Pharmacokinetic Evaluation of Infliximab in Pediatric Patients with Crohn's Disease: A Prospective Analysis

The primary objective of this study is to evaluate the proportion of pediatric patients with **infliximab** (IFX) trough levels of ≥ 5 µg/mL at week 12 without the need for treatment escalation. This is clinically relevant as maintaining adequate IFX levels is crucial for achieving and sustaining remission in patients with **Crohn's Disease**, thereby potentially reducing the need for additional therapeutic interventions.

Secondary objectives include: - Assessing the efficacy of an intensified IFX induction scheme in achieving clinical and biochemical remission at weeks 4, 12, and 24 without treatment escalation. - Evaluating whether an intensified induction scheme increases the frequency of anti-infliximab antibodies (ATI) and/or infusion reactions/adverse reactions. - Identifying factors predictive of response to IFX based on proteomic analysis.

The clinical trial involves a study population of **children** aged 1 to 15 years diagnosed with **Crohn's Disease** or Inflammatory Bowel Disease Unclassified (IBD-U). The trial includes both male and female participants. The sponsor has not provided the total number of participants. The trial population was selected based on specific criteria, including being anti-TNF-α naïve and having an indication to start infliximab (IFX) treatment, as determined by the attending physician. Participants are required to have a diagnosis of Crohn's Disease made according to the Porto criteria. The study considers vulnerable populations, and the inclusion criteria are aligned with ECCO-ESPGHAN guidelines, which include factors such as non-response to initial treatments, severe growth delay, and extensive or complicated disease presentations. Lifestyle considerations such as diet and physical activity are not specified in the provided data.

The clinical trial is designed to evaluate the pharmacokinetics of **infliximab** in pediatric patients diagnosed with **Crohn's Disease**. This is a phase IV, low-intervention trial, characterized by a **randomized**, **double-blind**, and **controlled** design. The trial aims to assess the proportion of patients achieving an infliximab trough level of ≥ 5 µg/mL at week 12 without treatment escalation. The study is expected to commence on August 2, 2023, and conclude by August 2, 2025, with an estimated duration of two years.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on the Porto criteria and ECCO-ESPGHAN guidelines. Eligible participants are anti-TNF-α naïve children aged 1-15 years with an indication to start infliximab treatment. Following the screening, participants will receive infliximab intravenously, with follow-up visits scheduled at weeks 4, 12, and 24. These visits will monitor infliximab trough levels, assess clinical and biochemical remission, and evaluate the need for treatment escalation. The end-of-study visit will occur at week 24, marking the completion of the participant's involvement in the trial.

The expected length of participant involvement is approximately 24 weeks. Conditions that may lead to early termination from the study include adverse reactions to infliximab, non-compliance with study protocols, or withdrawal of consent by the participant or their guardian. The primary endpoint is the proportion of patients with infliximab trough levels ≥ 5 µg/mL at week 12 without treatment escalation. Secondary endpoints include the proportion of patients achieving similar trough levels at week 24, and those in clinical or biochemical remission at weeks 4, 12, and 24. Predictors of infliximab trough levels at these intervals will also be analyzed.

The clinical trial involves the administration of **Remsima**, a **100 mg powder for concentrate for solution for infusion**. The active substance in this medication is **infliximab**, a protein-based therapeutic agent. The pharmaceutical form of Remsima is a solution for infusion, and it is administered intravenously. The dosing regimen is specified in the protocol, with the interval having been adjusted as per the study requirements. The maximum treatment period is set at 100,000 time units, although the specific unit is not detailed in the provided data. The medication is not formulated specifically for pediatric use, and it is not classified as an orphan drug. The product is authorized under the marketing authorization number EU/1/13/853/002 and is manufactured by Celltrion Healthcare Hungary Kft.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are mentioned. The focus is solely on the administration of Remsima. Participant compliance with the dosing schedule is monitored according to the study protocol, ensuring that the infliximab trough level is maintained at or above 5 µg/mL at week 12 without treatment escalation. The study aims to assess the pharmacokinetic profile of infliximab in pediatric patients with inflammatory bowel disease. Additional details regarding the dosing schedule and participant monitoring are outlined in the study protocol, which is not provided in the current data set.

Efficacy in this clinical trial will be assessed by evaluating the **infliximab** trough levels (IFX TL) in pediatric patients with inflammatory bowel disease. The primary endpoint is the proportion of patients achieving an IFX TL of ≥ 5 µg/mL at week 12 without the need for treatment escalation. Secondary endpoints include the proportion of patients with IFX TL ≥ 5 µg/mL at week 24, as well as the proportion of patients in clinical and/or biochemical remission at weeks 4, 12, and 24, without treatment escalation. Additionally, predictors of IFX TLs at weeks 4, 12, and 24 will be analyzed.