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

Clostridioides Difficile Infection Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04781387
• Other study ID #: 19-0021
• Secondary ID: 75N93019C00056
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: January 5, 2021
• Est. completion date: April 2024

Study information

• Verified date: February 2024
• Source: Crestone, Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 108
• Est. completion date: April 2024
• Est. primary completion date: February 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Clostridioides Difficile Infection
• Clostridium Infections
• Communicable Diseases
• Infections

Intervention

Drug:
• CRS3123
Study drug dosed at 200 mg PO BID (treatment arm A) or 400 mg PO BID (treatment arm B) for total of 10 days
• Active Comparator
Active comparator is administered 125 mg PO QID

Locations

Country	Name	City	State
Canada	University of Calgary/Foothills Medical Center Alberta Health Services	Calgary	Alberta
Canada	London Health Sciences Center and St. Joseph's Health Care London	London	Ontario
United States	Montefiore Medical Center	Bronx	New York
United States	Mercy Street Medical Group, PLLC	Butte	Montana
United States	UNC Medical Center	Chapel Hill	North Carolina
United States	Ascada Research	Fullerton	California
United States	Houston Endoscopy and Research Center	Houston	Texas
United States	Snake River Research, PLLC	Idaho Falls	Idaho
United States	Om Research, LLC	Lancaster	California
United States	Gastrointestinal Specialists of Georgia	Marietta	Georgia
United States	Continental Medical Research, Inc.	Miami	Florida
United States	Southern Clinical Research	Miami	Florida
United States	Providence Facey Medical Foundation/Clinical Research Center	Mission Hills	California
United States	UCI Center for Clinical Research	Orange	California
United States	Beaumont Health	Royal Oak	Michigan
United States	Southern Star Research Institute, LLC	San Antonio	Texas
United States	Frontier Clinical Research, LLC	Uniontown	Pennsylvania
United States	St. Charles Clinical Research	Weldon Spring	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
Crestone, Inc	National Institute of Allergy and Infectious Diseases (NIAID)

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	To assess the effect of CRS3123 on the microbiology, fecal microbiome, and fecal biomarkers of inflammation, to assess microbiological effect, and to evaluate metabolomics		Screening through Day 70
Other	To assess the fecal concentrations of CRS3123 in the CRS3123 200 mg and 400 mg dose groups		Screening through Day 10 (EOT)
Primary	Rate of Clinical Cure at Test of Cure (TOC) in the Intention to treat (ITT) population		Last dose plus two days
Secondary	Rate of Clinical cure at Test of Cure (TOC) in the Micro-Intent to Treat, Per Protocol and Microbiologically Evaluable populations		Last dose plus two days
Secondary	Rate of clinical cure at TOC as assessed by the investigator in the ITT, Micro-ITT, PP, and ME populations		Last dose plus two days
Secondary	Rate of total relief of symptoms of Clostridioides difficile infection at Test of Cure (TOC) in the Micro-Intent to Treat, Per Protocol and Microbiologically Evaluable populations		Last dose plus two days
Secondary	Time to resolution of diarrhea through Test of Cure (TOC) in the Micro-Intent to Treat, Per Protocol and Microbiologically Evaluable populations		Randomization until the date of documented resolution, assessed up to 2 days after the last dose of study treatment (TOC)
Secondary	Rate of early recurrence of Clostridioides difficile infection through Day 40 in the Micro-ITT and ME populations		TOC - Day 40
Secondary	Rate of late recurrence of Clostridioides difficile infection (between Day 40 and Day 70) in the Micro-Intent to Treat and Microbiologically Evaluable populations		Day 40 - Day 70
Secondary	Rate of recurrence of Clostridioides difficile infection through Day 70 in the Micro-Intent to Treat and Microbiologic Evaluable populations		TOC - Day 70
Secondary	Time to recurrence of Clostridioides difficile infection through Day 70 in the Micro-Intent to Treat, Per Protocol and Microbiologically Evaluable populations		from TOC until the date of recurrence, assessed up to Day 70
Secondary	Rate of global cure in the Micro-Intent to Treat, Per Protocol and Microbiologically evaluable populations		TOC - Day 40
Secondary	Clostridium difficile Infection-Daily Symptoms (CDI DaySyms) change from baseline to each post-baseline visit in domain scores (diarrhea symptoms, abdominal symptoms, and systemic/other symptoms) in the Micro-ITT and ME populations		Screening through TOC visit and at suspected recurrence