Back to resultsPersonalized Infliximab Induction Strategy With Model-informed Dosing in Patients With Crohn's Disease (REMODEL)
Primary Purpose
Crohn Disease
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
RoadMAB
Precision dosing with a dashboard
Sponsored by
About this trial
This is an interventional other trial for Crohn Disease
Eligibility Criteria
Inclusion Criteria:
- Written informed consent form from the patient (≥18 years old) or from parent/legal guardian if patient is <18 years old.
- Written informed assent form from patient ≥11 years old.
- Age criteria: ≥6 years to ≤22 years of age.
- Diagnosis of Crohn's Disease
- Starting infliximab (or biosimilar)
- Anti-TNF naïve (never received infliximab, adalimumab, golimumab, certolizumab or anti-TNF biosimilar)
- 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)
- wPCDAI >12.5 (up to 6 weeks) prior to the first infliximab infusion
- Negative urine pregnancy test for ALL female subjects
- Negative TB (tuberculosis) blood test
Exclusion Criteria:
- Diagnosis of ulcerative colitis or inflammatory bowel disease-unspecified
- Prior treatment with infliximab, adalimumab, certolizumab or golimumab (or anti-TNF biosimilar)
- Active or prior evidence in past 12 months of internal (abdominal/pelvic) penetrating fistula(e)
- Active intestinal stricture (luminal narrowing with pre-stenotic dilation >3mm), intra-abdominal abscess or perianal abscess
- Active Clostridium difficile infection or other known bacterial/viral gastroenteritis in last two weeks
- Current ileostomy, colostomy, ileoanal pouch, and/or previous extensive small bowel resection leading to short bowel syndrome
- History of autoimmune disease (including autoimmune hepatitis, primary sclerosing cholangitis, thyroiditis, psoriasis or juvenile idiopathic arthritis)
- Treatment with another investigational drug within four weeks.
- Treatment with intravenous antibiotics within four weeks.
- Planned continuation of 6-mercaptopurine or azathioprine (Imuran) during study.
- Planned continuation of methotrexate during study.
- Treatment with intravenous corticosteroids within two weeks.
- Currently pregnant, breast feeding or plans in next 12 months to become pregnant
- Inability or failure to provide informed assent/consent
Sites / Locations
- Cincinnati Children's HospitalRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
RoadMAB dashboard system
Arm 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.
Outcomes
Primary Outcome Measures
Obtain safety data for optimal dosing strategy and sample size estimation
Number of adverse and/or serious adverse events
Enrollment feasibility
Evaluate the rate of recruitment
Completion feasibility
Number of patients that complete the study
Rate of patient adherence to stool and blood sample collections
patient adherence to stool and blood sample collections
RoadMAB Usability
Evaluate rate of physician adherence to RoadMAB dosing recommendation
RoadMAB Efficacy
Rate of achieving infus3 (Visit 4) infliximab concentration between 16-24 μg/ml as a dichotomous outcome
Secondary Outcome Measures
Evaluate accuracy of infliximab concentration targets - Median difference infus3
Median difference of infus3 (Visit 4) levels between cases and controls
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
Evaluate accuracy of infliximab concentration targets - Median difference infus2
Median difference of infus2 (Visit 3) levels between cases and controls
Evaluate accuracy of infliximab concentration targets - Maintenance
Rates of achieving maintenance targets infus4-6 (Visits 5-7) between 5-10 μg/ml
Evaluate accuracy of infliximab concentration targets
Rate of development of antiinfliximab antibodies at any infusion between cases and controls
Infus4 (Visit 5) and infus6 (Visit 7): Clinical Response
Improvement in baseline wPCDAI by >17.5 or a wPCDAI<12.5
Infus4 (Visit 5) and infus6 (Visit 7): Clinical Remission
wPCDAI <12.5 and off corticosteroids
Sustained Remission
wPCDAI <12.5 and off prednisone for all visits from infus4 (Visit 5) to infus6 (Visit 7)
Infus4 (Visit 5) and Infus6 (Visit 7): Fecal Biochemical Response
≥50% improvement in fecal calprotectin
Infus4 (Visit 5) and Infus6 (Visit 7): Fecal Biochemical Remission
fecal calprotectin <250 μg/g
Infus6 (Visit 7): Rate of transmural ileal
ileum subscore stage 0 (score = 0)
Infus6 (Visit 7): Rate of colonic healing
all segments of colon subscore stage 0 (score = 0)
Infus6 (Visit 7): Rate of total bowel healing
total ileum and colonic subscore is not greater than stage 0 on either individual score
Full Information
NCT ID
NCT04974099
First Posted
June 29, 2021
Last Updated
January 25, 2023
Sponsor
Children's Hospital Medical Center, Cincinnati
Collaborators
Crohn's and Colitis Foundation
1. Study Identification
Unique Protocol Identification Number
NCT04974099
Brief Title
Personalized Infliximab Induction Strategy With Model-informed Dosing in Patients With Crohn's Disease
Acronym
REMODEL
Official Title
Personalized Infliximab Induction Strategy With Model-informed Dosing in Patients With Crohn's Disease
Study Type
Interventional
2. Study Status
Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 1, 2021 (Actual)
Primary Completion Date
August 1, 2023 (Anticipated)
Study Completion Date
August 1, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Children's Hospital Medical Center, Cincinnati
Collaborators
Crohn's and Colitis Foundation
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Crohn Disease
7. Study Design
Primary Purpose
Other
Study Phase
Phase 2, Phase 3
Interventional Study Model
Single Group Assignment
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).
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
RoadMAB dashboard system
Arm Type
Experimental
Arm 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.
