ACX-362E [Ibezapolstat] for Oral Treatment of Clostridioides Difficile Infection

Phase 2

Completed

• Conditions: Clostridium Difficile Infection
• Interventions: Drug: Ibezapolstat; Drug: Vancomycin

• Registration Number: NCT04247542
• Lead Sponsor: Acurx Pharmaceuticals Inc.

Brief Summary

Segments 2A and 2B of this trial evaluate the safety, efficacy, pharmacokinetics, fecal concentrations, and fecal microbiome effects of ACX-362E \[ibezapolstat\] in patients with C. difficile infection (CDI).

Detailed Description

This Phase 2, multicenter, open-label single-arm segment (2A) followed by a double-blind, randomized, active-controlled segment (2B) is designed to evaluate ACX-362E in the treatment of CDI. Segment 2A of this trial was an open-label study of up to 20 patients at 6 study centers and was terminated early at 10 patients based on the protocol-specified Trial Oversight Committee's assessment of the compelling efficacy and safety data. Patients were treated with 450 mg of oral ibezapolstat twice daily for 10 days. The trial will advance to Segment 2B which is a double-blind comparison of ibezapolstat to the standard of care, oral vancomycin, in approximately 64 subjects (1-1 randomization) at up to approximately 15 sites.

Subjects will be evaluated for cure, safety, and tolerability. All subjects in both segments will have stool samples tested for microbiome profiles. Pharmacokinetic (PK) testing for systemic exposure will be performed on blood samples. Stool samples will be tested for study drug concentration.

Study Timeline

• Study First Submitted: 2020-01-23
• Study First Submitted QC: 2020-01-29
• Study First Posted: 2020-01-30
• Study Start: 2020-03-06
• Primary Completion: 2023-10-03
• Study Completion: 2023-11-15
• Results First Submitted: 2024-11-20
• Status Verified: 2025-01
• Results First Submitted QC: 2025-01-15
• Last Update Submitted: 2025-01-15
• Results First Posted: 2025-01-17
• Last Update Posted: 2025-01-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 53

Inclusion Criteria

1. Male or female 18 to 90 years of age, inclusive, at the time of Screening.

2. Capable of reading, understanding, and signing the written informed consent; able to adhere to all study procedures and attend all scheduled study visits.

3. Confirmed diagnosis of mild or moderate CDI as defined by the Infectious Diseases Society of America/Society for Healthcare Epidemiology of America guidelines (McDonald et al. 2018). Subjects will be diagnosed with CDI based on clinical and laboratory findings:

   1. The presence of diarrhea, defined as passage of ≥ 3 UBMs within 24 hours before dosing; an unformed stool is defined as a Type 5, 6, or 7 on the Bristol Stool Chart (Appendix 2)
   2. A stool test result positive for the presence of C. difficile free toxins using tests that detect toxin A/B (and it is prospectively agreed with the Sponsor). The Sponsor will provide a toxin A/B test kit if the site does not have it as part of standard of care test.
   3. Mild or moderate CDI as defined as a white blood cell count of ≤ 15000 cells/mL and a serum creatinine level < 1.5 mg/dL.

Exclusion Criteria

1. Received more than 24 hours of dosing (> 4 doses) of oral vancomycin for the current episode of CDI before first dose of study drug.

2. Received more than 24 hours of dosing (> 2 doses) of oral fidaxomicin for the current episode of CDI before first dose of study drug.

3. Received more than 24 hours of dosing (> 3 doses) of oral/IV metronidazole for the current episode of CDI before first dose of study drug.

4. Received any other antibacterial therapy for the current CDI episode within 48 hours before the first dose of study drug.

5. Subjects considered treatment failures on prior antibiotics for their current episode of CDI will be excluded.

6. More than 3 episodes of CDI in the previous 12 months or more than 1 prior episode in the last 3 months, excluding the current episode.

7. Severe, complicated, or life-threatening fulminant CDI with evidence of hypotension (systolic blood pressure less than 90 mmHg), septic shock, peritoneal signs or ileus, or toxic megacolon.

8. Elevated liver transaminases (alanine aminotransferase [ALT], aspartate aminotransferase [AST]) greater than 2 times ULN.

