A Phase 3 Randomized, Double-blind, Placebo-Controlled, Parallel Group, Multicenter Protocol in Adults With an Open Label Study in Adolescents to Evaluate the Efficacy and Safety of Induction and Maintenance Therapy With Icotrokinra in Participants With Moderately to Severely Active Ulcerative Colitis
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 882
- 试验地点
- 527
- 主要终点
- Double-blind (DB) Induction Study: Percentage of Adult Participants in Clinical Remission at Week I-12
研究概览
简要总结
The purpose of this protocol is to evaluate the efficacy (how well it works), safety and tolerability of oral icotrokinra as therapy in adult and adolescent participants with moderately to severely active ulcerative colitis (UC, a chronic disease of the large intestine in which the lining of the colon becomes inflamed and develops tiny open ulcers).
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)
盲法说明
This study is double-blind for adults and open-label for adolescent participants.
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of ulcerative colitis (UC) established at least 12 weeks before screening including both endoscopic evidence and a histopathology report consistent with a diagnosis of UC
- •Moderately to severely active UC, defined as a baseline (Week I-0) modified Mayo score of 5 to 9, inclusive, using the endoscopy subscore obtained during the central review of the screening video endoscopy
- •An endoscopy subscore greater than or equal to (>=) 2 as obtained during central review of the screening video endoscopy
- •Adolescent Participants: body weight must be >= 40 kilograms (kg) at baseline (Week I-0)
- •Adult female participants of childbearing potential and all adolescent female participants must have a negative highly sensitive serum pregnancy test (beta-human chorionic gonadotropin [β-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 are naïve to advanced therapies (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 UC (ADT-inadequate responder [IR]) as defined in the protocol
排除标准
- •Participants with current known complications of UC such as fulminant colitis, toxic megacolon, or any other manifestation that might require colonic surgery while enrolled in the study
- •Presence of a stoma
- •Presence or history of a fistula
- •Colonic resection within 24 weeks before baseline or any other intra-abdominal or other major surgery performed within 12 weeks before baseline
- •History of extensive colonic resection (that is, less than [<] 30 centimeter [cm] of colon remaining) or colonic resection that could impair the use of disease severity assessments (for example Mayo Score) to assess response to study intervention
研究组 & 干预措施
Double-blind (DB) Induction Study: Icotrokinra
Adult participants will be randomized to receive icotrokinra daily, orally starting at induction Week 0 (Week I-0). At Week I-12, all participants will be evaluated for clinical response and will enter the Maintenance study.
干预措施: Icotrokinra (Drug)
DB Induction Study: Placebo
Adult participants will be randomized to receive placebo daily, orally starting at Week I-0. At Week I-12, all participants will be evaluated for clinical response and will enter the Maintenance study.
干预措施: Placebo (Drug)
Open-label (OL) Induction Phase: Icotrokinra
Adolescent participants will enter the Induction phase and receive icotrokinra daily, orally. At Week I-12 all participants will be evaluated for clinical response and will enter the Maintenance phase.
干预措施: Icotrokinra (Drug)
OL Maintenance Phase: Icotrokinra
Adolescent participants who are in clinical response to icotrokinra will enter the Maintenance phase at Week M-0 and continue to receive icotrokinra daily, orally up to Week M-40. Participants who are nonresponders to icotrokinra will also enter the Maintenance phase to receive icotrokinra daily. After completion of the Maintenance phase through Week M-40, eligible participants can participate in a LTE.
干预措施: Icotrokinra (Drug)
DB Maintenance Study: Placebo
Adult participants who are in clinical response to icotrokinra at the end of the Induction study will enter the Maintenance study and be randomized to receive placebo daily, orally starting at Week M-0 through Week M-40. Participants who are clinical responders to placebo will also enter the Maintenance study directly and continue to receive placebo daily. After completion of the Maintenance study through Week M-40, eligible participants can participate in a LTE.
干预措施: Placebo (Drug)
DB Maintenance Study: Icotrokinra
Adult participants who are in clinical response to icotrokinra at the end of the Induction study will enter the Maintenance study and be randomized to receive icotrokinra daily, orally starting at maintenance Week 0 (Week M-0) through Week M-40. Participants who are clinical nonresponders to icotrokinra or placebo will also enter the Maintenance study directly and receive icotrokinra daily. After completion of the Maintenance study through Week M-40, eligible participants can participate in a long-term extension (LTE).
干预措施: Icotrokinra (Drug)
结局指标
主要结局
Double-blind (DB) Induction Study: Percentage of Adult Participants in Clinical Remission at Week I-12
时间窗: At Week I-12
Percentage of adult participants in clinical remission at Week I-12 will be reported. Clinical remission is defined as stool frequency subscore of 0 or 1, a rectal bleeding subscore of 0, and an endoscopy subscore of 0 or 1.
DB Maintenance Study: Percentage of Adult Participants in Clinical Remission at Week M-40
时间窗: At Week M-40
Percentage of adult participants in clinical remission at Week M-40 will be reported. Clinical remission is defined as stool frequency subscore of 0 or 1, a rectal bleeding subscore of 0, and an endoscopy subscore of 0 or 1.
Open-Label (OL) Maintenance Phase: Percentage of Adolescent Participants in Clinical Remission at Week M-40
时间窗: At Week M-40
Percentage of adolescent participants in clinical remission at Week M-40 will be reported. Clinical remission is defined as stool frequency subscore of 0 or 1, a rectal bleeding subscore of 0, and an endoscopy subscore of 0 or 1.
