VE202 in Patients With Mild-to-Moderate Ulcerative Colitis

Study Overview
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Brief Summary
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A Phase 2 study to evaluate the safety, efficacy, and microbiota changes of VE202 in patients with mild to moderate ulcerative colitis (UC).

Detailed Description
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A Phase 2 double-blind, placebo-controlled, randomized study to evaluate the safety, efficacy, and microbiota changes of VE202 in biologic-naïve patients with mild to moderate UC. In Parts 1 and 2 of the study, patients will receive VE202 or placebo for 8 weeks or 2 weeks. In Part 3, patients will be followed for safety for 1 year from the start of treatment.

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

Conditions
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Ulcerative Colitis, Colitis, Ulcerative

Intervention / Treatment
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* Biological: VE202
* Drug: Vancomycin Oral Capsule
* Other: VE202 Placebo
* Other: Vancomycin Placebo


Participation Criteria
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Eligibility Criteria
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KEY INCLUSION CRITERIA 18 to 75 years of age Documented clinical and endoscopic diagnosis of UC at least 3 months prior to randomization Active mild to moderate UC, as defined by the following: Disease that extends at least 15 cm from the anal verge A modified Mayo score of 4 to 8 with: (i.) Mayo endoscopic subscore of ≥ 2 based on screening flexible sigmoidoscopy; (ii.) Rectal bleeding score of ≥ 1 Has never received a biologic agent, Janus kinase inhibitor, or sphingosine-1-phosphate modulator for the treatment of UC If receiving corticosteroids, dose must be stable for at least 4 weeks before randomization Doses of other allowable UC medications must be stable for at least 8 weeks before randomization KEY EXCLUSION CRITERIA Known history of Crohn's disease (CD) or indeterminate colitis A known diagnosis of primary sclerosing cholangitis Allergy to VE202 or any of its components Allergy to vancomycin or any of its components A diagnosis of any non-IBD diarrheal illness (eg, Clostridioides difficile, celiac disease, parasitic infection) within 3 months prior to randomization Use of probiotics or herbal, botanical, or traditional medicinal preparations within the 2 weeks prior to randomization (consumption of food products such as yogurt, kefir, kombucha, and herbal teas is permissible) Receipt of Fecal Microbiota Transplantation (FMT) or other fecal-derived preparation within 6 months prior to randomization Prior colectomy, ostomy, or other intestinal surgery (excluding cholecystectomy or appendectomy) Receipt of any investigational biologic within 60 days or 5 half-lives prior to randomization, whichever is longer