Intervention Type
Device
Intervention Name(s)
RoadMAB
Other Intervention Name(s)
Precision dosing with a dashboard
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Precision dosing with a dashboard
Intervention Description
The trial is testing whether precision dosing can more reliably achieve the targeted trough concentrations compared to standard dosing
Primary Outcome Measure Information:
Title
Obtain safety data for optimal dosing strategy and sample size estimation
Description
Number of adverse and/or serious adverse events
Time Frame
2 years
Title
Enrollment feasibility
Description
Evaluate the rate of recruitment
Time Frame
2 years
Title
Completion feasibility
Description
Number of patients that complete the study
Time Frame
2 years
Title
Rate of patient adherence to stool and blood sample collections
Description
patient adherence to stool and blood sample collections
Time Frame
2 years
Title
RoadMAB Usability
Description
Evaluate rate of physician adherence to RoadMAB dosing recommendation
Time Frame
2 years
Title
RoadMAB Efficacy
Description
Rate of achieving infus3 (Visit 4) infliximab concentration between 16-24 μg/ml as a dichotomous outcome
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Evaluate accuracy of infliximab concentration targets - Median difference infus3
Description
Median difference of infus3 (Visit 4) levels between cases and controls
Time Frame
2 years
Title
Evaluate accuracy of infliximab concentration targets - Incidence
Description
Incidence of achieving infus2 (Visit 3) level between target range of 26-34 μg/ml as a dichotomous outcome
Time Frame
2 years
Title
Evaluate accuracy of infliximab concentration targets - Median difference infus2
Description
Median difference of infus2 (Visit 3) levels between cases and controls
Time Frame
2 years
Title
Evaluate accuracy of infliximab concentration targets - Maintenance
Description
Rates of achieving maintenance targets infus4-6 (Visits 5-7) between 5-10 μg/ml
Time Frame
2 years
Title
Evaluate accuracy of infliximab concentration targets
Description
Rate of development of antiinfliximab antibodies at any infusion between cases and controls
Time Frame
2 years
Title
Infus4 (Visit 5) and infus6 (Visit 7): Clinical Response
Description
Improvement in baseline wPCDAI by >17.5 or a wPCDAI<12.5
Time Frame
2 years
Title
Infus4 (Visit 5) and infus6 (Visit 7): Clinical Remission
Description
wPCDAI <12.5 and off corticosteroids
Time Frame
2 years
Title
Sustained Remission
Description
wPCDAI <12.5 and off prednisone for all visits from infus4 (Visit 5) to infus6 (Visit 7)
Time Frame
2 years
Title
Infus4 (Visit 5) and Infus6 (Visit 7): Fecal Biochemical Response
Description
≥50% improvement in fecal calprotectin
Time Frame
2 years
Title
Infus4 (Visit 5) and Infus6 (Visit 7): Fecal Biochemical Remission
Description
fecal calprotectin <250 μg/g
Time Frame
2 years
Title
Infus6 (Visit 7): Rate of transmural ileal
Description
ileum subscore stage 0 (score = 0)
Time Frame
2 years
Title
Infus6 (Visit 7): Rate of colonic healing
Description
all segments of colon subscore stage 0 (score = 0)
Time Frame
2 years
Title
Infus6 (Visit 7): Rate of total bowel healing
Description
total ileum and colonic subscore is not greater than stage 0 on either individual score
Time Frame
2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
6 Years
Maximum Age & Unit of Time
22 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Written informed consent form from the patient (≥18 years old) or from parent/legal guardian if patient is <18 years old.
Written informed assent form from patient ≥11 years old.
Age criteria: ≥6 years to ≤22 years of age.
Diagnosis of Crohn's Disease
Starting infliximab (or biosimilar)
Anti-TNF naïve (never received infliximab, adalimumab, golimumab, certolizumab or anti-TNF biosimilar)
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)
wPCDAI >12.5 (up to 6 weeks) prior to the first infliximab infusion
Negative urine pregnancy test for ALL female subjects
Negative TB (tuberculosis) blood test
Exclusion Criteria:
Diagnosis of ulcerative colitis or inflammatory bowel disease-unspecified
Prior treatment with infliximab, adalimumab, certolizumab or golimumab (or anti-TNF biosimilar)
Active or prior evidence in past 12 months of internal (abdominal/pelvic) penetrating fistula(e)
Active intestinal stricture (luminal narrowing with pre-stenotic dilation >3mm), intra-abdominal abscess or perianal abscess
Active Clostridium difficile infection or other known bacterial/viral gastroenteritis in last two weeks
Current ileostomy, colostomy, ileoanal pouch, and/or previous extensive small bowel resection leading to short bowel syndrome
History of autoimmune disease (including autoimmune hepatitis, primary sclerosing cholangitis, thyroiditis, psoriasis or juvenile idiopathic arthritis)
Treatment with another investigational drug within four weeks.
Treatment with intravenous antibiotics within four weeks.
Planned continuation of 6-mercaptopurine or azathioprine (Imuran) during study.
Planned continuation of methotrexate during study.
Treatment with intravenous corticosteroids within two weeks.
Currently pregnant, breast feeding or plans in next 12 months to become pregnant
Inability or failure to provide informed assent/consent
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Phillip Minar, MD, MS
Phone
513-636-4415
Email
phillip.minar@cchmc.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Phillip Minar, MD, MS
Organizational Affiliation
Children's Hospital Medical Center, Cincinnati
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cincinnati Children's Hospital
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kimberly Jackson
Email
kimberly.jackson@cchmc.org
First Name & Middle Initial & Last Name & Degree
Phillip Minar, MD, MS
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Personalized Infliximab Induction Strategy With Model-informed Dosing in Patients With Crohn's Disease
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