Efficacy of Subcutaneous Infliximab Monotherapy Versus Infliximab with Immunosuppression in Moderate to Severe Crohn's Disease

The primary objective of this study is to evaluate the **efficacy** of subcutaneous infliximab (IFX) in the treatment of moderate to severe **Crohn's disease**, both with and without concomitant immunosuppression. This will be assessed by the proportion of patients achieving corticosteroid-free clinical remission, defined by a Crohn's Disease Activity Index (CDAI) score of less than 150, and endoscopic response, defined by a Simple Endoscopic Score for Crohn's Disease (SES-CD) reduction of at least 50% at week 26. The clinical relevance of this objective lies in determining whether subcutaneous IFX monotherapy is non-inferior to IFX combined with immunosuppressives in achieving these outcomes, which are critical for improving patient management and treatment strategies.

Secondary objectives include investigating the safety and efficacy of subcutaneous IFX monotherapy compared to IFX therapy combined with immunosuppressives over a 26-week treatment period. This will be evaluated through clinical scores, patient-reported outcomes, quality of life measures, biomarkers, and endoscopy. Additionally, the study will assess IFX trough concentration and the development of anti-drug antibodies, correlating these with HLA-haplotypes. These secondary objectives aim to provide a comprehensive understanding of the treatment's impact on patient health and its immunological implications.

The clinical trial focuses on individuals diagnosed with **Crohn's disease**, specifically targeting those with moderate to severe activity levels. The study population includes both male and female participants aged 18 years and older. Participants are required to have a Crohn's Disease Activity Index (CDAI) ranging from 220 to 450, along with objective evidence of inflammation, such as endoscopic ulceration in the terminal ileum, colon, or both. The trial includes individuals who have not responded to or have experienced unacceptable side effects from treatments like glucocorticoids, thiopurines, methotrexate, or adalimumab, or those deemed by their physician to require immediate top-down treatment with IFX. Participants must be capable of understanding and complying with protocol requirements and must provide informed consent. The study does not specify the total number of participants, as this information was not provided by the sponsor. Lifestyle considerations such as diet, physical activity, or habits are not detailed in the available data. The trial includes a vulnerable population, and both male and non-pregnant, non-lactating females are eligible to participate.

The clinical trial is designed as a **randomized**, controlled, open-label study to evaluate the efficacy of subcutaneous **infliximab** monotherapy compared to infliximab with concomitant immunosuppression in patients with moderate to severe **Crohn's disease**. The primary objective is to assess the proportion of patients achieving corticosteroid-free clinical remission and endoscopic response at week 26. The trial is expected to conclude by December 31, 2025, with recruitment having commenced on November 25, 2021.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, disease activity, and previous treatment responses. Follow-up visits will be scheduled to monitor patient progress, assess treatment efficacy, and ensure safety. The end-of-study visit will occur at week 26, where final assessments will be conducted to determine the primary and secondary endpoints.

The expected duration of participant involvement is approximately 26 weeks. Conditions that may lead to early termination from the study include non-compliance with protocol requirements, adverse events, or withdrawal of consent. The study aims to provide valuable insights into the treatment of Crohn's disease, with a focus on achieving clinical remission and improving patient outcomes.

The clinical trial involves the administration of **Remsima**, a 120 mg **solution for injection** in a pre-filled pen, containing the active substance **infliximab**. Infliximab is a protein-based therapeutic agent classified under the ATC code L04AB02. The pharmaceutical form of the medication is a solution for injection, specifically designed for subcutaneous administration. The maximum daily and total dose of Remsima is 120 mg, with a treatment period limited to one day. The administration route is via subcutaneous injection, ensuring direct delivery of the medication into the subcutaneous tissue. The product is manufactured by Celltrion Healthcare Hungary Kft and is not formulated for pediatric use.

In this study, Remsima is evaluated as a monotherapy and in combination with concomitant immunosuppression for the treatment of moderate to severe **Crohn's disease**. The trial aims to compare the efficacy of these two treatment regimens. The primary endpoint is the achievement of corticosteroid-free clinical remission and endoscopic response by week 26. The study does not involve any additional non-experimental treatments such as placebo or standard-of-care therapy. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the treatment protocol.

The efficacy of the clinical trial will be assessed by evaluating the primary and secondary endpoints related to the treatment of moderate to severe **Crohn's disease**. The primary endpoint is defined as the proportion of patients achieving corticosteroid-free clinical remission, indicated by a Crohn's Disease Activity Index (CDAI) score of less than 150, and an endoscopic response, characterized by a reduction of at least 50% in the Simple Endoscopic Score for Crohn's Disease (SES-CD) compared to baseline, at week 26. Secondary endpoints include the proportion of patients in endoscopic remission at week 26, defined as the absence of ulcerations larger than 5mm, and the proportion of patients with an SES-CD score of 2 or less. Additionally, the secondary endpoints will measure the proportion of patients achieving a 50% reduction in SES-CD from baseline and those in corticosteroid-free clinical remission at week 26, as defined by a CDAI score of less than 150.

The efficacy parameters will be measured and collected at specific timepoints, with the primary assessment occurring at week 26. The CDAI and SES-CD are validated scales used to quantify disease activity and endoscopic findings, respectively. These tools will be instrumental in determining the clinical and endoscopic outcomes of the trial participants. The analysis will focus on comparing the efficacy of subcutaneous infliximab monotherapy versus subcutaneous infliximab with concomitant immunosuppression, with the hypothesis that the monotherapy is non-inferior in achieving the combined primary endpoint by the specified timepoint.