Efficacy and Safety Evaluation of BI 3032950 in Moderate to Severe Ulcerative Colitis: A Phase IIa, Single-Arm, Open-Label, Multi-Center Study

The primary objective of this Phase IIa, single-arm, open-label, multi-center clinical trial is to assess the **efficacy** of BI 3032950 in achieving clinical remission at Week 12 in patients with moderate to severe **ulcerative colitis**. This objective is clinically relevant as achieving remission is a critical goal in the management of ulcerative colitis, potentially improving patient outcomes and quality of life.

Secondary objectives include:

• Characterizing the efficacy and safety of BI 3032950 using secondary endpoints at Week 12.
• Evaluating the long-term safety of maintenance treatment with BI 3032950 in trial participants who show a clinical response to induction treatment.

The clinical trial involves a total of **11 participants** diagnosed with **ulcerative colitis**. The study population includes both female and male subjects, aged between **18 to 80 years**. Participants were selected based on their diagnosis of ulcerative colitis for at least three months prior to screening, confirmed by clinical, endoscopic, and histopathological evidence. The trial includes individuals who have shown an inadequate response, loss of response, or intolerance to biologic or targeted therapy, or those who have discontinued such treatments for any reason. Both genders are represented, and female participants of childbearing potential are required to use highly effective birth control methods, while male participants must use condoms. The trial population is considered vulnerable, and further inclusion criteria apply. No specific lifestyle considerations such as diet or physical activity are mentioned for this study.

The clinical trial is a **Phase IIa**, single-arm, open-label, multi-center study designed to evaluate the efficacy, safety, and tolerability of intravenous induction and subcutaneous maintenance treatment with BI 3032950 in patients with moderate to severe **ulcerative colitis**. The primary objective is to assess the efficacy of BI 3032950, with the primary endpoint being clinical remission at Week 12, as measured by the modified Mayo score. Secondary endpoints include endoscopic remission, clinical response, endoscopic improvement, and the occurrence of treatment-emergent adverse events up to Week 104.

The trial will involve participants aged 18 to 80 years who have been diagnosed with ulcerative colitis for at least three months prior to screening. Participants must have shown an inadequate response, loss of response, or intolerance to previous biologic or targeted therapies. Female participants of childbearing potential are required to use highly effective birth control methods, and male participants must use condoms. The trial is expected to start recruitment on December 10, 2024, and conclude by August 3, 2028.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on the inclusion criteria. Following the screening, participants will receive the investigational product, BI 3032950, administered either intravenously or subcutaneously. Follow-up visits will be scheduled to monitor the participants' response to the treatment and to assess any adverse events. The end-of-study visit will mark the completion of the trial for each participant, where final assessments will be conducted.

The expected duration of participant involvement is up to 104 weeks, depending on individual response and tolerance to the treatment. Conditions that may lead to early termination from the study include the occurrence of significant adverse events, withdrawal of consent, or any other reason deemed necessary by the investigator for the safety and well-being of the participant. The trial is not classified as a low-intervention study, as it aims to investigate the safety and efficacy of a new therapy in patients with ulcerative colitis.

The clinical trial involves the administration of **BI 3032950**, an experimental medication developed by Boehringer Ingelheim International. This investigational product is a **solution for injection/infusion** and is intended for use in patients with moderate to severe **ulcerative colitis**. The pharmaceutical form of BI 3032950 is a solution that can be administered either **intravenously (IV)** or **subcutaneously (SC)**. The treatment regimen includes an initial intravenous induction phase followed by a subcutaneous maintenance phase. The maximum treatment period for BI 3032950 is 104 weeks. The active substance in BI 3032950 is of biological origin, specifically a protein classified as "Protein - Other." The trial aims to evaluate the efficacy, safety, and tolerability of this treatment, with the primary endpoint being clinical remission at Week 12.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The focus is solely on the administration of BI 3032950. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the treatment protocol. The trial is designed as a Phase IIa, single-arm, open-label, multi-center study, which allows for a comprehensive assessment of the investigational product's effects in the target patient population.

The efficacy of the investigational product BI 3032950 in the treatment of moderate to severe **ulcerative colitis** will be assessed in a Phase IIa, single-arm, open-label, multi-center clinical trial. The primary endpoint for evaluating efficacy is clinical remission at Week 12, as measured by the modified Mayo score (mMS). Clinical remission is defined by an mMS of 0 to 2, which includes a stool frequency subscore (SFS) of 0 or 1, a rectal bleeding subscore (RBS) of 0, and a centrally-read endoscopy subscore (ESS) of 0 or 1.

Secondary endpoints include endoscopic remission, defined as a centrally-read ESS of 0 at Week 12, and clinical response, characterized by a decrease from baseline in mMS of at least 2 and a reduction of at least 30% from baseline, along with a decrease in RBS of at least 1 or an absolute RBS of 0 or 1. Additional secondary endpoints are endoscopic improvement, mMS change from baseline, SFS of 0 or 1, and RBS of 0, all evaluated at Week 12. The occurrence of treatment-emergent adverse events (AEs) will also be monitored up to Week 12 and up to Week 104.