Personalized Infliximab Induction Strategy With Model-informed Dosing in Patients With Crohn's Disease
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Obtain Safety Data for Optimal Dosing Strategy and Sample Size Estimation
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, with many of those being young children and adolescents. Physicians need better ways to inform decisions on treatment.
The main reason for this research study is to determine if a computer program that formulates a dose based on a patient's blood testing results can better achieve the optimal drug level as compared to standard dosing.
详细描述
This is a Pilot study to evaluate safety, feasibility and efficacy of utilizing pharmacokinetic modeling to provide an individualized infliximab induction regimen in children and young adults with moderate to severe Crohn's disease. This clinical study is designed with the hypothesis that treatment regimens that account for individual (patient) drug clearance (pharmacokinetic modeling) will not only be safe and cost-effective, but also more effective in reducing intestinal inflammation than as-labeled dosing (ALD) regimens.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 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 form from the patient (≥18 years old) or from parent/legal guardian if patient is <18 years old.
- •Written informed assent form from patient ≥11 years old.
- •Age criteria: ≥6 years to ≤22 years of age.
- •Diagnosis of Crohn's Disease
- •Starting infliximab (or biosimilar)
- •Anti-TNF naïve (never received infliximab, adalimumab, golimumab, certolizumab or anti-TNF biosimilar)
- •Fecal calprotectin >250 µg/g or fecal lactoferrin >10 µg/g (up to 6 weeks prior to starting infliximab) or endoscopic evidence of active Crohn's disease (up to 90 days prior to starting infliximab)
- •wPCDAI >12.5 (up to 6 weeks) prior to the first infliximab infusion
- •Negative urine pregnancy test for ALL female subjects
- •Negative TB (tuberculosis) blood test
排除标准
- •Diagnosis of ulcerative colitis or inflammatory bowel disease-unspecified
- •Prior treatment with infliximab, adalimumab, certolizumab or golimumab (or anti-TNF biosimilar)
- •Active or prior evidence in past 12 months of internal (abdominal/pelvic) penetrating fistula(e)
- •Active intestinal stricture (luminal narrowing with pre-stenotic dilation >3mm), intra-abdominal abscess or perianal abscess
- •Active Clostridium difficile infection or other known bacterial/viral gastroenteritis in last two weeks
- •Current ileostomy, colostomy, ileoanal pouch, and/or previous extensive small bowel resection leading to short bowel syndrome
- •History of autoimmune disease (including autoimmune hepatitis, primary sclerosing cholangitis, thyroiditis, psoriasis or juvenile idiopathic arthritis)
- •Treatment with another investigational drug within four weeks.
- •Treatment with intravenous antibiotics within four weeks.
- •Planned continuation of 6-mercaptopurine or azathioprine (Imuran) during study.
- •Planned continuation of methotrexate during study.
- •Treatment with intravenous corticosteroids within two weeks.
- •Currently pregnant, breast feeding or plans in next 12 months to become pregnant
- •Inability or failure to provide informed assent/consent
研究组 & 干预措施
Interventional arm with precision dosing
The intervention includes utilizing Clinical and Patient Decision Support Software (RoadMABTM) that will guide the selection of the first infliximab dose followed by subsequent infliximab dose and dosing interval during the maintenance phase. During induction, three infusions will occur at 0, 2 and 6 weeks, respectively. The RoadMABTM dashboard will utilize PK modeling software to provide an infliximab starting dose recommendation (range of 5-12 mg/kg) based on the patients biochemical profile. As noted, dosing frequency (weeks) during induction will not be altered during this study. Following the first three doses, the clinician will be informed of their patients PK profile within the RoadMABTM program and with a shared document (paper). RoadMABTM will provide additional dosing recommendations after each infusion (based on the latest drug concentration measures and blood biomarkers) with the final dose and interval selected by the treating physician.
干预措施: RoadMAB precision dashboard (Device)
Interventional arm with precision dosing
The intervention includes utilizing Clinical and Patient Decision Support Software (RoadMABTM) that will guide the selection of the first infliximab dose followed by subsequent infliximab dose and dosing interval during the maintenance phase. During induction, three infusions will occur at 0, 2 and 6 weeks, respectively. The RoadMABTM dashboard will utilize PK modeling software to provide an infliximab starting dose recommendation (range of 5-12 mg/kg) based on the patients biochemical profile. As noted, dosing frequency (weeks) during induction will not be altered during this study. Following the first three doses, the clinician will be informed of their patients PK profile within the RoadMABTM program and with a shared document (paper). RoadMABTM will provide additional dosing recommendations after each infusion (based on the latest drug concentration measures and blood biomarkers) with the final dose and interval selected by the treating physician.
干预措施: Infliximab precision dosing (Drug)
结局指标
主要结局
Obtain Safety Data for Optimal Dosing Strategy and Sample Size Estimation
时间窗: 10 months
Percentage of total patients adverse and/or serious adverse events
Enrollment Feasibility
时间窗: 10 months
Number of patients consented for 10 month study
Completion Feasibility
时间窗: 10 months
Percentage of patients that complete the study
Percentage of Patient Adherence to Stool Sample Collections
时间窗: 10 months
Percentage of patients that collected a stool sample for the study
RoadMAB Usability
时间窗: 10 months
Evaluate rate of physician adherence to the Dashboard
RoadMAB Efficacy
时间窗: weeks 10-16
Percentage of patients achieving infus3 (Visit 4) infliximab concentration between \>16 μg/ml as a dichotomous outcome
Percentage of Patient Adherence to Blood Sample Collection
时间窗: 10 months
Percentage of patients who provided blood sample collections.
次要结局
- Evaluate Accuracy of Infliximab Concentration Targets - Median Difference Infusion 3(Weeks 4-8)
- Infus4 (Visit 5): Clinical Remission(Weeks 10-16)
- Evaluate Accuracy of Infliximab Concentration Targets - Incidence(Weeks 2-3)
- Evaluate Accuracy of Infliximab Concentration Targets - Median Difference infus2(Weeks 2-3)
- Evaluate Accuracy of Infliximab Concentration Targets - Maintenance(week2 10-30)
- Evaluate Accuracy of Infliximab Concentration Targets(6 months)
- Infus4 (Visit 5) and infus6 (Visit 7): Clinical Response(Weeks 10-30)
- Sustained Remission(Weeks 10-30)
- Infus4 (Visit 5): Fecal Biochemical Response(Weeks 10-16)
- Infus4 (Visit 5): Fecal Biochemical Remission(Week 10-16)
- Infus6 (Visit 7): Rate of Transmural Ileal(Weeks 18-30)
- Infus6 (Visit 7): Rate of Colonic Healing(Weeks 18-30)
- Infus6 (Visit 7): Rate of Total Bowel Healing(Weeks 10-30)