Efficacy and Safety of Obefazimod (ABX464) in Adults with Moderately to Severely Active Ulcerative Colitis: A Randomized Placebo‑Controlled Phase III Study

The primary objective of this phase III study is to compare the efficacy of **ABX464** versus placebo in achieving clinical remission in subjects 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:

• Comparing the efficacy of ABX464 versus placebo on endoscopic improvement.
• Evaluating the clinical response using the Modified Mayo Score (MMS).
• Assessing symptomatic remission.
• Examining histologic-endoscopic mucosal improvement (HEMI).
• Comparing the safety profile of ABX464 versus placebo during the induction phase.

The clinical trial involves a total of **380 participants** diagnosed with **moderately to severely active ulcerative colitis**. The study population includes both male and female subjects, with an age range starting from 16 years, although adolescent subjects are only enrolled if approved by the relevant regulatory authorities. Participants must weigh at least 40 kg and meet the definition of Tanner Stage 5 at the screening visit. The trial population was selected based on documented inadequate response to treatments such as corticosteroids, immunosuppressants, biologic therapies, S1P receptor modulators, and JAK inhibitors. Participants are required to have an active disease defined by a modified Mayo score of at least 5, with specific subscores for rectal bleeding and endoscopy. The study includes individuals who are able and willing to comply with study visits and procedures, and who are affiliated with a health insurance policy if required by their country or state. Both men and women of childbearing potential must agree to use highly effective contraception methods during the study. The trial also considers vulnerable populations, ensuring ethical standards are maintained throughout the study.

The clinical trial is a **randomized, double-blind, placebo-controlled** study designed to evaluate the efficacy and safety of **ABX464** in subjects with moderately to severely active **ulcerative colitis**. The trial is a Phase III study, conducted across multiple centers, with an estimated duration from February 15, 2023, to November 24, 2024. The primary objective is to compare the efficacy of ABX464 versus placebo in achieving clinical remission, as measured by the Modified Mayo Score at week 8. Secondary endpoints include endoscopic improvement, clinical response, symptomatic remission, and the incidence of treatment-emergent adverse events.

Participants will be involved in the study for a maximum of 8 weeks, with the possibility of early termination if adverse events occur or if the participant withdraws consent. The study begins with a screening visit to confirm eligibility, which includes criteria such as age, documented diagnosis of ulcerative colitis, and previous inadequate response to certain treatments. Following the screening, eligible participants will be randomized to receive either ABX464 or a placebo, administered orally in hard capsule form.

Study visits are scheduled at baseline, week 4, and week 8, with assessments conducted to monitor efficacy and safety. The end-of-study visit at week 8 will include a comprehensive evaluation of clinical remission and any adverse events. Participants are required to comply with study procedures and maintain effective contraception if applicable. The trial is not classified as low intervention, and participation is contingent upon meeting all inclusion criteria and none of the exclusion criteria. The study aims to provide robust data on the potential benefits of ABX464 for individuals with ulcerative colitis.

The clinical trial involves the administration of **ABX464**, a hard capsule formulation containing the active substance **obefazimod**. The pharmaceutical form is a hard capsule, and the medication is administered orally. Two dosage strengths are utilized in the study: 25 mg and 50 mg. The maximum daily dose for the 25 mg capsule is 25 mg, with a total maximum dose of 1400 mg over the treatment period. For the 50 mg capsule, the maximum daily dose is 50 mg, with a total maximum dose of 2800 mg. The treatment period for both dosages is up to 8 weeks. The medication is produced by ABIVAX and is classified as a chemical substance. Participant compliance with the dosing schedule is monitored throughout the study.

The trial also includes a **placebo** group, which receives a placebo designed to match the 25 mg and 50 mg ABX464 hard capsules in appearance. The placebo is administered orally, following the same dosing schedule as the active treatment groups. The use of a placebo allows for a double-blind, placebo-controlled study design, ensuring that neither the participants nor the investigators are aware of the treatment assignments, thereby reducing bias and enhancing the reliability of the study results.

The efficacy of ABX464 in the treatment of moderately to severely active **ulcerative colitis** will be assessed through a randomized, double-blind, placebo-controlled, multicenter phase III study. The primary endpoint for evaluating efficacy is the proportion of subjects who achieve clinical remission as measured by the Modified Mayo Score (MMS) at week 8. Secondary endpoints include the proportion of subjects who achieve endoscopic improvement, clinical response per MMS, symptomatic remission, and histological remission per Geboes scoring, all assessed at week 8. Additionally, the incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), adverse events leading to discontinuation, and clinically significant laboratory and vital sign abnormalities will be monitored.