A Phase 3, Randomized, Double-Blind, Placebo-Controlled Program to Evaluate the Efficacy and Safety of Tulisokibart in Participants With Moderately to Severely Active Crohn's Disease
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 1,200
- 试验地点
- 994
- 主要终点
- Study 1: Percentage of Participants Achieving Clinical Remission per CDAI Score at Week 12
研究概览
简要总结
The purpose of this protocol is to evaluate the efficacy and safety of tulisokibart in participants with moderately to severely active Crohn's disease. Study 1's primary hypotheses are that at least 1 tulisokibart dose level is superior to placebo in the proportion of participants achieving clinical remission per Crohn's Disease Activity Index score (<150, US/FDA) or per stool frequency and abdominal pain score (EU/EMA) and in the proportion of participants achieving endoscopic response at Week 52 (US/FDA and EU/EMA), and that at least 1 tulisokibart dose level is superior to placebo in the proportion of participants achieving clinical remission per Crohn's Disease Activity Index score (<150, US/FDA) or per stool frequency and abdominal pain score (EU/EMA) and in the proportion of participants achieving endoscopic response at Week 12 (US/FDA and EU/EMA). Study 2's primary hypothesis is that at least 1 tulisokibart dose level is superior to placebo in the proportion of participants achieving clinical remission per Crohn's Disease Activity Index score (<150, US/FDA) or stool frequency and abdominal pain score (EU/EMA) and in the proportion of participants achieving endoscopic response at Week 12 (US/FDA and EU/EMA).
详细描述
The protocol consists of 2 studies. Study 1 includes induction and maintenance treatment, and Study 2 includes only induction treatment. Each study has its own hypotheses and outcome measures that will be assessed independently.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 16 Years 至 80 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The main inclusion and
排除标准
- •include but are not limited to the following:
- •Inclusion Criteria:
- •Has had a diagnosis of Crohn's disease (CD) at least 3 months before study.
- •Has moderately to severely active CD.
- •Demonstrated inadequate response, loss of response, or intolerance to one or more of the following categories of drugs: oral locally acting steroids, systemic steroids, immunomodulators, biologic and/or small molecule advanced therapies.
- •Adolescent participants ≥16 and <18 years of age can participate if approved by the country or regulatory/health authority.
- •Exclusion Criteria:
- •Has diagnosis of ulcerative colitis (UC) or indeterminate colitis.
- •Has CD isolated to the stomach, duodenum, jejunum, or perianal region, without colonic and/or ileal involvement.
- •Currently has any of the following complications of CD: suspected or diagnosed with intra-abdominal or perianal abscess, known symptomatic stricture or colonic stenosis not passable in endoscopy, fulminant colitis, toxic megacolon, or any other manifestation that might require surgery while enrolled in the study.
- •Has current stoma or need for colostomy or ileostomy.
- •Is missing >2 segments of the following 5 segments: terminal ileum, right colon, transverse colon, sigmoid and left colon, and rectum.
- •Has been diagnosed with short gut or short bowel syndrome, or any other uncontrolled chronic diarrhea besides CD.
- •Has surgical bowel resection within 3 months of study.
- •Has prior or current gastrointestinal dysplasia.
- •Has chronic infection requiring ongoing antimicrobial treatment.
- •Has a history of cancer (except fully treated non-melanoma skin cell cancers or cervical carcinoma in situ after complete surgical removal) and is disease free for <5 years.
- •Is infected with Hepatitis B virus (HBV), Hepatitis C virus (HCV), or human immunodeficiency virus (HIV).
- •Has active tuberculosis.
- •Has confirmed or suspected coronavirus disease of 2019 (COVID-19) infection.
- •Prior exposure to tulisokibart (MK-7240, PRA023) or another anti-tumor necrosis factor-like cytokine 1A (TL1A) antibody (Ab).
研究组 & 干预措施
Study 1: Placebo
Participants receive IV placebo, followed by an SC placebo regimen.
干预措施: SC Placebo (Other)
Study 1: High Dose Induction, High Dose Maintenance
Participants receive high dose intravenous (IV) tulisokibart, followed by a high dose subcutaneous (SC) tulisokibart regimen.
干预措施: SC Tulisokibart (Drug)
Study 1: Placebo
Participants receive IV placebo, followed by an SC placebo regimen.
干预措施: IV Placebo (Other)
Study 1: High Dose Induction, Low Dose Maintenance
Participants receive high dose IV tulisokibart, followed by a low dose SC tulisokibart regimen.
