Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.
INCLUSION CRITERIA:
1. \[Phase 1b only\] Subject is a male or female and is between the age of 18 to 65 years, inclusive, at screening.
2. \[Phase 1b only\] Subject has had a documented pouchoscopy within 12 months prior to screening.
3. \[Phase 2 only\] Subject is a male or female and is aged 18 years or older at screening.
4. Subject or the subject's legally acceptable representative is willing and able to provide written informed consent prior to the initiation of any study-related procedures.
5. Subject has had an IPAA for at least 6 months prior to screening.
6. Subject has an average daily bowel movement frequency of at least 10 bowel movements recorded during screening and has correctly completed at least 7 days of electronic diary (eDiary) entries during the screening period.
7. Female subjects of childbearing potential must have a negative serum pregnancy test result at screening and must not be lactating and/or breastfeeding.
8. Female subjects of childbearing potential and male subjects with partners of childbearing potential must agree to use proper contraceptive methods to avoid pregnancy during the study.
9. \[Phase 2 OL extension only\] Subject must have completed the Phase 2 double-blinded part of the study and be willing to participate in the optional open-label extension phase.
10. \[Phase 2 OL extension only\] Subject must understand the study procedures, the risks involved, and be willing to continue to adhere to the study visit/protocol schedule.
EXCLUSION CRITERIA:
1. \[Phase 1b only\] Subject has Crohn's-like disease of the pouch, as indicated by their most recent pouchoscopy during the 12 months prior to screening.
2. \[Phase 1b only\] Subject has a stricture of the IPAA or afferent limb stricture, as indicated by their most recent pouchoscopy during the 12 months prior to screening.
3. \[Phase 2 only\] Subject has Crohn's-like disease of the pouch, as indicated by the pouchoscopy conducted during study screening.
4. \[Phase 2 only\] Subject has isolated severe cuffitis without pouch inflammation (endoscopic modified Pouch Disease Activity Index (mPDAI) score of 2 or lower).
5. \[Phase 2 only\] Subject has a stricture of the IPAA or afferent limb stricture as indicated by the pouchoscopy conducted during study screening.
6. Subject has enterocutaneous or recto- or pouch-vaginal fistula.
7. Subject has active Clostridium difficile infection.
8. Subject has known or suspected active cytomegalovirus (CMV) infection.
9. Subject initiated a new treatment with antibiotics or antimotility therapies within the 2 weeks prior to screening or plans to start a new or change doses of a current treatment during the study period.
10. Subject has taken biologics, azathioprine, or methotrexate within the 12 weeks prior to screening or systemic steroids within 4 weeks of screening.
11. Subject is taking NSAIDs as a long-term treatment (i.e., consistent use for at least 4 days/week each month).
12. Subject has a known history or positive test during screening for HIV, HIV-1, HIV-2, or active hepatitis B virus (HBV) or hepatitis C virus (HCV).
13. Subject has a positive reverse transcriptase-polymerase chain reaction (PCR) diagnostic test for SARS-CoV-2 (COVID-19) within the 14 days prior to screening.
14. Subject has a history of malignancy within the 5 years prior to screening, with the exception of nonmelanoma skin cancer that has been treated with no evidence of recurrence, treated cervical dysplasia, or treated in situ grade 1 cervical cancer.
15. Subject has estimated glomerular filtration rate \<30 mL/min/1.73 m\^2 at screening.
16. Subject has uncontrolled hypertension at screening.
17. Subject has known hypersensitivity to EXE-346 or any product components.
18. Female subject is pregnant or lactating and/or breastfeeding.
19. Subject has participated in any clinical study of an approved or unapproved investigational medicinal product within the 30 days prior to screening.
20. Subject has any disorder that, in the investigator's opinion, might jeopardize the subject's safety or compliance with the protocol, including but not limited to:
1. Decompensated liver disease
2. Elevation of aspartate aminotransferase (AST), alanine aminotransferase (ALT), or bilirubin \>2 × upper limit of normal (ULN)
3. Primary sclerosing cholangitis with elevated transaminases
21. \[Phase 2 OL extension only\] Subject has developed any medical or psychologic condition excluded in the Phase 2 double-blinded part of the study or which, in the investigator's opinion, might create undue risk to the subject, interfere with the subject's ability to comply with the protocol requirements, or interfere with the subject's ability to complete the study.
Note: Other protocol defined Inclusion/Exclusion Criteria may apply.
Eligibility last updated 5/15/2024. Questions regarding updates should be directed to the study team contact.