Evaluation of Obefazimod Efficacy and Safety in Patients with Moderately to Severely Active Crohn's Disease: A Phase 2b Multicenter, Double-Blind, Placebo-Controlled Study

The primary objective of this phase 2b, multicenter, double-blind, placebo-controlled study is to evaluate the **efficacy** of obefazimod compared to placebo as induction and maintenance therapy in subjects with moderately to severely active **Crohn's disease** (CD) who have shown an inadequate response, including no response, loss of response, or intolerance, to conventional and/or advanced therapies. This evaluation is clinically relevant as it aims to provide an alternative therapeutic option for patients with limited treatment success from existing therapies.

Secondary objectives include:

• Assessing the **safety** and tolerability of obefazimod during the induction and maintenance treatment phases, which is crucial for understanding the risk-benefit profile of the treatment.
• Evaluating the pharmacokinetic (PK) profile by assessing the concentration of obefazimod and its metabolite ABX464-N-Glu in subjects with moderately to severely active CD during the induction, maintenance, and extension phases. This objective is important for determining the appropriate dosing regimen and understanding the drug's behavior in the body.

The clinical trial involves a total of **83 participants** diagnosed with **Crohn's disease**, characterized by moderately to severely active disease. The study population includes both male and female subjects, aged between 18 to 75 years. Participants were selected based on their documented inadequate response to conventional and/or advanced therapies, excluding those who only failed 5-ASA treatment. The trial does not include a vulnerable population. Participants are required to have a confirmed diagnosis of Crohn's disease through endoscopy and histology reports. Lifestyle considerations such as diet and physical activity are not specified. The trial ensures that all participants are affiliated with a health insurance policy if required by their country or state. The study aims to evaluate the efficacy and safety of obefazimod compared to placebo in this specific patient group.

The clinical trial is a **phase 2b**, multicenter, double-blind, placebo-controlled study designed to evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of **obefazimod** in subjects with moderately to severely active **Crohn's disease**. The trial will involve a randomized allocation of participants to receive either obefazimod or a placebo, with the primary objective being to assess the efficacy of obefazimod as both induction and maintenance therapy. The trial is expected to commence recruitment on January 15, 2025, and conclude by July 12, 2028.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, documented diagnosis of Crohn's disease, and previous inadequate response to conventional therapies. Following successful screening, participants will be randomized and enter the induction phase, with follow-up visits scheduled to monitor efficacy and safety outcomes. The primary endpoint will be the change from baseline in the Crohn's Disease Activity Index (CDAI) score at Week 12 and Week 52. Secondary endpoints include changes in the Simple Endoscopic Score for Crohn's Disease (SES-CD) and the proportion of subjects achieving clinical remission or response.

The trial will include an extension phase to further evaluate the safety and tolerability of obefazimod. Participants will be involved in the study for a maximum treatment period of 100 weeks, with conditions for early termination including the occurrence of serious adverse events or non-compliance with study procedures. The study will ensure rigorous monitoring of treatment-emergent adverse events and laboratory abnormalities throughout the trial duration.

The clinical trial involves the administration of **obefazimod**, a chemical compound also known by its sponsor product code **ABX464**. Obefazimod is provided in the form of a hard capsule and is administered orally. The trial includes three different dosages of obefazimod: 12.5 mg, 25 mg, and 50 mg. The maximum daily dose for each participant is set at 12.5 mg, 25 mg, or 50 mg, depending on the assigned treatment group. The total maximum dose over the treatment period is 8.75 g, 17.5 g, or 35 g, respectively. The treatment period is capped at 100 days. The active substance, obefazimod, is of chemical origin and is produced by ABIVAX. The trial aims to evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of obefazimod in subjects with moderately to severely active Crohn's disease.

A placebo is also utilized in this study as a comparator treatment. The placebo is designed to match the 12.5 mg, 25 mg, and 50 mg ABX464 hard capsules in appearance but does not contain the active substance, obefazimod. The placebo is administered orally in the same manner as the experimental medication, ensuring blinding of the study. The use of a placebo allows for a controlled comparison to assess the true efficacy and safety of obefazimod. Participants are randomly assigned to receive either the active treatment or the placebo, maintaining the double-blind nature of the trial.

The efficacy of **obefazimod** in the clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoint for the induction and maintenance phases is the change from baseline in the Crohn's Disease Activity Index (CDAI) score at Week 12 and Week 52. Secondary endpoints include several measures of efficacy: the change from baseline in the Simple Endoscopic Score for Crohn's Disease (SES-CD) at Week 12 and Week 52, the proportion of subjects with endoscopic response, and the proportion of subjects with no SES-CD ulcer subscore greater than 1 in at least one segment at these same timepoints.

Additional secondary endpoints involve the proportion of subjects achieving CDAI clinical remission, sustained CDAI clinical remission, and CDAI clinical response at Week 12 and Week 52. The trial will also evaluate the proportion of subjects with PRO-2 clinical remission and response, as well as the proportion achieving both CDAI clinical response and endoscopic response. Endoscopic remission will also be assessed at Week 12 and Week 52. These efficacy parameters will be measured and collected at specified timepoints using validated scales and clinical assessments to ensure accurate and reliable data collection.