A Phase 2, Multi-center, Randomized, Double-blind, Placebo-controlled Parallel-group Study to Evaluate the Efficacy and Safety of Dupilumab Therapy in Patients With Moderately to Severely Active Ulcerative Colitis With an Eosinophilic Phenotype
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- Sanofi
- 入组人数
- 68
- 试验地点
- 153
- 主要终点
- Proportion of participants achieving clinical response at Week 24
研究概览
简要总结
The protocol of this Phase 2 clinical trial consists of a double-blind, placebo-controlled, parallel-group, multicenter study to evaluate the efficacy and safety of dupilumab in participants with moderately to severely active Ulcerative Colitis (UC) with an eosinophilic phenotype.
Screening period: 2 to up to 4 weeks
Treatment period:
52-week investigational medicinal product (IMP) intervention (dupilumab or matching placebo) from Week 0 to Week 52 Open-label arm (optional): administration of open-label dupilumab therapy for study participants who qualify. Follow-up period: 12 weeks The maximum duration of study per participant is up to 68 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
- •Participants must be ≥18 years of age at the time of signing the informed consent.
- •Evidence of biomarker enrichment at time of screening.
- •Moderately to severely active UC, defined as a baseline modified Mayo score of 5 to 9, inclusive, using the Mayo endoscopic subscore assigned during the concurrent local and central reading of the video endoscopy.
- •Has a screening endoscopy with ≥2 endoscopic subscore in the Mayo score component assessment as determined by concurrent local and central reading of the video endoscopy.
- •Has a baseline rectal bleeding subscore of ≥1 and baseline a stool frequency score of ≥1 as determined by the Mayo score component assessment.
- •Participants with inadequate response/non-response, loss of response, or are intolerant of standard biologic therapy for their UC AND/OR Inadequate or non-responders, have shown loss of response, or are intolerant to at least 1 of the following treatments: oral corticosteroids (≤20 mg/day), 5-aminosalicylic acid (ASA) compounds, immunomodulators, small molecules.
排除标准
- •Participants are excluded from the study if any of the following criteria apply:
- •Severe extensive colitis as evidenced by:
- •Current hospitalization
- •Likely to require surgery for the treatment of UC within 12 weeks of Screening Visit
- •UC limited to the rectum only or to <20 cm of the colon as determined by central reading.
- •Presence of an ileal pouch, ostomy, stoma or fistula or history of a fistula.
- •Require, or required within the 2 months before screening, surgery for active gastrointestinal bleeding, peritonitis, intestinal obstruction, or intra-abdominal or pancreatic abscess requiring surgical drainage, or other conditions possibly confounding the evaluation of benefit from study agent treatment.
- •Has a prior medical history of eosinophilic colitis.
- •Participants with abdominal abscess, fulminant disease, or toxic megacolon.
- •Participants with intestinal failure or short bowel syndrome.
- •Presence of symptomatic colonic or small bowel obstruction, confirmed by objective radiographic or endoscopic evidence of a stricture with resulting obstruction (dilation of the colon or small bowel proximal to the stricture on barium radiograph or an inability to traverse the stricture at endoscopy).
- •History of extensive colonic resection (eg, less than 30 cm of colon remaining) that would prevent adequate evaluation of the effect of study agent on clinical disease activity.
- •History of colonic mucosal dysplasia or presence of adenomatous colonic polyps not removed OR presence of colonic mucosal dysplasia or adenomatous colonic polyps not removed during colonoscopy at screening visit.
- •If the participant has extensive colitis for ≥8 years or disease limited to left side of colon (ie, distal to splenic flexure) for >10 years, regardless of age, a colonoscopy within 1 year of the screening visit is required to survey for dysplasia. Participants with dysplasia or cancer identified on biopsies will be excluded.
- •Diagnosis of indeterminate colitis, microscopic colitis, ischemic colitis, or Crohn's disease or clinical findings suggestive of Crohn's disease.
- •The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
研究组 & 干预措施
Placebo
Initial loading dose followed by regular administration for the duration of the treatment period.
干预措施: Placebo (Drug)
Dupilumab
Initial loading dose followed by regular administration for the duration of the treatment period.
