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

Crohn Disease Clinical Trial

— REMODEL  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04974099
• Other study ID #: 2020-0282
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: October 1, 2021
• Est. completion date: August 1, 2024

Study information

• Verified date: January 2024
• Source: Children's Hospital Medical Center, Cincinnati
• Contact: Phillip Minar, MD, MS
• Phone: 513-636-4415
• Email: phillip.minar[@]cchmc.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: August 1, 2024
• Est. primary completion date: August 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 22 Years

Eligibility

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

Related Conditions & MeSH terms

• Crohn Disease

Intervention

Device:
• RoadMAB
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:
• Precision dosing with a dashboard
The trial is testing whether precision dosing can more reliably achieve the targeted trough concentrations compared to standard dosing

Locations

Country	Name	City	State
United States	Cincinnati Children's Hospital	Cincinnati	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Children's Hospital Medical Center, Cincinnati	Crohn's and Colitis Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Obtain safety data for optimal dosing strategy and sample size estimation	Number of adverse and/or serious adverse events	2 years
Primary	Enrollment feasibility	Evaluate the rate of recruitment	2 years
Primary	Completion feasibility	Number of patients that complete the study	2 years
Primary	Rate of patient adherence to stool and blood sample collections	patient adherence to stool and blood sample collections	2 years
Primary	RoadMAB Usability	Evaluate rate of physician adherence to RoadMAB dosing recommendation	2 years
Primary	RoadMAB Efficacy	Rate of achieving infus3 (Visit 4) infliximab concentration between 16-24 µg/ml as a dichotomous outcome	2 years
Secondary	Evaluate accuracy of infliximab concentration targets - Median difference infus3	Median difference of infus3 (Visit 4) levels between cases and controls	2 years
Secondary	Evaluate accuracy of infliximab concentration targets - Incidence	Incidence of achieving infus2 (Visit 3) level between target range of 26-34 µg/ml as a dichotomous outcome	2 years
Secondary	Evaluate accuracy of infliximab concentration targets - Median difference infus2	Median difference of infus2 (Visit 3) levels between cases and controls	2 years
Secondary	Evaluate accuracy of infliximab concentration targets - Maintenance	Rates of achieving maintenance targets infus4-6 (Visits 5-7) between 5-10 µg/ml	2 years
Secondary	Evaluate accuracy of infliximab concentration targets	Rate of development of antiinfliximab antibodies at any infusion between cases and controls	2 years
Secondary	Infus4 (Visit 5) and infus6 (Visit 7): Clinical Response	Improvement in baseline wPCDAI by >17.5 or a wPCDAI<12.5	2 years
Secondary	Infus4 (Visit 5) and infus6 (Visit 7): Clinical Remission	wPCDAI <12.5 and off corticosteroids	2 years
Secondary	Sustained Remission	wPCDAI <12.5 and off prednisone for all visits from infus4 (Visit 5) to infus6 (Visit 7)	2 years
Secondary	Infus4 (Visit 5) and Infus6 (Visit 7): Fecal Biochemical Response	=50% improvement in fecal calprotectin	2 years
Secondary	Infus4 (Visit 5) and Infus6 (Visit 7): Fecal Biochemical Remission	fecal calprotectin <250 µg/g	2 years
Secondary	Infus6 (Visit 7): Rate of transmural ileal	ileum subscore stage 0 (score = 0)	2 years
Secondary	Infus6 (Visit 7): Rate of colonic healing	all segments of colon subscore stage 0 (score = 0)	2 years
Secondary	Infus6 (Visit 7): Rate of total bowel healing	total ileum and colonic subscore is not greater than stage 0 on either individual score	2 years