Study of EXE-346 Live Biotherapeutic to Reduce High Bowel Movement Frequency in Subjects With an IPAA (PROF)

1. Subject has Crohn's-like disease of the pouch, as indicated by their most recent pouchoscopy during the 12 months prior to screening.

2. 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. Subject has taken biologics, azathioprine, or methotrexate within the 12 weeks prior to screening or systemic steroids within 4 weeks of screening.

4. Subject has a positive reverse transcriptase-PCR diagnostic test for SARS-CoV-2 within the 14 days prior to screening.

5. Subject has uncontrolled hypertension (systolic pressure \>160 mm Hg or diastolic pressure \>95 mm Hg on at least 2 measures performed at least 10 minutes apart) at screening.

1. Subject has Crohn's-like disease of the pouch, as indicated by the pouchoscopy conducted during study screening.

2. Subject has isolated severe cuffitis without pouch inflammation (endoscopic mPDAI score of 2 or lower), as indicated by the pouchoscopy conducted during study screening.

3. Subject has a clinically significant stricture of the IPAA or afferent limb stricture which requires surgery or recurrent dilations more than every 3 months, as indicated by the pouchoscopy conducted during study screening. Subjects who have a planned dilation during the active study period are excluded (dilation during the screening pouchoscopy is allowed).

4. Subject has taken biologics, azathioprine, methotrexate or small molecules (e.g., JAK inhibitors, S1P receptor modulators) within the 12 weeks prior to screening or systemic steroids within 4 weeks prior to screening.

5. Subject has a positive reverse transcriptase-PCR diagnostic test for SARS-CoV-2 within the 7 days prior to screening, per subject self report.

6. Subject has an average daily bowel movement frequency of \>25 bowel movements recorded during the screening period (Days -21 to 0).

7. Subject is taking opioid therapy as a long-term treatment or has taken opioids within 2 weeks prior to screening.

8. Subject has taken probiotics within 2 weeks prior to screening.

9. Subject has previously received EXE-346 for any duration. Subjects who participated in Phase 1b are excluded from Phase 2.

10. Subject has a concurrent, clinically significant, serious, unstable or uncontrolled medical or psychiatric condition that, in the opinion of the investigator, might confound study results, pose additional risk to the subject, or interfere with the subject's ability to participate fully in the study.

1. Subject has enterocutaneous or recto- or pouch-vaginal fistula.

2. Subject has active Clostridium difficile infection.

3. Subject has known or suspected active CMV infection.

4. 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 (screening visit through the safety follow-up visit \[Day 57 in the Phase 1b part or Day 71 in the Phase 2 part\]). Subjects taking antibiotics to treat antibiotic-dependent pouchitis or antidiarrheal medication are eligible for the study provided they have been on the therapy at a stable dose for at least 2 weeks prior to screening.

5. Subject is taking NSAIDs as a long-term treatment (ie, consistent use for at least 4 days/week each month). Acute use of NSAIDs is allowed.

6. Subject has a known history or positive test during screening for HIV, HIV-1, HIV-2, or active HBV or HCV. Active HCV infection is defined as a subject with a positive hepatitis C antibody and detectable hepatitis C viral load RNA.

7. 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.

8. Subject has estimated glomerular filtration rate \<30 mL/min/1.73 m2 at screening.

9. Subject has known hypersensitivity to EXE-346 or any product components.

10. Female subject is pregnant or lactating and/or breastfeeding.

11. Subject has participated in any clinical study of an approved or nonapproved investigational medicinal product within the 30 days prior to screening.

12. 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 AST, ALT, or bilirubin \>2 × ULN

3. Primary sclerosing cholangitis with elevated transaminases

1\. Subjects who have developed any medical or psychologic condition, which was excluded in the Phase 2 double-blinded part of the study or in the opinion of the investigator and/or medical monitor might create undue risk to the subject or interfere with the subject's ability to comply with the protocol requirements, or to complete the study.

Study of EXE-346 Live Biotherapeutic to Reduce High Bowel Movement Frequency in Subjects With an IPAA (PROF)

What this study is about

Study of EXE-346 Live Biotherapeutic to Reduce High Bowel Movement Frequency in Subjects With an IPAA (PROF)

What this study is about