Clinical trial NCT04781387: Evaluation of CRS3123 vs. Oral Vancomycin in Adult Patients With Clostridioides Difficile Infection
Official title: A Phase 2, Randomized, Double-Blind, Comparator-Controlled, Multicenter Study to Evaluate the Safety and Efficacy of CRS3123 Compared With Oral Vancomycin in Adults With Clostridioides Difficile Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Clostridioides Difficile Infection
Keywords: CDI
Cdiff Infection
Clostridiodes difficile infection
Cdiff
Lead sponsor: Crestone, Inc
Sponsor class: INDUSTRY
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2021-03-04
Enrollment: 43
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this research is to evaluate the primary objectives of safety and efficacy (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.


Eligibility criteria: Inclusion Criteria

1. Adults, ≥ 18 years of age.
2. More than or equal to 3 diarrheal (Bristol Stool Scale scores 5, 6, or 7) stools/day in a 24-hour period during screening prior to randomization and in the judgment of the investigator that C. difficile is the likely causative agent for the diarrhea.
3. Stool positive for C. difficile Toxin A and/or B antigen using an FDA or Health Canada approved/cleared EIA or ELISA laboratory test.
4. Participants with a primary episode or first recurrence of CDI are eligible.
5. In the judgment 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.
6. Female participants of childbearing potential must not be pregnant, plan to become pregnant during the study, or be breastfeeding; and must be willing to commit to either sexual abstinence or use highly effective methods of birth control contraception from screening through Day 70.
7. Males must use a condom and spermicide from screening through Day 70 (if the female partner(s) is of childbearing potential) and must not donate sperm from screening through Day 70.
8. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form.

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.

Primary outcomes:
measure: Rate of Clinical Cure at the Test of Cure [TOC] Visit in the Intent-to-treat [ITT] Population
timeFrame: TOC/Day 12
Secondary outcomes:
measure: Rate of Clinical Cure at Test of Cure (TOC) in the Microbiological-ITT (mITT) Population
timeFrame: TOC/Day 12
measure: Rate of Clinical Cure at Test of Cure (TOC) in the Per Protocol (PP) and Microbiologically Evaluable (ME) Populations
timeFrame: TOC/Day 12
measure: Rate of Total Relief of Symptoms of Clostridioides Difficile Infection at Test of Cure (TOC) in the Microbiological-ITT (mITT) Population
timeFrame: TOC/Day 12
measure: Rate of Total Relief of Symptoms of Clostridioides Difficile Infection at Test of Cure (TOC) in the Per Protocol (PP) and Microbiologically Evaluable (ME) Populations
timeFrame: TOC/Day 12
measure: Time to Resolution of Diarrhea Through Test of Cure (TOC) in the Microbiological-ITT (mITT) Population
timeFrame: Study Day 1 until the date of documented resolution, assessed up to TOC/Day 12
measure: Time to Resolution of Diarrhea Through Test of Cure (TOC) in the Per Protocol (PP) and Microbiologically Evaluable (ME) Populations
timeFrame: Study Day 1 until the date of documented resolution, assessed up to TOC/Day 12
measure: Rate of Early Recurrence of Clostridioides Difficile Infection Through Day 40 in the Microbiological-ITT (mITT) Population
timeFrame: Post TOC/Day 12 visit through Day 40
measure: Rate of Early Recurrence of Clostridioides Difficile Infection Through Day 40 in the Microbiologically Evaluable (ME) Population
timeFrame: Post TOC/Day 12 visit through Day 40
measure: Rate of Late Recurrence of Clostridioides Difficile Infection (Between Day 40 and Day 70) in the Microbiological-ITT (mITT) Population
timeFrame: Day 40 - Day 70
measure: Rate of Late Recurrence of Clostridioides Difficile Infection (Between Day 40 and Day 70) in the Microbiologically Evaluable (ME) Population
timeFrame: Day 40 - Day 70
measure: Rate of Recurrence of Clostridioides Difficile Infection Through Day 70 in the Microbiological-ITT (mITT) Population
timeFrame: Post TOC/Day 12 visit through Day 70
measure: Rate of Recurrence of Clostridioides Difficile Infection Through Day 70 in the Microbiologic Evaluable (ME) Population
timeFrame: Post TOC/Day 12 visit through Day 70
measure: Rate of Global Cure in the Microbiological-ITT (mITT) Population
timeFrame: Post TOC/Day 12 visit through Day 40
measure: Rate of Global Cure in the Per Protocol (PP) and Microbiologically Evaluable (ME) Populations
timeFrame: Post TOC/Day 12 visit through Day 40
Other outcomes:
Locations:
city: Fullerton
country: United States
facility: 131
state: California
city: Lancaster
country: United States
facility: 117
state: California
city: Mission Hills
country: United States
facility: 143
state: California
city: Orange
country: United States
facility: 138
state: California
city: Miami
country: United States
facility: 146
state: Florida
city: Miami
country: United States
facility: 122
state: Florida
city: Marietta
country: United States
facility: 140
state: Georgia
city: Idaho Falls
country: United States
facility: 110
state: Idaho
city: Winfield
country: United States
facility: 129
state: Illinois
city: Royal Oak
country: United States
facility: 130
state: Michigan
city: Weldon Spring
country: United States
facility: 139
state: Missouri
city: Butte
country: United States
facility: 128
state: Montana
city: Bronx
country: United States
facility: 134
state: New York
city: Chapel Hill
country: United States
facility: 147
state: North Carolina
city: Uniontown
country: United States
facility: 114
state: Pennsylvania
city: Cedar Park
country: United States
facility: 104
state: Texas
city: Houston
country: United States
facility: 123
state: Texas
city: San Antonio
country: United States
facility: 101
state: Texas
city: Calgary
country: Canada
facility: 116
state: Alberta
city: London
country: Canada
facility: 120
state: Ontario
Study officials:
affiliation: Crestone, Inc
name: Urs Ochsner, PhD
role: PRINCIPAL_INVESTIGATOR
References: