Precise Infliximab Exposure and Pharmacodynamic Control to Achieve Deep Remission in Pediatric Crohn's Disease
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 180
- 试验地点
- 22
- 主要终点
- Rate of Deep Remission
研究概览
简要总结
Approximately 3 million people in the United States are living with inflammatory bowel disease, which includes Crohn's Disease (CD). There are limited treatment options approved for use in children and adults with Crohn's disease. Physicians need better ways to inform decisions on treatment.
The main reason for this research study is to determine if a computer program that calculates an individualized dose based on a patient's blood testing results (precision dosing) can better achieve the best possible response to infliximab compared to standard dosing (conventional dosing).
详细描述
This is an open-label, cluster randomized clinical trial to test whether precision infliximab dosing with a targeted concentration intervention is superior in achieving deep remission (endoscopic healing and clinical remission) compared to patients receiving conventional infliximab dosing.
With recognition that CD patients who achieve the "target" of deep remission with anti-TNF dose optimizations following pharmacodynamic monitoring had a significant reduction in CD-related adverse events, our central hypothesis is precision dosing with infliximab during induction and maintenance will achieve superior rates of deep remission vs. conventional care (control arm)
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 6 Years 至 22 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent from the patient (≥18 years old) or from parent/legal guardian if patient is <18 years old
- •Written informed assent from patient when age appropriate
- •Diagnosis of Crohn's disease within the last 90 days (luminal-only or luminal with a perianal fistula or abscess treated with antibiotics for at least 7 days)
- •≥6 years to ≤22 years of age, anti-TNF naïve and starting infliximab
- •Clinical activity and luminal inflammation, defined by both (1) and (2)
- •(1) PCDAI≥10 (<18 years old) or CDAI ≥150 (≥18 years old) in last 60 days before the decision to start infliximab
- •(2) SES-CD>6, or SES-CD>3 for isolated ileal disease (or a report of large intestinal ulcerations)* within the last 60 days or a fecal calprotectin >250 μg/g within last 75 days prior to screening
- •C-reactive protein >1.0 mg/dL in last 30 days and/or fecal calprotectin >250 μg/g within last 75 days prior to screening
- •Negative TB (tuberculosis) interferon-gamma release test and a negative urine pregnancy test for female patients (if menstruation has started)
排除标准
- •Diagnosis of ulcerative colitis or inflammatory bowel disease-unspecified
- •Prior use of anti-TNF therapy (infliximab, adalimumab, certolizumab pegol, or golimumab)
- •Internal (abdominal/pelvic) penetrating fistula(e) in last 180 days
- •Intra-abdominal abscess/phlegmon/inflammatory mass in the last 180 days
- •Active perianal abscess (receiving oral antibiotics for <7 days)
- •Intestinal stricture (luminal narrowing with pre-stenotic dilation >3 cm) and surgery planned in the next 90 days
- •Have tested positive for Clostridium difficile toxin (stool assay) or other intestinal pathogens within 14 days of screening unless a repeat examination is negative and there are no signs of ongoing infection with that pathogen.
- •Current hospitalization for complications of severe Crohn's disease
- •Planned use of methotrexate or 6-mercaptopurine (azathioprine) during the induction (first 3 doses of infliximab) phase
- •Current ileostomy, colostomy, ileoanal pouch, and/or previous extensive small bowel resection (>35 cm) or any CD surgery planned within the next 90 days
- •History of autoimmune hepatitis, primary sclerosing cholangitis, thyroiditis, or juvenile idiopathic arthritis
- •Treatment with another investigational drug in the last four weeks
- •History of malignancy (including lymphoma or leukemia)
- •Currently receiving treatment for histoplasmosis
- •History of TB, human immunodeficiency virus (HIV), an immunodeficiency syndrome, a central nervous system demyelinating disease, history of heart failure or receiving intravenous antibiotics in last 14 days for any infection
- •Currently pregnant, breast feeding or plans to become pregnant in the next 1 year
- •Inability or failure to provide informed assent/consent
- •Any developmental disabilities that would impede providing assent/consent
研究组 & 干预措施
Conventional dosing
Induction Phase: 5-7.5 mg/kg at 0, 2, and 6 weeks. Maintenance Phase : 5-10 mg/kg at every 4-8 weeks based on results of drug concentration monitoring for a flat target of 5-10 μg/mL.
