Phase 2 Randomized, Double-Blind, Placebo-Controlled Study of VE202 in Mild-to-Moderate Ulcerative Colitis Patients

The primary objective of this randomized, double-blind, placebo-controlled, Phase 2 study is to evaluate the **efficacy** of an 8-week treatment with VE202 in patients with mild-to-moderate **ulcerative colitis**. The efficacy will be assessed in terms of endoscopic response at Day 56. This is clinically relevant as it aims to determine the potential of VE202 to induce mucosal healing, which is a critical therapeutic goal in managing ulcerative colitis. Additionally, the study seeks to evaluate the **safety** of VE202 in both Part 1 and Part 2 of the study, ensuring that the treatment is not only effective but also safe for patient use.

The clinical trial involves a total of **98 participants** diagnosed with **mild-to-moderate ulcerative colitis**. The study population includes both male and female subjects, aged between **18 to 75 years**. Participants were selected based on their documented clinical and endoscopic diagnosis of ulcerative colitis, with active disease extending at least 15 cm from the anal verge and a modified Mayo score of 4 to 8. The trial population is characterized by individuals who have not previously received biologic agents, Janus kinase inhibitors, or sphingosine-1-phosphate modulators for the treatment of ulcerative colitis. Participants are required to have stable doses of corticosteroids and other allowable ulcerative colitis medications prior to randomization. The study includes individuals who are up to date with local colorectal cancer surveillance recommendations. Both male and female participants must adhere to specific reproductive health guidelines during the study period. The trial also considers vulnerable populations, ensuring comprehensive ethical oversight.

The clinical trial is designed as a **randomized, double-blind, placebo-controlled, Phase 2 study** to evaluate the efficacy and safety of VE202 in patients with mild-to-moderate **ulcerative colitis**. The trial aims to assess the endoscopic response after 8 weeks of treatment with VE202, with the primary endpoint being a reduction of 1 point or more in the Mayo endoscopic subscore from baseline to Day 56. The study will also monitor treatment-emergent adverse events and serious adverse events related to VE202 or its placebo. The trial is expected to last until May 2025, with recruitment having started in May 2023.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, disease status, and medication history. Following randomization, participants will receive either VE202, a placebo, or vancomycin hydrochloride, all administered orally in capsule form. The study includes follow-up visits to monitor the participants' health, collect blood and stool samples, and assess the treatment's efficacy and safety. The end-of-study visit will occur at the conclusion of the 8-week treatment period, where final assessments will be conducted.

The expected length of participant involvement is approximately 8 weeks, with conditions for early termination including the occurrence of grade ≥3 treatment-emergent adverse events or serious adverse events related to the study drug. Participants must adhere to the study protocol, including maintaining stable doses of any concurrent medications and following contraceptive guidelines if applicable. The trial's design ensures that all participants, investigators, and study staff remain blinded to the treatment assignments to maintain the integrity of the study results.

The clinical trial involves the administration of **VE202**, an experimental medication formulated as a capsule. VE202 contains a consortium of live bacterial strains, including various **Clostridia** and **Bacilli** species, which are structurally diverse substances. The capsule is designed for **oral use**. The treatment period for VE202 is set at 8 weeks, with the dosage measured in colony-forming units per gram (CFU/g). The specific dosing schedule and frequency of administration are not detailed in the provided data.

In addition to VE202, the trial includes a **placebo** control, referred to as the VE202 Placebo drug product. This placebo consists of microcrystalline cellulose encapsulated in a size 0 Vcaps® enteric-coated capsule. The placebo is also administered orally, mirroring the form and route of the experimental treatment to maintain blinding in the study.

Another component of the trial is the use of **Vancomycin Hydrochloride**, a non-experimental treatment. This medication is provided in capsule form and is also administered orally. The vancomycin capsules are over-encapsulated to ensure blinding. The treatment period for vancomycin is 5 days, although specific dosing details are not provided in the data.

The trial also includes a **Vancomycin Placebo**, which contains microcrystalline cellulose (Avicel® PH-102) and is encapsulated in a hard gelatin capsule, size 00, Swedish Orange Opaque. This placebo is used to maintain the double-blind nature of the study and is administered orally, similar to the active vancomycin treatment.

The efficacy of the investigational product VE202 in the treatment of mild-to-moderate **Ulcerative Colitis** will be assessed through a randomized, double-blind, placebo-controlled, Phase 2 clinical trial. The primary endpoint for evaluating efficacy is the endoscopic response rate, defined as a reduction of 1 point or more in the Mayo endoscopic subscore on flexible sigmoidoscopy from baseline to Day 56. This endpoint will be measured using validated endoscopic techniques to ensure accuracy and reliability of the data collected.

Data collection will occur at specified timepoints, with the primary assessment scheduled for Day 56. The analysis will focus on comparing the endoscopic response rates between the VE202 treatment group and the placebo group. Additionally, the trial will monitor for Grade ≥ 3 treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) related to VE202 or its placebo, as these are also considered primary endpoints. The trial is designed to ensure rigorous assessment of both efficacy and safety, providing comprehensive insights into the potential benefits and risks associated with VE202 treatment in this patient population.