Development of a Biomarker of Efficacy of Vedolizumab (EnTyvio®) in Patients With ulcErative ColiTis (DETECT)
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 入组人数
- 19
- 试验地点
- 4
- 主要终点
- Demonstrate the feasibility of an ex vivo labeling of intestinal immune cells with a combination of two markers: vedolizumab-FITC and adalimumab-Alexa Fluor 647
研究概览
简要总结
The main objective of this project is to demonstrate the feasability of an endomicroscopic biomarker of efficacy of vedolizumab and adalimumab, in Ulcerative colitis (UC) by coupling vedolizumab to a fluorescent component, FITC (Fluorescein isothiocyanate) , and adalimumab to rhodamine.
This project should allow the development of a biomarker of therapeutic efficacy for vedolizumab and adalimumab that can be used in a single time-frame in vivo in humans, while respecting manufacturing standards and Good manufacturing procedures.
详细描述
Patients will be recruited before initiation of vedolizumab injections. The schedule for vedolizumab infusions will corresponding to the protocol follow-up visits (Week 0, W2, W6, W14, W22), and flexible sigmoidoscopy appointments will be performed at Week 0 and 22.
For responder patients, the end of the study will occured two weeks after the last vedolizumab infusion (W24).
At week 22, nonresponder patients to vedolizumab may be treated by adalimumab in the absence of contraindication and depending on the decision of the physician responsible for the patient. Patients will be treated every two weeks during 8 weeks. The protocol follow up will end 2 weeks after the fourth adalimumab injection.
During W0 and W22, colon biopsies will be collected. Blood samples will be collected on W0, W2, W6, W14, W22 (and W30 for non responder).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
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
- •Patients with moderate to severe UC defined by an overall Mayo score ≥ 5 and an endoscopic sub-score ≥ 2 points and rectal bleeding score ≥ 1 point
- •Extension > 15 cm from the anal margin
- •Requiring treatment with biotherapy and meeting the indications for the treatment
- •Affiliated with a social security scheme
排除标准
- •Crohn's disease or unclassified colitis
- •Severe acute colitis
- •Requirement for immediate surgical treatment
- •Previous treatment with vedolizumab or anti-TNF-α
- •Contraindication to the use of vedolizumab or an anti-TNF-α agent
- •Contraindication to the use of adalimumab
- •Corticosteroid therapy > 20 mg/day
- •Corticosteroid therapy started within the previous two weeks
- •Conventional Immunosppressor started within the previous month
- •Colonic dysplasia or known cancer
- •Likelihood to refuse two rectosigmoidoscopies, performed eighteen weeks apart
- •Pregnant or lactating women
研究组 & 干预措施
VEDOLIZUMAB
300 mg IV
干预措施: VEDOLIZUMAB (Drug)
VEDOLIZUMAB
300 mg IV
干预措施: ADALIMUMAB (Drug)
结局指标
主要结局
Demonstrate the feasibility of an ex vivo labeling of intestinal immune cells with a combination of two markers: vedolizumab-FITC and adalimumab-Alexa Fluor 647
时间窗: week 0
Presence of fluorescent cells by Cellvizio® examination field for each of the antibodies: FITCcoupled vedolizumab and Alexa Fluor 647-coupled adalimumab at week 0 for all the patients.
次要结局
- Quantify, ex vivo, the number of cells labeled with FITC-coupled vedolizumab in the intestinal mucosa of patients with moderate to severe UC that are associated with clinical remission at week 22 (W22) after the initiation of treatment with vedolizumab.(Week 22)
- Evaluate the association between the number of cells labeled with FITC-coupled vedolizumab in the intestinal mucosa and the rate of endoscopic remission induced by treatment with a standard dose of vedolizumab(week 22)
- Evaluate the association between the number of cells labeled with FITC-coupled vedolizumab in the intestinal mucosa and the rate of histologic remission induced by treatment with a standard dose of vedolizumab(week 22)
- Evaluate the association between the Alexa Fluor 647-coupled adalimumab biomarker, and the rate of clinical response at w30 to adalimumab(from week 0 to week 30)
- Evaluate the association between the Alexa Fluor 647-coupled adalimumab biomarker, and the rate of endoscopic remission at w30 to adalimumab(from week 0 to week 30)
- Evaluate the association between the Alexa Fluor 647-coupled adalimumab biomarker, and the rate of clinical remission at w30 to adalimumab(from week 0 to week 30)
- Evaluate the association between the number of cells labeled with FITC-coupled vedolizumab in the intestinal mucosa and the rate of clinical response induced by treatment with a standard dose of vedolizumab(week 22)
- Compare the number of positive immune cells FITC-coupled vedolizumab in the intestinal mucosa of patients with UC(week 0)
- Compare the number of positive immune cells Alexa Fluor 647-coupled adalimumab in the intestinal mucosa of patients with UC(week 0)