干预措施: SC Placebo (Other)
Study 1: Low Dose Induction, Low Dose Maintenance
Participants receive low dose IV tulisokibart, followed by a low dose SC tulisokibart regimen.
干预措施: IV Tulisokibart (Drug)
Study 1: Low Dose Induction, Low Dose Maintenance
Participants receive low dose IV tulisokibart, followed by a low dose SC tulisokibart regimen.
干预措施: SC Tulisokibart (Drug)
Study 1: Low Dose Induction, Low Dose Maintenance
Participants receive low dose IV tulisokibart, followed by a low dose SC tulisokibart regimen.
干预措施: SC Placebo (Other)
Study 1: Placebo
Participants receive IV placebo, followed by an SC placebo regimen.
干预措施: IV Tulisokibart (Drug)
Study 2: Placebo
Participants receive IV placebo.
干预措施: IV Placebo (Other)
Study 2: Placebo
Participants receive IV placebo.
干预措施: IV Tulisokibart (Drug)
Study 2: Low Dose Induction
Participants receive low dose IV tulisokibart.
干预措施: IV Tulisokibart (Drug)
Study 2: Low Dose Induction
Participants receive low dose IV tulisokibart.
干预措施: SC Placebo (Other)
Study 2: High Dose Induction
Participants receive high dose IV tulisokibart.
干预措施: IV Tulisokibart (Drug)
Study 2: Placebo
Participants receive IV placebo.
干预措施: SC Placebo (Other)
Study 1: High Dose Extension
Participants receive a high dose SC tulisokibart regimen. Participants may continue in this arm after completing participation in their original arm, if they meet protocol-specific prerequisites.
干预措施: SC Tulisokibart (Drug)
Study 1: High Dose Induction, High Dose Maintenance
Participants receive high dose intravenous (IV) tulisokibart, followed by a high dose subcutaneous (SC) tulisokibart regimen.
干预措施: IV Tulisokibart (Drug)
Study 2: Low Dose Extension
Participants receive a low dose SC tulisokibart regimen. Participants may continue in this arm only after completing participation in their original arm, if they meet protocol-specific prerequisites.
干预措施: SC Tulisokibart (Drug)
Study 2: High Dose Extension
Participants receive a high dose SC tulisokibart regimen. Participants may continue in this arm only after completing participation in their original arm, if they meet protocol-specific prerequisites.
干预措施: SC Tulisokibart (Drug)
Study 1: High Dose Induction, Low Dose Maintenance
Participants receive high dose IV tulisokibart, followed by a low dose SC tulisokibart regimen.
干预措施: SC Tulisokibart (Drug)
Study 1: High Dose Induction, Low Dose Maintenance
Participants receive high dose IV tulisokibart, followed by a low dose SC tulisokibart regimen.
干预措施: IV Tulisokibart (Drug)
Study 1: Low Dose Extension
Participants receive a low dose SC tulisokibart and placebo regimen. Participants may continue in this arm after completing participation in their original arm, if they meet protocol-specific prerequisites.
干预措施: SC Tulisokibart (Drug)
Study 1: Low Dose Extension
Participants receive a low dose SC tulisokibart and placebo regimen. Participants may continue in this arm after completing participation in their original arm, if they meet protocol-specific prerequisites.
干预措施: SC Placebo (Other)
结局指标
主要结局
Study 1: Percentage of Participants Achieving Clinical Remission per CDAI Score at Week 12
时间窗: Week 12
The percentage of participants achieving clinical remission, as defined by CDAI score \<150 for study 1 will be presented.
Study 1: Percentage of Participants Achieving Clinical Remission per Stool Frequency and Abdominal Pain Score at Week 12
时间窗: Week 12
The percentage of participants achieving clinical remission per SF/APS, as defined by average daily SF ≤2.8 and average daily APS ≤1.0 and both not greater than baseline for study 1 will be presented.
Study 1 [US/FDA Only]: Percentage of Participants Achieving Clinical Remission per Crohn's Disease Activity Index (CDAI) Score at Week 52
时间窗: Week 52
The percentage of participants achieving clinical remission, as defined by CDAI score \<150 for Study 1 will be presented.
Study 1 [EU/EMA Only]: Percentage of Participants Achieving Clinical Remission per Stool Frequency and Abdominal Pain Score at Week 52
时间窗: Week 52
The percentage of participants achieving clinical remission per stool frequency/abdominal pain score (SF/APS), as defined by average daily SF ≤2.8 and average daily APS ≤1.0 and both not greater than baseline for Study 1 will be presented.
