Ensayos clínicos

Inclusion Criteria:

• More than or equal to 3 diarrheal stools/day in 24 hours prior to randomization and in the judgment of the investigator that C difficile is the likely causative agent for the diarrhea.
• Stool positive for C. difficile GDH plus Toxin A and/or B.
• Participants with a primary episode or first recurrence of CDI are eligible.
• In the judgement of the investigator, the expectation that the participant will survive with effective antibiotic therapy and appropriate supportive care for the anticipated duration of the study.
• Participants may be either inpatient or outpatient.

Exclusion Criteria:

• Participants with any of the following conditions:
  • Intractable vomiting preventing oral medication intake;
  • Severe underlying disease with an expected survival time less than the duration of the study (approximately 70 days);
  • More than 1 prior CDI occurrence within the last 3 months or more than 2 prior episodes of CDI in the last 12 months;
  • A history of a recent CDI episode within 3 months prior to enrollment that was non-responsive to vancomycin;
  • In the investigator’s opinion, the participant is anticipated to require oral or intravenous systemic antibiotic therapy between randomization and FUV4;
  • Inflammatory bowel disease (Crohn’s disease or ulcerative colitis), Hirschsprung’s disease, short gut syndrome, prior bowel resection surgery, gastric bypass and other conditions known to significantly impact bowel motility and/or malabsorption;
  • Any other known pathogen associated with diarrhea.
• Life-threatening or fulminant CDI as defined by IDSA/SHEA Guidelines (McDonald et al, 2018):
  • Any signs of severe sepsis, including shock or profound hypotension defined as systolic blood pressure < 90 mmHg or a decrease of > 40 mmHg from baseline;
  • Ileus;
  • Toxic megacolon;
  • Colonic perforation;
  • Concurrent laxatives or tube feeds, toxin binders, bile acid sequestrants, fecal microbiota transplant (FMT) (within 1 year of randomization), or any phage therapy (within 1 year of randomization);
  • Participants treated with another antimicrobial agent directed at the current episode of CDI (metronidazole, fidaxomicin, rifaximin, tigecycline, or oral vancomycin) for ≥ 24 hours prior to randomization will not be eligible for enrollment;
  • Patients who have chronic diarrheal symptoms without specified cause where resolution of diarrhea is not possible History of epilepsy or known seizure disorder (excluding a history of childhood febrile seizures).
• Receipt of any investigational medication during the last month (30 days or 5 half-lives, whichever is longer) prior to randomization.
• Known history of human immunodeficiency virus (HIV) infection or known current cluster of differentiation 4 (CD4) count < 200/mm^3.
• Presence of another immunodeficiency or an immunocompromised condition including current hematologic malignancy, bone marrow transplant, or receiving immunosuppressive therapy such as cancer chemotherapy in the last 6 months, current medications for the rejection of transplantation, and or long term (≥ 2 weeks) use of systemic corticosteroids.
• Neutropenia with an absolute neutrophil count (ANC) of < 1,000 cells/mm^3.
• Severe hepatic impairment at screening, as determined by one or more of the following:
  • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 3 x upper limit of normal (ULN) or total bilirubin ≥ 2x ULN; or
  • Clinical signs of cirrhosis; or
  • End-stage hepatic disease (eg, ascites, hepatic encephalopathy).
• Any other surgical or medical condition (including a clinically significant laboratory abnormality) as determined by the investigator and/or InClin’s 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.
• Known hypersensitivity to CRS3123 or oral vancomycin or any of the excipients used in the respective formulations.
• 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.
• Unwillingness to stop consuming non-dietary probiotics from randomization to Day 70. (Non-dietary probiotics include capsules, powders, or liquids that are nutraceutical probiotics [primary ingredient is bacteria or yeast]. Yogurt, kombucha, kimchi, kefir, brine pickles, cheese, and other foods that are considered “dietary probiotics” are permitted).
• Participants currently taking digoxin within 1 week of screening.
• Unwillingness to refrain from consumption of grapefruit and its juices as well as nutraceutical supplements containing curcumin (i.e.., turmeric) from randomization until 24 hours after EOT.
• Unwillingness to stop use of antidiarrheals from randomization to Day 70.

Eligibility last updated 2/24/22. Questions regarding updates should be directed to the study team contact.