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| ID | Type | Description | Link |
|---|---|---|---|
| R01DK132408-01 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) | NIH |
| Janssen Scientific Affairs, LLC | INDUSTRY |
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Approximately 3 million people in the United States are living with inflammatory bowel disease, which includes Crohn's Disease (CD). There are limited treatment options approved for use in children and adults with Crohn's disease. Physicians need better ways to inform decisions on treatment.
The main reason for this research study is to determine if a computer program that calculates an individualized dose based on a patient's blood testing results (precision dosing) can better achieve the best possible response to infliximab compared to standard dosing (conventional dosing).
This is an open-label, cluster randomized clinical trial to test whether precision infliximab dosing with a targeted concentration intervention is superior in achieving deep remission (endoscopic healing and clinical remission) compared to patients receiving conventional infliximab dosing.
With recognition that CD patients who achieve the "target" of deep remission with anti-TNF dose optimizations following pharmacodynamic monitoring had a significant reduction in CD-related adverse events, our central hypothesis is precision dosing with infliximab during induction and maintenance will achieve superior rates of deep remission vs. conventional care (control arm)
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Conventional dosing | Active Comparator | Induction Phase: 5-7.5 mg/kg at 0, 2, and 6 weeks. Maintenance Phase : 5-10 mg/kg at every 4-8 weeks based on results of drug concentration monitoring for a flat target of 5-10 μg/mL. |
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| Precision dosing | Experimental | Induction: 5-12.5 mg/kg at 0, 2, and 6 weeks to target a week6 concentration of 18-24 μg/mL with dosing support provided by the RoadMABTM clinical decision support tool. Maintenance: 5-15 mg/kg every 4-8 weeks to achieve apriori pharmacokinetic and pharmacodynamic targets (CRP, disease activity scores and fecal calprotectin) with dosing support provided by the RoadMABTM clinical decision support tool. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| RoadMAB | Device | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Rate of Deep Remission | Pediatric Crohn's disease activity index (PCDAI) <10 (child) or Crohn's disease activity index<150 (adult), off prednisone/budesonide for >8 weeks and Simple Endoscopic Scorer Crohn's Disease (SES-CD) SES-CD≤2 | Week 52 |
| Measure | Description | Time Frame |
|---|---|---|
| Rate of Steroid-free Clinical Remission | Pediatric Crohn's disease activity index (PCDAI) <10 (child) or Crohn's disease activity index(CDAI)<150 (adult) and off prednisone/budesonide for ≥4 weeks | Week 14 and Week 52 |
| Rate of Clinical Response |
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Inclusion Criteria:
Written informed consent from the patient (≥18 years old) or from parent/legal guardian if patient is <18 years old
Written informed assent from patient when age appropriate
Diagnosis of Crohn's disease within the last 90 days (luminal-only or luminal with a perianal fistula or abscess treated with antibiotics for at least 7 days)
≥6 years to ≤22 years of age, anti-TNF naïve and starting infliximab
Clinical activity and luminal inflammation, defined by both (1) and (2)
C-reactive protein >1.0 mg/dL in last 30 days and/or fecal calprotectin >250 μg/g within last 75 days prior to screening
Negative TB (tuberculosis) interferon-gamma release test and a negative urine pregnancy test for female patients (if menstruation has started)
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Phillip Minar, MD, MS | Contact | 513-636-4415 | phillip.minar@cchmc.org |
| Name | Affiliation | Role |
|---|---|---|
| Phillip Minar, MD,MS | Children's Hospital Medical Center, Cincinnati | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Children's Hospital of Los Angeles | Recruiting | Los Angeles | California | 90027 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38531570 | Derived | Minar PP, Colman RJ, Zhang N, Mizuno T, Vinks AA. Precise infliximab exposure and pharmacodynamic control to achieve deep remission in paediatric Crohn's disease (REMODEL-CD): study protocol for a multicentre, open-label, pragmatic clinical trial in the USA. BMJ Open. 2024 Mar 25;14(3):e077193. doi: 10.1136/bmjopen-2023-077193. |
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| ID | Term |
|---|---|
| D003424 | Crohn Disease |
| ID | Term |
|---|---|
| D015212 | Inflammatory Bowel Diseases |
| D005759 | Gastroenteritis |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
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| ID | Term |
|---|---|
| D000069285 | Infliximab |
| ID | Term |
|---|---|
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
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Patients newly diagnosed with Crohn's disease (ages 6-22 years inclusive) within the last 90 days AND starting infliximab
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| Infliximab | Drug | Conventional dosing. Induction: 5-7.5 mg/kg at 0, 2, and 6 weeks. Maintenance: 5-10 mg/kg at every 4-8 weeks based on results of drug concentration monitoring for a flat target of 5-10 μg/mL. Precision dosing. Induction: 5-12.5 mg/kg at 0, 2, and 6 weeks to target a week6 concentration of 18-24 μg/mL with dosing support provided by the RoadMABTM clinical decision support tool. Maintenance: 5-15 mg/kg every 4-8 weeks to achieve apriori pharmacokinetic and pharmacodynamic targets (CRP, disease activity scores and fecal calprotectin) with dosing support provided by the RoadMABTM clinical decision support tool. |
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Decrease from baseline PCDAI of at least 12.5 points & total PCDAI<30 or a PCDAI<10 (child) or a reduction of CDAI>70 from baseline or CDAI<150 (adult)