Study 1: Percentage of Participants Achieving Endoscopic Response at Week 52
时间窗: Week 52
The percentage of participants achieving endoscopic response, as defined by a ≥50% decrease in Simplified endoscopic score for Crohn's disease (SES-CD) from baseline for Study 1 will be presented.
Study 1: Percentage of Participants Achieving Endoscopic Response at Week 12
时间窗: Week 12
The percentage of participants achieving endoscopic response, as defined by a ≥50% decrease in SES-CD from baseline for Study 1 will be presented.
Study 2 [US/FDA Only]: Percentage of Participants Achieving Clinical Remission per CDAI Score at Week 12
时间窗: Week 12
The percentage of participants achieving clinical remission, as defined by CDAI score \<150 for Study 2 will be presented.
Study 2 [EU/EMA Only]: Percentage of Participants Achieving Clinical Remission per Stool Frequency and Abdominal Pain Score at Week 12
时间窗: Week 12
The percentage of participants achieving clinical remission per SF/APS, as defined by average daily SF ≤2.8 and average daily APS ≤1.0 and both not greater than baseline for Study 2 will be presented.
Study 2: Percentage of Participants Achieving Endoscopic Response at Week 12
时间窗: Week 12
The percentage of participants achieving endoscopic response, as defined by a ≥50% decrease in SES-CD from baseline for Study 2 will be presented.
Study 1 [US/FDA Only]: Percentage of Participants Achieving Clinical Remission per CDAI Score at Week 12
时间窗: Week 12
The percentage of participants achieving clinical remission, as defined by CDAI score \<150 for Study 1 will be presented.
Study 1 [EU/EMA Only]: Percentage of Participants Achieving Clinical Remission per Stool Frequency and Abdominal Pain Score at Week 12
时间窗: Week 12
The percentage of participants achieving clinical remission per SF/APS, as defined by average daily SF ≤2.8 and average daily APS ≤1.0 and both not greater than baseline for Study 1 will be presented.
次要结局
- Study 1: Percentage of Participants Who Experienced an Adverse Event (AE)(Up to approximately 52 weeks)
- Study 1: Percentage of Participants who Discontinue Study Intervention due to an AE(Up to approximately 52 weeks)
- Study 1: Percentage of Participants with Decrease of ≥100 Points in CDAI Score from Baseline to Week 12(Week 12)
- Study 1: Mean Change from Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) Score at Week 12(Baseline and Week 12)
- Study 1 and 2: Percentage of Participants in Diagnostic Assay Positive (Dx+) Subpopulation Achieving Clinical Remission per CDAI at Week 12(Week 12)
- Study 1 and 2: Percentage of Participants in Diagnostic Assay Positive (Dx+) Subpopulation Achieving Endoscopic Response at Week 12(Week 12)
- Study 1: Percentage of Participants Achieving Clinical Remission per CDAI Score at Week 52(Week 52)
- Study 1: Percentage of Participants with Decrease of ≥100 Points in CDAI Score from Baseline to Week 52(Week 52)
- Study 1: Percentage of Participants Achieving Corticosteroid-Free Clinical Remission per CDAI Score at Week 52(Week 52)
- Study 1: Percentage of Participants Achieving Corticosteroid-Free Clinical Remission per Stool Frequency and Abdominal Pain Score at Week 52(Week 52)
- Study 1: Percentage of Participants Achieving Clinical Remission per CDAI and Endoscopic Remission at Week 52(Week 52)
- Study 1: Mean Change from Baseline in FACIT-Fatigue Score at Week 52(Baseline and Week 52)
- Study 1: Mean Change from Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Score at Week 52(Baseline and Week 52)
- Study 1: Percentage of Participants with Ulcer-Free Endoscopy at Week 52(Week 52)
- Study 2: Percentage of Participants Who Experienced an AE(Up to approximately 12 weeks)
- Study 2: Percentage of Participants who Discontinue Study Intervention due to an AE(Up to approximately 12 weeks)
- Study 2 [US/FDA Only]: Percentage of Participants Achieving Clinical Remission per Stool Frequency and Abdominal Pain Score at Week 12(Week 12)
- Study 2: Percentage of Participants with Decrease of ≥100 Points in CDAI Score from Baseline to Week 12(Week 12)
