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

Overview

About this study

The purpose of this research is to evaluate the primary objectives of safety and effectiveness (rate of clinical cure) of 2 dosages of CRS3123 (200 mg and 400 mg) administered orally (po) twice daily (bid) and vancomycin administered 125 mg PO 4 times daily (qid) in adults > or equal to 18 years of age with a primary episode or first recurrence of CDI. The study will investigate the plasma concentrations and HRQoL outcomes of CRS3123 and additional efficacy endpoints as secondary objectives.

Participation eligibility

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:

  • 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.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Cuong Nguyen, M.D.

Closed for enrollment

More information

Publications

Publications are currently not available
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CLS-20539923

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