD score can range from 0 to 56. Higher scores indicating more severe disease.
次要结局
- Induction Study 1: Number of Participants with Clinical Remission at Week 12(At Week 12)
- Induction Study 1: Number of Participants with Endoscopic Response at Week 12(At Week 12)
- Induction Study 1: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)(Up to 4 weeks after last dose of study drug (i.e., up to Week 16))
- Induction Study 2: Number of Participants with Clinical Remission at Week 4(At Week 4)
- Induction Study 2: Number of Participants with AEs and SAEs(Up to 4 weeks after last dose of study drug (i.e., up to Week 16))
- Maintenance Study: Number of Participants with PRO-2 remission at Week 40(At Week 40)
- Maintenance Study: Number of Participants with 90-Day Corticosteroid-Free Clinical Remission at Week 40(At Week 40)
- Maintenance Study: Number of Participants with IBDQ Remission at Week 40(At Week 40)
- Maintenance Study: Number of Participants with Fatigue Response at Week 40(At Week 40)
- Maintenance Study : Number of Participants with AEs and SAEs(Up to 4 weeks after last dose of study drug (i.e., up to Week 44))
- Induction Study 2: Number of Participants Reporting Both Histologic Remission and Endoscopic Remission at Week 12(At Week 12)
- Maintenance Study: Number of Participants Reporting Both Histologic Remission and Endoscopic Remission at Week 40(At Week 40)
- Induction Study 2: Number of Participants with Clinical Remission at Week 4(At Week 4)
- Induction Study 1: Number of Participants with Clinical Remission at Week 12(At Week 12)
- Induction Study 1: Number of Participants with Endoscopic Response at Week 12(At Week 12)
- Induction Study 1: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)(Up to 4 weeks after last dose of study drug (i.e., up to Week 16))
- Induction Study 2: Number of Participants with Patient Reported Outcomes (PRO)-2 Remission at Week 12(At Week 12)
- Induction Study 2: Number of Participants with Clinical Response at Week 12(At Week 12)
- Induction Study 2: Number of Participants Reporting Both Clinical Remission and Endoscopic Response at Week 12(At Week 12)
- Induction Study 2: Number of Participants with Clinical Response at Week 4(At Week 4)
- Induction Study 2: Number of Participants with Endoscopic Remission at Week 12(At Week 12)
- Induction Study 2: Number of Participants with Deep Remission at Week 12(At Week 12)
- Induction Study 2: Number of Participants with Inflammatory Bowel Disease Questionnaire (IBDQ) Remission at Week 12(At Week 12)
- Induction Study 2: Number of Participants with Fatigue Response at Week 12(At Week 12)
- Induction Study 2: Number of Participants with AEs and SAEs(Up to 4 weeks after last dose of study drug (i.e., up to Week 16))
- Maintenance Study: Number of Participants with PRO-2 remission at Week 40(At Week 40)
- Maintenance Study: Number of Participants with Endoscopic Remission at Week 40(At Week 40)
- Maintenance Study: Number of Participants with 90-Day Corticosteroid-Free Clinical Remission at Week 40(At Week 40)
- Maintenance Study: Number of Participants with Maintenance of Clinical Remission at Week 40(At Week 40)
- Maintenance Study: Number of Participants Reporting Both Clinical Remission and Endoscopic Response at Week 40(At Week 40)
- Maintenance Study: Number of Participants with Deep Remission at Week 40(At Week 40)
- Maintenance Study: Number of Participants with IBDQ Remission at Week 40(At Week 40)
- Maintenance Study: Number of Participants with Fatigue Response at Week 40(At Week 40)
- Maintenance Study : Number of Participants with AEs and SAEs(Up to 4 weeks after last dose of study drug (i.e., up to Week 44))