Evaluation of CRS3123 vs. Oral Vancomycin in Adult Patients With Clostridioides Difficile Infection

Exclusion Criteria

• •1. Participants with any of the following conditions:
• •1. Intractable vomiting preventing oral medication intake
• •2. Severe underlying disease with an expected survival time less than the duration of the study (approximately 70 days).
• •3. More than 1 prior CDI occurrence within the last 3 months or more than 2 prior episodes of CDI in the last 12 months.
• •4. A history of a recent CDI episode within 3 months prior to enrollment that was non- responsive to vancomycin.
• •5. In the investigator's opinion, the participant is anticipated to require oral or intravenous systemic antibiotic therapy for a non-CDI infection between screening and Day 70.
• •6. Inflammatory bowel disease (Crohn's disease or ulcerative colitis), uncorrected Hirschsprung's disease, short gut syndrome, or any other condition known to significantly impact bowel motility and/or malabsorption.
• •7. Any other known pathogen associated with diarrhea.
• •8. Life-threatening or fulminant CDI as defined by IDSA/SHEA Guidelines.
• •9. Colonic perforation.
• •10. Need for concurrent laxatives or tube feeds, toxin binders, bile acid sequestrants during the study. Microbiota restoration therapy (MRT) or any phage therapy within 1 year of randomization. Receipt of bezlotoxumab within 3 months of randomization.
• •11. Participants treated with another antimicrobial agent directed at the current episode of CDI (metronidazole, fidaxomicin, rifaximin, tigecycline, or oral vancomycin) for \>24 hours of treatment within the 3 days prior to randomization will not be eligible for enrollment.
• •2. Pregnant or breastfeeding women.
• •3. Receipt of any investigational medication during the last month (30 days or 5 half lives, whichever is longer) prior to randomization.
• •4. Active and uncontrolled HIV with CD4 \<200/mm3.
• •5. Presence of active malignancy undergoing chemotherapy that is expected to cause significant immunosuppression, hematologic malignancy undergoing induction chemotherapy, or recent bone marrow or solid organ transplant (within 1 month prior to randomization) undergoing treatment with medications for the rejection of transplantation. In the investigator's opinion, is expected not to survive through the duration of the study (approximately 70 days) due to complications of the malignancy, or in the investigator's opinion will require oral or intravenous systemic antibiotic therapy during the study for malignancy related conditions.
• •6. Severe neutropenia defined as ANC \<500 cells/mm3
• •7. Severe hepatic impairment at screening including clinical signs of cirrhosis, end-stage hepatic disease (eg, ascites, hepatic encephalopathy), or Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 3x upper limit of normal (ULN) or total bilirubin ≥ 2x ULN.
• •8. Any other surgical or medical condition (including a clinically significant laboratory abnormality) as determined by the investigator or the medical monitor, that could interfere with the participant's ability to participate in the study, the administration of study treatment, and/or the interpretation of study results that, in the investigator's opinion, may confound study assessments or study procedures.
• •9. Known hypersensitivity to CRS3123 or oral vancomycin.
• •10. An employee of the investigator or study center with direct involvement in the proposed study or other studies under the direction of that investigator or study center, as well as a family member of the employee or the investigator.
• •11. Unwillingness to stop consuming non-dietary probiotics from randomization to Day 70.
• •12. Participants currently taking digoxin within 1 week of screening.
• •13. Unwillingness to refrain from consumption of grapefruit and its juices as well as nutraceutical supplements containing curcumin from randomization until 24 hours after EOT.
• •14. Unwillingness to stop use of anti-diarrheals from randomization to Day 70.