Precise Infliximab Exposure and Pharmacodynamic Control (REMODEL-CD)

Precise Infliximab Exposure and Pharmacodynamic Control to Achieve Deep Remission in Pediatric Crohn's Disease

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).

Study Overview

• Status: Recruiting
• Conditions: Crohn Disease
• Intervention / Treatment: Drug: Infliximab; Device: RoadMAB

Detailed Description

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)

• Study Type: Interventional
• Enrollment (Estimated): 180
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Phillip Minar, MD, MS; Phone Number: 513-636-4415; Email: phillip.minar@cchmc.org

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90027
      • Recruiting
      • Children's Hospital of Los Angeles
      • Contact: Mallory Chavannes
      • Principal Investigator: Mallory Chavannes, MD
    • Palo Alto, California, United States, 94304
      • Recruiting
      • Lucile Packard Children's Hospital Stanford
      • Contact: Alka Goyal
      • Principal Investigator: Alka Goyal, MD
    • San Diego, California, United States, 92123
      • Recruiting
      • Rady Children's Hospital San Diego
      • Contact: Laura Bauman
      • Principal Investigator: Laura Bauman, MD
  • Delaware
    • Wilmington, Delaware, United States, 19803
      • Recruiting
      • Nemours Children's Health System-Wilmington
      • Contact: Zarela Molle-Rios
      • Principal Investigator: Zarela Molle-Rios, MD
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Recruiting
      • Nemours Children's Health System-Jacksonville
      • Contact: Jill Dorsey
      • Principal Investigator: Jill Dorsey, MD
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Recruiting
      • Riley Hospital for Children
      • Contact: Steven Steiner
      • Principal Investigator: Steven Steiner, MD
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Recruiting
      • Cincinnati Children's Hospital
      • Contact: Kimberly Jackson; Email: kimberly.jackson@cchmc.org
      • Principal Investigator: Phillip Minar, MD, MS
    • Cleveland, Ohio, United States, 44106
      • Recruiting
      • Cleveland Clinic Children's Hospital
      • Contact: Jacob Kurowski
      • Principal Investigator: Jacob Kurowski, MD
    • Columbus, Ohio, United States, 43205
      • Recruiting
      • Nationwide Children's Hospital
      • Contact: Brendan Boyle
      • Principal Investigator: Brendan Boyle
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Recruiting
      • Children's Specialty Group
      • Contact: Amy Quinn; Email: Amy.quinn@chkd.org
      • Principal Investigator: Rana Ammoury, MD
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Recruiting
      • Medical College of Wisconsin, Children's of Wisconsin
      • Principal Investigator: Joshua Noe, MD
      • Contact: Joshua Noe

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 22 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Written informed consent from the patient (≥18 years old) or from parent/legal guardian if patient is <18 years old
2. Written informed assent from patient when age appropriate
3. 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)
4. ≥6 years to ≤22 years of age, anti-TNF naïve and starting infliximab

5. Clinical activity and luminal inflammation, defined by both (1) and (2)

   • (1) PCDAI≥10 (<18 years old) or CDAI ≥150 (≥18 years old) in last 60 days before the decision to start infliximab
   • (2) SES-CD>6, or SES-CD>3 for isolated ileal disease (or a report of large intestinal ulcerations)* within the last 60 days or a fecal calprotectin >250 μg/g within last 75 days prior to screening
6. 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
7. Negative TB (tuberculosis) interferon-gamma release test and a negative urine pregnancy test for female patients (if menstruation has started)

Exclusion Criteria:

1. Diagnosis of ulcerative colitis or inflammatory bowel disease-unspecified
2. Prior use of anti-TNF therapy (infliximab, adalimumab, certolizumab pegol, or golimumab)
3. Internal (abdominal/pelvic) penetrating fistula(e) in last 180 days
4. Intra-abdominal abscess/phlegmon/inflammatory mass in the last 180 days
5. Active perianal abscess (receiving oral antibiotics for <7 days)
6. Intestinal stricture (luminal narrowing with pre-stenotic dilation >3 cm) and surgery planned in the next 90 days
7. Have tested positive for Clostridium difficile toxin (stool assay) or other intestinal pathogens within 14 days of screening unless a repeat examination is negative and there are no signs of ongoing infection with that pathogen.
8. Current hospitalization for complications of severe Crohn's disease
9. Planned use of methotrexate or 6-mercaptopurine (azathioprine) during the induction (first 3 doses of infliximab) phase
10. Current ileostomy, colostomy, ileoanal pouch, and/or previous extensive small bowel resection (>35 cm) or any CD surgery planned within the next 90 days
11. History of autoimmune hepatitis, primary sclerosing cholangitis, thyroiditis, or juvenile idiopathic arthritis
12. Treatment with another investigational drug in the last four weeks
13. History of malignancy (including lymphoma or leukemia)
14. Currently receiving treatment for histoplasmosis
15. History of TB, human immunodeficiency virus (HIV), an immunodeficiency syndrome, a central nervous system demyelinating disease, history of heart failure or receiving intravenous antibiotics in last 14 days for any infection
16. Currently pregnant, breast feeding or plans to become pregnant in the next 1 year
17. Inability or failure to provide informed assent/consent
18. Any developmental disabilities that would impede providing assent/consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Conventional dosing; 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.	Drug: Infliximab; 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.; Other Names: Remicade; Avsola; Inflectra; Ixifi; Renflexis
Experimental: 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.	Drug: Infliximab; 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.; Other Names: Remicade; Avsola; Inflectra; Ixifi; Renflexis; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 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 - 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
PK of infliximab in pediatric patients	Measured infliximab clearance at baseline and at week52	Week 0 - 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
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	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 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 - Surgery	Occurrence of Crohn's disease related surgery	Week 0 - 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
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

Collaborators and Investigators

• Sponsor: Children's Hospital Medical Center, Cincinnati
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); Janssen Scientific Affairs, LLC
• Investigators: Principal Investigator: Phillip Minar, MD,MS, Children's Hospital Medical Center, Cincinnati

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2023
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): March 31, 2027

Study Registration Dates

• First Submitted: November 29, 2022
• First Submitted That Met QC Criteria: December 19, 2022
• First Posted (Actual): December 21, 2022

Study Record Updates

• Last Update Posted (Actual): May 5, 2026
• Last Update Submitted That Met QC Criteria: April 29, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Crohn's
• Additional Relevant MeSH Terms: Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Crohn Disease; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Infliximab
• Other Study ID Numbers: 2022-0071; R01DK132408-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No