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

NCT ID: NCT04247542

Last Updated: 2025-01-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 53 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-03-06
• Study Completion Date: 2023-11-15

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.

Conditions

Clostridium Difficile Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Ibezapolstat

Active investigational antibacterial agent: ibezapolstat 450 mg po Q12H x 10 days

Group Type: EXPERIMENTAL

Ibezapolstat

Intervention Type: DRUG

Investigational antibacterial agent

Vancomycin

Standard of care: Vancomycin 125 mg po Q6H x 10 days

Group Type: ACTIVE_COMPARATOR

Vancomycin

Intervention Type: DRUG

Active comparator

Interventions

Ibezapolstat

Investigational antibacterial agent

Intervention Type: DRUG

Vancomycin

Active comparator

Intervention Type: DRUG

Other Intervention Names

ACX-362E; Vancomycin oral

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Acurx Pharmaceuticals Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael H Silverman, MD

Role: STUDY_DIRECTOR

Acurx Pharmaceuticals Inc.

Locations

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 #101: Dr Idalia Acosta

Miami, Florida, United States

Acurx Site #124: Dr Yunior Silva-Barrero

Miami, Florida, United States

Acurx Site #108: Dr Idania Garcia Del Sol

Miami, Florida, United States

Acurx Site #116: Dr Erick Juarez

Miami, Florida, United States

Acurx Site #119: Dr Jorge Paoli-Bruno

Miami, Florida, United States

Acurx Site #107: Dr Belkis Delgado

Miami Springs, Florida, United States

Acurx Site #117: Dr Rafael Companioni

Panama City, Florida, United States

Acurx Site #102: Dr Richard Nathan

Idaho Falls, Idaho, United States

Acurx Site #123: Dr Harry Schrager

Newton, Massachusetts, United States

Acurx Site #104: Dr JeanMarie Houghton

Worcester, Massachusetts, United States

Acurx Site #103: Dr John Pullman

Butte, Montana, United States

Acurx Site #130: Dr Michael DiGiovanna

North Massapequa, New York, United States

Acurx Site #127: Dr Christopher Connolley

Winston-Salem, North Carolina, United States

Acurx Site #126: Dr Andrew Pearson

Myrtle Beach, South Carolina, United States

Acurx Site #114: Dr Eugene Ryan

Chattanooga, Tennessee, United States

Acurx Site #121: Dr Ramesh Gowrappala

Houston, Texas, United States

Acurx Site #120: Dr Vanna Gold

Lampasas, Texas, United States

Acurx Site #113: Dr Jennifer Vincent

Temple, Texas, United States

Acurx Site #110: Dr Val Hansen

Bountiful, Utah, United States

Acurx Site #106: Dr Bezawit Tekola

Fairfax, Virginia, United States

Acurx Site #109: Dr Robert Brennan

Lynchburg, Virginia, United States

Countries

United States

References

Xu WC, Silverman MH, Yu XY, Wright G, Brown N. Discovery and development of DNA polymerase IIIC inhibitors to treat Gram-positive infections. Bioorg Med Chem. 2019 Aug 1;27(15):3209-3217. doi: 10.1016/j.bmc.2019.06.017. Epub 2019 Jun 11.

Reference Type: BACKGROUND

PMID: 31221610 (View on PubMed)

Dvoskin S, Xu WC, Brown NC, Yanachkov IB, Yanachkova M, Wright GE. A novel agent effective against Clostridium difficile infection. Antimicrob Agents Chemother. 2012 Mar;56(3):1624-6. doi: 10.1128/AAC.06097-11. Epub 2011 Dec 27.

Reference Type: BACKGROUND

PMID: 22203600 (View on PubMed)

Garey KW, Begum K, Lancaster C, Gonzales-Luna A, Bui D, Mercier J, Seng Yue C, Ducharme MP, Hu M, Vince B, Silverman MH, Alam MJ, Kankam M. A randomized, double-blind, placebo-controlled, single and multiple ascending dose Phase 1 study to determine the safety, pharmacokinetics and food and faecal microbiome effects of ibezapolstat administered orally to healthy subjects. J Antimicrob Chemother. 2020 Dec 1;75(12):3635-3643. doi: 10.1093/jac/dkaa364.

Reference Type: BACKGROUND

PMID: 32892222 (View on PubMed)

Garey KW, McPherson J, Dinh AQ, Hu C, Jo J, Wang W, Lancaster CK, Gonzales-Luna AJ, Loveall C, Begum K, Jahangir Alam M, Silverman MH, Hanson BM. Efficacy, Safety, Pharmacokinetics, and Microbiome Changes of Ibezapolstat in Adults with Clostridioides difficile Infection: A Phase 2a Multicenter Clinical Trial. Clin Infect Dis. 2022 Sep 30;75(7):1164-1170. doi: 10.1093/cid/ciac096.

Reference Type: RESULT

PMID: 35134880 (View on PubMed)

Eubank TA, Alam MJ, Begum K, McPherson JK, Jo J, Silverman MH, and Garey KW. A phase 2b, randomized double-blind study of ibezapolstat compared with vancomycin for the treatment of C. difficile infection: clinical and microbiome evaluation. Poster session presented at: IDWeek 2024; 2024 October 16-19; Los Angeles, CA.

Reference Type: RESULT

Garey KW, Alam MJ, Begum K, McPherson JK, Eubank TA, Jo J, and Silverman MH. Microbiome Results from the phase 2, randomized, double-blind study of ibezapolstat compared with vancomycin for the treatment of Clostridioides difficile infection. Slide presentation at: 8th International Clostridioides difficile Symposium; 2024 September 17-19; Bled, Slovenia.

Reference Type: RESULT

Eubank TA, Jo J, Alam MJ, Begum K, McPherson JK, Le TM, Horvath TD, Haidacher SJ, Poggio EC, Lin R, Yue CS, Ducharme MP, Koudssi G, Mercier J, Alder JD, Silverman MH, Garey KW; Ibezapolstat Phase 2 Investigator Group. Efficacy, safety, pharmacokinetics, and associated microbiome changes of ibezapolstat compared with vancomycin in adults with Clostridioides difficile infection: a phase 2b, randomised, double-blind, active-controlled, multicentre study. Lancet Microbe. 2025 Aug;6(8):101126. doi: 10.1016/j.lanmic.2025.101126. Epub 2025 Jun 11.

Reference Type: DERIVED

PMID: 40516571 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

http://www.acurxpharma.com

Sponsor website-Acurx Pharmaceuticals

Other Identifiers

ACX-362E-201

Identifier Type: -

Identifier Source: org_study_id