Clinical trial NCT04974099: Personalized Infliximab Induction Strategy With Model-informed Dosing in Patients With Crohn's Disease
Official title: Personalized Infliximab Induction Strategy With Model-informed Dosing in Patients With Crohn's Disease
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Crohn Disease
Lead sponsor: Children's Hospital Medical Center, Cincinnati
Sponsor class: OTHER
Collaborators: name: Crohn's and Colitis Foundation
First posted: 2021-07-23
Enrollment: 6
Sex: ALL
Minimum age (years): 6
Maximum age (years): 22
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: The intervention cohort includes patients, age 6-22 years old who have been diagnosed with CD, are naïve to anti-TNF medications and are scheduled to start infliximab (or infliximab biosimilar).
Primary purpose: OTHER

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.

Eligibility criteria: 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

Primary outcomes:
measure: Obtain safety data for optimal dosing strategy and sample size estimation
timeFrame: 2 years
measure: Enrollment feasibility
timeFrame: 2 years
measure: Completion feasibility
timeFrame: 2 years
measure: Rate of patient adherence to stool and blood sample collections
timeFrame: 2 years
measure: RoadMAB Usability
timeFrame: 2 years
measure: RoadMAB Efficacy
timeFrame: 2 years
Secondary outcomes:
measure: Evaluate accuracy of infliximab concentration targets - Median difference infus3
timeFrame: 2 years
measure: Evaluate accuracy of infliximab concentration targets - Incidence
timeFrame: 2 years
measure: Evaluate accuracy of infliximab concentration targets - Median difference infus2
timeFrame: 2 years
measure: Evaluate accuracy of infliximab concentration targets - Maintenance
timeFrame: 2 years
measure: Evaluate accuracy of infliximab concentration targets
timeFrame: 2 years
measure: Infus4 (Visit 5) and infus6 (Visit 7): Clinical Response
timeFrame: 2 years
measure: Infus4 (Visit 5) and infus6 (Visit 7): Clinical Remission
timeFrame: 2 years
measure: Sustained Remission
timeFrame: 2 years
measure: Infus4 (Visit 5) and Infus6 (Visit 7): Fecal Biochemical Response
timeFrame: 2 years
measure: Infus4 (Visit 5) and Infus6 (Visit 7): Fecal Biochemical Remission
timeFrame: 2 years
measure: Infus6 (Visit 7): Rate of transmural ileal
timeFrame: 2 years
measure: Infus6 (Visit 7): Rate of colonic healing
timeFrame: 2 years
measure: Infus6 (Visit 7): Rate of total bowel healing
timeFrame: 2 years
Other outcomes:
Locations:
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital
state: Ohio
Study officials:
affiliation: Children's Hospital Medical Center, Cincinnati
name: Phillip Minar, MD, MS
role: PRINCIPAL_INVESTIGATOR
References: