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

Sponsor

Acurx Pharmaceuticals Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04247542

Collaborator

(none)

Enrollment

Locations

Arms

34.9

Anticipated Duration (Months)

4.6

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Study Design

Study Type:

Interventional

Anticipated 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.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 :

Mar 6, 2020

Anticipated Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

Feb 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ibezapolstat Active investigational antibacterial agent: ibezapolstat 450 mg po Q12H x 10 days	Drug: Ibezapolstat Investigational antibacterial agent Other Names: ACX-362E
Active Comparator: Vancomycin Standard of care: Vancomycin 125 mg po Q6H x 10 days	Drug: Vancomycin Active comparator Other Names: Vancomycin oral

Arm

Intervention/Treatment

Experimental: Ibezapolstat

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

Drug: Ibezapolstat

Investigational antibacterial agent

Other Names:

ACX-362E

Active Comparator: Vancomycin

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

Drug: Vancomycin

Active comparator

Other Names:

Vancomycin oral

Outcome Measures

Primary Outcome Measures

Clinical cure [12 days]
Percentage of patients with clinical cure at the test of cure visit
Percentage of patients with adverse events [38 days]
Safety

Secondary Outcome Measures

Percentage of patients with sustained clinical cure [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
Plasma and fecal concentrations of ACX-362E [10 days]
Pharmacokinetics and systemic exposure

Other Outcome Measures

Microbiome effects [38 days]
Quantitative changes in relevant fecal bacterial communities and microbial diversity
Time to resolution of diarrhea [12 days]
Time in days from outset of treatment to the first formed bowel movement
Time from outset of treatment to the first formed bowel movement [12 days]
Time in days from outset of treatment to day of discharge
Change in EQ-5D-5L Quality of Life scores [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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 90 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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.

Exclusion Criteria:

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.
Anticipated that systemic antibacterial therapy for a non-CDI infection will be required for > 7 days after start of study therapy.
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).
Actively taking Saccharomyces boulardii and unwilling to discontinue during the study period.
Received a fecal transplant in the previous 3 months.
Received laxatives in the last 48 hours.
Unable or unwilling to stop taking oral probiotics for the duration of the study.
Received intravenous immunoglobulin within 3 months before study drug treatment.
Sepsis.
Have a known current history of significantly compromised immune system such as:
Subjects with a known history of human immunodeficiency virus infection and CD4 <200 cells/mm3 within 6 months of start of study therapy.
Severe neutropenia with neutrophil count < 500 cells/mL.
Concurrent intensive induction chemotherapy, radiotherapy, or biologic treatment for active malignancy.
Pregnant or lactating women.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Acurx Site #118: Dr Janet Reiser	Scottsdale	Arizona	United States	85251
2	Acurx Site #115: Dr Neera Grover	Apple Valley	California	United States	92307
3	Acurx Site #111: Dr Jatinder Pruthi	Lancaster	California	United States	93534
4	Acurx Site #105	Doral	Florida	United States	33166
5	Acurx Site #107: Dr Belkis Delgado	Miami Springs	Florida	United States	33166
6	Acurx Site #101: Dr Idalia Acosta	Miami	Florida	United States	33015
7	Acurx Site #108: Dr Idania Garcia Del Sol	Miami	Florida	United States	33142
8	Acurx Site #116: Dr Erick Juarez	Miami	Florida	United States	33155
9	Acurx Site #117: Dr Rafael Companioni	Panama City	Florida	United States	32405
10	Acurx Site #102: Dr Richard Nathan	Idaho Falls	Idaho	United States	83404
11	Acurx Site #104: Dr JeanMarie Houghton	Worcester	Massachusetts	United States	01655
12	Acurx Site #103: Dr John Pullman	Butte	Montana	United States	59701
13	Acurx Site #114: Dr Eugene Ryan	Chattanooga	Tennessee	United States	37404
14	Acurx Site #110: Dr Val Hansen	Bountiful	Utah	United States	84010
15	Acurx Site #106: Dr Bezawit Tekola	Fairfax	Virginia	United States	22031
16	Acurx Site #109: Dr Robert Brennan	Lynchburg	Virginia	United States	24501