VEDO-PREDIRESP Project: Value of Pharmacokinetic Assays (Vedolizumab and Anti-vedolizumab Antibody) in the Prediction of Induction and Maintenance Therapeutic Response in Crohn's Disease
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 入组人数
- 47
- 试验地点
- 5
- 主要终点
- Vedolizumab concentration at week 6
研究概览
简要总结
Vedolizumab (VDZ) is a monoclonal antibody which has shown its efficacy in Crohn's disease by inducing and maintaining clinical response/remission. The French marketing authorization was obtained for Crohn's disease in patients in failure with anti-TNF (Tumor Necrosis Factor) agents.
For Crohn's disease patients treated with vedolizumab, a strong association between vedolizumab serum levels and clinical response to induction and maintenance was demonstrated by anterior studies.
It could be of paramount interest to early identify Crohn's Disease patients under vedolizumab who will be responders to vedolizumab induction and to identify those who will achieve clinical remission under maintenance therapy with vedolizumab.
Researchers decided to assess the clinical response to vedolizumab induction at week 10. For clinically non-responders at week 10, an additional dose of 300 mg of vedolizumab will be infused at week 10 and then every four weeks.
详细描述
Vedolizumab (VDZ) is a monoclonal antibody that binds to the heterodimer alpha 4 beta 7 integrin and which has shown its efficacy in Crohn's disease by inducing and maintaining clinical response/remission. The French marketing authorization was obtained for Crohn's disease in patients in failure with anti-TNF (Tumor Necrosis Factor) agents.
For Crohn's disease patients treated with vedolizumab, a strong association between vedolizumab serum levels and clinical response to induction and maintenance was demonstrated by anterior studies.
It could be of paramount interest to early identify Crohn's Disease patients under vedolizumab who will be responders to vedolizumab induction and to identify those who will achieve clinical remission under maintenance therapy with vedolizumab.
Researchers decided to assess the clinical response to vedolizumab induction at week 10, as the Gemini III trial has reported, among patients who had experienced previous TNF (Tumor Necrosis Factor) antagonist failure. 15% of those given vedolizumab were in remission at week 6 (P=0.433) versus 12% under placebo. At week 10, 26% under vedolizumab were in remission versus 12% in the placebo arm.
Moreover, at week 10, the proportion of patients presenting a clinical response was significantly higher in Crohn's Disease patients treated with vedolizumab (46% vs 24%).
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
- 未提供
排除标准
- •Existing pregnancy, lactation, or intended pregnancy within the next 15 months
- •Minors or History of disease, including mental/emotional disorder that might interfere with their participation in the study
- •Serious secondary illnesses of an acute or chronic nature, which in the opinion of the investigator renders the patient unsuitable for inclusion into the study
- •Inability to comply with the protocol requirements
- •Inability to fill in the diary cards during the last 7 days before each visit
- •Presence of an ileo-/colonic stoma
- •Patients with known colonic stricture and exclusive or predominant anal or perineal Crohn's disease lesions
- •Known previous or concurrent malignancy (other than that considered surgically cured, with no evidence for recurrence for 5 years)
- •Short bowel syndrome
- •Previous treatments with natalizumab, efalizumab or rituximab.
- •Prior extensive colonic resection, obstructive (symptomatic) intestinal stricture, abdominal abscess, active or latent tuberculosis,
- •Documented Clostridium difficile superinfection;
- •Indeterminate colitis
- •Concomitant leukocyte apheresis.
- •Any contraindication to vedolizumab therapy
- •Patients who denied the protocol, not ability to accept or sign consent of the protocol
- •Subject involved in another interventional clinical trial
研究组 & 干预措施
Crohn's disease patients
The patients will receive vedolizumab in compliance with the marketing authorization regimen (300 mg at weeks 0, 2, 6 and then every 8 weeks) in Crohn's Disease patients in clinical failure or intolerant to anti-TNF (Tumor Necrosis Factor) drugs. In case of lack of clinical response at week 10 or loss of response in the follow-up, all patients will be optimized with vedolizumab 300 mg at week 10 (additional infusion) and every following 4 weeks in contrast with responder patients at week 10 who will not have vedolizumab infusion at this time-point but will receive the next vedolizumab infusion at week 14 and then every 8 weeks, as recommended.
干预措施: Vedolizumab (Drug)
结局指标
主要结局
Vedolizumab concentration at week 6
时间窗: Week 6
The primary objective is to determine the optimal threshold of Vedolizumab serum concentration measured at week 6 capable to predict the clinical response at week 10 with Vedolizumab.
次要结局
- Vedolizumab concentration at week 14(Week 14)
- Concentration of Vedolizumab at week 2(Week 2)
- Presence of specific antibodies (anti-integrins) at week 2(Week 2)
- Vedolizumab and calprotectin levels at week 2(Week 2)
- Vedolizumab and calprotectin levels at week 14(Week 14)
- Concentration of Vedolizumab at week 54(Week 54)
- Proportion of loss of clinical response(Week 54)
- Vedolizumab serum levels(Week 54)
- Specific antibodies (anti-integrins) level at week 54(Week 54)
- Concentration of Vedolizumab at week 14(Week 14)
- Presence of specific antibodies (anti-integrins) at week 14(Week 14)
- Intra and inter-individual heterogeneity of Vedolizumab levels(Week 54)