Personalized Infliximab Induction Strategy With Model-informed Dosing in Patients With Crohn's Disease (REMODEL)

Cincinnati Children's Hospital Medical Center

Status and phase: Terminated; Phase 3; Phase 2

Conditions: Crohn Disease

Treatments: Drug: Precision dosing with a dashboard; Device: RoadMAB

Study type: Interventional

Funder types: Other

Identifiers

NCT04974099

2020-0282

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 6 patients

Sex: All

Ages: 6 to 22 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Written informed consent form from the patient (≥18 years old) or from parent/legal guardian if patient is <18 years old.
2. Written informed assent form from patient ≥11 years old.
3. Age criteria: ≥6 years to ≤22 years of age.
4. Diagnosis of Crohn's Disease
5. Starting infliximab (or biosimilar)
6. Anti-TNF naïve (never received infliximab, adalimumab, golimumab, certolizumab or anti-TNF biosimilar)
7. 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)
8. wPCDAI >12.5 (up to 6 weeks) prior to the first infliximab infusion
9. Negative urine pregnancy test for ALL female subjects
10. Negative TB (tuberculosis) blood test

Exclusion criteria

1. Diagnosis of ulcerative colitis or inflammatory bowel disease-unspecified
2. Prior treatment with infliximab, adalimumab, certolizumab or golimumab (or anti-TNF biosimilar)
3. Active or prior evidence in past 12 months of internal (abdominal/pelvic) penetrating fistula(e)
4. Active intestinal stricture (luminal narrowing with pre-stenotic dilation >3mm), intra-abdominal abscess or perianal abscess
5. Active Clostridium difficile infection or other known bacterial/viral gastroenteritis in last two weeks
6. Current ileostomy, colostomy, ileoanal pouch, and/or previous extensive small bowel resection leading to short bowel syndrome
7. History of autoimmune disease (including autoimmune hepatitis, primary sclerosing cholangitis, thyroiditis, psoriasis or juvenile idiopathic arthritis)
8. Treatment with another investigational drug within four weeks.
9. Treatment with intravenous antibiotics within four weeks.
10. Planned continuation of 6-mercaptopurine or azathioprine (Imuran) during study.
11. Planned continuation of methotrexate during study.
12. Treatment with intravenous corticosteroids within two weeks.
13. Currently pregnant, breast feeding or plans in next 12 months to become pregnant
14. Inability or failure to provide informed assent/consent

Trial design

Primary purpose: Other

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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6 participants in 1 patient group

RoadMAB dashboard system

Experimental group

Description:

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.

Treatment:

Device: RoadMAB

Drug: Precision dosing with a dashboard