EFFICACI : EFFicacy of Intravenous Infliximab Versus Vedolizumab After Failure of subCutaneous Anti-TNF in Patients With UlCerative Colitis : A Double Blinded Randomized Clinical Trial
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 151
- 试验地点
- 19
- 主要终点
- Remission
研究概览
简要总结
Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) that results from immune dysregulation. Arguably, the development of Tumor Necrosis Factor (TNF) antagonists (including infliximab, adalimumab and golimumab) revolutionized the management of immune-mediated chronic diseases in the past two decades.
However, about one third of patients will not respond to a first anti-TNF treatment and 10% to 30% will loose response to anti-TNF during the follow-up.
Historically, a switch between anti-TNF was performed to recapture remission and response to anti-TNF. Recently, a new biologic therapy blocking another target has been approved and is now reimbursed during ulcerative colitis, namely vedolizumab. Vedolizumab is an anti-integrin agent avoiding the recruitment of lymphocytes specifically in inflamed gut tissue.
Emerging data suggest that a switch of therapeutic class (meaning a change of biologic target with Non-TNF-targeted biologic) in case of clinical failure or insufficient response to anti-TNF may be the best choice. This idea of a switch out of the anti-TNF class is also supported by data on drug monitoring that may help physician decision making in case of loss of response. However, no trial is currently available and ongoing to assess the best therapeutic strategy. The aim of the proposed study is to assess the best biological based strategy in patient losing response to a first subcutaneous anti-TNF (golimumab and/or adalimumab).
详细描述
Design :
A prospective, multicenter, randomized, double blind clinical trial
Primary objective :
To determine whether a non-TNF-targeted biologic (vedolizumab) is superior to infliximab to treat patient with UC losing response or with a primary failure to a first subcutaneous anti-TNF drug at week 14.
Secondary objective :
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
- Triple (Participant, Care Provider, Investigator)
盲法说明
The investigator will proceed to the patient randomization as follows :
- The investigator fulfill the electronic case report form (eCRF)
- The randomization will be performed through the eCRF.
- A mail will be sent to the pharmacy that included the inclusion number of the patient, the group allocated and the dose of infliximab or vedolizumab to be infused.
- A mail will be sent to the investigator that included only the inclusion number of the patient.
The trial is conducted in a double-blind manner. The biostatistician who generated the randomization list, the person in charge of pharmacovigilance, the pharmacy of the clinical trials of the Rennes university hospital and the pharmacist of the recruiting center can have access to the arm of treatment under study.
Patients and physicians will not know the nature of the molecules administered.
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or non-pregnant female, non-lactating female;
- •18 years of age or older and less than 75 years ;
- •Documented diagnosis of UC for at least 6 months ;
- •Left side colitis or pancolitis ;
- •Moderate to severe disease according to a Mayo score equal or above 6 with a Mayo endoscopic sub-score of 2 or 3 ;
- •Active disease despite ongoing treatment with adalimumab or golimumab for at least 12 weeks (inadequate response, failure, loss of response or intolerance) ;
- •Ability of the subject to participate fully in all aspects of this clinical trial ;
- •Written informed consent must be obtained and documented ;
- •Naïve to Janus kinase inhibitor (JAK inhibitor) ;
- •Affiliation to the national health insurance.
- •Non inclusion Criteria:
- •Contraindication to continue TNF antagonist (ongoing abscess(es), clinical suspicion of tuberculosis, past allergic reaction) ;
- •Contraindication to vedolizumab treatment ;
- •Steroid treatment > 20 mg/day for at least two weeks before baseline ;
- •Proctitis ;
- •Proctocolectomy or subtotal colectomy ;
- •Planned surgery within the year of the trial ;
- •Previous exposure to vedolizumab or infliximab ;
- •History of cancer during the past 5 years ;
- •Pregnancy or breastfeeding
- •Adults legally protected (under judicial protection, guardianship, or supervision), persons deprived of their liberty.
- •Ongoing participation to another interventional study
排除标准
- 未提供
研究组 & 干预措施
Infliximab
Infliximab : The treatment is infused at a dose of 5 mg/kg at week 0, 2 and 6 and then every 8 weeks.
干预措施: Infliximab (Drug)
Vedolizumab
Vedolizumab : The treatment is infused at a dose of 300 mg at week 0, 2 and 6 and then every 8 weeks.
干预措施: Vedolizumab Injection (Drug)
结局指标
主要结局
Remission
时间窗: Week 14
The rate of patients with clinical and endoscopic steroid free-remission (Mayo score ≤ 2 without subscore \> 1) at week 14
次要结局
- anti-drug antibodies concentration(baseline)
- Blood trough concentration of infliximab or vedolizumab(at baseline, weeks 0, 2, 6, 14 and 54)
- Fecal trough concentration of infliximab or vedolizumab(at baseline, weeks 0, 2, 6, 14 and 54)
- Mayo score(Week 54)
- Faecal calprotectin level(At week 14 and 54)
- Colectomy or hospitalization for disease flare(through study completion, an average of 1 year)
- Partial Mayo score(at week 2, 6, 14, 54)
- Endoscopic subscore of the mayo Score(at week 14 and 54)
- Inflammatory Bowel Disease Questionnaire (IBDQ) index(at baseline week 14 and 54)
- Inflammatory Bowel Disease-Disability Index (IBD-DI)(at baseline week 14 and 54)
- Inflammatory Bowel Disease-Disk (IBD-Disk)(at baseline week 14 and 54)
- Adverse events(through study completion, an average of 1 year)
- Last trough concentration of the first subcutaneous agent(baseline)