9. Active inflammatory bowel disease (Crohn's disease, ulcerative colitis, Irritable Bowel Syndrome with chronic diarrhea).

10. Any other non-C. difficile diarrhea.

11. Active gastroenteritis because of Salmonella, Shigella, Escherichia coli 0157H7, Yersinia or Campylobacter, a parasite, or virus within the past 2 weeks.

12. Had a known positive diagnostic test for other relevant gastrointestinal [GI] pathogens in the 2 weeks before study drug treatment and/or colonization/infection by ova or parasites.

13. Major GI surgery (ie, significant bowel resection) within 3 months of enrollment (does not include appendectomy or cholecystectomy).

14. Prior or current use of anti-C. difficile toxin antibodies.

15. Have received a vaccine against C. difficile or its toxins.

16. Anticipated that systemic antibacterial therapy for a non-CDI infection will be required for > 7 days after start of study therapy.

17. Actively taking anti-diarrheals, and unable to discontinue anti-diarrheal medication, or any medication with the potential to slow bowel movement (for opiates, a stable dose, including use as needed, is permitted).

18. Actively taking Saccharomyces boulardii and unwilling to discontinue during the study period.

19. Received a fecal transplant in the previous 3 months.

20. Received laxatives in the last 48 hours.

21. Unable or unwilling to stop taking oral probiotics for the duration of the study.

22. Received intravenous immunoglobulin within 3 months before study drug treatment.

23. Sepsis.

24. Have a known current history of significantly compromised immune system such as:

    1. Subjects with a known history of human immunodeficiency virus infection and CD4 <200 cells/mm3 within 6 months of start of study therapy.
    2. Severe neutropenia with neutrophil count < 500 cells/mL.
    3. Concurrent intensive induction chemotherapy, radiotherapy, or biologic treatment for active malignancy.

25. Pregnant or lactating women.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Ibezapolstat	Ibezapolstat	Active investigational antibacterial agent: ibezapolstat 450 mg po Q12H x 10 days
Vancomycin	Vancomycin	Standard of care: Vancomycin 125 mg po Q6H x 10 days

Primary Outcome Measures

Name	Time	Method
Segment 2A: Clinical Cure (CC) of Clostridioides Difficile Infection (CDI) Per Protocol (PP)/Modified Intent-to-Treat (mITT) Population	12 days	Percentage of patients with CC at the test of cure (TOC) visit on day 12. CC was defined as survival and the resolution of diarrhea in the 24-hour period immediately before end of treatment (EOT--day 10) that was maintained for 48 hours post EOT without a requirement for additional CDI treatment. Diarrhea was defined as 3 or more unformed bowel movements (UBMs) in a 24-hour period; fewer than 3 UBMs was considered as resolution of diarrhea. A UBM was defined as a Type 5, 6, or 7 bowel movement on the Bristol Stool Chart.
Segment 2B Per Protocol (PP) Population: Clinical Cure (CC) of Clostridioides Difficile Infection (CDI)	12 days	Percentage of patients with CC at the test of cure (TOC) visit on day 12. CC was defined as survival and the resolution of diarrhea in the 24-hour period immediately before end of treatment (EOT--day 10) that was maintained for 48 hours post EOT without a requirement for additional CDI treatment. Diarrhea was defined as 3 or more unformed bowel movements (UBMs) in a 24-hour period; fewer than 3 UBMs was considered as resolution of diarrhea. A UBM was defined as a Type 5, 6, or 7 bowel movement on the Bristol Stool Chart.
Segment 2B Intent-to-Treat (ITT) Population: Clinical Cure (CC) of Clostridioides Difficile Infection (CDI)	12 days	Percentage of patients with CC at the test of cure (TOC) visit on day 12. CC was defined as survival and the resolution of diarrhea in the 24-hour period immediately before end of treatment (EOT--day 10) that was maintained for 48 hours post EOT without a requirement for additional CDI treatment. Diarrhea was defined as 3 or more unformed bowel movements (UBMs) in a 24-hour period; fewer than 3 UBMs was considered as resolution of diarrhea. A UBM was defined as a Type 5, 6, or 7 bowel movement on the Bristol Stool Chart.

