ACX-362E [Ibezapolstat] for Oral Treatment of Clostridioides Difficile Infection

Inclusion Criteria

• Male or female 18 to 90 years of age, inclusive, at the time of Screening.
• Capable of reading, understanding, and signing the written informed consent; able to adhere to all study procedures and attend all scheduled study visits.
• Confirmed diagnosis of mild or moderate CDI as defined by the Infectious Diseases Society of America/Society for Healthcare Epidemiology of America guidelines (McDonald et al. 2018). Subjects will be diagnosed with CDI based on clinical and laboratory findings:
• The presence of diarrhea, defined as passage of ≥ 3 UBMs within 24 hours before dosing; an unformed stool is defined as a Type 5, 6, or 7 on the Bristol Stool Chart (Appendix 2)
• A stool test result positive for the presence of C. difficile free toxins using tests that detect toxin A/B (and it is prospectively agreed with the Sponsor). The Sponsor will provide a toxin A/B test kit if the site does not have it as part of standard of care test.
• Mild or moderate CDI as defined as a white blood cell count of ≤ 15000 cells/mL and a serum creatinine level 4 doses) of oral vancomycin for the current episode of CDI before first dose of study drug.
• Received more than 24 hours of dosing (> 2 doses) of oral fidaxomicin for the current episode of CDI before first dose of study drug.
• Received more than 24 hours of dosing (> 3 doses) of oral/IV metronidazole for the current episode of CDI before first dose of study drug.
• Received any other antibacterial therapy for the current CDI episode within 48 hours before the first dose of study drug.
• Subjects considered treatment failures on prior antibiotics for their current episode of CDI will be excluded.
• More than 3 episodes of CDI in the previous 12 months or more than 1 prior episode in the last 3 months, excluding the current episode.
• Severe, complicated, or life-threatening fulminant CDI with evidence of hypotension (systolic blood pressure less than 90 mmHg), septic shock, peritoneal signs or ileus, or toxic megacolon.
• Elevated liver transaminases (alanine aminotransferase [ALT], aspartate aminotransferase [AST]) greater than 2 times ULN.
• Active inflammatory bowel disease (Crohn's disease, ulcerative colitis, Irritable Bowel Syndrome with chronic diarrhea).
• Any other non-C. difficile diarrhea.
• Active gastroenteritis because of Salmonella, Shigella, Escherichia coli 0157H7, Yersinia or Campylobacter, a parasite, or virus within the past 2 weeks.
• Had a known positive diagnostic test for other relevant gastrointestinal [GI] pathogens in the 2 weeks before study drug treatment and/or colonization/infection by ova or parasites.
• Major GI surgery (ie, significant bowel resection) within 3 months of enrollment (does not include appendectomy or cholecystectomy).
• Prior or current use of anti-C. difficile toxin antibodies.
• Have received a vaccine against C. difficile or its toxins.
• Anticipated that systemic antibacterial therapy for a non-CDI infection will be required for > 7 days after start of study therapy.
• Actively taking anti-diarrheals, and unable to discontinue anti-diarrheal medication, or any medication with the potential to slow bowel movement (for opiates, a stable dose, including use as needed, is permitted).
• Actively taking Saccharomyces boulardii and unwilling to discontinue during the study period.
• Received a fecal transplant in the previous 3 months.
• Received laxatives in the last 48 hours.
• Unable or unwilling to stop taking oral probiotics for the duration of the study.
• Received intravenous immunoglobulin within 3 months before study drug treatment.
• Sepsis.
• Have a known current history of significantly compromised immune system such as:
• Subjects with a known history of human immunodeficiency virus infection and CD4 <200 cells/mm3 within 6 months of start of study therapy.
• Severe neutropenia with neutrophil count < 500 cells/mL.
• Concurrent intensive induction chemotherapy