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Group A: Part 1 Active and Part 2 Placebo Treatment with Vancomycin pretreatment.<br>In Part 1 of the study, patients in Group A will receive VE202 for 8 weeks. In Part 2 of the study, patients in Group A will receive VE202 placebo for 2 weeks. In Part 3, patients will be followed for safety for 1 year from the start of treatment. | Biological: VE202<br>* VE202 is a rationally defined, live biotherapeutic product for oral administration.<br>Drug: Vancomycin Oral Capsule<br>* Vancomycin is an antibiotic used to treat or prevent infection<br>Other: VE202 Placebo<br>* VE202 Placebo<br>Other: Vancomycin Placebo<br>* Vancomycin Placebo<br>|
| Other: Group B: Part 1 Placebo and Part 2 Active Treatment with Vancomycin pretreatment.<br>In Part 1 of the study, patients in Group B will receive VE202 placebo for 8 weeks. In Part 2 of the study, patients in Group B will receive VE202 for 2 weeks. In Part 3, patients will be followed for safety for 1 year from the start of treatment. | Biological: VE202<br>* VE202 is a rationally defined, live biotherapeutic product for oral administration.<br>Drug: Vancomycin Oral Capsule<br>* Vancomycin is an antibiotic used to treat or prevent infection<br>Other: VE202 Placebo<br>* VE202 Placebo<br>Other: Vancomycin Placebo<br>* Vancomycin Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants with endoscopic response on flexible sigmoidoscopy after 8 weeks of treatment with VE202 or placebo. | Endoscopic response is defined as a reduction from baseline of 1 point or more in Mayo endoscopic subscore. The Mayo endoscopic subscore is evaluated on a scale of 0 to 3, with a higher score representing more severe disease. | 8 Weeks | 
| Percentage of participants with Grade ≥ 3 Treatment-Emergent Adverse Events (TEAEs) that are treatment-related or Serious Adverse Events (SAEs) that are treatment-related in Part 1 and Part 2 of the study. | The safety of VE202 and placebo in Parts 1 and 2 of the study, which include an 8-week and 2-week course of treatment, respectively, will be evaluated. | 16 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants with endoscopic response on flexible sigmoidoscopy at Week 8, following treatment with VE202 for 2 weeks. | Endoscopic response is defined as a reduction from baseline of 1 point or more in Mayo endoscopic subscore. The Mayo endoscopic subscore is evaluated on a scale of 0 to 3, with a higher score representing more severe disease. | 8 Weeks | 
| Number of participants with TEAEs, SAEs, and Adverse Events of Special Interest (AESIs) in Parts 1, 2, and 3 of the study. | The safety of VE202 and placebo in Parts 1, 2, and 3 of the study, which include an 8-week and 2-week course of treatment followed by a long-term follow-up period, will be evaluated. AESIs are defined as treatment-related Grade ≥2 TEAEs that are gastrointestinal or bacterial infections. | 52 Weeks | 
| Percentage of participants with clinical remission at Week 8 of Part 1 and Week 8 of Part 2. | Participants will receive 8 weeks of VE202/placebo in Part 1 and 2 weeks of VE202/placebo in Part 2. Clinical remission is defined as attaining a Mayo stool frequency subscore of ≤1 and an improvement in stool frequency subscore of ≥1 point from baseline, a rectal bleeding subscore of 0 and an endoscopic subscore ≤1. Each component of the Mayo score is evaluated on a scale of 0 to 3, with a higher score representing more severe disease. | 8 Weeks | 
| Percentage of participants with clinical response at Week 8 of Part 1 and Week 8 of Part 2. | Participants will receive 8 weeks of VE202/placebo in Part 1 and 2 weeks of VE202/placebo in Part 2. Clinical response is defined as having met the definition of clinical remission or having a decrease from baseline of ≥2 points and a decrease of ≥30% in modified Mayo score, with either a rectal bleeding score of 0 or a decrease in rectal bleeding of ≥1 point. Each component of the modified Mayo score (stool frequency, rectal bleeding, endoscopy findings) is evaluated on a scale of 0 to 3, with a higher score representing more severe disease. | 8 Weeks | 
| Percentage of participants with endoscopic remission on flexible sigmoidoscopy at Week 8 of Part 1 and Week 8 of Part 2. | Participants will receive 8 weeks of VE202/placebo in Part 1 and 2 weeks of VE202/placebo in Part 2. Endoscopic response is defined as a Mayo endoscopic subscore of 0 or 1 point. The Mayo endoscopic subscore is evaluated on a scale of 0 to 3, with a higher score representing more severe disease. | 8 Weeks | 
| Change in Mayo score compared with baseline at Week 8 of Part 1 and Week 8 of Part 2. | Participants will receive 8 weeks of VE202/placebo in Part 1 and 2 weeks of VE202/placebo in Part 2. The Mayo score is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy findings, and physician global assessment), with each parameter evaluated on a scale of 0 to 3. The total score ranges from 0 to 12, and a higher score represents more severe disease. | 8 Weeks | 
| Histologic improvement at Week 8 of Part 1 and Week 8 of Part 2 as measured by Geboes score. | Participants will receive 8 weeks of VE202/placebo in Part 1 and 2 weeks of VE202/placebo in Part 2. The Geboes score encompasses 6 dimensions, each with 4 subcategories: architectural changes, chronic inflammatory infiltrate, lamina propria neutrophils and eosinophils, neutrophils in the epithelium, crypt destruction, and erosions or ulcerations. The Geboes score ranges from grade 0 to 5.4. A higher Geboes score represents more severe disease. | 8 Weeks | 
| Histologic improvement at Week 8 of Part 1 and Week 8 of Part 2 as measured by the Robarts Histopathology Index (RHI). | Participants will receive 8 weeks of VE202/placebo in Part 1 and 2 weeks of VE202/placebo in Part 2. The RHI provides a score between 0 and 33, based on the levels of chronic inflammatory infiltrate, neutrophils in lamina propria and epithelium, and erosion/ulceration. A higher RHI score represents more severe disease. | 8 Weeks | 
| Change in fecal calprotectin levels after 2- and 8-week courses of VE202. | The change in fecal calprotectin level from baseline will be evaluated. | 52 Weeks | 
| Change in colonization with VE202 strains detected in feces at various time points in patients treated with 2- and 8-week courses of VE202. | VE202 colonization will be characterized in patients treated with 2- and 8-week courses of VE202. | 52 Weeks | 
| Change in the total percent of relative abundance of VE202 strains in feces at various time points in patients treated with 2- and 8-week courses of VE202. | VE202 colonization will be characterized in patients treated with 2- and 8-week courses of VE202. | 52 Weeks | 
| Change in taxonomic composition of gut microbiome in patients treated with 2- and 8-week courses of VE202. | Microbiome composition will be evaluated by measuring the sum of species and the genera or higher-level taxonomic groupings at baseline and at subsequent time points in patients treated with 2- and 8-week courses of VE202 or placebo. | 52 Weeks | 
| Change in fecal metabolite profiles at baseline and post-VE202 or placebo at various time points. | Short-chain fatty acid and bile acid concentrations will be evaluated at baseline and at subsequent time points in patients treated with 2- and 8-week courses of VE202 or placebo. | 52 Weeks | 
| Number of participants with hospitalization or surgical procedure related to UC after 2- and 8-week courses of VE202. | To evaluate the impact of 2- and 8-week courses of VE202 on Inflammatory bowel disease (IBD) specific healthcare resource utilization. | 52 weeks | 
| Change in patient-reported outcome measures using the Inflammatory Bowel Disease Questionnaire (IBDQ) to evaluate the impact of 2- and 8-week courses of VE202 IBD-specific health-related quality of life. | The 32-item IBDQ uses a 7-point scale to assess disease-specific health-related quality of life across 4 dimensions: bowel symptoms, systemic symptoms, emotional wellbeing, and social function. The total IBDQ score is calculated by adding the scores within each domain. Scores can range from 32 to 224, with a higher score indicating a better outcome. | 52 Weeks | 
| Change in patient-reported outcome measures using the EuroQoL-5D Health Assessment Questionnaire (EQ-5D) scores to evaluate the impact of 2- and 8-week courses of VE202 IBD-specific health-related quality of life. | The EuroQoL-5D Health Assessment Questionnaire (EQ-5D) is a standardized, self-administered, non-disease-specific instrument for measuring generic health status for routine clinical outcome measurement in the delivery of operational healthcare. Scores range from 0 to 100, with a higher score indicating better outcome. | 52 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ulcerative Colitis, VE202, Vedanta, Clostridia