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

NCT04781387 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 19-002175N93019C00056
• Study Type: interventional
• Target: 43
• Locations: 2 countries
• Sites: 20

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.

Conditions

Clostridioides Difficile Infection

Keywords

CDI; Cdiff Infection; Clostridiodes difficile infection; Cdiff

Outcome Measures

Primary Outcomes (1)

• Rate of Clinical Cure at the Test of Cure [TOC] Visit in the Intent-to-treat [ITT] Population

  Clinical cure is defined as survival through TOC/Day 12 and resolution of diarrhea (i.e., \<3 unformed bowel movements \[UBM\] \[Bristol Stool Scale score of 5, 6, or 7\] at end-of-treatment (EOT)/Day 10 with maintenance of resolution through TOC/Day 12 and no further requirement for treatment of CDI through TOC/Day 12. Numbers reported below indicate participants from each cohort that were clinical cures, clinical failures, or indeterminate at the TOC/Day 12 visit.

  TOC/Day 12

Secondary Outcomes (14)

• Rate of Clinical Cure at Test of Cure (TOC) in the Microbiological-ITT (mITT) Population

  TOC/Day 12

• Rate of Clinical Cure at Test of Cure (TOC) in the Per Protocol (PP) and Microbiologically Evaluable (ME) Populations

  TOC/Day 12

• Rate of Total Relief of Symptoms of Clostridioides Difficile Infection at Test of Cure (TOC) in the Microbiological-ITT (mITT) Population

  TOC/Day 12

• 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

  TOC/Day 12

• Time to Resolution of Diarrhea Through Test of Cure (TOC) in the Microbiological-ITT (mITT) Population

  Study Day 1 until the date of documented resolution, assessed up to TOC/Day 12

Study Arms (3)

CRS3123 200 milligram

EXPERIMENTAL

CRS3123 200 milligram dose (400 mg/day) given orally at approximately 6-hour intervals for 10 days. Due to the difference in dosing schedules between CRS3123 (twice a day) and the standard of care vancomycin (four times a day) and appearance of study drugs used in the 3 Arms, placebo will be used to match the total number of capsules in each arm.

Drug: CRS3123

CRS3123 400 milligram

EXPERIMENTAL

CRS3123 400 milligram dose (800 mg/day) given orally at approximately 6-hour intervals for 10 days. Due to the difference in dosing schedules between CRS3123 (twice a day) and the standard of care vancomycin (four times a day) and appearance of study drugs used in the 3 Arms, placebo will be used to match the total number of capsules in each arm.

Drug: CRS3123

Vancomycin 125 milligram

ACTIVE COMPARATOR

Vancomycin 125 milligram dose (500 mg/day) given orally at approximately 6-hour intervals for 10 days.

Drug: Active Comparator

Interventions

CRS3123 DRUG

Study drug dosed PO BID for a total of 10 days

CRS3123 200 milligram; CRS3123 400 milligram

Active Comparator DRUG

Active comparator dosed PO QID for 10 days

Vancomycin 125 milligram

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults, ≥ 18 years of age.
• 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.
• Stool positive for C. difficile Toxin A and/or B antigen using an FDA or Health Canada approved/cleared EIA or ELISA laboratory test.
• Participants with a primary episode or first recurrence of CDI are eligible.
• 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.
• 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.
• 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.
• Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form.

You may not qualify if:

• 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 for a non-CDI infection between screening and Day 70.
• 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.
• Any other known pathogen associated with diarrhea.
• Life-threatening or fulminant CDI as defined by IDSA/SHEA Guidelines.
• Colonic perforation.
• 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.
• 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.
• Pregnant or breastfeeding women.
• Receipt of any investigational medication during the last month (30 days or 5 half lives, whichever is longer) prior to randomization.
• Active and uncontrolled HIV with CD4 \<200/mm3.

Sponsors & Collaborators

• Crestone, Inc: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (20)

131

Fullerton, California, 92835, United States

Location

117

Lancaster, California, 93534, United States

Location

143

Mission Hills, California, 91345, United States

Location

138

Orange, California, 92868, United States

Location

146

Miami, Florida, 33125, United States

Location

122

Miami, Florida, 33144, United States

Location

140

Marietta, Georgia, 30060, United States

Location

110

Idaho Falls, Idaho, 83404, United States

Location

129

Winfield, Illinois, 60190, United States

Location

130

Royal Oak, Michigan, 48073, United States

Location

139

Weldon Spring, Missouri, 63304, United States

Location

128

Butte, Montana, 59701, United States

Location

134

The Bronx, New York, 10467, United States

Location

147

Chapel Hill, North Carolina, 27514, United States

Location

114

Uniontown, Pennsylvania, 15401, United States

Location

104

Cedar Park, Texas, 78613, United States

Location

123

Houston, Texas, 77079, United States

Location

101

San Antonio, Texas, 78229, United States

Location

116

Calgary, Alberta, T2N2T9, Canada

Location

120

London, Ontario, N6A 4V2, Canada

Location

Related Publications (1)

• Louie T, Ribble W, Boccumini L, Johnson K, De Groote MA, Day J, Mason C, Sun X, Freeman J, Gu K, Tillotson G, Wilcox MH, Janjic N, Jarvis TC, Nayak SU, Ochsner UA, Bruss JB. Safety and efficacy of CRS3123 in adults with a primary episode or first recurrence of Clostridioides difficile infection: a phase 2, randomised, double-blind, multicentre, vancomycin-controlled study. Lancet Infect Dis. 2026 Jan 22:S1473-3099(25)00721-2. doi: 10.1016/S1473-3099(25)00721-2. Online ahead of print.

  PMID: 41581516 DERIVED

MeSH Terms

Conditions

Clostridium Infections

Interventions

REP 3123

Condition Hierarchy (Ancestors)

Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Results Point of Contact

• Title: Vice President, Clinical Development
• Organization: Crestone, Inc.

lboccumini@crestonepharma.com

(609) 900-5733

Study Officials

• Urs Ochsner, PhD

  Crestone, Inc

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 19, 2021
• First Posted: March 4, 2021
• Study Start: January 5, 2021
• Primary Completion: April 16, 2024
• Study Completion: April 16, 2024
• Last Updated: March 27, 2026
• Results First Posted: May 25, 2025

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (2); US (18)