Secondary Outcome Measures

Name	Time	Method
Segment 2A: Sustained Clinical Cure (SCC) of Clostridioides Difficile Infection (CDI) Per Protocol (PP)/Modified Intent-to-Treat (mITT) Population	38 days	Clinical cure (CC) at the test of cure (TOC) visit (ie, at least 48 hours after end of treatment \[day 10\]) and no recurrence within 28 days. Recurrence was defined as a new episode of diarrhea (3 or more UBMs in a 24-hour period) with a positive toxin result, using a Sponsor-approved C. difficile free toxin test and, in the opinion of the Investigator, requiring retreatment with an antibacterial agent for C. difficile.
Segment 2A: Pharmacokinetics and Systemic Exposure to Ibezapolstat (ACX-362E), Plasma Concentrations	Days 1, 5, and 10: 2 and 4 hours post-dose	Plasma ibezapolstat concentrations were measured at specified day and time points following dose administration. Amount listed as zero not included in determination of Geometric Mean and CV%.
Segment 2B: Pharmacokinetics and Systemic Exposure to Ibezapolstat (ACX-362E), Fecal Concentrations	Days -2, 3, 5, 8,10,12, 20, 30, and 38	Fecal ibezapolstat concentrations were measured for specified days following dose administration. Specified days were 3, 5, 8, 10, 12, and 20. Amount listed as zero not included in determination of Geometric Mean and CV%.
Segment 2B Per Protocol (PP) Population: Sustained Clinical Cure (SCC) of Clostridioides Difficile Infection (CDI)	38 days	Clinical cure (CC) at the test of cure (TOC) visit (ie, at least 48 hours after end of treatment \[day 10\]) and no recurrence within 28 days. Recurrence was defined as a new episode of diarrhea (3 or more UBMs in a 24-hour period) with a positive toxin result, using a Sponsor-approved C. difficile free toxin test and, in the opinion of the Investigator, requiring retreatment with an antibacterial agent for C. difficile.
Segment 2B Intent-to-Treat (ITT) Population: Sustained Clinical Cure (SCC) of Clostridioides Difficile Infection (CDI)	38 days	Clinical cure (CC) at the test of cure (TOC) visit (ie, at least 48 hours after end of treatment \[day 10\]) and no recurrence within 28 days. Recurrence was defined as a new episode of diarrhea (3 or more UBMs in a 24-hour period) with a positive toxin result, using a Sponsor-approved C. difficile free toxin test and, in the opinion of the Investigator, requiring retreatment with an antibacterial agent for C. difficile.
Segment 2B: Pharmacokinetics and Systemic Exposure to Ibezapolstat (ACX-362E), Plasma Concentrations	Days 1 and 5: 2 and 4 hours post-dose	Plasma ibezapolstat concentrations were measured at specified day and time points following dose administration. Amount listed as zero not included in determination of Geometric Mean and CV%
Segment 2A: Pharmacokinetics and Systemic Exposure to Ibezapolstat (ACX-362E), Fecal Concentrations	Days -2, 3, 5, 8,10, 12, 20, 30, and 38	Fecal ibezapolstat concentrations were measured for specified days following dose administration. Specified days were 3, 5, 8, 10, 12, 20, and 38. Amount listed as zero not included in determination of Geometric Mean and CV%.

Trial Locations

Locations (29)

Acurx Site #118: Dr Janet Reiser; 🇺🇸 Scottsdale, Arizona, United States

Acurx Site #115: Dr Neera Grover; 🇺🇸 Apple Valley, California, United States

Acurx Site #125: Dr Karen Simon; 🇺🇸 Camarillo, California, United States

Acurx Site #111: Dr Jatinder Pruthi; 🇺🇸 Lancaster, California, United States

Acurx Site #131: Dr Michael Jardula; 🇺🇸 Palm Springs, California, United States

Acurx Site #129: Dr Stuart Cohen; 🇺🇸 Sacramento, California, United States

Acurx Site #105; 🇺🇸 Doral, Florida, United States

Acurx Site #122: Dr Faride Ramos; 🇺🇸 Doral, Florida, United States

Acurx Site #107: Dr Belkis Delgado; 🇺🇸 Miami Springs, Florida, United States

Acurx Site #101: Dr Idalia Acosta; 🇺🇸 Miami, Florida, United States

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