Clostridioides Difficile InfectionPhase 2NCT04781387
Evaluation of CRS3123 vs. Oral Vancomycin in Adult Patients With Clostridioides Difficile Infection
A Phase 2 study testing CRS3123 and Active Comparator in people with Clostridioides Difficile Infection, run by Crestone, Inc at 20 sites in 2 countries.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Clostridioides Difficile Infection
- What is being tested?
- CRS3123 and Active Comparator
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 43 participants
- Where
- 20 sitesin 2 countries
- Study dates
- 5 Jan 2021to 16 Apr 2024
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
- 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.
- Severe neutropenia defined as ANC <500 cells/mm3
- 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.
- 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.
- Known hypersensitivity to CRS3123 or oral vancomycin.
- 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.
- 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 from randomization until 24 hours after EOT.
- Unwillingness to stop use of anti-diarrheals from randomization to Day 70.
Trial locations and contacts
20 sites in 2 countries.
20 sites in 2 countries
United States18 sites
128
Butte, Montana, 59701
104
Cedar Park, Texas, 78613
147
Chapel Hill, North Carolina, 27514
131
Fullerton, California, 92835
123
Houston, Texas, 77079
110
Idaho Falls, Idaho, 83404
117
Lancaster, California, 93534
140
Marietta, Georgia, 30060
146
Miami, Florida, 33125
122
Miami, Florida, 33144
143
Mission Hills, California, 91345
138
Orange, California, 92868
130
Royal Oak, Michigan, 48073
101
San Antonio, Texas, 78229
134
The Bronx, New York, 10467
114
Uniontown, Pennsylvania, 15401
139
Weldon Spring, Missouri, 63304
129
Winfield, Illinois, 60190
About this study
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
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
- Being tested
- CRS3123, Active Comparator
- Keywords
- CDI, Cdiff Infection, Clostridiodes difficile infection, Cdiff
- Medical subject headings
- Clostridium Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CRS3123Drug
Study drug dosed PO BID for a total of 10 days
Active ComparatorDrug
Active comparator dosed PO QID for 10 days
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: CRS3123 |
| Vancomycin 125 milligram | Active comparator | Vancomycin 125 milligram dose (500 mg/day) given orally at approximately 6-hour intervals for 10 days. Receives: Drug: Active Comparator |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: TOC/Day 12
Secondary outcomes (14)
Rate of Clinical Cure at Test of Cure (TOC) in the Microbiological-ITT (mITT) 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/Day12 visit.
Measured: TOC/Day 12
Rate of Clinical Cure at Test of Cure (TOC) in the Per Protocol (PP) and Microbiologically Evaluable (ME) Populations
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/Day12 visit.
Measured: TOC/Day 12
Rate of Total Relief of Symptoms of Clostridioides Difficile Infection at Test of Cure (TOC) in the Microbiological-ITT (mITT) Population
Total relief of symptoms at TOC/Day 12 is defined as resolution (< 3 per day) of unformed bowel movements, an investigator's assessment of clinical cure, and the resolution of signs or symptoms of CDI recorded at baseline. Numbers reported below indicate participants from each cohort that had total relief of symptoms at TOC/Day 12 and those that did not.
Measured: 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
Total relief of symptoms at TOC/Day 12 is defined as resolution (< 3 per day) of unformed bowel movements, an investigator's assessment of clinical cure, and the resolution of signs or symptoms of CDI recorded at baseline. Numbers reported below indicate participants from each cohort that had total relief of symptoms at TOC/Day 12 and those that did not.
Measured: TOC/Day 12
Time to Resolution of Diarrhea Through Test of Cure (TOC) in the Microbiological-ITT (mITT) Population
The time to resolution of diarrhea is defined as the time elapsed from the first dose of study treatment to the last unformed bowel movement before 2 consecutive days of < 3 unformed bowel movements (Bristol Stool Scale score of 5, 6, or 7) per day through TOC/Day 12. Values reported below are median days to resolution for each cohort.
Measured: Study Day 1 until the date of documented resolution, assessed up to TOC/Day 12
Time to Resolution of Diarrhea Through Test of Cure (TOC) in the Per Protocol (PP) and Microbiologically Evaluable (ME) Populations
The time to resolution of diarrhea is defined as the time elapsed from the first dose of study treatment to the last unformed bowel movement before 2 consecutive days of < 3 unformed bowel movements (Bristol Stool Scale score of 5, 6, or 7) per day through TOC/Day 12. Values reported below are median days to resolution for each cohort.
Measured: Study Day 1 until the date of documented resolution, assessed up to TOC/Day 12
Rate of Early Recurrence of Clostridioides Difficile Infection Through Day 40 in the Microbiological-ITT (mITT) Population
Rate of early recurrence of C. difficile infection (CDI) is defined as a new episode of diarrhea (≥ 3 unformed bowel movements [Bristol Stool Scale score of 5, 6, or 7] in a 24-hour period) with a positive toxin result and requires retreatment for CDI before Day 40. The table below shows the number of participants per cohort that experienced a recurrence before Day 40 and those that did not. Only participants that were clinical cures at TOC/Day 12 were included in the analysis.
