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

Phase 2

Terminated

• Conditions: Crohn Disease
• Interventions: Device: RoadMAB; Drug: Precision dosing with a dashboard

• Registration Number: NCT04974099
• Lead Sponsor: Children's Hospital Medical Center, Cincinnati

Brief Summary

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.

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 Timeline

• Study First Submitted: 2021-06-29
• Study First Submitted QC: 2021-07-13
• Study First Posted: 2021-07-23
• Study Start: 2021-10-01
• Status Verified: 2024-01
• Primary Completion: 2024-08-01
• Study Completion: 2024-08-01
• Last Update Submitted: 2024-12-12
• Last Update Posted: 2024-12-17

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 6

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
RoadMAB dashboard system	Precision dosing with a dashboard	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.
RoadMAB dashboard system	RoadMAB	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.

Primary Outcome Measures

Name	Time	Method
Completion feasibility	2 years	Number of patients that complete the study
Obtain safety data for optimal dosing strategy and sample size estimation	2 years	Number of adverse and/or serious adverse events
Enrollment feasibility	2 years	Evaluate the rate of recruitment
Rate of patient adherence to stool and blood sample collections	2 years	patient adherence to stool and blood sample collections
RoadMAB Usability	2 years	Evaluate rate of physician adherence to RoadMAB dosing recommendation
RoadMAB Efficacy	2 years	Rate of achieving infus3 (Visit 4) infliximab concentration between 16-24 μg/ml as a dichotomous outcome

Secondary Outcome Measures

Name	Time	Method
Infus6 (Visit 7): Rate of colonic healing	2 years	all segments of colon subscore stage 0 (score = 0)
Evaluate accuracy of infliximab concentration targets - Incidence	2 years	Incidence of achieving infus2 (Visit 3) level between target range of 26-34 μg/ml as a dichotomous outcome
Evaluate accuracy of infliximab concentration targets - Median difference infus2	2 years	Median difference of infus2 (Visit 3) levels between cases and controls
Sustained Remission	2 years	wPCDAI \<12.5 and off prednisone for all visits from infus4 (Visit 5) to infus6 (Visit 7)
Infus4 (Visit 5) and infus6 (Visit 7): Clinical Remission	2 years	wPCDAI \<12.5 and off corticosteroids
Infus4 (Visit 5) and Infus6 (Visit 7): Fecal Biochemical Response	2 years	≥50% improvement in fecal calprotectin
Infus4 (Visit 5) and Infus6 (Visit 7): Fecal Biochemical Remission	2 years	fecal calprotectin \<250 μg/g
Infus6 (Visit 7): Rate of total bowel healing	2 years	total ileum and colonic subscore is not greater than stage 0 on either individual score
Evaluate accuracy of infliximab concentration targets - Median difference infus3	2 years	Median difference of infus3 (Visit 4) levels between cases and controls
Evaluate accuracy of infliximab concentration targets	2 years	Rate of development of antiinfliximab antibodies at any infusion between cases and controls
Evaluate accuracy of infliximab concentration targets - Maintenance	2 years	Rates of achieving maintenance targets infus4-6 (Visits 5-7) between 5-10 μg/ml
Infus4 (Visit 5) and infus6 (Visit 7): Clinical Response	2 years	Improvement in baseline wPCDAI by \>17.5 or a wPCDAI\<12.5
Infus6 (Visit 7): Rate of transmural ileal	2 years	ileum subscore stage 0 (score = 0)

Trial Locations

Locations (1)

Cincinnati Children's Hospital; 🇺🇸 Cincinnati, Ohio, United States