Crohn Disease
Conditions
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.
Interventions
DEVICERoadMAB 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.
DRUGInfliximab precision dosing
The trial is testing whether precision dosing can more reliably achieve the targeted trough concentrations compared to standard dosing
Sponsors
Children's Hospital Medical Center, Cincinnati
Crohn's and Colitis Foundation
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
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).
Eligibility
Sex/Gender
ALL
Age
6 Years to 22 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| RoadMAB Usability | 10 months | Evaluate rate of physician adherence to the Dashboard |
| RoadMAB Efficacy | weeks 10-16 | Percentage of patients achieving infus3 (Visit 4) infliximab concentration between \>16 μg/ml as a dichotomous outcome |
| Percentage of Patient Adherence to Blood Sample Collection | 10 months | Percentage of patients who provided blood sample collections. |
| Obtain Safety Data for Optimal Dosing Strategy and Sample Size Estimation | 10 months | Percentage of total patients adverse and/or serious adverse events |
| Enrollment Feasibility | 10 months | Number of patients consented for 10 month study |
| Completion Feasibility | 10 months | Percentage of patients that complete the study |
| Percentage of Patient Adherence to Stool Sample Collections | 10 months | Percentage of patients that collected a stool sample for the study |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Infus4 (Visit 5): Fecal Biochemical Response | Weeks 10-16 | Percentage of patients with a ≥50% improvement in fecal calprotectin |
| Infus4 (Visit 5): Fecal Biochemical Remission | Week 10-16 | Percentage of patients with a fecal calprotectin \<250 μg/g |
| Evaluate Accuracy of Infliximab Concentration Targets - Median Difference Infusion 3 | Weeks 4-8 | Median difference of infusion 3 (Visit 4) levels between cases and controls |
| Evaluate Accuracy of Infliximab Concentration Targets - Incidence | Weeks 2-3 | Incidence of achieving infus2 (Visit 3) level between target range of \>26 μg/ml as a dichotomous outcome |
| Evaluate Accuracy of Infliximab Concentration Targets - Median Difference infus2 | Weeks 2-3 | Median difference of infus2 (Visit 3) levels between cases and controls |
| Infus6 (Visit 7): Rate of Colonic Healing | Weeks 18-30 | all segments of colon subscore stage 0 (score = 0) |
| Infus6 (Visit 7): Rate of Transmural Ileal | Weeks 18-30 | ileum subscore stage 0 (score = 0) |
| Infus6 (Visit 7): Rate of Total Bowel Healing | Weeks 10-30 | total ileum and colonic subscore is not greater than stage 0 on either individual score |
| Evaluate Accuracy of Infliximab Concentration Targets - Maintenance | week2 10-30 | Percentage of achieving maintenance targets infus4-6 (Visits 5-7) \>5 μg/ml |
| Evaluate Accuracy of Infliximab Concentration Targets | 6 months | Rate of development of anti-infliximab antibodies at any infusion between cases and controls |
| Infus4 (Visit 5) and infus6 (Visit 7): Clinical Response | Weeks 10-30 | Percent of patients that had an improvement in baseline wPCDAI by \>17.5 or a wPCDAI\<12.5 |
| Infus4 (Visit 5): Clinical Remission | Weeks 10-16 | Percentage of patients who had a wPCDAI \<12.5 and off corticosteroids |
| Sustained Remission | Weeks 10-30 | Percentage of patients with a wPCDAI \<12.5 and off prednisone for all visits from infus4 (Visit 5) to infus6 (Visit 7) |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORPhillip Minar, MD, MS
Children's Hospital Medical Center, Cincinnati
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 6 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age, Continuous | 13 years STANDARD_DEVIATION 3.3 |
| Crohn's disease | 6 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 4 Participants |
| Region of Enrollment United States | 6 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 6 |
| other Total, other adverse events | 3 / 6 |
| serious Total, serious adverse events | 0 / 6 |
Outcome results
None listed