- Study 2: Mean Change from Baseline in FACIT-Fatigue Score at Week 12(Baseline and Week 12)
- Study 2: Mean Change from Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Score at Week 12(Baseline and Week 12)
- Study 2: Percentage of Participants Achieving Endoscopic Remission at Week 12(Week 12)
- Study 2: Percentage of Participants with Decrease of ≥100 Points in CDAI Score from Baseline to Week 6(Week 6)
- Study 2: The percentage of Participants with Ulcer-Free Endoscopy at Week 12(Week 12)
- Study 1 [US/FDA Only]: Percentage of Participants Achieving Clinical Remission per Stool Frequency and Abdominal Pain Score at Week 12(Week 12)
- Study 1 [EU/EMA Only]: Percentage of Participants Achieving Clinical Remission per CDAI Score at Week 12(Week 12)
- Study 1: Percentage of Participants Achieving Endoscopic Remission at Week 12(Week 12)
- Study 1 [US/FDA Only]: Percentage of Participants Achieving Clinical Remission per Stool Frequency and Abdominal Pain Score at Week 52(Week 52)
- Study 1: Percentage of Participants Achieving Endoscopic Remission at Week 52(Week 52)
- Study 1: Percentage of Participants Achieving Sustained Clinical Remission per CDAI at Both Week 12 and Week 52(Week 12 and Week 52)
- Study 1: Percentage of Participants Achieving Clinical Remission per Stool Frequency, Abdominal Pain Score, and Endoscopic Remission at Week 52(Week 52)
- Study 2 [EU/EMA Only]: Percentage of Participants Achieving Clinical Remission per CDAI Score at Week 12(Week 12)
- Study 1: Number of Participants Who Experienced an Adverse Event (AE)(Up to approximately 52 weeks)
- Study 1: Number of Participants Who Discontinue Study Intervention due to an AE(Up to approximately 52 weeks)
- Study 1: Percentage of Participants With Clinical Response per CDAI Score (Decrease From Baseline of ≥100 Points) at Week 12(Week 12)
- Study 1: Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) Score at Week 12(Baseline and Week 12)
- Study 1 and 2: Percentage of Participants in Diagnostic Assay Positive (Dx+) Subpopulation Achieving Clinical Remission per CDAI Score at Week 12(Week 12)
- Study 1 and 2: Percentage of Participants in Dx+ Subpopulation Achieving Endoscopic Response at Week 12(Week 12)
- Study 1: Percentage of Participants With Clinical Response (Decrease From Baseline at Least 100 Points) or Clinical Remission (<150) per CDAI Score at Week 6(Week 6)
- Study 1 [EU/EMA Only]: Percentage of Participants Achieving Clinical Remission per CDAI Score at Week 52(Week 52)
- Study 1: Percentage of Participants With Clinical Response per CDAI Score (Decreased From Baseline of ≥100 Points) at Week 52(Week 52)
- Study 1 [US/FDA Only]: Percentage of Participants Achieving Corticosteroid-Free Clinical Remission per CDAI Score at Week 52(Week 52)
- Study 1 [EU/EMA Only]: Percentage of Participants Achieving Corticosteroid-Free Clinical Remission per Stool Frequency and Abdominal Pain Score at Week 52(Week 52)
- Study 1: Percentage of Participants Achieving Clinical Remission per CDAI Score and Endoscopic Remission at Week 52(Week 52)
- Study 1: Mean Change From Baseline in FACIT-Fatigue Score at Week 52(Baseline and Week 52)
- Study 1 [EU/EMA Only]: Mean Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Score at Week 52(Baseline and Week 52)
- Study 1: Percentage of Participants With Ulcer-Free Endoscopy at Week 52(Week 52)
- Study 2: Number of Participants Who Experienced an AE(Up to approximately 12 weeks)
- Study 2: Number of Participants Who Discontinue Study Intervention due to an AE(Up to approximately 12 weeks)
- Study 2: Percentage of Participants With Clinical Response per CDAI Score (Decreased From Baseline of ≥100 Points) at Week 12(Week 12)
- Study 2: Mean Change From Baseline in FACIT-Fatigue Score at Week 12(Baseline and Week 12)
- Study 2 [EU/EMA Only]: Mean Change From Baseline in IBDQ Score at Week 12(Baseline and Week 12)
- Study 2: Percentage of Participants With Clinical Response (Decreased From Baseline of ≥100 Points) or Clinical Remission (<150) per CDAI Score at Week 6(Week 6)
- Study 2: Percentage of Participants With Ulcer-Free Endoscopy at Week 12(Week 12)