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

Clostridium Difficile Infection Clinical Trial

Official title:

ACX-362E [Ibezapolstat] for Oral Treatment of Clostridioides Difficile Infection: A Phase 2A Open-Label Segment Followed by a Phase 2B Double-Blind Vancomycin-Controlled Segment

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04247542
• Other study ID #: ACX-362E-201
• Status: Completed
• Phase: Phase 2
• Start date: March 6, 2020
• Est. completion date: November 15, 2023

Study information

• Verified date: May 2024
• Source: Acurx Pharmaceuticals Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 bid for 10 days. In segment 2A all (10 of 10) patients were cured of CDI at end of treatment and all (10 of 10) were sustained clinical cures 30 days after EOT. Ibezapolstat was well tolerated with no reported SAEs. 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: November 15, 2023
• Est. primary completion date: October 3, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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.

Related Conditions & MeSH terms

• Clostridium Difficile Infection
• Clostridium Infections
• Communicable Diseases
• Infections

Intervention

Drug:
• Ibezapolstat
Investigational antibacterial agent
• Vancomycin
Active comparator

Locations

Country	Name	City	State
United States	Acurx Site #115: Dr Neera Grover	Apple Valley	California
United States	Acurx Site #110: Dr Val Hansen	Bountiful	Utah
United States	Acurx Site #103: Dr John Pullman	Butte	Montana
United States	Acurx Site #125: Dr Karen Simon	Camarillo	California
United States	Acurx Site #114: Dr Eugene Ryan	Chattanooga	Tennessee
United States	Acurx Site #105	Doral	Florida
United States	Acurx Site #122: Dr Faride Ramos	Doral	Florida
United States	Acurx Site #106: Dr Bezawit Tekola	Fairfax	Virginia
United States	Acurx Site #121: Dr Ramesh Gowrappala	Houston	Texas
United States	Acurx Site #102: Dr Richard Nathan	Idaho Falls	Idaho
United States	Acurx Site #120: Dr Vanna Gold	Lampasas	Texas
United States	Acurx Site #111: Dr Jatinder Pruthi	Lancaster	California
United States	Acurx Site #109: Dr Robert Brennan	Lynchburg	Virginia
United States	Acurx Site #101: Dr Idalia Acosta	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 #124: Dr Yunior Silva-Barrero	Miami	Florida
United States	Acurx Site #107: Dr Belkis Delgado	Miami Springs	Florida
United States	Acurx Site #126: Dr Andrew Pearson	Myrtle Beach	South Carolina
United States	Acurx Site #123: Dr Harry Schrager	Newton	Massachusetts
United States	Acurx Site #130: Dr Michael DiGiovanna	North Massapequa	New York
United States	Acurx Site #131: Dr Michael Jardula	Palm Springs	California
United States	Acurx Site #117: Dr Rafael Companioni	Panama City	Florida
United States	Acurx Site #129: Dr Stuart Cohen	Sacramento	California
United States	Acurx Site #118: Dr Janet Reiser	Scottsdale	Arizona
United States	Acurx Site #113: Dr Jennifer Vincent	Temple	Texas
United States	Acurx Site #127: Dr Christopher Connolley	Winston-Salem	North Carolina
United States	Acurx Site #104: Dr JeanMarie Houghton	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Acurx Pharmaceuticals Inc.

Country where clinical trial is conducted

United States, 

References & Publications (4)

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. — View Citation

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. — View Citation

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 diff — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Microbiome effects	Quantitative changes in relevant fecal bacterial communities and microbial diversity	38 days
Other	Time to resolution of diarrhea	Time in days from outset of treatment to the first formed bowel movement	12 days
Other	Time from outset of treatment to the first formed bowel movement	Time in days from outset of treatment to day of discharge	12 days
Other	Change in EQ-5D-5L Quality of Life scores	Change from baseline in each of the 5 dimensions of the EQ-5D-5L score, each scored on a scale of 1-5, with 1 being normal and 5 indicating extreme difficulty or impairment	38 days
Primary	Clinical cure	Percentage of patients with clinical cure at the test of cure visit	12 days
Primary	Percentage of patients with adverse events	Safety	38 days
Secondary	Percentage of patients with sustained clinical cure	Clinical cure at the test of cure visit (ie, at least 48 hours post end of treatment) and no recurrence within 28 days	38 days
Secondary	Plasma and fecal concentrations of ACX-362E	Pharmacokinetics and systemic exposure	10 days

External Links

•   Sponsor website