VE202 in Patients With Mild-to-Moderate Ulcerative Colitis

Ulcerative Colitis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05370885
• Other study ID #: VE202-002
• Secondary ID: 2021-001280-24
• Status: Recruiting
• Phase: Phase 2
• Start date: May 8, 2023
• Est. completion date: November 10, 2025

Study information

• Verified date: March 2024
• Source: Vedanta Biosciences, Inc.
• Contact: Mary Garfield, MS
• Phone: 203.906.5693
• Email: Consortium02-ctinquiries[@]vedantabio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: November 10, 2025
• Est. primary completion date: July 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

KEY INCLUSION CRITERIA

1. 18 to 75 years of age

2. Documented clinical and endoscopic diagnosis of UC at least 3 months prior to randomization

3. Active mild to moderate UC, as defined by the following:

1. Disease that extends at least 15 cm from the anal verge

2. 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

4. Has never received a biologic agent, Janus kinase inhibitor, or sphingosine-1-phosphate modulator for the treatment of UC

5. If receiving corticosteroids, dose must be stable for at least 4 weeks before randomization

6. Doses of other allowable UC medications must be stable for at least 8 weeks before randomization

KEY EXCLUSION CRITERIA

1. Known history of Crohn's disease (CD) or indeterminate colitis

2. A known diagnosis of primary sclerosing cholangitis

3. Allergy to VE202 or any of its components

4. Allergy to vancomycin or any of its components

5. A diagnosis of any non-IBD diarrheal illness (eg, Clostridioides difficile, celiac disease, parasitic infection) within 3 months prior to randomization

6. 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)

7. Receipt of Fecal Microbiota Transplantation (FMT) or other fecal-derived preparation within 6 months prior to randomization

8. Prior colectomy, ostomy, or other intestinal surgery (excluding cholecystectomy or appendectomy)

9. Receipt of any investigational biologic within 60 days or 5 half-lives prior to randomization, whichever is longer

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer
• Ulcerative Colitis

Intervention

Biological:
• VE202
VE202 is a rationally defined, live biotherapeutic product for oral administration.

Drug:
• Vancomycin Oral Capsule
Vancomycin is an antibiotic used to treat or prevent infection

Other:
• VE202 Placebo
VE202 Placebo
• Vancomycin Placebo
Vancomycin Placebo

Locations

Country	Name	City	State
Bulgaria	Medical Center Medconsult Pleven OOD	Pleven
Bulgaria	UMHAT Medica Ruse OOD	Ruse
Bulgaria	Medical Centre Asklepion Main	Sofia
Bulgaria	Medical Centre Leo Clinic EOOD	Varna
Czechia	Vojenská nemocnice Brno, Interní oddelení	Brno
Czechia	Hepato-Gastroenterologie HK, s.r.o.	Hradec Králové
Czechia	PreventaMed s.r.o, Vila zdraví	Olomouc
Hungary	Pannónia Magánorvosi Centrum Kft	Budapest
Hungary	Semmelweis Egyetem Belgyógyászati és Hematológiai Klinika	Budapest
Hungary	Dept. Gastroenterology, Univ. Debrecen	Debrecen
Lithuania	Klaipeda University Hospital	Klaipeda
Lithuania	Vilnius University Hospital Santaros klinikos	Vilnius
Netherlands	Leiden University Medical Center	Leiden
Netherlands	Radboud Universitair Medisch Centrum	Nijmegen	Gelderland
Netherlands	Zuyderland Medical Center	Sittard	Limburg
Poland	Vita Longa Sp. z o.o.	Katowice
Poland	Institution name: Krakowskie Centrum Medyczne	Kraków	Malopolskie
Poland	Bonifraterskie Centrum Medyczne Sp. z o.o	Lódz	Lódzkie
Poland	Medrise Sp. z o.o.	Lublin	Lubelskie
Poland	Clinical Research Center Spólka z ograniczona odpowiedzialnoscia Medic-R Spólka komandytowa	Poznan	Wielkopolskie
Poland	Endoskopia Sp. z o.o.	Sopot	Pomorskie
Poland	Niepubliczny Zaklad Opieki Zdrowotnej (NZOZ) VIVAMED Jadwiga Miecz	Warszawa	Mazowieckie
Poland	Vistamed & Vertigo Sp. z o.o.	Wroclaw	Dolnoslaskie
Ukraine	Chernivtsi Regional Clinical Hospital	Chernivtsi
Ukraine	Regional Clinical Hospital of the Ivano-Frankivsk Regional Council	Ivano-Frankivs'k
Ukraine	LLC Medical Center "Consilium Medical"	Kyiv
Ukraine	Medical Center Medical Clinic Blagomed LLC	Kyiv
Ukraine	Medical Center OK!Clinic+	Kyiv
Ukraine	National Institute of Surgery and Transplantology named after O. O. Shalimova	Kyiv
Ukraine	Volyn Regional Clinical hospital	Luts'k
Ukraine	Ternopil Regional Clinical Hospital	Ternopil'
Ukraine	Transcarpathian Regional Clinical Hospital named after Andria Novak	Úzhgorod
Ukraine	Uzhgorod City Multidisciplinary Clinical Hospital	Úzhgorod
Ukraine	Vinnytsia City Clinical Hospital No. 1	Vinnytsia
Ukraine	Vinnytsia Regional Clinical Hospital named after M.I. Pirogov	Vinnytsia
United Kingdom	Barts Health NHS TrustThe Royal London Hospital	London
United States	Boston Medical Center	Boston	Massachusetts
United States	University of Virginia Health System	Charlottesville	Virginia
United States	Atlanta Center for Gastroenterology, P.C. & Atlanta Endoscopy Center, LTD	Decatur	Georgia
United States	Digestive Health Specialists	Dothan	Alabama
United States	Baylor College of Medicine	Houston	Texas
United States	GastroIntestinal BioSciences	Los Angeles	California
United States	University of Miami	Miami	Florida
United States	GI Pros Research	Naples	Florida
United States	Advanced Research Institute, Inc.	New Port Richey	Florida
United States	Manhattan Clinical Research, LLC	New York	New York
United States	NYU IBD Center	New York	New York
United States	Omega Research Orlando, LLC	Orlando	Florida
United States	Revival Clinical Research	Orlando	Florida
United States	Mayo Clinic	Rochester	Minnesota
United States	University of Utah Hospitals and Clinics	Salt Lake City	Utah
United States	Gastroenterology Research of America, LLC	San Antonio	Texas
United States	Clinical Applications Laboratories	San Diego	California

Sponsors (1)

Lead Sponsor	Collaborator
Vedanta Biosciences, Inc.

Countries where clinical trial is conducted

United States,  Bulgaria,  Czechia,  Hungary,  Lithuania,  Netherlands,  Poland,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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