Precise Infliximab Exposure and Pharmacodynamic Control to Achieve Deep Remission in Pediatric Crohn's Disease
Children's Hospital Medical Center, Cincinnati
Summary
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).
Description
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 achiev…
Eligibility
- Age range
- 6–22 years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: 1. Written informed consent from the patient (≥18 years old) or from parent/legal guardian if patient is \<18 years old 2. Written informed assent from patient when age appropriate 3. 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) 4. ≥6 years to ≤22 years of age, anti-TNF naïve and starting infliximab 5. 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 t…
Interventions
- DeviceRoadMAB
The RoadMAB Dashboard is a real-time decision support system that incorporates PK model-informed Bayesian estimation to provide precision dosing at the point of care.
- DrugInfliximab
Conventional dosing. Induction: 5-7.5 mg/kg at 0, 2, and 6 weeks. Maintenance: 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. 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.
Locations (11)
- Children's Hospital of Los AngelesLos Angeles, California
- Lucile Packard Children's Hospital StanfordPalo Alto, California
- Rady Children's Hospital San DiegoSan Diego, California
- Nemours Children's Health System-WilmingtonWilmington, Delaware
- Nemours Children's Health System-JacksonvilleJacksonville, Florida
- Riley Hospital for ChildrenIndianapolis, Indiana