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

NCT04247542 | Completed Phase 2 Results FDA Drug

• 1 other identifier: ACX-362E-201
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 29

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).

Conditions

Clostridium Difficile Infection

Keywords

Clostridioides difficile; CDAD (Clostridioides difficile-associated diarrhea); DNA polymerase IIIC

Outcome Measures

Primary Outcomes (3)

• Segment 2A: Clinical Cure (CC) of Clostridioides Difficile Infection (CDI) Per Protocol (PP)/Modified Intent-to-Treat (mITT) Population

  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.

  12 days

• Segment 2B Per Protocol (PP) Population: Clinical Cure (CC) of Clostridioides Difficile Infection (CDI)

  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.

  12 days

• Segment 2B Intent-to-Treat (ITT) Population: Clinical Cure (CC) of Clostridioides Difficile Infection (CDI)

  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.

  12 days

Secondary Outcomes (7)

• Segment 2A: Sustained Clinical Cure (SCC) of Clostridioides Difficile Infection (CDI) Per Protocol (PP)/Modified Intent-to-Treat (mITT) Population

  38 days

• Segment 2B Per Protocol (PP) Population: Sustained Clinical Cure (SCC) of Clostridioides Difficile Infection (CDI)

  38 days

• Segment 2B Intent-to-Treat (ITT) Population: Sustained Clinical Cure (SCC) of Clostridioides Difficile Infection (CDI)

  38 days

• Segment 2A: Pharmacokinetics and Systemic Exposure to Ibezapolstat (ACX-362E), Plasma Concentrations

  Days 1, 5, and 10: 2 and 4 hours post-dose

• Segment 2B: Pharmacokinetics and Systemic Exposure to Ibezapolstat (ACX-362E), Plasma Concentrations

  Days 1 and 5: 2 and 4 hours post-dose

Other Outcomes (5)

• Segment 2A: Time to Resolution of Diarrhea

  10 days

• Segment 2B: Time to Resolution of Diarrhea

  40 days

• Segment 2A: Microbiome Effects

  Days 10 and 40

Study Arms (2)

Ibezapolstat

EXPERIMENTAL

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

Drug: Ibezapolstat

Vancomycin

ACTIVE COMPARATOR

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

Drug: Vancomycin

Interventions

Ibezapolstat DRUG

Investigational antibacterial agent

Also known as: ACX-362E

Ibezapolstat

Vancomycin DRUG

Active comparator

Also known as: Vancomycin oral

Vancomycin

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female 18 to 90 years of age, inclusive, at the time of Screening.
• Capable of reading, understanding, and signing the written informed consent; able to adhere to all study procedures and attend all scheduled study visits.
• 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:
• 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)
• 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.
• 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.

You may not qualify if:

• Received more than 24 hours of dosing (\> 4 doses) of oral vancomycin for the current episode of CDI before first dose of study drug.
• Received more than 24 hours of dosing (\> 2 doses) of oral fidaxomicin for the current episode of CDI before first dose of study drug.
• 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.
• Received any other antibacterial therapy for the current CDI episode within 48 hours before the first dose of study drug.
• Subjects considered treatment failures on prior antibiotics for their current episode of CDI will be excluded.
• 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.
• 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.
• Elevated liver transaminases (alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\]) greater than 2 times ULN.
• Active inflammatory bowel disease (Crohn's disease, ulcerative colitis, Irritable Bowel Syndrome with chronic diarrhea).
• Any other non-C. difficile diarrhea.
• Active gastroenteritis because of Salmonella, Shigella, Escherichia coli 0157H7, Yersinia or Campylobacter, a parasite, or virus within the past 2 weeks.
• 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.
• Major GI surgery (ie, significant bowel resection) within 3 months of enrollment (does not include appendectomy or cholecystectomy).
• Prior or current use of anti-C. difficile toxin antibodies.
• Have received a vaccine against C. difficile or its toxins.

