Evaluation of Early Proactive Therapeutic Drug Monitoring on Infliximab Efficacy and Durability in Pediatric Inflammatory Bowel Disease

The primary objective of this study is to evaluate the efficacy of early proactive therapeutic drug monitoring (**E-pTDM**) compared to the standard infliximab (**IFX**) dosing schedule in improving IFX durability and efficacy during the first year of treatment in pediatric patients with **Inflammatory Bowel Disease**. This is clinically relevant as optimizing IFX therapy could enhance treatment outcomes and reduce the risk of disease relapse or progression.

Secondary objectives include evaluating the efficacy of E-pTDM in:

• Reducing the frequency of subtherapeutic IFX concentrations,
• Achieving endoscopic healing,
• Attaining clinical remission at week 14,
• Achieving clinical and biochemical remission at week 14,
• Reducing the frequency of anti-drug antibodies (ATI),
• Reducing the frequency of infusion reactions.

The clinical trial involves a study population of **children and adolescents** aged 6 to 17 years, diagnosed with **Inflammatory Bowel Disease** (IBD). The trial includes both male and female participants. The total number of participants is not provided by the sponsor. Participants were selected based on specific criteria, including being anti-TNF naïve and having a confirmed diagnosis of IBD through a prior endoscopic biopsy. Additionally, participants must have an indication to start anti-TNF therapy according to current pediatric guidelines and exhibit active inflammation, as evidenced by a C-reactive protein (CRP) level greater than 5 mg/L and/or fecal calprotectin (FC) greater than 150 μg/g before the first dose of infliximab (IFX). The trial population includes a vulnerable group, emphasizing the need for careful consideration of ethical standards in the study design and execution.

The clinical trial is designed to evaluate the efficacy of early proactive therapeutic drug monitoring compared to the standard dosing schedule of **infliximab** in improving its durability and efficacy during the first year of treatment in pediatric patients with **inflammatory bowel disease**. This is a multicenter, open-label, randomized controlled trial. Participants will be randomly assigned to either the test group receiving proactive monitoring or the control group following the standard dosing regimen. The trial is expected to last until December 31, 2025, with recruitment having started on March 9, 2022.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (6-17 years), a confirmed diagnosis of inflammatory bowel disease via endoscopic biopsy, and active inflammation indicated by specific biomarkers. Following the screening, participants will receive **infliximab** as a solution for infusion, with the test group receiving a maximum daily dose of 15 mg/kg and the control group receiving up to 10 mg/kg. The maximum treatment period is 56 weeks.

Throughout the trial, follow-up visits will be conducted to monitor the participants' response to treatment, assess any adverse events, and adjust dosing as necessary. The primary endpoint is the frequency of **infliximab** discontinuation due to treatment failure, adverse events, or the need for treatment intensification. Secondary endpoints include the cumulative probability of discontinuation, loss of response, subtherapeutic concentrations, occurrence of anti-drug antibodies, infusion reactions, and remission rates at specified weeks.

The expected length of participant involvement is up to 56 weeks, with conditions for early termination including significant adverse events, non-compliance with the study protocol, or withdrawal of consent. The end-of-study visit will evaluate the overall treatment response and collect final data for analysis. The trial aims to provide valuable insights into optimizing **infliximab** therapy for pediatric patients with inflammatory bowel disease.

The clinical trial involves the administration of **Infliximab**, a **solution for infusion**. Infliximab is a protein-based therapeutic agent classified under the category "Protein - Other." The trial utilizes two different dosing regimens of Infliximab. The first regimen involves a maximum daily dose of 15 mg/kg, with a total maximum dose of 15 mg/kg over a treatment period of 56 days. The administration route is via a concentrate for solution for infusion. The dosing schedule has been modified to optimize the administration interval, ensuring the efficacy and durability of the treatment in pediatric patients with inflammatory bowel disease.

The second regimen of **Infliximab** is also administered as a **solution for infusion**. This regimen involves a maximum daily dose of 10 mg/kg, with a total maximum dose of 10 mg/kg over the same treatment period of 56 days. The administration route remains consistent as a concentrate for solution for infusion. This regimen serves as a comparator to evaluate the efficacy of early proactive therapeutic drug monitoring (E-pTDM) against the standard dosing schedule. Both regimens are designed to assess the impact on the durability and efficacy of Infliximab therapy in the specified patient population.

Efficacy in this clinical trial will be assessed by evaluating the impact of early proactive therapeutic drug monitoring (E-pTDM) on the durability and efficacy of **infliximab** therapy in pediatric inflammatory bowel disease. The primary endpoint is a composite measure that includes the frequency of infliximab discontinuation due to treatment failure or adverse events, or the need for treatment intensification due to non-response or loss of response (LOR) during the first year of treatment. Secondary endpoints include the cumulative probability of infliximab discontinuation, the cumulative probability of LOR, subtherapeutic infliximab concentrations, occurrence of anti-drug antibodies (ATI), occurrence of infusion reactions, endoscopic remission at 54 weeks, treatment response at the end of induction between 12-14 weeks, clinical remission at week 14, and clinical and biochemical remission at week 14.

The trial will utilize a multicenter open-label randomized-control design to compare E-pTDM with the standard infliximab dosing schedule. Efficacy parameters will be measured at specified timepoints, including weeks 12-14 and week 54, to assess treatment response and remission rates. The trial aims to provide insights into the effectiveness of E-pTDM in maintaining infliximab therapy and improving patient outcomes in pediatric patients with inflammatory bowel disease.