Mild-to-moderate ulcerative colitis (UC) MedDRA version: 20.1 Level: LLT Classification code 10045365 Term: Ulcerative colitis System Organ Class: 100000004856
Conditions
Interventions
Product Name: VE202
Product Code: VE202
Pharmaceutical Form: Capsule
INN or Proposed INN: Not applicable
Current Sponsor code: VE202-01,3,4,6,7,9,13,14,15,16,18,21,26-29
Other descriptive name: JNJ-72
Sponsors
Vedanta Biosciences, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Able and willing to provide written informed consent prior to initiation of any study-specific procedure or drug administration and understands the potential risks and benefits of study enrollment and study drug administration. When appropriate, informed consent may be provided by a legally authorized representative (LAR). 2. Male or female patient who is 18 to 75 years of age. 3. Documented clinical and endoscopic diagnosis of UC at least 3 months prior to enrollment. 4. 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 - Mayo endoscopic subscore as follows, based on screening flexible sigmoidoscopy: i. Subscore of 1, combined with a fecal calprotectin level of = 150 µg/g, or ii. Subscore of 2 - Rectal bleeding score of = 1 5. Is up to date with current local colorectal cancer surveillance recommendations (eg, has had a surveillance colonoscopy within 12 months if indicated based on extent and duration of UC); this may be performed during screening. 6. Has not received a biologic agent or Janus kinase inhibitor for the treatment of UC or any other medical condition. 7. If receiving corticosteroids, dose must be stable for at least 4 weeks and be no higher than 10 mg QD prednisone (or prednisone equivalent) or budesonide 9 mg QD. 8. Doses of other allowable UC medications (see Section 8.2.2 for details) must be stable for at least 8 weeks. 9. If a female patient: - Is not of childbearing potential, defined as post-menopausal for at least 1 year or surgically sterile due to hysterectomy, bilateral oophorectomy, or bilateral tubal ligation - If of childbearing potential, must have a negative pregnancy test and agree to either remain celibate or use a highly effective form of birth control (as defined in Appendix 1) from the time of enrollment until 3 months after the last dose of study drug - Agrees not to donate eggs (ova, oocytes) for purposes of assisted reproduction from the time of enrollment until 3 months after the last dose of study drug - Is not breastfeeding 10. If a male patient: - If not vasectomized, agrees to wear a condom when engaging in sexual intercourse with any partner of childbearing potential from the time of enrollment until 3 months after the last dose of study drug - Agrees not to donate sperm for purpose of reproduction from the time of enrollment until 3 months after the last dose of study drug 11. Able and willing to follow study procedures (eg, comply with study visits and procedures, provide blood and stool samples). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 75 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 25
Exclusion criteria
Exclusion criteria: 1. Known history of CD or indeterminate colitis 2. A known diagnosis of primary sclerosing cholangitis 3. Allergy to vancomycin 4. A diagnosis of any non-IBD diarrheal illness (eg, Clostridioides difficile, celiac disease, parasitic infection) within 3 months prior to enrollment 5. Known or suspected toxic megacolon, abdominal abscess, and/or small bowel ileus at the time of enrollment 6. Any other anatomic or medical contraindication to flexible sigmoidoscopy 7. Evidence of an active infection 8. Recent fever, defined as > 38.0 °C (rectal equivalent) within 3 days prior to randomization 9. Receipt of FMT or other fecal-derived preparation within 6 months prior to enrollment 10. Use of systemic or non-absorbable oral antibiotics within the prior 4 weeks or anticipated within the study period 11. Use of probiotics within the prior 2 weeks (consumption of yogurt and kefir are permissible) 12. Receipt of herbal, botanical, or traditional medicinal preparations within the prior 2 weeks (consumption of mint, turmeric, or other herbal teas is permissible) 13. Active drug or alcohol abuse 