Clinical trial NCT04160468: Direct Lysis of Staph Aureus Resistant Pathogen Trial of Exebacase
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Staphylococcus Aureus Bacteremia
Staphylococcus Aureus Endocarditis
Keywords: S. aureus bloodstream infection
S. aureus bacteremia
S. aureus right-sided infective endocarditis
Lead sponsor: ContraFect
Sponsor class: INDUSTRY
First posted: 2019-11-13
Enrollment: 259
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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)

Primary outcomes:
measure: Clinical Responder Rate at Day 14 in the MRSA Population in the Microbiological Intent-to-treat (mITT) Analysis Set
timeFrame: Day 14
measure: Treatment-emergent Adverse Events (TEAEs) Through Day 60
timeFrame: Through Day 60
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Cf 301-105
state: Alabama
city: Orange
country: United States
facility: CF-301-105 Study Site
state: California
city: Sacramento
country: United States
facility: Cf 301-105
state: California
city: San Diego
country: United States
facility: Cf 301-105
state: California
city: Sylmar
country: United States
facility: CF-301-105 Investigator Site
state: California
city: Torrance
country: United States
facility: Cf 301-105
state: California
city: Hartford
country: United States
facility: CF-301-105 Study Site
state: Connecticut
city: New Haven
country: United States
facility: Cf 301-105
state: Connecticut
city: Washington
country: United States
facility: Cf 301-105
state: District of Columbia
city: Washington
country: United States
facility: Cf 301-105
state: District of Columbia
city: Gainesville
country: United States
facility: Cf 301-105
state: Florida
city: Atlanta
country: United States
facility: Cf 301-105
state: Georgia
city: Augusta
country: United States
facility: Cf 301-105
state: Georgia
city: Decatur
country: United States
facility: Cf 301-105
state: Georgia
city: Idaho Falls
country: United States
facility: CF-301-105 Study Site
state: Idaho
city: Chicago
country: United States
facility: CF-301-105 Investigator Site
state: Illinois
city: Glenview
country: United States
facility: Cf 301-105
state: Illinois
city: Highland Park
country: United States
facility: Cf 301-105
state: Illinois
city: Maywood
country: United States
facility: Cf 301-105
state: Illinois
city: Fort Wayne
country: United States
facility: Cf 301-105
state: Indiana
city: Kansas City
country: United States
facility: Cf 301-105
state: Kansas
city: Baltimore
country: United States
facility: Cf 301-105
state: Maryland
city: Baltimore
country: United States
facility: Cf 301-105
state: Maryland
city: Boston
country: United States
facility: CF 301-105 Study Site
state: Massachusetts
city: Burlington
country: United States
facility: CF-301-105 Study Site
state: Massachusetts
city: Worcester
country: United States
facility: Cf 301-105
state: Massachusetts
city: Detroit
country: United States
facility: Cf 301-105
state: Michigan
city: Royal Oak
country: United States
facility: Cf 301-105
state: Michigan
city: Rochester
country: United States
facility: Cf 301-105
state: Minnesota
city: Columbia
country: United States
facility: CF-301-105 Study Site
state: Missouri
city: Saint Louis
country: United States
facility: Cf 301-105
state: Missouri
city: Butte
country: United States
facility: CF-301-105 Study Site
state: Montana
city: Omaha
country: United States
facility: Cf 301-105
state: Nebraska
city: Omaha
country: United States
facility: Cf 301-105
state: Nebraska
city: Neptune
country: United States
facility: Cf 301-105
state: New Jersey
city: Newark
country: United States
facility: Cf 301-105
state: New Jersey
city: New York
country: United States
facility: Cf 301-105
state: New York
city: Valhalla
country: United States
facility: Cf 301-105
state: New York
city: Chapel Hill
country: United States
facility: Cf 301-105
state: North Carolina
city: Charlotte
country: United States
facility: Cf 301-105
state: North Carolina
city: Durham
country: United States
facility: Cf 301-105
state: North Carolina
city: Greenville
country: United States
facility: CF-301-105 Study Site
state: North Carolina
city: Columbus
country: United States
facility: CF-301-105 Study Site
state: Ohio
city: Toledo
country: United States
facility: Cf 301-105
state: Ohio
city: Allentown
country: United States
facility: Cf 301-105
state: Pennsylvania
city: Philadelphia
country: United States
facility: Cf 301-105
state: Pennsylvania
city: Philadelphia
country: United States
facility: Cf 301-105
state: Pennsylvania
city: West Reading
country: United States
facility: CF 301-105 Investigator Site
state: Pennsylvania
city: Memphis
country: United States
facility: Cf 301-105
state: Tennessee
city: Memphis
country: United States
facility: Cf 301-105
state: Tennessee
city: Nashville
country: United States
facility: Cf 301-105
state: Tennessee
city: Houston
country: United States
facility: Cf 301-105
state: Texas
city: Salt Lake City
country: United States
facility: CF-301-105 Study Site
state: Utah
city: Burlington
country: United States
facility: Cf 301-105
state: Vermont
city: Milwaukee
country: United States
facility: Cf 301-105
state: Wisconsin
Study officials:
References:
citation: 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.