Direct Lysis of Staph Aureus Resistant Pathogen Trial of Exebacase
Condition: Staphylococcus Aureus Bacteremia; Staphylococcus Aureus Endocarditis
MeSH terms: Staphylococcal Infections; Bacteremia; Endocarditis
Intervention: Exebacase; Placebo
Intervention description: 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.; Participants will receive a single IV infusion of placebo in addition to SoCA selected by the investigator.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 259.0
Sex: All
Minimum age: 12 Years
Healthy volunteers: No
Keywords: S. aureus bloodstream infection; S. aureus bacteremia; S. aureus right-sided infective endocarditis

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.
    

Eligibility criteria:

        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)