干预措施: Dupilumab (Drug)
Open-label arm (optional)
Regular administration of open label dupilumab
干预措施: Dupilumab (Drug)
结局指标
主要结局
Proportion of participants achieving clinical response at Week 24
时间窗: Week 24
Clinical response by modified Mayo score is defined as a decrease from baseline in the modified Mayo score of ≥2 points and at least a 30% reduction from baseline, and a decrease in rectal bleeding subscore of ≥1 OR an absolute rectal bleeding subscore of 0 or 1. The modified Mayo score consists of 3 subscores; a patient-reported subscore for rectal bleeding, a patient-reported subscore for stool frequency, and a Mayo endoscopic subscore. Each subscore ranges 0-3 with higher scores indicating greater disease severity. The total modified Mayo score ranges 0-9 with higher scores indicating greater disease severity.
Proportion of participants achieving clinical response at Week 24
时间窗: Week 24
Clinical response by modified Mayo score is defined as a decrease from baseline in the modified Mayo score of ≥2 points and at least a 30% reduction from baseline, and a decrease in rectal bleeding subscore of ≥1 OR an absolute rectal bleeding subscore of 0 or 1. The modified Mayo score consists of 3 subscores; a patient-reported subscore for rectal bleeding, a patient-reported subscore for stool frequency, and a Mayo endoscopic subscore. Each subscore ranges 0-3 with higher scores indicating greater disease severity. The total modified Mayo score ranges 0-9 with higher scores indicating greater disease severity.
次要结局
- Change from baseline in the partial Mayo score at Week 8, Week 24, and Week 52(Baseline to Week 8, Week 24 and Week 52)
- Proportion of participants who are in clinical response at Week 52(Week 52)
- Proportion of participants who are in clinical remission at Week 24 and Week 52(Week 24 and Week 52)
- Proportion of participants in symptomatic remission over time(Baseline up to Week 52)
- Proportion of participants achieving histologic-endoscopic healing at Week 24, and Week 52(Week 24 and Week 52)
- Proportion of participants in clinical remission at Week 52 who are off concomitant oral corticosteroids (OCS) at least 4 weeks prior to Week 52(Baseline up to Week 52)
- Incidence of treatment-emergent adverse events (TEAEs) or serious adverse events (SAEs)(Baseline up to Week 64)
- Proportion of participants who are in clinical response at Week 52(Week 52)
- Proportion of participants who are in clinical remission at Week 24 and Week 52(Week 24 and Week 52)
- Proportion of participants in symptomatic remission over time(Baseline up to Week 52)
- Proportion of participants achieving histologic-endoscopic healing at Week 24, and Week 52(Week 24 and Week 52)
- Proportion of participants with a Mayo endoscopic subscore of 0 or 1 without friability at Week 24, and Week 52(Week 24 and Week 52)
- Proportion of participants with a Mayo endoscopic subscore of 0 at Week 24, and Week 52(Week 24 and Week 52)
- Change from baseline in the partial Mayo score at Week 8, Week 24, and Week 52(Baseline to Week 8, Week 24 and Week 52)
- Proportion of participants in clinical remission at Week 52 who are off concomitant oral corticosteroids (OCS) at least 4 weeks prior to Week 52(Baseline up to Week 52)
- Proportion of participants in clinical remission at Week 52 who are off concomitant oral corticosteroids (OCS) at least 4 weeks prior to Week 52 among participants receiving OCS at baseline(Baseline up to Week 52)
- Change from baseline in abdominal pain assessed by Abdominal Pain Numerical Rating Scale (NRS) at Week 8, Week 24, and Week 52(Baseline to Week 8, Week 24 and Week 52)
- Incidence of treatment-emergent adverse events (TEAEs) or serious adverse events (SAEs)(Baseline up to Week 64)
- Concentration of dupilumab in serum over time.(Baseline up to Week 64)
- Incidence of treatment-emergent antidrug antibodies (ADA) against dupilumab.(Baseline up to Week 64)
- Change from baseline (Screening visit) in the normalized enrichment scores (NES) in type 2 inflammation transcriptome signature at Week 24 and Week 52.(Baseline to Week 24 and Week 52)