Evaluation of Subcutaneous Infliximab Administration Following Intravenous Dose Optimization in Patients with Ulcerative Colitis, IBDU, and Crohn's Disease

The primary objective of this study is to compare the **clinical** and biological outcomes between a regimen with subcutaneous infliximab administered every week and every other week among patients who were in clinical and biological remission with an optimized intravenous schedule when they switched to subcutaneous infliximab. This comparison is clinically relevant as it aims to determine the most effective dosing schedule for maintaining remission in patients with **ulcerative colitis**, inflammatory bowel disease type unclassified, and **Crohn's disease**.

Secondary objectives include:

• Comparing treatment optimization and discontinuation between a regimen with subcutaneous infliximab every week and every other week among patients who were in clinical and biological remission with an optimized intravenous schedule when they switched to subcutaneous infliximab.
• Evaluating the willingness and experience of patients switching to subcutaneous infliximab.
• Comparing clinical and biological outcomes, as well as treatment optimization and discontinuation, between a regimen with subcutaneous infliximab (every week or every other week) and intravenous infliximab among patients who were in clinical and biological remission with an optimized intravenous schedule.

The clinical trial involves participants diagnosed with **ulcerative colitis**, inflammatory bowel disease type unclassified, and Crohn's disease. The study population includes both male and female subjects aged 18 years and older. Participants are required to be in steroid-free clinical remission, as well as biological remission, at the time of screening. The trial does not include a vulnerable population. Participants must have been receiving intravenous infliximab for at least 26 consecutive weeks and maintained a stable dosing schedule for at least 20 weeks. They should have an average intravenous infliximab dosage of more than 8 mg/kg but not exceeding 22 mg/kg based on the two most recent administrations. The trial population was selected based on these criteria, and participants must be fluent in Dutch, French, or English and capable of providing informed consent. The sponsor has not provided information regarding the total number of participants in the study.

The clinical trial is designed to evaluate the efficacy of **infliximab** administered subcutaneously in patients with **ulcerative colitis**, **inflammatory bowel disease type unclassified**, and **Crohn's disease**. The study employs a randomized, double-blind, controlled design to compare clinical and biological outcomes between two dosing regimens of subcutaneous infliximab: weekly and every other week. Participants must have been in clinical and biological remission with an optimized intravenous schedule before switching to subcutaneous administration. The trial is expected to last until May 31, 2026, with recruitment starting on April 1, 2024.

Participants will undergo a series of study visits, beginning with a screening visit to confirm eligibility based on specific inclusion criteria, such as being in steroid-free clinical remission and having received intravenous infliximab for at least 26 consecutive weeks. Follow-up visits will occur at regular intervals to monitor the maintenance of remission and assess any adverse events. The primary endpoint is the proportion of patients maintaining steroid-free clinical and biological remission by week 52 without treatment optimization. Secondary endpoints include the maintenance of remission with or without treatment optimization at various time points and the time to clinical relapse or treatment discontinuation.

The expected length of participant involvement is up to 52 weeks, with conditions for early termination including clinical relapse, adverse events, or withdrawal of consent. Participants will be closely monitored throughout the study to ensure safety and efficacy, with the option to switch back to intravenous infliximab if necessary. The trial aims to provide valuable insights into the long-term management of these chronic conditions with subcutaneous infliximab therapy.

The clinical trial involves the use of **Infliximab**, a biological medicinal product, in two different pharmaceutical forms. The first form is a **solution for infusion** administered intravenously. The dosage for this form is calculated based on body weight, with a maximum daily dose of 10 mg/kg and a total maximum dose of 140 mg over a treatment period of 56 days. This form is utilized as part of an optimized intravenous schedule to achieve clinical and biological remission before transitioning to the subcutaneous form.

The second form of **Infliximab** is a **solution for injection** administered subcutaneously. This form is used as the experimental treatment in the trial, with a maximum daily dose of 120 mg and a total maximum dose of 6240 mg over a treatment period of 52 weeks. The trial aims to compare the clinical and biological outcomes between two dosing regimens: subcutaneous administration every week versus every other week. The subcutaneous form is intended for patients who have achieved remission with the intravenous form and are transitioning to a maintenance phase.

Both forms of **Infliximab** are classified as biological products and are not pediatric formulations. The trial does not involve any orphan drug designation. Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the treatment protocol. The trial's main objective is to evaluate the efficacy and safety of the subcutaneous form in maintaining remission achieved by the intravenous form.

Efficacy in this clinical trial will be assessed by evaluating the maintenance of steroid-free clinical and biological remission among patients with previously documented **Crohn's Disease (CD)**, **Ulcerative Colitis (UC)**, or **Inflammatory Bowel Disease Unclassified (IBDU)**. The primary endpoint is the proportion of patients maintaining steroid-free clinical and biological remission by week 52 without treatment optimization after switching to subcutaneous infliximab. Secondary endpoints include the proportion of patients maintaining remission by week 52 with or without treatment optimization, as well as at earlier timepoints such as week 8 and week 24. Additional secondary endpoints involve the time to clinical relapse, treatment optimization, or discontinuation, and patient experience and satisfaction with the switch to subcutaneous therapy.

Measurements will be collected at specified intervals, including weeks 8, 24, and 52, to assess the efficacy of the treatment regimen. The trial will utilize patient-reported outcomes and clinical assessments to determine remission status, with specific criteria for clinical remission including a rectal bleeding score of 0 and a stool frequency score of ≤1 for UC/IBDU, or an average daily abdominal pain score of ≤1 and a liquid stool frequency score of ≤2.8 for CD. Biological remission is defined by a C-reactive protein (CRP) level of less than 10 mg/L and fecal calprotectin of less than 250 µg/g. These parameters will be used to evaluate the effectiveness of subcutaneous infliximab in maintaining remission in the patient population.