Pharmacokinetic Infliximab Data in Pediatric Crohn's Disease

NCT05552287 | Recruiting Phase 4

• 1 other identifier: ProRAPID
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Rationale: Crohn's disease (CD) is a chronic, debilitating inflammatory bowel disease (IBD) which is diagnosed during childhood in up to one in ten patients. The use of anti-tumor necrosis factor (TNF)-α agents has significantly ameliorated CD management. Infliximab (IFX) is the first anti-TNF-α agent registered for pediatric CD. The current dosing recommendation of IFX is extrapolated from adult studies, and it is a weight-based dose (5 mg/kg) delivered during induction (infusion at weeks 0, 2, and 6) and maintenance (every 8 weeks). However, pediatric patients have a 25-40% lower drug exposure compared to adults, particularly children under 10 years of age, resulting in diminished efficacy and an increased risk of developing a complicated disease course. The investigators hypothesize that an intensified IFX induction scheme (instead of the current dosing recommendation) is more effective in the treatment of pediatric CD patients. Objective: The primary study objective of our study is to assess the efficacy of an IFX intensified induction scheme vs. a standard dosing schedule in improving drug exposure without treatment escalation in pediatric CD patients. Secondary objectives are clinical and biochemical remission without treatment escalation, development of antibodies to IFX (ATI) and adverse reactions. Study design: An international, multicenter, prospective, open-label trial. Study population: Anti-TNF-α naïve children (age 1-15 years) with CD and an indication to start IFX treatment. Intervention: IFX will be given intravenously at 10 mg/kg at week 0, and 5 mg/kg at weeks 2, 4, and 8 to all patients (induction). Maintenance will start at week 12, and then ideally continue every 6 weeks till week 24 (end of study). IFX trough levels will be measured at weeks 4, 12, and 24. During the maintenance, the IFX dose and/or interval adjustments, the IFX discontinuation or the start of a co-medication (i.e., an immunomodulator) will be possible on indication (i.e., primary nonresponse, secondary loss of response, intolerance to study medication) at the physicians' discretion. Follow-up will continue for the duration of the study (week 24). Main endpoint: Proportion of patients with IFX TL ≥ 5 µg/mL at week 12 without treatment escalation.

Conditions

Crohn Disease; Child, Only; Biologic; Inadequate

Outcome Measures

Primary Outcomes (1)

• Proportion of patients with IFX Trough Levels ≥ 5 µg/mL at week 12 without treatment escalation

  Treatment escalation is defined as any additional CD-related medication or IBD-related abdominal surgery

  12 weeks

Secondary Outcomes (6)

• Proportion of patients with IFX Trough Levels ≥ 5 µg/mL at week 24 without the need for treatment escalation

  24 weeks

• Clinical and biochemical remission at weeks 4, 12, and 24 without the need for treatment escalation in patients with TL ≥ 5 µg/mL and in patients with TL < 5 µg/mL.

  24 weeks

• Predictors of IFX Trough Levels at weeks 4, 12, and 24. Factors included in this analysis will be sex, age, body mass index (BMI), wPCDAI, IBD laboratory values, antibodies to Infliximab (ATI), dose, and interval of IFX infusions.

  24 weeks

• Development of antibodies to IFX until week 24

  24 weeks

• Prediction of reponders versus non-responders to IFX based on proteomic analysis.

  24 weeks

Other Outcomes (23)

• Proportions of patients with primary non-response

  24 weeks

• Proportions of patients with secondary loss of response (LOR)

  24 weeks

• Evaluation of number of adverse events

  24 weeks

Study Arms (1)

Intensified induction scheme with Infliximab

EXPERIMENTAL

Intensified induction scheme with Infliximab. IFX will be given intravenously at 10 mg/kg at week 0, and 5 mg/kg at weeks 2, 4, and 8 to all patients (induction). Maintenance will start at week 12, and then ideally continue every 6 weeks.

Drug: Infliximab

Interventions

Infliximab DRUG

IFX will be given intravenously at 10 mg/kg at week 0, and 5 mg/kg at weeks 2, 4, and 8 to all patients (induction). Maintenance will start at week 12, and then ideally continue every 6 weeks till week 24 (end of study). IFX trough levels will be measured at weeks 4, 12, and 24. During the maintenance, the IFX dose and/or interval adjustments, the IFX discontinuation or the start of a co-medication (i.e., an immunomodulator) will be possible on indication (i.e., primary nonresponse, secondary loss of response, intolerance to study medication) at the physicians' discretion.

Intensified induction scheme with Infliximab

Eligibility Criteria

• Age: 1 Year - 15 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may not qualify if:

• Established monogenetic IBD
• Diagnosis with UC or IBD-U, ulcerative colitis like
• Active fistulizing/perianal disease at start of IFX treatment (patients with inactive fistulizing/perianal disease are allowed to participate)
• Severe comorbidity (not related to IBD)
• Immediate need for surgery (i.e., symptomatic stenosis or stricture in the bowel)
• Severe infection such as sepsis or opportunistic infections, positive tuberculin test or a chest radiograph consistent with tuberculosis or malignancy
• Pregnancy, suspected or definitive
• Treatment with anti-TNF or other biological drugs in the past
• Start of corticosteroids or mesalazine less than 2 weeks prior to first IFX infusion
• Start of Exclusive Enteral Nutrition less than 2 week prior to first IFX infusion

Sponsors & Collaborators

• Erasmus Medical Center: lead

Study Sites (1)

Erasmus Medical Center

Rotterdam, 3015 GD, Netherlands

RECRUITING

MeSH Terms

Conditions

Crohn Disease

Interventions

Infliximab

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Lissy de Ridder, PhD

  Erasmus Medical Center - Sophia Children's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lissy de Ridder, PhD

CONTACT

0107036076; l.deridder@erasmusmc.nl

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Doctor; Associate Professor

Study Record Dates

• First Submitted: July 11, 2022
• First Posted: September 23, 2022
• Study Start: August 2, 2023
• Primary Completion: August 1, 2025
• Study Completion: August 1, 2025
• Last Updated: September 19, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)