Sponsors & Collaborators

• Acurx Pharmaceuticals Inc.: lead

Study Sites (29)

Acurx Site #118: Dr Janet Reiser

Scottsdale, Arizona, 85251, United States

Location

Acurx Site #115: Dr Neera Grover

Apple Valley, California, 92307, United States

Location

Acurx Site #125: Dr Karen Simon

Camarillo, California, 93012, United States

Location

Acurx Site #111: Dr Jatinder Pruthi

Lancaster, California, 93534, United States

Location

Acurx Site #131: Dr Michael Jardula

Palm Springs, California, 92262, United States

Location

Acurx Site #129: Dr Stuart Cohen

Sacramento, California, 95817, United States

Location

Acurx Site #105

Doral, Florida, 33166, United States

Location

Acurx Site #122: Dr Faride Ramos

Doral, Florida, 33172, United States

Location

Acurx Site #101: Dr Idalia Acosta

Miami, Florida, 33015, United States

Location

Acurx Site #124: Dr Yunior Silva-Barrero

Miami, Florida, 33125, United States

Location

Acurx Site #108: Dr Idania Garcia Del Sol

Miami, Florida, 33142, United States

Location

Acurx Site #116: Dr Erick Juarez

Miami, Florida, 33155, United States

Location

Acurx Site #119: Dr Jorge Paoli-Bruno

Miami, Florida, 33186, United States

Location

Acurx Site #107: Dr Belkis Delgado

Miami Springs, Florida, 33166, United States

Location

Acurx Site #117: Dr Rafael Companioni

Panama City, Florida, 32405, United States

Location

Acurx Site #102: Dr Richard Nathan

Idaho Falls, Idaho, 83404, United States

Location

Acurx Site #123: Dr Harry Schrager

Newton, Massachusetts, 02462, United States

Location

Acurx Site #104: Dr JeanMarie Houghton

Worcester, Massachusetts, 01655, United States

Location

Acurx Site #103: Dr John Pullman

Butte, Montana, 59701, United States

Location

Acurx Site #130: Dr Michael DiGiovanna

North Massapequa, New York, 11758, United States

Location

Acurx Site #127: Dr Christopher Connolley

Winston-Salem, North Carolina, 27103, United States

Location

Acurx Site #126: Dr Andrew Pearson

Myrtle Beach, South Carolina, 29572, United States

Location

Acurx Site #114: Dr Eugene Ryan

Chattanooga, Tennessee, 37404, United States

Location

Acurx Site #121: Dr Ramesh Gowrappala

Houston, Texas, 77024, United States

Location

Acurx Site #120: Dr Vanna Gold

Lampasas, Texas, 76550, United States

Location

Acurx Site #113: Dr Jennifer Vincent

Temple, Texas, 76508, United States

Location

Acurx Site #110: Dr Val Hansen

Bountiful, Utah, 84010, United States

Location

Acurx Site #106: Dr Bezawit Tekola

Fairfax, Virginia, 22031, United States

Location

Acurx Site #109: Dr Robert Brennan

Lynchburg, Virginia, 24501, United States

Location

Related Publications (7)

• 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.

  PMID: 31221610 BACKGROUND

• 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.

  PMID: 22203600 BACKGROUND

• 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.

  PMID: 32892222 BACKGROUND

• 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.

  PMID: 35134880 RESULT

• 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.

  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.

  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.

  PMID: 40516571 DERIVED

Related Links

• Sponsor website-Acurx Pharmaceuticals

MeSH Terms

Conditions

Clostridium Infections

Interventions

Ibezapolstat; Vancomycin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Glycopeptides; Glycoconjugates; Carbohydrates; Peptides; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Robert J DeLuccia
• Organization: Acurx Pharmaceuticals, Inc.

rjdeluccia@acurxpharma.com

914-949-3898

Study Officials

• Michael H Silverman, MD

  Acurx Pharmaceuticals Inc.

  STUDY DIRECTOR

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
• Masking Details: Vancomycin capsules will be over-encapsulated to have identical appearance to ibezapolstat capsules. Placebo capsules will be used to enable a double-dummy, double-blind design.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: In Segment 2B, approximately 64 patients will be randomly assigned in a 1:1 fashion to ibezapolstat or the standard of care positive control, vancomycin.

Study Record Dates

• First Submitted: January 23, 2020
• First Posted: January 30, 2020
• Study Start: March 6, 2020
• Primary Completion: October 3, 2023
• Study Completion: November 15, 2023
• Last Updated: January 17, 2025
• Results First Posted: January 17, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (29)