| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Mild-to-moderate ulcerative colitis (UC) |
|
| E.1.1.1 | Medical condition in easily understood language |
| Long-term condition where the colon and rectum become inflamed |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10045365 |
| E.1.2 | Term | Ulcerative colitis |
| E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
• To evaluate the efficacy of 8 weeks of treatment with VE202 in terms of endoscopic response at Day 56
• To evaluate the safety of VE202 in Part 1 and Part 2 of the study |
|
| E.2.2 | Secondary objectives of the trial |
• Evaluate the efficacy of 2 weeks of treatment with VE202 in terms of endoscopic response at Day 56
• Evaluate the safety of VE202 in Parts 1, 2, and 3 of the study
• 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
• Characterize VE202 colonization in patients treated with 2- and 8-week courses of VE202
• Determine microbiome and metabolite composition in patients treated with 2- and 8-week courses of VE202
• 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 |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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. 18 to 75 years of age.
3. Documented clinical and endoscopic diagnosis of UC at least 3 months prior to randomization
4. Active mild to moderate UC, as defined by the following:
a. Disease that extends at least 15 cm from the anal verge
b. 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
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 never received a biologic agent, Janus kinase inhibitor, or sphingosine-1-phosphate modulators for the treatment of UC
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 before randomization.
9. If a female patient (according to sex assignment at birth):
‒ 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 (according to sex assignment at birth):
‒ 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). |
|
| E.4 | Principal exclusion criteria |
1. Known history of CD or indeterminate colitis
2. A known diagnosis of primary sclerosing cholangitis
3. Allergy to VE202 or any of its components (Section 9.1.1)
4. Allergy to vancomycin or any of its components (Section 9.2)
5. A diagnosis of any non-IBD diarrheal illness (eg, Clostridioides difficile, celiac disease, parasitic infection) within 3 months prior to randomization
6. Known or suspected toxic megacolon, abdominal abscess, and/or small bowel ileus at the time of screening
7. Any other anatomic or medical contraindication to flexible sigmoidoscopy
8. Evidence of an active infection
9. Recent fever, defined as > 38.0 °C (rectal equivalent) within 3 days prior to randomization
10. Receipt of FMT or other fecal-derived preparation within 6 months prior to randomization
11. Use of systemic or non-absorbable oral antibiotics within the prior 4 weeks before randomization or anticipated within the study period
12. Use of probiotics within the prior 2 weeks before randomization (consumption of food products such as yogurt, kombucha, kimchi, and kefir is permissible)
13. Receipt of herbal, botanical, or traditional medicinal preparations within the 2 weeks prior to randomization (consumption of mint, turmeric, or other herbal teas is permissible)
14. Active drug or alcohol abuse
15. Active colonic dysplasia
16. Presence of adenomatous polyp on screening endoscopy, or history of adenomatous polyps that were not removed
17. Prior colectomy, ostomy, or other intestinal surgery (excluding cholecystectomy or appendectomy)
18. Active malignancy within the 2 years prior to randomization, 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
19. For female patients (according to sex assignment at birth), expectation of pregnancy or lactation during the study period
20. Receipt of any investigational drug or vaccine within the 30 days prior to randomization
21. Receipt of any investigational biologic within 60 days or 5 half-lives prior to randomization, whichever is longer
22. Aspartate aminotransferase or alanine aminotransferase levels > 3×ULN
23. Total or direct bilirubin > 1.5×ULN or direct-to-total bilirubin ratio > 0.5
24. Evidence of decompensated cirrhosis
25. Serum albumin < 3.0 g/dL
26. Known active hepatitis B or hepatitis C, or any positive laboratory result consistent with active disease (eg, hepatitis B surface antigen, hepatitis C antibody [unless patient has a history of treatment with successful resolution and an undetectable viral load])
27. Known human immunodeficiency virus infection or other serious congenital or acquired immunodeficiency
28. Absolute neutrophil count < 1000/μL
29. Serum creatinine > 2×ULN or calculated creatine clearance < 30 mL/min
30. Inability or unwillingness to comply with protocol requirements
31. 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 |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
• Endoscopic response rate defined as a reduction of 1 point or more in Mayo endoscopic subscore on flexible sigmoidoscopy from baseline to Day 56
• Grade ≥ 3 Treatment-emergent adverse event (TEAEs) that are related to VE202 or VE202 placebo
• Serious adverse event (SAEs) that are related to VE202 or VE202 placebo |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Day 56 and throughout the study |
|
| E.5.2 | Secondary end point(s) |
• Endoscopic response rate, defined as a reduction of 1 point or more in Mayo endoscopic subscore on flexible sigmoidoscopy from baseline to Day 56
• TEAEs
• SAEs
• Adverse event of special interest (AESIs)
• 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
• Fecal microbiota diversity and taxonomic composition at various time points
• Fecal metabolite profiles (eg, bile acids, SCFA) at various time points
• Hospitalization or surgical procedure related to UC
• Change in patient-reported outcome measures using the IBDQ and 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 |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Please refer to schedule of assessment |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 32 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Ukraine |
| United Kingdom |
| United States |
| Bulgaria |
| Czechia |
| Hungary |
| Lithuania |
| Netherlands |
| Poland |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
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