Predicting Response to Vedolizumab in Pediatric Inflammatory Bowel Diseases (IBD) Including Drug Levels: a Multi-center Prospective Cohort Study, From the Pediatric IBD Porto Group of European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN)
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 142
- 试验地点
- 15
- 主要终点
- Complete remission at week 108
研究概览
简要总结
Vedolizumab (VDZ) is a humanized immunoglobulin G1 monoclonal antibody acting against α4β7 integrin which modulates lymphocyte trafficking in the gut.
Results from the adult GEMINI-1 and GEMINI-2 trials demonstrated clinical efficacy in induction and maintenance of remission in both ulcerative colitis (UC) and Crohn's disease (CD), respectively.
Recent real life cohorts in adults support the effectiveness of VDZ in inducing and maintaining remission, both in CD and UC. In pediatrics, there are very limited data on the use of VDZ besides two retrospective case series.
Data on immunogenicity and therapeutic drug monitoring (TDM) of VDZ is conflicting in adults and practically non-existent in children.
The investigators aim to prospectively explore the real life short and longer term outcomes of VDZ in pediatric IBD (including growth) and to develop a prediction model for treatment success based on VDZ trough levels and other clinical and laboratory variables.
详细描述
This is a multi-center prospective cohort study in which the investigators are aim to enroll 140 children under the age of 18 years, diagnosed with CD, inflammatory bowel disease unclassified (IBDU) or UC (approximately 70 in UC/IBDU and 70 in the CD group) who commenced on Vedolizumab for any reason at the discretion of the treating physician.
Patients will be followed up to 3 years at 8 different time points: week 0, week 2, week 6, week 14, week 30, week 54 (1 year), week 108 (2 years) and week 162 (3 years). Blood work will be collected at each visit during the time of venous access insertion for the drug infusion for serum and stool sample will be collected at visits 0, 14, 30, and 54. In addition, at week 0 and 14 whole blood will be collected into a PaxGene tube for gene expression analysis.
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
- — 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Children under the age of 18 years.
- •IBD Diagnosis
- •Initiating Vedolizumab therapy
排除标准
- •Starting Vedolizumab to prevent post operative recurrence
研究组 & 干预措施
Vedolizumab
IV Vedolizumab 177mg/m2 Body Surface Area (BSA), max. 300mg Induction regimen: 0,2,6 and then every 8 weeks
干预措施: Vedolizumab (Drug)
结局指标
主要结局
Complete remission at week 108
时间窗: weeks 108
As defined by all three criteria: i. Steroids and Exclusive enteral nutrition (EEN) (defined as \>50% of daily calories with enteral nutrition)- free ii. Clinical remission (i.e. weighted Pediatric Crohn's Disease Activity Index (wPCDAI) \<12.5 points in CD, and Paediatric Ulcerative Colitis Activity Index (PUCAI) \<10 in UC) iii. CRP lower than 1.5 times upper normal limit (UNL) (may be substituted by Erythocytes Sedimentation Rate (ESR) if CRP missing)
Complete remission at week 14
时间窗: weeks 14
As defined by all three criteria: i. Steroids and Exclusive enteral nutrition (EEN) (defined as \>50% of daily calories with enteral nutrition)- free ii. Clinical remission (i.e. weighted Pediatric Crohn's Disease Activity Index (wPCDAI) \<12.5 points in CD, and Paediatric Ulcerative Colitis Activity Index (PUCAI) \<10 in UC) iii. CRP lower than 1.5 times upper normal limit (UNL) (may be substituted by Erythocytes Sedimentation Rate (ESR) if CRP missing)
Complete remission at week 162
时间窗: weeks 162
As defined by all three criteria: i. Steroids and Exclusive enteral nutrition (EEN) (defined as \>50% of daily calories with enteral nutrition)- free ii. Clinical remission (i.e. weighted Pediatric Crohn's Disease Activity Index (wPCDAI) \<12.5 points in CD, and Paediatric Ulcerative Colitis Activity Index (PUCAI) \<10 in UC) iii. CRP lower than 1.5 times upper normal limit (UNL) (may be substituted by Erythocytes Sedimentation Rate (ESR) if CRP missing)
Complete remission at week 30
时间窗: weeks 30
As defined by all three criteria: i. Steroids and Exclusive enteral nutrition (EEN) (defined as \>50% of daily calories with enteral nutrition)- free ii. Clinical remission (i.e. weighted Pediatric Crohn's Disease Activity Index (wPCDAI) \<12.5 points in CD, and Paediatric Ulcerative Colitis Activity Index (PUCAI) \<10 in UC) iii. CRP lower than 1.5 times upper normal limit (UNL) (may be substituted by Erythocytes Sedimentation Rate (ESR) if CRP missing)
Complete remission at week 54
时间窗: weeks 54
As defined by all three criteria: i. Steroids and Exclusive enteral nutrition (EEN) (defined as \>50% of daily calories with enteral nutrition)- free ii. Clinical remission (i.e. weighted Pediatric Crohn's Disease Activity Index (wPCDAI) \<12.5 points in CD, and Paediatric Ulcerative Colitis Activity Index (PUCAI) \<10 in UC) iii. CRP lower than 1.5 times upper normal limit (UNL) (may be substituted by Erythocytes Sedimentation Rate (ESR) if CRP missing)
次要结局
- Adverse events(week 30, week 54, week 108, week 162)
- Steroid and EEN free clinical response (without the need for normal CRP) using PCDAI or PUCAI score and concomitant medication list.(week 30, week 54, week 108, week 162)
- Fecal calprotectin levels(week 30, week 54, week 108, week 162)
- Rate of loss of response including drug levels(week 30, week 54, week 108, week 162)
- Time to induction of remission(week 30, week 54, week 108, week 162)
- Longitudinal Physician Global Assessment (PGA)(week 30, week 54, week 108, week 162)
- Height velocity as compared with the year prior to commencing VDZ(week 30, week 54, week 108, week 162)
- Need for surgical interventions (including resections, colectomy, and dilatations)(week 30, week 54, week 108, week 162)
- Steroid and EEN free clinical remission (without the need for normal CRP) using PCDAI or PUCAI score and concomitant medication list.(week 30, week 54, week 108, week 162)
- Steroid dependency (defined as cumulative use of >4 months in a year with at least one need to increase dose while weaning)(week 30, week 54, week 108, week 162)
- serum CRP levels(week 30, week 54, week 108, week 162)
- Measures of mucosal inflammation as available as part of clinical care using endoscopy, imaging or capsule endoscopy.(week 30, week 54, week 108, week 162)
研究者
Dr Dan Turner
Head, The Juliet Keidan Institute of Pediatric Gastroenterology, Hepatology and Nutrition, Shaare Zedek Medical Center, Jerusalem, Israel
Shaare Zedek Medical Center