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

Official title

A Phase 2 Interventional, Open-Label, Single-Arm Trial of Oral Ibezapolstat (ACX-362E) for Treatment and Reduction of Recurrent Clostridioides Difficile Infection in Patients With Multiple Recurrent Infections (IBZ-PATHFINDER)

Overview

Single-arm trial to evaluate the safety and efficacy of ACX-362E \[ibezapolstat\] in patients with recurrent C. difficile infection (CDI).

Detailed description

Phase 2 multicenter, open-label, single-arm study is designed to evaluate the efficacy, safety, and tolerability of ibezapolstat in the treatment and reduction of recurrence of CDI in an adult patient population that has experienced ≥3 episodes of CDI within the past 12 months. Up to 20 participants will be treated with ibezapolstat 450 mg taken with food every 12 hours for 14 days (28 total doses) and followed for Clinical Cure (Day 16), Sustained Clinical Cure (Day 42), rate of CDI recurrence (Up to Week 24), and Extended Clinical Cure (ECC) (Up to Week 24).

Interventions

• Drug Ibezapolstat
  Ibezapolstat 450 mg po Q12H x14 days

Primary outcome measures

• Evaluate the rate of CDI Clinical Cure (CC) [Time frame: Day 16]
• Evaluate the rate of Sustained Clinical Cure (SCC) [Time frame: Day 42]
• Evaluate the rate of CDI recurrence (rCDI) [Time frame: Day 70]

Secondary outcome measures (5)

• Assess the rate of CDI recurrence (rCDI) [Time frame: Day 42]
• Assess the effects of ibezapolstat on quantitative changes to the fecal microbiome [Time frame: Day 1 to Week 24]
• Assess time to resolution of diarrhea during the treatment period [Time frame: Day 16]
• Assess the incidence of Extended Clinical Cure (ECC) [Time frame: Weeks 8, 12, and 24]
• Assess the rate of CDI recurrence (rCDI) [Time frame: Weeks 12 and 24]

Eligibility criteria

Inclusion criteria

• Confirmed diagnosis of CDI as defined by 1) the presence of diarrhea, defined as passage of ≥ 3 UBMs within 24 hours before study Day 1, AND 2) a stool test result positive for the presence of C. difficile free toxins
• Three or more CDI episodes in the past 12 months, including the current episode, with each episode defined as ≥ 3 unformed stools in 24 hours associated with positive C. difficile toxin test.
• At least 1 of the protocol-qualifying prior CDI episodes, not including the current episode, has been treated with oral vancomycin or with fidaxomicin

Exclusion criteria

• Severe, complicated, or life-threatening fulminant CDI with evidence of hypotension (systolic blood pressure < 90 mmHg), septic shock, peritoneal signs or ileus, or toxic megacolon
• Received more than 24 hours of dosing with antibiotics for the current CDI episode:
• Received a live biotherapeutic product (LBP) (Rebyota® or Vowst™) within the past 12 weeks
• Received or current use of anti-C. difficile antibodies, eg, IV immunoglobulin \[IVIG\], bezlotoxumab
• Active inflammatory bowel disease (Crohn's disease, ulcerative colitis) with chronic diarrhea within 12 weeks before Baseline, or with a history of symptoms > 12 weeks before Baseline without evidence of mucosal healing on colonoscopy within the past year.
• Active irritable bowel syndrome with chronic diarrhea in the past 12 weeks.
• Active gastroenteritis because of Salmonella, Shigella, Escherichia coli 0157H7, Yersinia or Campylobacter, other bacteria, a parasite, or a virus within the past 2 weeks
• Major GI surgery (eg, significant bowel resection) within 3 months of enrollment (does not include appendectomy or cholecystectomy).
• Known current history of a severely compromised immune system

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Publications

• 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
• McDonald LC, Gerding DN, Johnson S, Bakken JS, Carroll KC, Coffin SE, Dubberke ER, Garey KW, Gould CV, Kelly C, Loo V, Shaklee Sammons J, Sandora TJ, Wilcox MH. Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis. 2018 Mar PMID 29562266
• 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
• 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, randomis PMID 40516571

Identifiers

NCT: NCT07513285 · ACX-362E-202

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