Measured: Post TOC/Day 12 visit through Day 40
Rate of Early Recurrence of Clostridioides Difficile Infection Through Day 40 in the Microbiologically Evaluable (ME) Population
Rate of early recurrence of C. difficile infection (CDI) is defined as a new episode of diarrhea (≥ 3 unformed bowel movements [Bristol Stool Scale score of 5, 6, or 7] in a 24-hour period) with a positive toxin result and requires retreatment for CDI before Day 40. The table below shows the number of participants per cohort that experienced a recurrence before Day 40 and those that did not. Only participants that were clinical cures at TOC/Day 12 were included in the analysis.
Measured: Post TOC/Day 12 visit through Day 40
Rate of Late Recurrence of Clostridioides Difficile Infection (Between Day 40 and Day 70) in the Microbiological-ITT (mITT) Population
Rate of late recurrence of CDI is defined as a new episode of diarrhea (≥ 3 unformed bowel movements [Bristol Stool Scale score of 5, 6, or 7] in a 24-hour period), with a positive toxin result and requires retreatment of CDI between Day 40 and Day 70. The table below shows the number of participants per cohort that experienced a recurrence between Day 40 and Day 70 and those that did not. Analysis populations for this assessment only includes participants that had an investigator assessment of clinical cure at TOC/Day 12. Participants that were indeterminate at TOC/Day 12 or recurrent prior to Day 40 were excluded.
Measured: Day 40 - Day 70
Rate of Late Recurrence of Clostridioides Difficile Infection (Between Day 40 and Day 70) in the Microbiologically Evaluable (ME) Population
Rate of late recurrence of CDI is defined as a new episode of diarrhea (≥ 3 unformed bowel movements [Bristol Stool Scale score of 5, 6, or 7] in a 24-hour period), with a positive toxin result and requires retreatment of CDI between Day 40 and Day 70. The table below shows the number of participants per cohort that experienced a recurrence between Day 40 and Day 70 and those that did not. Analysis populations for this assessment only includes participants that had an investigator assessment of clinical cure at TOC/Day 12. Participants that were indeterminate at TOC/Day 12 or recurrent prior to Day 40 were excluded.
Measured: Day 40 - Day 70
Rate of Recurrence of Clostridioides Difficile Infection Through Day 70 in the Microbiological-ITT (mITT) Population
Rate of recurrence of CDI is defined as a new episode of diarrhea (≥3 unformed bowel movements [Bristol Stool Scale score of 5, 6, or 7] in a 24-hour period) with a positive toxin result and requires retreatment for CDI at any point between TOC/Day 12 and Day 70. The table below shows the number of participants per cohort that experienced a recurrence between TOC/Day 12 and Day 70 and those that did not. Analysis populations for this assessment only includes participants that had an investigator assessment of clinical cure at TOC/Day 12.
Measured: Post TOC/Day 12 visit through Day 70
Rate of Recurrence of Clostridioides Difficile Infection Through Day 70 in the Microbiologic Evaluable (ME) Population
Rate of recurrence of CDI is defined as a new episode of diarrhea (≥3 unformed bowel movements [Bristol Stool Scale score of 5, 6, or 7] in a 24-hour period) with a positive toxin result and requires retreatment for CDI at any point between TOC/Day 12 and Day 70. The table below shows the number of participants per cohort that experienced a recurrence between TOC/Day 12 and Day 70 and those that did not. Analysis populations for this assessment only includes participants that had an investigator assessment of clinical cure at TOC/Day 12.
Measured: Post TOC/Day 12 visit through Day 70
Rate of Global Cure in the Microbiological-ITT (mITT) Population
Global cure is defined as a clinical cure at TOC/Day 12 without recurrence through Day 40. The table below shows the number of participants per cohort that experienced a recurrence between TOC/Day 12 and Day 40 and those that did not.
Measured: Post TOC/Day 12 visit through Day 40
Rate of Global Cure in the Per Protocol (PP) and Microbiologically Evaluable (ME) Populations
Global cure is defined as a clinical cure at TOC/Day 12 without recurrence through Day 40. The table below shows the number of participants per cohort that experienced a recurrence between TOC/Day 12 and Day 40 and those that did not.
Measured: Post TOC/Day 12 visit through Day 40
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Mar 2021
- Study start5 Jan 2021
- Primary completion16 Apr 2024
- Study completion16 Apr 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Clostridioides Difficile InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 43 participants (actual)
Sponsor and investigators
- Lead sponsor
- Crestone, Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Urs Ochsner, PhD, Principal investigator, Crestone, Inc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04781387
- Sponsor's protocol ID
- 19-0021
- Other IDs
- 75N93019C00056
- Status last verified
- Mar 2026
- First submitted
- 19 Jan 2021
- Last updated
- 27 Mar 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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 May;26(5):535-548. doi: 10.1016/S1473-3099(25)00721-2. Epub 2026 Jan 22.
PubMed 41581516