干预措施: Infliximab (Drug)
Precision dosing
Induction: 5-12.5 mg/kg at 0, 2, and 6 weeks to target a week6 concentration of 18-24 μg/mL with dosing support provided by the RoadMABTM clinical decision support tool. Maintenance: 5-15 mg/kg every 4-8 weeks to achieve apriori pharmacokinetic and pharmacodynamic targets (CRP, disease activity scores and fecal calprotectin) with dosing support provided by the RoadMABTM clinical decision support tool.
干预措施: Infliximab (Drug)
Precision dosing
Induction: 5-12.5 mg/kg at 0, 2, and 6 weeks to target a week6 concentration of 18-24 μg/mL with dosing support provided by the RoadMABTM clinical decision support tool. Maintenance: 5-15 mg/kg every 4-8 weeks to achieve apriori pharmacokinetic and pharmacodynamic targets (CRP, disease activity scores and fecal calprotectin) with dosing support provided by the RoadMABTM clinical decision support tool.
干预措施: RoadMAB (Device)
结局指标
主要结局
Rate of Deep Remission
时间窗: Week 52
Pediatric Crohn's disease activity index (PCDAI) \<10 (child) or Crohn's disease activity index\<150 (adult), off prednisone/budesonide for \>8 weeks and Simple Endoscopic Scorer Crohn's Disease (SES-CD) SES-CD≤2
次要结局
- Rate of Complete Endoscopic Healing(Week 52)
- Rate of Endoscopic Remission(Week 52)
- Rate of IBD related event - Fistula(Week 0 - Week 52)
- Rate of Endoscopic Healing(Week 52)
- Rate of Clinical Response(Week 14 and Week 52)
- Rate of Primary Biologic Nonresponse(Week 16)
- Rate of Steroid-free Clinical Remission(Week 14 and Week 52)
- Rate of Mucosal Healing(Week 52)
- PK Model Bias(Week 0 - Week 52)
- Rate of IBD related event - Intestinal stricture(Week 0 - Week 52)
- Rate of IBD related event - Starting corticosteroids(Week 0 - Week 52)
- Rate of Primary Clinical Nonresponse(Week 16)
- Rate of Sustained Steroid-free Remission(Week 22 - Week 52)
- Rate of Steroid-free Remission -biomarker composite(Week 14 and Week 52)
- Rate of Growth Restoration - Weight change(Week 14 - Week 52)
- PK Model Precision(Week 0 - Week 52)
- Rate of IBD related - Hospitalization(Week 0 - Week 52)
- Rate of IBD related event - Surgery(Week 0 - Week 52)
- Rate of IBD related event - Antibodies to infliximab(Week 0 - Week 52)
- Correlation between infliximab induction exposure and endoscopic remission(Exposure Week 0 - Week 14, Efficacy Week 52)
- Correlation between infliximab induction exposure and deep remission(Exposure Week 0 - Week 14, Efficacy Week 52)
- Rate of Serious Adverse events(Week 0 - Week 52)
- Rate of Growth Restoration- Height velocity(Week 14 - Week 52)
- PK of infliximab in pediatric patients(Week 0 - Week 52)
- Patient Reported Outcome-2 (PRO2) Response(Week 6, Week 14, Week 26, Week 52)
- Quality of Life & Disability -IMPACT-III score(Week 52)
- Quality of Life & Disability - Short Inflammatory Bowel Disease score(Week 52)
- Process Evaluation -Usability of Decision Support Tool(Week 0 - Week 52)
- Patient Reported Outcome-2 (PRO2) Remission(Week 6, Week 14, Week 26, Week 52)
- Quality of Life & Disability - Inflammatory Bowel Disease Disk score(Week 52)
- Rate of Adverse events(Week 0 - Week 52)