Personalized infliximab dosing for Crohn's disease treatment

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

This study is testing whether a computer program that customizes infliximab doses based on blood tests can help people with Crohn's disease feel better compared to the usual dosing methods.

Quick facts

• Phase: Phase2; Phase3
• Study type: Interventional
• Enrollment: 180 (estimated)
• Ages: 6 Years to 22 Years
• Sex: All
• Sponsor: Children's Hospital Medical Center, Cincinnati (Academic / other)
• Drugs / interventions: infliximab, adalimumab, certolizumab, golimumab, methotrexate
• Locations: 11 sites (Los Angeles, California and 10 other locations)
• Trial ID: NCT05660746 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the effectiveness of a computer program that calculates individualized infliximab doses based on patients' blood test results, compared to standard dosing methods. It is an open-label, cluster randomized trial focusing on achieving deep remission in patients with Crohn's disease. The study will monitor patients receiving precision dosing during both the induction and maintenance phases of treatment to determine if this approach leads to better outcomes than conventional care.

Who should consider this trial

Good fit: Ideal candidates for this study are children and young adults aged 6 to 22 years who have been diagnosed with Crohn's disease and are starting infliximab treatment.

Not a fit: Patients who are older than 22 years or those who have previously received anti-TNF therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a more effective treatment option for patients with Crohn's disease, potentially leading to higher rates of remission and fewer adverse events.

How similar studies have performed: Previous studies have shown promising results with precision dosing approaches in other conditions, suggesting potential success for this novel method in Crohn's disease.

Eligibility criteria

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

Where this trial is running

Los Angeles, California and 10 other locations

• Children's Hospital of Los Angeles — Los Angeles, California, United States (Recruiting)
• Lucile Packard Children's Hospital Stanford — Palo Alto, California, United States (Recruiting)
• Rady Children's Hospital San Diego — San Diego, California, United States (Recruiting)
• Nemours Children's Health System-Wilmington — Wilmington, Delaware, United States (Recruiting)
• Nemours Children's Health System-Jacksonville — Jacksonville, Florida, United States (Recruiting)
• Riley Hospital for Children — Indianapolis, Indiana, United States (Recruiting)
• Cincinnati Children's Hospital — Cincinnati, Ohio, United States (Recruiting)
• Cleveland Clinic Children's Hospital — Cleveland, Ohio, United States (Recruiting)
• Nationwide Children's Hospital — Columbus, Ohio, United States (Recruiting)
• Children's Specialty Group — Norfolk, Virginia, United States (Recruiting)
• Medical College of Wisconsin, Children's of Wisconsin — Milwaukee, Wisconsin, United States (Recruiting)

Study contacts

• Principal investigator: Phillip Minar, MD,MS — Children's Hospital Medical Center, Cincinnati
• Study coordinator: Phillip Minar, MD, MS

Conditions Crohn Disease; Crohn's