次要结局
- DB Induction Study: Percentage of Adult Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)(Up to Week I-12)
- DB Induction Study: Percentage of Adult Participants in Symptomatic Remission at Week I-4(At Week I-4)
- DB Induction Study: Percentage of Adult Participants in Endoscopic Remission at Week I-12(At Week I-12)
- DB Induction Study: Percentage of Adult Participants with No Bowel Urgency at Week I-12(At Week I-12)
- DB Induction Study: Percentage of Adult Participants with No Abdominal Pain at Week I-12(At Week I-12)
- DB Induction Study: Percentage of Adult Participants with No Bowel Incontinence at Week I-12(At Week I-12)
- DB Maintenance Study: Percentage of Adult Participants with 90-day Corticosteroid-free Clinical Remission at Week M-40(At Week M-40)
- DB Maintenance Study: Percentage of Adult Participants with HEMI at Week M-40(At Week M-40)
- DB Maintenance Study: Percentage of Adult Participants with IBDQ Remission at Week M-40(At Week M-40)
- DB Maintenance Study: Percentage of Adult Participants with Disease Clearance at Week M-40(At Week M-40)
- DB Maintenance Study: Percentage of Adult Participants with No Bowel Urgency at Week M-40(At Week M-40)
- DB Induction Study: Percentage of Adult Participants with Inflammatory Bowel Disease Questionnaire (IBDQ) Remission at Week I-12(At Week I-12)
- DB Induction Study: Percentage of Adult Participants with Histologic-Endoscopic Mucosal Improvement (HEMI) at Week I-12(At Week I-12)
- DB Maintenance Study: Percentage of Adult Participants in Symptomatic Remission at Week M-40(At Week M-40)
- DB Induction Study: Percentage of Adult Participants in Clinical Response at Week I-12(At Week I-12)
- DB Induction Study: Percentage of Adult Participants with Endoscopic Improvement at Week I-12(At Week I-12)
- DB Induction Study: Percentage of Adult Participants in Symptomatic Remission at Week I-12(At Week I-12)
- DB Induction Study: Percentage of Adult Participants with Fatigue Response at Week I-12(At Week I-12)
- DB Maintenance Study: Percentage of Adult Participants with Endoscopic Improvement at Week M-40(At Week M-40)
- DB Maintenance Study: Percentage of Adult Participants in Clinical Remission at Week M-40 Among the Participants who had Achieved Clinical Remission at Maintenance Baseline(At Week M-40)
- DB Maintenance Study: Percentage of Adult Participants in Histologic-Endoscopic Mucosal Remission at Week M-40(At Week M-40)
- OL Induction Phase: Percentage of Adolescent Participants in Clinical Response at Week I-12(At Week I-12)
- OL Induction Phase: Percentage of Adolescent Participants with Endoscopic Improvement at Week I-12(At Week I-12)
- DB Maintenance Study: Percentage of Adult Participants in Endoscopic Remission at Week M-40(At Week M-40)
- OL Induction Phase: Percentage of Adolescent Participants in Endoscopic Remission at Week I-12(At Week I-12)
- OL Maintenance Phase: Percentage of Adolescent Participants with Histologic-Endoscopic Mucosal Remission at Week M-40(At Week M-40)
- DB Maintenance Study: Percentage of Adult Participants with Fatigue Response at Week M-40(At Week M-40)
- DB Maintenance Study: Percentage of Adult Participants with No Abdominal Pain at Week M-40(At Week M-40)
- DB Maintenance Study: Percentage of Adult Participants with No Bowel Incontinence at Week M-40(At Week M-40)
- DB Maintenance Study: Percentage of Adult Participants with AEs and SAEs(Up to Week M-40)
- OL Induction Phase: Percentage of Adolescent Participants in Clinical Remission at Week I-12(At Week I-12)
- OL Induction Phase: Percentage of Adolescent Participants with HEMI at Week I-12(At Week I-12)
- OL Induction Phase: Percentage of Adolescent Participants in Symptomatic Remission at Week I-12(At Week I-12)
- OL Induction Phase: Percentage of Adolescent Participants in Pediatric Ulcerative Colitis Activity Index (PUCAI) Remission at Week I-12(At Week I-12)
- OL Induction Phase: Percentage of Adolescent Participants with AEs and SAEs(Up to Week I-12)
- OL Maintenance Study: Percentage of Adolescent Participants with Endoscopic Improvement at Week M-40(At Week M-40)
- OL Maintenance Phase: Percentage of Adolescent Participants in Symptomatic Remission at Week M-40(At Week M-40)
- OL Maintenance Phase: Percentage of Adolescent Participants in 90-day Corticosteroid-free Clinical Remission at Week M-40(At Week M-40)
- OL Maintenance Phase: Percentage of Adolescent Participants with HEMI at Week M-40(At Week M-40)
- OL Maintenance Phase: Percentage of Adolescent Participants with Endoscopic Remission at Week M-40(At Week M-40)
- OL Maintenance Phase: Percentage of Adolescent Participants in Clinical Remission at Week M-40 Among the Participants who had Achieved Clinical Remission at Maintenance Baseline(At Week M-40)
- OL Maintenance Phase: Percentage of Adolescent Participants in Clinical Response at Week M-40 Among the Participants who had Achieved Clinical Response at Maintenance Baseline(At Week M-40)
- OL Maintenance Phase: Percentage of Adolescent Participants in PUCAI Remission at Week-40(At Week M-40)
- OL Maintenance Phase: Percentage of Adolescent Participants with AEs and SAEs(Up to Week M-40)