Evaluation of Adalimumab in a Selective Top-Down Treatment Strategy for Patients with Severe Ulcerative Colitis: The DUCT Trial

The primary objective of the study titled "Debut of Ulcerative Colitis: selective Top-down strategy - the DUCT trial" is to evaluate a **selective top-down treatment algorithm** for a subgroup of patients with **ulcerative colitis** who are identified as having a probable severe 1-year outcome based on a bio-signature. This bio-signature is defined by a mucosal **TNF transcript** level of ≥ 14100 copies/µg RNA and a **RHI** of ≥ 9. The hypothesis posits that for the most severe cases, early biologic therapy (top-down approach) has a higher likelihood of achieving deep remission at one year post-debut compared to the conventional step-up regimen. This study is clinically relevant as it aims to optimize treatment strategies for patients with severe ulcerative colitis, potentially improving long-term outcomes and quality of life.

The clinical trial focuses on individuals diagnosed with **ulcerative colitis**, specifically targeting a subgroup identified as having a probable severe 1-year outcome based on a bio-signature. The study population includes both male and female participants aged 18 to 65 years. Participants are required to be newly diagnosed with ulcerative colitis, confirmed through colonoscopy and biopsy. The trial does not involve a vulnerable population. Participants must be capable of providing informed consent and, if applicable, women of childbearing potential are required to use highly efficient contraception during the study and for five months following the last administration of adalimumab. The sponsor has not provided information regarding the total number of participants. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed to evaluate a selective top-down treatment strategy for patients with **ulcerative colitis** who are identified as having a probable severe 1-year outcome based on a specific bio-signature. This study is a randomized, double-blind, controlled trial, with a primary objective to assess the efficacy of early biologic therapy in achieving deep remission at one year compared to the traditional step-up regimen. The trial is set to commence recruitment on January 1, 2025, and is estimated to conclude by December 31, 2031, with a total duration of approximately seven years.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (18 to 65 years), a new diagnosis of ulcerative colitis confirmed by colonoscopy and biopsy, and the ability to provide informed consent. Women of childbearing potential must adhere to strict contraceptive measures during and for five months following the last administration of **adalimumab**. The study will involve follow-up visits to monitor the participants' response to treatment and to collect data on primary and secondary endpoints, including patient-reported outcomes and medical expenditures. The end-of-study visit will assess the primary outcome, which is the percentage of patients in deep remission one year after the debut of the disease.

The expected length of participant involvement is up to 104 weeks, corresponding to the maximum treatment period with the investigational product, AMGEVITA 40 mg solution for injection in a pre-filled pen, administered via subcutaneous injection. Conditions that may lead to early termination from the study include non-compliance with the study protocol, withdrawal of consent, or any adverse events that necessitate discontinuation of the investigational product. The trial will also explore the improvement of the proposed bio-signature based on data from all 200 included subjects, contributing to the understanding of treatment efficacy and patient outcomes in severe cases of ulcerative colitis.

The clinical trial involves the administration of **AMGEVITA**, a biologic medication containing the active substance **adalimumab**. AMGEVITA is provided as a 40 mg **solution for injection** in a pre-filled pen, designed for ease of use and accurate dosing. The pharmaceutical form is a solution intended for **subcutaneous injection**, allowing for direct delivery into the subcutaneous tissue. The dosing regimen for AMGEVITA in this trial is a maximum daily dose of 40 mg, with a total maximum dose of 160 mg over the course of the treatment. The treatment period is set to last up to 104 weeks, providing a comprehensive evaluation of the medication's efficacy and safety over an extended duration.

In this study, AMGEVITA is utilized as part of a selective top-down treatment strategy for patients with **ulcerative colitis** who are identified as having a probable severe 1-year outcome based on a specific bio-signature. The trial aims to assess the potential benefits of early biologic therapy in achieving deep remission compared to the traditional step-up regimen. The administration of AMGEVITA is monitored to ensure participant compliance, with adherence to the dosing schedule being a critical component of the study protocol. No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are specified in the trial documentation.

Efficacy in the clinical trial titled "Debut of Ulcerative Colitis: selective Top-down strategy - the DUCT trial" will be assessed using both primary and secondary endpoints. The primary endpoint focuses on the percentage of patients achieving deep remission one year after the debut of the disease. Deep remission is defined by a **Mayo score** of ≤2, an endoscopic Mayo score of 0, and a RHI of <3. Additionally, a sub-study will evaluate the percentage of patients who initiate biological medication or undergo surgical intervention within the first year after the disease onset.

Secondary endpoints include patient-reported outcomes, specifically the Inflammatory Bowel Disease Quality of Life (IBD-QoL) and the Simple Clinical Colitis Activity Index (SCCAI). These will be used to evaluate changes in scores from baseline. Furthermore, medical expenditures will be assessed through a retrospective questionnaire and review of medical records, with evaluations conducted after three years. An exploratory outcome will focus on the improvement of the proposed biosignature based on data from all 200 included subjects.