A randomized, double-blind, multicenter phase III study to evaluate the long-term efficacy and safety of ABX464 25 mg or 50 mg once daily as a maintenance therapy in subjects with moderately to severely active ulcerative colitis

The primary objective of this study is to evaluate the **efficacy** of ABX464 compared to placebo in achieving clinical remission in patients with moderately to severely active **ulcerative colitis**. Clinical remission is a critical endpoint in the management of ulcerative colitis, as it indicates a significant reduction in disease activity and improvement in patient quality of life.

Secondary objectives include: - Evaluating the efficacy of ABX464 versus placebo on endoscopic improvement, symptomatic remission, and corticosteroid-free clinical remission. - Assessing the ability of ABX464 to sustain clinical remission and achieve histologic-endoscopic mucosal improvement (HEMI) compared to placebo. - Evaluating the efficacy of ABX464 versus placebo on endoscopic remission. - Assessing the safety profile of different dose groups of ABX464 compared to placebo. These secondary objectives provide a comprehensive understanding of the therapeutic potential and safety of ABX464 in the long-term management of ulcerative colitis.

The clinical trial involves a total of **697 participants** diagnosed with **moderately to severely active ulcerative colitis**. The study population includes both male and female subjects, with an age range encompassing adolescents, adults, and the elderly. Participants were selected based on their completion of a prior induction treatment study, with clinical response status and valid endoscopy results available. The trial includes a vulnerable population, indicating that special considerations are in place for these individuals. Participants are required to adhere to specific lifestyle considerations, such as the use of highly effective contraception methods for women of childbearing potential and their partners. Additionally, subjects must be affiliated with a health insurance policy if required by their country or state. The trial aims to evaluate the efficacy of ABX464 versus placebo on clinical remission in this patient population.

The clinical trial is a **randomized, double-blind, controlled** study designed to evaluate the long-term efficacy and safety of **ABX464** as a maintenance therapy in subjects with moderately to severely active **ulcerative colitis**. The trial involves two dosages of ABX464, 25 mg and 50 mg, administered once daily in the form of hard capsules. The study is structured to include a placebo group for comparison. The primary objective is to assess the proportion of subjects achieving clinical remission at Week 44, with secondary endpoints including endoscopic improvement, symptomatic remission, and corticosteroid-free clinical remission, among others. The trial is expected to run until September 2025, with recruitment having commenced in March 2023.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as completion of a prior induction treatment study and availability of clinical response status. Following the screening, participants will attend regular follow-up visits to monitor their response to the treatment and any adverse events. The end-of-study visit will occur at Week 44, where the primary and secondary endpoints will be evaluated. The expected duration of participant involvement is approximately 44 weeks, aligning with the maximum treatment period.

Conditions that may lead to early termination from the study include the occurrence of serious adverse events, non-compliance with study procedures, or withdrawal of consent. Participants are required to adhere to the study protocol, including the use of highly effective contraception methods for women of childbearing potential and male participants with partners of childbearing potential. The trial is conducted in accordance with ethical standards, and informed consent is obtained from all participants prior to any protocol-specific procedures.

The clinical trial involves the administration of **ABX464**, a hard capsule formulation containing the active substance **obefazimod**. This investigational medication is provided in two dosages: 25 mg and 50 mg. The capsules are administered orally once daily. The maximum daily dose for the 25 mg formulation is 25 mg, with a total maximum dose of 7700 mg over a treatment period of 44 weeks. Similarly, the 50 mg formulation has a maximum daily dose of 50 mg, with a total maximum dose of 15400 mg over the same treatment period. The active substance, obefazimod, is of chemical origin and is produced by ABIVAX. The primary objective of the trial is to evaluate the efficacy of ABX464 in achieving clinical remission in subjects with moderately to severely active **ulcerative colitis**.

The study also includes a **placebo** group to serve as a comparator for evaluating the efficacy of ABX464. The placebo is designed to match the 25 mg and 50 mg ABX464 hard capsules in appearance but does not contain the active substance. The placebo is administered orally once daily, following the same dosing schedule as the active treatment groups. The use of a placebo allows for a double-blind study design, ensuring that neither the participants nor the investigators are aware of the treatment assignments, thereby reducing bias in the assessment of the treatment's efficacy and safety.

The efficacy of ABX464 as a maintenance therapy for moderately to severely active **ulcerative colitis** will be assessed in a randomized, double-blind, multicenter phase III clinical trial. The primary endpoint for evaluating efficacy is the proportion of subjects achieving clinical remission at Week 44. Secondary endpoints include the proportion of subjects with endoscopic improvement, symptomatic remission, corticosteroid-free clinical remission, sustained clinical remission, and endoscopic remission, all assessed at Week 44. Additionally, the proportion of subjects with HEMI per Geboes scoring at Week 44 will be evaluated.

The trial will also monitor the incidence of treatment-emergent adverse events (TEAEs), causally related adverse events (AEs), serious adverse events (SAEs), and causally related SAEs, classified by severity. The incidence of AEs leading to discontinuation of the investigational medicinal product and study discontinuation, as well as adverse events of special interest (AESIs), will be recorded. Clinically significant laboratory abnormalities and abnormalities regarding vital signs and ECG will also be assessed. These efficacy and safety parameters will be collected and analyzed at the specified timepoint of Week 44 to determine the long-term efficacy and safety of ABX464 compared to placebo.