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

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.

Study Overview

• Status: Terminated
• Conditions: Crohn Disease
• Intervention / Treatment: Device: RoadMAB precision dashboard; Drug: Infliximab precision dosing

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 22 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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.

Device: RoadMAB precision dashboard; 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.; Drug: Infliximab precision dosing; The trial is testing whether precision dosing can more reliably achieve the targeted trough concentrations compared to standard dosing

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Obtain Safety Data for Optimal Dosing Strategy and Sample Size Estimation	Percentage of total patients adverse and/or serious adverse events	10 months
Enrollment Feasibility	Number of patients consented for 10 month study	10 months
Completion Feasibility	Percentage of patients that complete the study	10 months
Percentage of Patient Adherence to Stool Sample Collections	Percentage of patients that collected a stool sample for the study	10 months
RoadMAB Usability	Evaluate rate of physician adherence to the Dashboard	10 months
RoadMAB Efficacy	Percentage of patients achieving infus3 (Visit 4) infliximab concentration between >16 μg/ml as a dichotomous outcome	weeks 10-16
Percentage of Patient Adherence to Blood Sample Collection	Percentage of patients who provided blood sample collections.	10 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate Accuracy of Infliximab Concentration Targets - Median Difference Infusion 3	Median difference of infusion 3 (Visit 4) levels between cases and controls	Weeks 4-8
Evaluate Accuracy of Infliximab Concentration Targets - Incidence	Incidence of achieving infus2 (Visit 3) level between target range of >26 μg/ml as a dichotomous outcome	Weeks 2-3
Evaluate Accuracy of Infliximab Concentration Targets - Median Difference infus2	Median difference of infus2 (Visit 3) levels between cases and controls	Weeks 2-3
Evaluate Accuracy of Infliximab Concentration Targets - Maintenance	Percentage of achieving maintenance targets infus4-6 (Visits 5-7) >5 μg/ml	week2 10-30
Evaluate Accuracy of Infliximab Concentration Targets	Rate of development of anti-infliximab antibodies at any infusion between cases and controls	6 months
Infus4 (Visit 5) and infus6 (Visit 7): Clinical Response	Percent of patients that had an improvement in baseline wPCDAI by >17.5 or a wPCDAI<12.5	Weeks 10-30
Infus4 (Visit 5): Clinical Remission	Percentage of patients who had a wPCDAI <12.5 and off corticosteroids	Weeks 10-16
Sustained Remission	Percentage of patients with a wPCDAI <12.5 and off prednisone for all visits from infus4 (Visit 5) to infus6 (Visit 7)	Weeks 10-30
Infus4 (Visit 5): Fecal Biochemical Response	Percentage of patients with a ≥50% improvement in fecal calprotectin	Weeks 10-16
Infus4 (Visit 5): Fecal Biochemical Remission	Percentage of patients with a fecal calprotectin <250 μg/g	Week 10-16
Infus6 (Visit 7): Rate of Transmural Ileal	ileum subscore stage 0 (score = 0)	Weeks 18-30
Infus6 (Visit 7): Rate of Colonic Healing	all segments of colon subscore stage 0 (score = 0)	Weeks 18-30
Infus6 (Visit 7): Rate of Total Bowel Healing	total ileum and colonic subscore is not greater than stage 0 on either individual score	Weeks 10-30

Collaborators and Investigators

• Sponsor: Children's Hospital Medical Center, Cincinnati
• Collaborators: Crohn's and Colitis Foundation
• Investigators: Principal Investigator: Phillip Minar, MD, MS, Children's Hospital Medical Center, Cincinnati

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2021
• Primary Completion (Actual): August 1, 2024
• Study Completion (Actual): August 1, 2024

Study Registration Dates

• First Submitted: June 29, 2021
• First Submitted That Met QC Criteria: July 13, 2021
• First Posted (Actual): July 23, 2021

Study Record Updates

• Last Update Posted (Actual): March 11, 2026
• Last Update Submitted That Met QC Criteria: March 9, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Crohn Disease
• Other Study ID Numbers: 2020-0282

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No