| Week 14 and Week 52 |
| Rate of Primary Clinical Nonresponse | On prednisone >16 consecutive weeks from start of infliximab or a PCDAI>30 or CDAI>220 for first four infusions | Week 16 |
| Rate of Primary Biologic Nonresponse | Failure to improve baseline fecal calprotectin by >100 μg/g (limited to patients with a baseline fecal calprotectin >250 μg/g) or Failure to improve baseline c-reactive protein ≥0.5 mg/dL (limited to patients with a baseline c-reactive protein >1.0 mg/dL) | Week 16 |
| Rate of Sustained Steroid-free Remission | PCDAI<10 (child) or CDAI<150 (adult) at dose5 to week52 and off prednisone/budesonide from week 22-52 | Week 22 - Week 52 |
| Rate of Steroid-free Remission -biomarker composite | PCDAI<10 (child) or CDAI<150 (adult), off prednisone/budesonide for ≥4 weeks, CRP≤0.5 mg/dL and fecal calprotectin <250 μg/g | Week 14 and Week 52 |
| Rate of Endoscopic Healing | Simple endoscopic score-Crohn's disease (SES-CD) ≤2 | Week 52 |
| Rate of Complete Endoscopic Healing | SES-CD=0 | Week 52 |
| Rate of Endoscopic Remission | SES-CD<4 | Week 52 |
| Rate of Mucosal Healing | SES-CD≤2 and Ileal Global Histologic Activity Score (GHAS)/ Colon Global Histologic Activity Score (CGHAS) ≤2 | Week 52 |
| PK Model Bias | Model predicted vs. actual infliximab concentration. Bias: mean predictive error (MPE) | Week 0 - Week 52 |
| PK Model Precision | Model predicted vs. actual infliximab concentration. Precision: root mean squared error (RMSE) | Week 0 - Week 52 |
| Rate of IBD related event - Fistula | Occurrence of fistula and presence of antibody to infliximab >200 ng/mL | Week 0 - Week 52 |
| Rate of IBD related - Hospitalization | Occurrence of Crohn's disease related hospitalization | Week 0 - Week 52 |
| Rate of IBD related event - Surgery | Occurrence of Crohn's disease related surgery | Week 0 - Week 52 |
| Rate of IBD related event - Intestinal stricture | Occurrence of Crohn's disease related intestinal stricture | Week 0 - Week 52 |
| Rate of IBD related event - Starting corticosteroids | Occurrence of subjects starting a corticosteroid after week20 | Week 0 - Week 52 |
| Rate of IBD related event - Antibodies to infliximab | Occurrence of antibodies to infliximab defined as >200 ng/mL | Week 0 - Week 52 |
| Rate of Growth Restoration - Weight change | In Tanner stage I-III subjects: change in baseline weight (kg) by gender and age group | Week 14 - Week 52 |
| Rate of Growth Restoration- Height velocity | In Tanner stage I-III subjects: change in height velocity (z-score) by gender | Week 14 - Week 52 |
| PK of infliximab in pediatric patients | Measured infliximab clearance at baseline and at week52 | Week 0 - Week 52 |
| Correlation between infliximab induction exposure and endoscopic remission | The correlation analysis to be performed for the total area under the curve (infliximab exposure, μg*h/mL from week0-week14) and patients achieving endoscopic remission. Endoscopic remission is defined as a SES-CD≤2. | Exposure Week 0 - Week 14, Efficacy Week 52 |
| Correlation between infliximab induction exposure and deep remission | The correlation analysis to be performed for the total area under the curve (infliximab exposure, μg*h/mL from week0-week14) and patients in deep remission. Deep remission is defined as a PCDAI<10 (child) or CDAI<150 (adult), off prednisone/budesonide for >8 weeks and a SES-CD≤2. | Exposure Week 0 - Week 14, Efficacy Week 52 |
| Patient Reported Outcome-2 (PRO2) Response | >50% improvement in total score from baseline | Week 6, Week 14, Week 26, Week 52 |
| Patient Reported Outcome-2 (PRO2) Remission | Stool frequency ≤3.0 and abdominal pain ≤1.0 (from baseline) | Week 6, Week 14, Week 26, Week 52 |
| Quality of Life & Disability -IMPACT-III score | Total IMPACT-III (child) score | Week 52 |
| Quality of Life & Disability - Inflammatory Bowel Disease Disk score | Total Inflammatory Bowel Disease Disk (without sexual function assessment) score | Week 52 |
| Quality of Life & Disability - Short Inflammatory Bowel Disease score | Total Short IBD Questionnaire (adult) score | Week 52 |
| Process Evaluation -Usability of Decision Support Tool | Total System Usability Scale score | Week 0 - Week 52 |
| Rate of Adverse events | Number of Adverse Events | Week 0 - Week 52 |
| Rate of Serious Adverse events | Number of Serious Adverse Events | Week 0 - Week 52 |
| Lucile Packard Children's Hospital Stanford | Recruiting | Palo Alto | California | 94304 | United States |
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| Rady Children's Hospital San Diego | Recruiting | San Diego | California | 92123 | United States |
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| Nemours Children's Health System-Wilmington | Recruiting | Wilmington | Delaware | 19803 | United States |
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| Nemours Children's Health System-Jacksonville | Recruiting | Jacksonville | Florida | 32207 | United States |
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| Riley Hospital for Children | Recruiting | Indianapolis | Indiana | 46202 | United States |
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| Cincinnati Children's Hospital | Recruiting | Cincinnati | Ohio | 45229 | United States |
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| Cleveland Clinic Children's Hospital | Recruiting | Cleveland | Ohio | 44106 | United States |
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| Nationwide Children's Hospital | Recruiting | Columbus | Ohio | 43205 | United States |
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| Children's Specialty Group | Recruiting | Norfolk | Virginia | 23507 | United States |
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| Medical College of Wisconsin, Children's of Wisconsin | Recruiting | Milwaukee | Wisconsin | 53226 | United States |
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| D007410 | Intestinal Diseases |
| D001798 |
| Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |