A Multicenter, Multinational, Randomized, Double-blind, Placebo-controlled Phase 3, Induction Study to Evaluate the Efficacy and Safety of Duvakitug in Participants With Moderately to Severely Active Crohn's Disease
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- Sanofi
- 入组人数
- 980
- 试验地点
- 327
- 主要终点
- Sub-Study 2: Co-primary endpoints US/FDA: Proportion of participants achieving clinical remission per Crohn's Disease Activity Index (CDAI) at Week 12
研究概览
简要总结
This is a multinational, multicenter, randomized, double-blind, placebo-controlled, Phase 3 induction study, comprised of 3 sub-studies, to evaluate the efficacy and safety of duvakitug in participants with moderately to severely active CD. Study details include:
The study duration may be up to 35 weeks with:
- Up to 5-week Screening Period.
- 12-week Sub-Study 1 (Single Arm Open-Label Feeder Induction) or Sub-Study 2 (Pivotal Induction).
- 12-week Sub-Study 3 (Extended Induction for non-responders).
- 6 weeks (45 days) follow-up period for participants who do not enroll into the Pivotal Maintenance Study (EFC18327). The treatment duration will be up to 12 weeks in each sub-study.
The number of scheduled study visits for participants who continue to the Pivotal Maintenance Study (EFC18327) will be up to 8 (Sub-Study 1 and Sub-Study 2) and up to 15 for participants who enroll in Sub-Study 3.
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
- •Participants aged ≥18 and ≤80 years of age at Screening. Where permitted locally, participants 16 to <18 years of age who meet the definition of Tanner Stage 5 for development
- •Confirmed diagnosis of moderately to severely active Crohn's Disease (CD) for at least 3 months prior to baseline
- •Demonstrated inadequate response, have shown loss of response or intolerance to conventional therapies or advanced therapies (ATs)
排除标准
- •Participants with Ulcerative Colitis (UC) or indeterminate colitis
- •Participants with two entire missing segments of the: terminal ileum, right colon transverse colon, sigmoid and left colon, and rectum
- •Prior or current high-grade gastrointestinal (GI) dysplasia
- •Participants on treatment with but not on stable doses of conventional therapy prior to baseline
- •Participants receiving prohibited medications or therapies
- •Participants with previous exposure to anti-TL1A investigational therapy
- •The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
研究组 & 干预措施
Placebo
SC injection as per protocol
干预措施: Placebo (Drug)
Duvakitug Dose 2
SC injection as per protocol
干预措施: Duvakitug (Drug)
Duvakitug Dose 1
Subcutaneous (SC) Injection as per protocol
干预措施: Duvakitug (Drug)
结局指标
主要结局
Sub-Study 2: Co-primary endpoints US/FDA: Proportion of participants achieving clinical remission per Crohn's Disease Activity Index (CDAI) at Week 12
时间窗: Week 12
Clinical Remission by CDAI: CDAI score \<150. The CDAI is a measure of disease activity based on symptoms, signs, and a laboratory test. Scores on the CDAI scale range from 0 to 600, with scores below 150 indicating relative disease quiescence (remission), 150 to 219 indicating mild disease activity, 220 to 450 indicating moderate activity, and scores exceeding 450 indicating severe disease.
Sub-Study 2: Co-primary endpoints US/FDA: Proportion of participants achieving endoscopic response (Simple Endoscopic Score for Crohn's Disease [SES-CD]) at Week 12
时间窗: Week 12
Endoscopic Response is defined as decrease in SES-CD ≥50% from baseline (or a decrease of at least 2 points for participants with a baseline score of 4 or more, and isolated ileal disease) based on central reading. The SES-CD is a standardized method for evaluating disease activity. The total score is the sum of the 4 endoscopic variable scores and ranges from 0 to 56, where higher scores represent more severe disease.
Sub-Study 2: Co-primary endpoints EU/EMA: Proportion of participants achieving clinical remission per 2-item patient-reported outcome (PRO-2) at Week 12
时间窗: Week 12
Clinical Remission per PRO-2: average daily stool frequency (SF) ≤3 and not worse than the Baseline, and average daily abdominal pain (AP) ≤1 and not worse than the Baseline.
Sub-Study 2: Co-primary endpoints EU/EMA: Proportion of participants achieving endoscopic response (SES-CD) at Week 12
时间窗: Week 12
Endoscopic Response is defined as decrease in SES-CD ≥50% from baseline (or a decrease of at least 2 points for participants with a baseline score of 4 or more, and isolated ileal disease) based on central reading. The SES-CD is a standardized method for evaluating disease activity. The total score is the sum of the 4 endoscopic variable scores and ranges from 0 to 56, where higher scores represent more severe disease.
次要结局
- Sub-Study 2: Proportion of participants achieving CDAI clinical response at Week 12(Week 12)
- Sub-study 2: Proportion of participants achieving CDAI clinical response and endoscopic response (SES-CD) at Week 12(Week 12)
- Sub-study 2: Proportion of participants achieving endoscopic SES-CD remission at Week 12(Week 12)
- Sub-study 2: US/FDA: Proportion of participants achieving clinical remission per PRO-2 at Week 12(Week 12)
- Sub-study 2: EU/EMA: Proportion of participants achievingclinical remission per CDAI at Week 12(Week 12)
- Sub-study 2: Proportion of participants achieving ulcer-free endoscopy (in the subset of participants with ulcers at baseline) at Week 12(Week 12)
- Sub-study 2: Change from baseline in Patient-Reported Outcomes Measurement Information System (PROMIS)-Fatigue Short Form 7a T-score at Week 12(Baseline, Week 12)
- Sub-study 2: Proportion of participants achieving CDAI clinicalresponse at Week 4(Week 4)
- Sub-study 2: US/FDA: Proportion of participants achievingcorticosteroid free remission (in the subset ofparticipants with corticosteroids at baseline) perCDAI at Week 12(Week 12)
- Sub-study 2: EU/EMA: Proportion of participants achievingcorticosteroid free remission per PRO-2 (in thesubset of participants with corticosteroids atbaseline) at Week 12(Week 12)
- Sub-study 2: Proportion of participants achieving CDAI clinical remission and endoscopic remission (SES-CD) at Week 12(Week 12)
- Sub-study 2: Change from baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) total score at Week 12(Baseline, Week 12)
- Sub-study 2: Proportion of participants with no bowel urgency byNumeric Rating Scale (NRS) at Week 12(Week 12)
- Sub-study 2: Proportion of participants with CD-related hospitalizations by Week 12(Baseline through Week 12)
- Sub-study 2: Number of participants with any Treatment Emergent Adverse Events (TEAEs), TEAE of special interest (TEAESIs), TE serious adverse event (TESAEs), and TEAEs leading to permanent study intervention discontinuation(Baseline through 45 days after the last dose)
- Sub-study 2: Serum concentrations of duvakitug(Baseline to Week 12)
- Sub-study 2: Incidence of treatment-emergent Anti-drug Antibodies (ADA) against duvakitug(Baseline to Week 12)