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

Phase 2

Completed

Conditions: Clostridioides Difficile Infection

Interventions: Drug: CRS3123
Drug: Active Comparator

Registration Number: NCT04781387

Lead Sponsor: Crestone, Inc

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 43

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CRS3123 200 milligram	CRS3123	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.
CRS3123 400 milligram	CRS3123	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.
Vancomycin 125 milligram	Active Comparator	Vancomycin 125 milligram dose (500 mg/day) given orally at approximately 6-hour intervals for 10 days.

Primary Outcome Measures

Name	Time	Method
Rate of Clinical Cure at the Test of Cure [TOC] Visit in the Intent-to-treat [ITT] Population	TOC/Day 12	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.

Secondary Outcome Measures

Name	Time	Method
Rate of Clinical Cure at Test of Cure (TOC) in the Microbiological-ITT (mITT) Population	TOC/Day 12	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.
Rate of Clinical Cure at Test of Cure (TOC) in the Per Protocol (PP) and Microbiologically Evaluable (ME) Populations	TOC/Day 12	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.
Rate of Total Relief of Symptoms of Clostridioides Difficile Infection at Test of Cure (TOC) in the Microbiological-ITT (mITT) Population	TOC/Day 12	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.
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	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.
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	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.
Time to Resolution of Diarrhea Through Test of Cure (TOC) in the Per Protocol (PP) and Microbiologically Evaluable (ME) Populations	Study Day 1 until the date of documented resolution, assessed up to TOC/Day 12	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.
Rate of Early Recurrence of Clostridioides Difficile Infection Through Day 40 in the Microbiological-ITT (mITT) Population	Post TOC/Day 12 visit through Day 40	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.
Rate of Early Recurrence of Clostridioides Difficile Infection Through Day 40 in the Microbiologically Evaluable (ME) Population	Post TOC/Day 12 visit through Day 40	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.
Rate of Late Recurrence of Clostridioides Difficile Infection (Between Day 40 and Day 70) in the Microbiological-ITT (mITT) Population	Day 40 - Day 70	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.
Rate of Late Recurrence of Clostridioides Difficile Infection (Between Day 40 and Day 70) in the Microbiologically Evaluable (ME) Population	Day 40 - Day 70	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.
Rate of Recurrence of Clostridioides Difficile Infection Through Day 70 in the Microbiological-ITT (mITT) Population	Post TOC/Day 12 visit through Day 70	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.
Rate of Recurrence of Clostridioides Difficile Infection Through Day 70 in the Microbiologic Evaluable (ME) Population	Post TOC/Day 12 visit through Day 70	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.
Rate of Global Cure in the Microbiological-ITT (mITT) Population	Post TOC/Day 12 visit through Day 40	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.
Rate of Global Cure in the Per Protocol (PP) and Microbiologically Evaluable (ME) Populations	Post TOC/Day 12 visit through Day 40	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.

Trial Locations

Locations (20): 131
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Fullerton, California, United States
117
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Lancaster, California, United States
143
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Mission Hills, California, United States
138
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Orange, California, United States
146
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Miami, Florida, United States
122
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Miami, Florida, United States
140
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Marietta, Georgia, United States
110
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Idaho Falls, Idaho, United States
129
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Winfield, Illinois, United States
130
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Royal Oak, Michigan, United States
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131
🇺🇸Fullerton, California, United States