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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04247542
Recruitment Status : Recruiting
First Posted : January 30, 2020
Last Update Posted : April 15, 2022
Sponsor:
Information provided by (Responsible Party):
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).

Condition or disease Intervention/treatment Phase
Clostridium Difficile Infection Drug: Ibezapolstat Drug: Vancomycin Phase 2

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 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 74 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 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.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: 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.
Primary Purpose: Treatment
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
Actual Study Start Date : March 6, 2020
Estimated Primary Completion Date : June 2022
Estimated Study Completion Date : August 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Ibezapolstat
Active investigational antibacterial agent: ibezapolstat 450 mg po Q12H x 10 days
Drug: Ibezapolstat
Investigational antibacterial agent
Other Name: ACX-362E

Active Comparator: Vancomycin
Standard of care: Vancomycin 125 mg po Q6H x 10 days
Drug: Vancomycin
Active comparator
Other Name: Vancomycin oral




Primary Outcome Measures :
  1. Clinical cure [ Time Frame: 12 days ]
    Percentage of patients with clinical cure at the test of cure visit

  2. Percentage of patients with adverse events [ Time Frame: 38 days ]
    Safety


Secondary Outcome Measures :
  1. Percentage of patients with sustained clinical cure [ Time Frame: 38 days ]
    Clinical cure at the test of cure visit (ie, at least 48 hours post end of treatment) and no recurrence within 28 days

  2. Plasma and fecal concentrations of ACX-362E [ Time Frame: 10 days ]
    Pharmacokinetics and systemic exposure


Other Outcome Measures:
  1. Microbiome effects [ Time Frame: 38 days ]
    Quantitative changes in relevant fecal bacterial communities and microbial diversity

  2. Time to resolution of diarrhea [ Time Frame: 12 days ]
    Time in days from outset of treatment to the first formed bowel movement

  3. Time from outset of treatment to the first formed bowel movement [ Time Frame: 12 days ]
    Time in days from outset of treatment to day of discharge

  4. Change in EQ-5D-5L Quality of Life scores [ Time Frame: 38 days ]
    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



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Ages Eligible for Study:   18 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04247542


Contacts
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Contact: Michael H Silverman, MD 7816318596 msilverman@acurxpharma.com

Locations
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United States, Arizona
Acurx Site #118 Recruiting
Scottsdale, Arizona, United States, 85251
Contact: Study Coordinator         
United States, California
Acurx Site #115 Recruiting
Apple Valley, California, United States, 92307
Contact: Study Coordinator         
Acurx Site #111 Recruiting
Lancaster, California, United States, 93534
Contact: Study Coordinator         
United States, Florida
Acurx Site #105 Completed
Doral, Florida, United States, 33166
Acurx Site #108 Recruiting
Hialeah, Florida, United States, 33012
Contact: Study Coordinator         
Acurx Site #107 Recruiting
Miami Springs, Florida, United States, 33166
Contact: Study Coordinator         
Acurx Site #101 Recruiting
Miami, Florida, United States, 33015
Contact: Study Coordinator         
Acurx Site #116 Recruiting
Miami, Florida, United States, 33155
Contact: Study Coordinator         
United States, Idaho
Acurx Site #102 Recruiting
Idaho Falls, Idaho, United States, 83404
Contact: Study Coordinator         
United States, Massachusetts
Acurx Site #104 Recruiting
Worcester, Massachusetts, United States, 01655
Contact: Study Coordinator         
United States, Montana
Acurx Site #103 Recruiting
Butte, Montana, United States, 59701
Contact: Study Coordinator         
United States, Tennessee
Acurx Site #114 Recruiting
Chattanooga, Tennessee, United States, 37404
Contact: Study Coordinator         
United States, Utah
Acurx Site #110 Recruiting
Bountiful, Utah, United States, 84010
Contact: Study Coordinator         
United States, Virginia
Acurx Site #106 Recruiting
Fairfax, Virginia, United States, 22031
Contact: Study Coordinator         
Acurx Site #109 Recruiting
Lynchburg, Virginia, United States, 24501
Contact: Study Coordinator         
Sponsors and Collaborators
Acurx Pharmaceuticals Inc.
Investigators
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Study Director: Michael H Silverman, MD Acurx Pharmaceuticals Inc.
Additional Information:
Publications of Results:
Other Publications:
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Responsible Party: Acurx Pharmaceuticals Inc.
ClinicalTrials.gov Identifier: NCT04247542    
Other Study ID Numbers: ACX-362E-201
First Posted: January 30, 2020    Key Record Dates
Last Update Posted: April 15, 2022
Last Verified: April 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Acurx Pharmaceuticals Inc.:
Clostridioides difficile
CDAD (Clostridioides difficile-associated diarrhea)
DNA polymerase IIIC
Additional relevant MeSH terms:
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Infections
Communicable Diseases
Clostridium Infections
Disease Attributes
Pathologic Processes
Gram-Positive Bacterial Infections
Bacterial Infections
Bacterial Infections and Mycoses
Vancomycin
Anti-Bacterial Agents
Anti-Infective Agents