A Phase 2, Multi-Center, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of Induction Therapy With PRA023 in Subjects With Moderately to Severely Active Ulcerative Colitis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 178
- 试验地点
- 88
- 主要终点
- Percentage of Participants Who Discontinued Due to an AE
研究概览
简要总结
The purpose of this study is to assess the safety and efficacy of tulisokibart in participants with moderately to severely active Ulcerative Colitis (UC). After the completion of the 12-week induction, all participants have the option to continue in the open-label extension for up to 170 weeks.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The main inclusion criteria include but are not limited to the following:
- •Confirmed diagnosis of ulcerative colitis (UC)
- •Has moderately to severely active UC as defined by 3-component Modified Mayo score
- •Must have corticosteroid dependence or have had no response, insufficient response, loss of response, and/or intolerance to at least one of the following therapies: corticosteroid, immunosuppressants, or an approved anti-tumor necrosis factor (anti-TNF), anti-integrin, anti-interleukin 12/23 (anti-IL12/23), Janus kinase (JAK) inhibitor, Sphingosine 1-phosphate receptor (S1PR) modulator.
排除标准
- •The main exclusion criteria include but are not limited to the following:
- •Has diagnosis of Crohn's disease or indeterminate colitis
- •Has current evidence of fulminant colitis, toxic megacolon, bowel perforation, total proctocoloectomy or partial colectomy
- •Has current or impending need for colostomy or ileostomy
- •Has had surgical bowel resection within 3 months before screening
- •Has past or current evidence of definite low-grade or high-grade colonic dysplasia not completely removed
研究组 & 干预措施
Cohort 2 Placebo
Participants who are CDx+ will receive placebo administered by intravenous (IV) infusion on Day 1, Week 0 and the first day of Weeks 2, 6, and 10. After the completion of the 12-week induction, all participants have the option to continue in the open-label extension for up to 170 weeks.
干预措施: Companion Diagnostic (CDx) Testing (Device)
Cohort 2 Tulisokibart
Participants who are CDx+ will receive tulisokibart administered by intravenous (IV) infusion at 1000 mg on Day 1, Week 0 and 500 mg on the first day of Weeks 2, 6, and 10. After the completion of the 12-week induction, all participants have the option to continue in the open-label extension for up to 170 weeks.
干预措施: Companion Diagnostic (CDx) Testing (Device)
Cohort 1 Placebo
Participants who are CDx+ and CDx- will receive placebo administered by intravenous (IV) infusion on Day 1, Week 0 and the first day of Weeks 2, 6, and 10. After the completion of the 12-week induction, all participants have the option to continue in the open-label extension for up to 170 weeks.
干预措施: Placebo (Other)
Cohort 2 Placebo
Participants who are CDx+ will receive placebo administered by intravenous (IV) infusion on Day 1, Week 0 and the first day of Weeks 2, 6, and 10. After the completion of the 12-week induction, all participants have the option to continue in the open-label extension for up to 170 weeks.
干预措施: Placebo (Other)
Cohort 1 Tulisokibart
Participants who are CDx+ and CDx- will receive tulisokibart administered by intravenous (IV) infusion at 1000 mg on Day 1, Week 0, and 500 mg on the first day of Weeks 2, 6, and 10. After the completion of the 12-week induction, all participants have the option to continue in the open-label extension for up to 170 weeks.
干预措施: Tulisokibart (Drug)
Cohort 2 Tulisokibart
Participants who are CDx+ will receive tulisokibart administered by intravenous (IV) infusion at 1000 mg on Day 1, Week 0 and 500 mg on the first day of Weeks 2, 6, and 10. After the completion of the 12-week induction, all participants have the option to continue in the open-label extension for up to 170 weeks.
干预措施: Tulisokibart (Drug)
结局指标
主要结局
Percentage of Participants Who Discontinued Due to an AE
时间窗: Up to ~14 weeks
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product was also an AE. Reported adverse experiences used the Common Terminology for Adverse Events (CTCAE) Version 4.0. Per protocol, adverse events are reported by treatment with tulisokibart or placebo regardless of assigned cohort. Participants received identical treatment regiments regardless of cohort. The percentage of participants who discontinued due to an AE is reported.
Percentage of Participants in Cohort 1 Achieving Clinical Remission
时间窗: Baseline and Week 12
The 3-component Modified Mayo Score (MMS) ranges from 0 to 9 and is composed of endoscopic assessment, rectal bleeding (RB), and stool frequency (SF) subscores with each of the components ranging from 0 to 3, with higher scores indicating more severe disease. Clinical remission is defined as endoscopic subscore of 0 or 1, RB subscore of 0, and SF subscore of 0 or 1 and not greater than baseline. Per protocol participants in Cohort 1 were analyzed for this outcome measure.
Percentage of Participants Who Had One or More Serious Adverse Events
时间窗: Up to ~14 weeks
Reported adverse experiences used the Common Terminology for Adverse Events (CTCAE) Version 4.0. Serious adverse events are defined as: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living (ADL), Life-threatening consequences; urgent intervention indicated, and death. Per protocol, adverse events are reported by treatment with tulisokibart or placebo regardless of assigned cohort. Participants received identical treatment regiments regardless of cohort. The percentage of participants experiencing a serious AE are presented.
Percentage of Participants Who Experienced an Adverse Event (AE)
时间窗: Up to ~14 weeks
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product was also an AE. Reported adverse experiences used the Common Terminology for Adverse Events (CTCAE) Version 4.0. Per protocol, adverse events are reported by treatment with tulisokibart or placebo regardless of assigned cohort. Participants received identical treatment regiments regardless of cohort. The percentage of participants who experienced at least one AE is reported.
次要结局
- Percentage of Participants in Cohort 1 With Symptomatic Remission(Baseline and Week 12)
- Percentage of Participants in Cohort 1 With Histologic-endoscopic Mucosal Improvement(Baseline and Week 12)
- Percentage of Participants Who Were CDx+ (Cohorts 1 + 2) With Clinical Response(Baseline and Week 12)
- Percentage of Participants Who Were CDx+ (Cohorts 1 + 2) With Symptomatic Remission(Baseline and Week 12)
- Percentage of Participants Who Were CDx+ (Cohorts 1 + 2) With Histologic Improvement(Baseline and Week 12)
- Percentage of Participants Who Were CDx+ (Cohorts 1 + 2) With Endoscopic Improvement(Baseline and Week 12)
- Percentage of Participants Who Were CDx+ (Cohorts 1 + 2) With Histologic-endoscopic Mucosal Improvement(Baseline and Week 12)
- Percentage of Participants in Cohort 1 With Endoscopic Improvement(Baseline and Week 12)
- Percentage of Participants in Cohort 1 Achieving Clinical Response(Baseline and Week 12)
- Percentage of Participants Who Were CDx+ (Cohorts 1 + 2) With Clinical Remission(Baseline and Week 12)
- Percentage of Participants in Cohort 1 With Histologic Improvement(Baseline and Week 12)
- Percentage of Participants in Cohort 1 With Histologic-endoscopic Mucosal Healing(Baseline and Week 12)
- Percentage of Participants in Cohort 1 With an Inflammatory Bowel Disease Questionnaire (IBDQ) Response(Baseline and Week 12)
- Percentage of Participants Who Were CDx+ (Cohorts 1 + 2) With Histologic-endoscopic Mucosal Healing(Baseline and Week 12)
- Percentage of Participants Who Are CDx+ (Cohorts 1 + 2) Who Had an IBDQ Response(Baseline and Week 12)