14. Active colonic dysplasia 15. Presence of adenomatous polyp on screening endoscopy, or history of adenomatous polyps that were not removed 16. Prior colectomy, ostomy, or other intestinal surgery (excluding cholecystectomy or appendectomy) 17. Active malignancy within the past 2 years, with the exception of non-melanoma skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix or breast that has been treated with local excision for curative intent 18. For female patients, expectation of pregnancy or lactation during the study period 19. Receipt of any investigational drug or vaccine within the 30 days prior to enrollment 20. Receipt of any investigational biologic within 60 days or 5 half-lives prior to enrollment, whichever is longer 21. Aspartate aminotransferase or alanine aminotransferase levels > 3 × ULN 22. Total or direct bilirubin > 1.5 × ULN 23. Evidence of decompensated cirrhosis 24. Serum albumin 2 × ULN or calculated creatine clearance < 30 mL/min 29. Inability or unwillingness to comply with protocol requirements 30. Any other active or poorly controlled comorbid condition that, in the opinion of the Investigator, may be expected to interfere with either study compliance or interpretation of study results
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of 8 weeks of treatment with VE202 in terms of endoscopic response at Day 56;Secondary Objective: • Evaluate the safety of VE202 • Evaluate the efficacy of 2 weeks of treatment with VE202 in terms of endoscopic response at Day 56 • Evaluate the efficacy of 2- and 8-week courses of VE202 in terms of response as measured by Mayo score at Day 56, compared with baseline • Evaluate the efficacy of 2- and 8-week courses of VE202 in terms of histologic improvement • Evaluate the efficacy of 2- and 8-week courses of VE202 in terms of effect on fecal calprotectin levels • Evaluate the impact of 2- and 8-week courses of VE202 on inflammatory bowel disease (IBD)-specific healthcare resource utilization • Evaluate the impact of 2- and 8-week courses of VE202 on IBD-specific health-related quality of life • Evaluate pharmacokinetics of 2- and 8-week courses of VE202 • Evaluate pharmacodynamics of 2- and 8-week courses of VE202;Primary end point(s): Endoscopic response rate defined as a reduction of 1 point or more in Mayo endoscopic subscore on flexible sigmoidoscopy;Timepoint(s) of evaluation of this end point: Day 56 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Treatment-emergent adverse events (TEAEs) • TEAEs that are related to study treatment • Serious adverse events (SAEs) • SAEs that are related to treatment • Infections • Mayo endoscopic subscore on flexible sigmoidoscopy at baseline and Day 56 • Clinical response • Clinical remission • Mean change in modified Mayo score • Proportion of patients with decrease of at least 1 point and at least 2 points in total Mayo score • Endoscopic remission • Change in each component of the total Mayo score • Histologic change in colonic biopsy as measured by Geboes score and Robarts Histopathology Index (RHI) • Histologic response (Geboes score < 3.1; RHI reduction of = 7 points or = 50%) • Histologic remission (Geboes score < 2.0; RHI score = 6) • Change in fecal calprotectin level • Detection of VE202 strains in feces at various time points • Abundance of VE202 strains in feces at various time points • Duration of VE202 strains in feces • Changes in fecal microbiota diversity and taxonomic composition • Changes in fecal metabolomic profile (eg, bile acids, SCFA) • Hospitalization or surgical procedure related to UC • Change in patient-reported outcome measures using the Inflammatory Bowel Disease Questionnaire (IBDQ) and EuroQoL-5D Health Assessment (EQ-5D) • Stool Candida burden • Immune cell markers on biopsy tissue • Inflammatory signals in biopsy tissue • Immune cell markers in blood • Soluble immune markers in blood;Timepoint(s) of evaluation of this end point: Please refer to schedule of assessment | — |
Countries
Bulgaria, Czechia, Hungary, Lithuania, Netherlands, Poland, Russian Federation, Ukraine, United States
Contacts
Public ContactVE202 Clinical Operations
Vedanta Biosciences, Inc.
Outcome results
None listed