Direct Lysis of Staph Aureus Resistant Pathogen Trial of Exebacase

Study Overview
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Brief Summary
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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.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy and Safety of a Single Dose of Exebacase in Patients Receiving Standard-of-Care Antibiotics for the Treatment of Staphylococcus Aureus Bloodstream Infections (Bacteremia), Including Right-Sided Infective Endocarditis

Conditions
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Staphylococcus Aureus Bacteremia, Staphylococcus Aureus Endocarditis

Intervention / Treatment
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* Drug: Exebacase
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, 12 years or older Blood culture positive for S. aureus At least two signs or symptoms attributable to S. aureus BSI/IE Known or suspected complicated S. aureus BSI and/or right-sided IE based on Modified Duke Criteria Not pregnant or breastfeeding and not of reproductive potential or agrees to remain abstinent or use contraception if of reproductive potential Exclusion Criteria: Previously received exebacase Known or suspected left-sided IE Treatment with effective systemic anti-staphylococcal antibiotic for more than 72 hours within 7 days before randomization Presence of prosthetic valve or cardiac valve support ring, or presence of known or suspected infected hardware (orthopedic), prosthetic joint, or cardiac device Known polymicrobial BSI, or known ongoing systemic infection caused by other bacterial and/or fungal pathogen(s), and/or known to have coronavirus disease 2019 (COVID-19)

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Exebacase<br> | Drug: Exebacase<br>* Participants will receive a single IV infusion of exebacase in addition to SoCA selected by the investigator. Participants with normal renal function or mild renal impairment will be administered a dose of 18 mg; participants with moderate or severe renal impairment will be administered a dose of 12 mg of exebacase; participants with end-stage renal disease, including those on hemodialysis, will be administered a dose of 8 mg of exebacase.<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Participants will receive a single IV infusion of placebo in addition to SoCA selected by the investigator.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Responder Rate at Day 14 in the MRSA Population in the Microbiological Intent-to-treat (mITT) Analysis Set | Clinical outcome of responder was defined as survival with resolution or 2-grade improvement of attributable signs and symptoms and negative blood cultures by Day 14, and without new signs or symptoms, new metastatic foci or septic emboli, or change in antibiotics due to lack of response. | Day 14 | 
| Treatment-emergent Adverse Events (TEAEs) Through Day 60 | Number and percentage of patients with treatment-emergent adverse events (TEAEs) | Through Day 60 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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S. aureus bloodstream infection, S. aureus bacteremia, S. aureus right-sided infective endocarditis