Direct Lysis of Staph Aureus Resistant Pathogen Trial of Exebacase
Summary
The purpose of this superiority study is to evaluate the efficacy and safety of exebacase in addition to standard of care antibiotics (SoCA) compared with SoCA alone for the treatment of patients with Staphylococcus aureus (S. aureus) bloodstream infections (BSI), including right-sided infective endocarditis (IE). Patients will be randomized to receive a single intravenous dose of exebacase or placebo. Patients will receive SoCA selected by the investigators based on the protocol. Exebacase, a direct lytic agent, is an entirely new treatment modality against S. aureus. Exebacase is a recombinantly-produced, purified cell wall hydrolase enzyme that results in rapid bacteriolysis, potent biofilm eradication, synergy with antibiotics, low propensity for resistance, and the potential to suppress antibiotic resistance when used together with antibiotics. Exebacase represents a first-in-field, first-in-class treatment with the potential to improve clinical outcome when used in addition to SoCA to treat S. aureus BSI including IE.
Timeline
- Start
- 2019-12-20
- Primary completion
- 2022-09-09
- Completion
- 2022-09-09
Outcome
Missed primary endpoint
Stopped: “The independent DSMB recommended that the study be stopped for futility following interim efficacy analysis.”
registry analysis (superiority test); Exebacase + SoCA vs SoCA Alone; p = 0.392; Risk Difference (RD) -10.6 (95% CI -33.6 to 12.4); Fisher Exact NCT04160468 ↗
paper Exebacase + antibiotics failed to improve clinical response at day 14 in patients with MRSA bacteremia/endocarditis. PMID 38297916 ↗
Publications
- Fowler VG Jr, Das AF, Lipka-Diamond J, Ambler JE, Schuch R, Pomerantz R, Cassino C, Jauregui-Peredo L, Moran GJ, Rupp ME, Lachiewicz AM, Kuti JL, Wise RA, Kaye KS, Zervos MJ, Nichols WG. Exebacase in Addition to Standard-of-Care Antibiotics for Staphylococcus aureus Bloodstream Infections and Right-Sided Infective Endocarditis: A Phase 3, Superiority-Design, Placebo-Controlled, Randomized Clinical Trial (DISRUPT). Clin Infect Dis. 2024 Jun 14;78(6):1473-1481. doi: 10.1093/cid/ciae043.
- Traczewski MM, Ambler JE, Schuch R. Determination of MIC Quality Control Parameters for Exebacase, a Novel Lysin with Antistaphylococcal Activity. J Clin Microbiol. 2021 Jun 18;59(7):e0311720. doi: 10.1128/JCM.03117-20. Epub 2021 Jun 18.