Direct Lysis of Staph Aureus Resistant Pathogen Trial of Exebacase

Staphylococcus Aureus Bacteremia Clinical Trial

— DISRUPT  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04160468
• Other study ID #: CF-301-105
• Status: Terminated
• Phase: Phase 3
• Start date: December 20, 2019
• Est. completion date: September 9, 2022

Study information

• Verified date: October 2023
• Source: ContraFect
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 259
• Est. completion date: September 9, 2022
• Est. primary completion date: September 9, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Bacteremia
• Endocarditis
• Staphylococcal Infections
• Staphylococcus Aureus Bacteremia
• Staphylococcus Aureus Endocarditis

Intervention

Drug:
• Exebacase
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.
• Placebo
Participants will receive a single IV infusion of placebo in addition to SoCA selected by the investigator.

Locations

Country	Name	City	State
United States	Cf 301-105	Allentown	Pennsylvania
United States	Cf 301-105	Atlanta	Georgia
United States	Cf 301-105	Augusta	Georgia
United States	Cf 301-105	Baltimore	Maryland
United States	Cf 301-105	Baltimore	Maryland
United States	Cf 301-105	Birmingham	Alabama
United States	CF 301-105 Study Site	Boston	Massachusetts
United States	Cf 301-105	Burlington	Vermont
United States	CF-301-105 Study Site	Burlington	Massachusetts
United States	CF-301-105 Study Site	Butte	Montana
United States	Cf 301-105	Chapel Hill	North Carolina
United States	Cf 301-105	Charlotte	North Carolina
United States	CF-301-105 Investigator Site	Chicago	Illinois
United States	CF-301-105 Study Site	Columbia	Missouri
United States	CF-301-105 Study Site	Columbus	Ohio
United States	Cf 301-105	Decatur	Georgia
United States	Cf 301-105	Detroit	Michigan
United States	Cf 301-105	Durham	North Carolina
United States	Cf 301-105	Fort Wayne	Indiana
United States	Cf 301-105	Gainesville	Florida
United States	Cf 301-105	Glenview	Illinois
United States	CF-301-105 Study Site	Greenville	North Carolina
United States	CF-301-105 Study Site	Hartford	Connecticut
United States	Cf 301-105	Highland Park	Illinois
United States	Cf 301-105	Houston	Texas
United States	CF-301-105 Study Site	Idaho Falls	Idaho
United States	Cf 301-105	Kansas City	Kansas
United States	Cf 301-105	Maywood	Illinois
United States	Cf 301-105	Memphis	Tennessee
United States	Cf 301-105	Memphis	Tennessee
United States	Cf 301-105	Milwaukee	Wisconsin
United States	Cf 301-105	Nashville	Tennessee
United States	Cf 301-105	Neptune	New Jersey
United States	Cf 301-105	New Haven	Connecticut
United States	Cf 301-105	New York	New York
United States	Cf 301-105	Newark	New Jersey
United States	Cf 301-105	Omaha	Nebraska
United States	Cf 301-105	Omaha	Nebraska
United States	CF-301-105 Study Site	Orange	California
United States	Cf 301-105	Philadelphia	Pennsylvania
United States	Cf 301-105	Philadelphia	Pennsylvania
United States	Cf 301-105	Rochester	Minnesota
United States	Cf 301-105	Royal Oak	Michigan
United States	Cf 301-105	Sacramento	California
United States	Cf 301-105	Saint Louis	Missouri
United States	CF-301-105 Study Site	Salt Lake City	Utah
United States	Cf 301-105	San Diego	California
United States	CF-301-105 Investigator Site	Sylmar	California
United States	Cf 301-105	Toledo	Ohio
United States	Cf 301-105	Torrance	California
United States	Cf 301-105	Valhalla	New York
United States	Cf 301-105	Washington	District of Columbia
United States	Cf 301-105	Washington	District of Columbia
United States	CF 301-105 Investigator Site	West Reading	Pennsylvania
United States	Cf 301-105	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
ContraFect

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Treatment-emergent Adverse Events (TEAEs) Through Day 60	Number and percentage of patients with treatment-emergent adverse events (TEAEs)	Through Day 60