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
Verified date | May 2024 |
Source | Acurx Pharmaceuticals Inc. |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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).
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. |
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 |
Lead Sponsor | Collaborator |
---|---|
Acurx Pharmaceuticals Inc. |
United States,
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
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 |
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT02214771 -
Description of the Use of fidAxomicin in Hospitalized Patients With Documented Clostridium diFficile iNfection and of the managEment of These Patients
|
N/A | |
Withdrawn |
NCT01552668 -
Fidaxomicin to Prevent Clostridium Difficile Colonization
|
Phase 4 | |
Recruiting |
NCT03325855 -
Fecal Microbiota Transplant National Registry
|
||
Not yet recruiting |
NCT03586206 -
Relationship Between C. Difficile Toxins' Serum Level With C. Difficile Infection
|
||
Suspended |
NCT03350711 -
A Screening and Recruitment Study in Adults Expressing Interest in the Emory Microbiota Enrichment Program
|
||
Withdrawn |
NCT03643887 -
Phase II Trial of Fecal Microbiota Transplant (FMT) for VRE and CRE Patients
|
Phase 2 | |
Terminated |
NCT04000555 -
Oral Vancomycin for Secondary Prophylaxis of Clostridium Difficile Infection (CDI)
|
Phase 4 | |
Terminated |
NCT03065374 -
Treatment for Clostridium-difficile Infection With IMM529
|
Phase 1/Phase 2 | |
Completed |
NCT03710694 -
Safety and Efficacy of DAV132 in Patients at High-Risk for Clostridium Difficile Infection (CDI)
|
N/A | |
Completed |
NCT02865616 -
MET-2 Clinical Study for Recurrent Clostridium Difficile Infection (CDI)
|
Phase 1 | |
Recruiting |
NCT04940468 -
High- Fiber/ Low-fat Diet for Prevention of Recurrent Clostridioides Difficile Infection in Oncology
|
N/A | |
Completed |
NCT02589847 -
Microbiota Restoration Therapy for Recurrent Clostridium Difficile Infection
|
Phase 2 | |
Not yet recruiting |
NCT01942447 -
Fecal Microbiota Transplantation in Recurrent or Refractory Clostridium Difficile Colitis
|
N/A | |
Active, not recruiting |
NCT02086916 -
Novel Biomarkers to Predict Outcome in Clostridium Difficile Infection
|
N/A | |
Completed |
NCT01230957 -
Study of Different Formulations of a Clostridium Difficile Toxoid Vaccine Given at Three Different Schedules in Adults
|
Phase 2 | |
Completed |
NCT01241552 -
A Study of MK-3415, MK-6072, and MK-3415A in Participants Receiving Antibiotic Therapy for Clostridium Difficile Infection (MK-3415A-001)
|
Phase 3 | |
Not yet recruiting |
NCT04567134 -
Clostridioides Difficile Infection - a Prospective Nationwide Epidemiologic Study in Korea
|
||
Completed |
NCT04075422 -
Bezlotoxumab - in "Real Life" - During the First Episode of Clostridium Difficile Infection in Patients With High Risk of Recurrence.
|
||
Recruiting |
NCT03712722 -
Fecal Microbiota Transplantation (FMT) for Clostridium Difficile
|
||
Recruiting |
NCT05192148 -
Seroprevalence of Antibodies to Surface Antigens and Toxins of Clostridioides Difficile
|
N/A |