Long-term Safety and Efficacy Evaluation of Obefazimod (ABX464) in Moderate to Severe Ulcerative Colitis: A Phase II Open-label Study

The primary objective of this study is to evaluate the long-term **safety** of ABX464, administered at a dose of 25 mg once daily, in subjects with moderate to severe active **ulcerative colitis**. This is clinically relevant as it aims to ensure the safety of prolonged use of ABX464 in managing this chronic inflammatory bowel disease, which can significantly impact patients' quality of life.

Secondary objectives include evaluating the long-term effects of ABX464 on various clinical and biological parameters:

• Clinical remission
• Endoscopic remission
• Clinical response
• Endoscopic improvement
• Inflammatory markers, specifically C-reactive protein (CRP) and calprotectin
• Safety profile
• miR-124 expression in total blood at defined timepoints
• Cardiac function as assessed through echocardiograms

The clinical trial involves a total of **42 participants** diagnosed with **Moderate to Severe Ulcerative Colitis**. The study population includes both male and female subjects, with an age range corresponding to categories 3 and 4, which typically represent adults. Participants were selected based on their previous completion of the ABX464-102 or ABX464-104 clinical studies, and they must have demonstrated endoscopic improvement with a rectal bleeding sub-score of 0 at the end of the treatment period in the prior study. The trial includes a vulnerable population, indicating that special considerations are in place to ensure their safety and compliance. Participants are required to adhere to specific lifestyle considerations, including the use of highly effective contraceptive methods for both men and women of childbearing potential during the study and for a follow-up period. The trial does not specify any particular dietary or physical activity requirements. The selection criteria ensure that participants are able and willing to comply with study visits and procedures, and they must provide informed consent prior to participation.

The clinical trial is a **Phase II** open-label study designed to evaluate the long-term safety and efficacy of **ABX464** administered at a dose of 25 mg once daily in subjects with moderate to severe active **ulcerative colitis**. The trial employs a non-randomized, open-label design, focusing on subjects who have previously completed the ABX464-102 or ABX464-104 studies. The primary objective is to assess the long-term safety profile of ABX464, with secondary endpoints including the percentage of subjects achieving clinical and endoscopic remission, as well as changes in biomarkers such as CRP and fecal calprotectin levels. The trial is expected to run until March 31, 2026, with recruitment having commenced on December 1, 2021.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as endoscopic improvement and compliance with study procedures. Follow-up visits will occur at regular intervals to monitor safety and efficacy outcomes, including the assessment of adverse events and clinical response. The end-of-study visit will conclude the participant's involvement, with data collected on long-term outcomes and any adverse events experienced during the trial.

The expected duration of participant involvement is up to 54 weeks, with conditions for early termination including the occurrence of serious adverse events or non-compliance with study protocols. Participants are required to adhere to contraceptive guidelines throughout the study and for a four-week follow-up period post-treatment. The trial's design and procedures are structured to ensure rigorous monitoring of safety and efficacy, providing valuable insights into the long-term use of ABX464 in the target population.

The clinical trial involves the administration of the experimental medication **ABX464**, which is a **hard capsule** formulation. The active substance in ABX464 is **obefazimod**, a chemical compound developed by ABIVAX. The medication is administered **orally** at a dosage of **25 mg** once daily. The maximum treatment period for this study is **54 weeks**. The primary objective of the trial is to evaluate the long-term safety and efficacy of ABX464 in subjects with **Moderate to Severe Active Ulcerative Colitis**.

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 ABX464. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the prescribed regimen. The trial does not involve any pediatric formulations, and ABX464 is not classified as an orphan drug. The study is designed to provide comprehensive data on the safety profile of ABX464 over the extended treatment period.

The efficacy of the investigational product, **obefazimod**, will be assessed in subjects with Moderate to Severe Active Ulcerative Colitis through a series of secondary endpoints. These endpoints include the percentage of subjects achieving clinical remission, endoscopic remission, clinical response, and endoscopic improvement at yearly visits. Additionally, changes from baseline in C-reactive protein (CRP) and fecal calprotectin levels will be evaluated. The study will also monitor changes in miRNA-124 expression in total blood at every defined timepoint.

Further assessments will involve echocardiography endpoints, such as the absolute percentage change from baseline in left ventricular ejection fraction (LVEF) and left ventricular global longitudinal strain (LVGLS). The number of subjects with clinically relevant reductions in these parameters will be recorded. These efficacy parameters will be collected and analyzed according to the Statistical Analysis Plan (SAP) to ensure accurate and reliable results.