Direct Lysis of Staph Aureus Resistant Pathogen Trial of Exebacase (DISRUPT)

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

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.

Study Overview

• Status: Terminated
• Conditions: Staphylococcus Aureus Bacteremia; Staphylococcus Aureus Endocarditis
• Intervention / Treatment: Drug: Exebacase; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 259
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Cf 301-105
  • California
    • Orange, California, United States, 92868
      • CF-301-105 Study Site
    • Sacramento, California, United States, 95817
      • Cf 301-105
    • San Diego, California, United States, 92037
      • Cf 301-105
    • Sylmar, California, United States, 91342
      • CF-301-105 Investigator Site
    • Torrance, California, United States, 90502
      • Cf 301-105
  • Connecticut
    • Hartford, Connecticut, United States, 06102
      • CF-301-105 Study Site
    • New Haven, Connecticut, United States, 06510
      • Cf 301-105
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Cf 301-105
    • Washington, District of Columbia, United States, 20037
      • Cf 301-105
  • Florida
    • Gainesville, Florida, United States, 32608
      • Cf 301-105
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Cf 301-105
    • Augusta, Georgia, United States, 30912
      • Cf 301-105
    • Decatur, Georgia, United States, 30033
      • Cf 301-105
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
      • CF-301-105 Study Site
  • Illinois
    • Chicago, Illinois, United States, 60637
      • CF-301-105 Investigator Site
    • Glenview, Illinois, United States, 60026
      • Cf 301-105
    • Highland Park, Illinois, United States, 60035
      • Cf 301-105
    • Maywood, Illinois, United States, 60153
      • Cf 301-105
  • Indiana
    • Fort Wayne, Indiana, United States, 46804
      • Cf 301-105
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Cf 301-105
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Cf 301-105
    • Baltimore, Maryland, United States, 21224
      • Cf 301-105
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • CF 301-105 Study Site
    • Burlington, Massachusetts, United States, 01805
      • CF-301-105 Study Site
    • Worcester, Massachusetts, United States, 01605
      • Cf 301-105
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Cf 301-105
    • Royal Oak, Michigan, United States, 48073
      • Cf 301-105
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Cf 301-105
  • Missouri
    • Columbia, Missouri, United States, 65212
      • CF-301-105 Study Site
    • Saint Louis, Missouri, United States, 63110
      • Cf 301-105
  • Montana
    • Butte, Montana, United States, 59701
      • CF-301-105 Study Site
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • Cf 301-105
    • Omaha, Nebraska, United States, 68124
      • Cf 301-105
  • New Jersey
    • Neptune, New Jersey, United States, 07753
      • Cf 301-105
    • Newark, New Jersey, United States, 07102
      • Cf 301-105
  • New York
    • New York, New York, United States, 10029
      • Cf 301-105
    • Valhalla, New York, United States, 10595
      • Cf 301-105
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Cf 301-105
    • Charlotte, North Carolina, United States, 28203
      • Cf 301-105
    • Durham, North Carolina, United States, 27710
      • Cf 301-105
    • Greenville, North Carolina, United States, 27834
      • CF-301-105 Study Site
  • Ohio
    • Columbus, Ohio, United States, 43210
      • CF-301-105 Study Site
    • Toledo, Ohio, United States, 43608
      • Cf 301-105
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18103
      • Cf 301-105
    • Philadelphia, Pennsylvania, United States, 19104
      • Cf 301-105
    • Philadelphia, Pennsylvania, United States, 19107
      • Cf 301-105
    • West Reading, Pennsylvania, United States, 19611
      • CF 301-105 Investigator Site
  • Tennessee
    • Memphis, Tennessee, United States, 38103
      • Cf 301-105
    • Memphis, Tennessee, United States, 38105
      • Cf 301-105
    • Nashville, Tennessee, United States, 37232
      • Cf 301-105
  • Texas
    • Houston, Texas, United States, 77030
      • Cf 301-105
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • CF-301-105 Study Site
  • Vermont
    • Burlington, Vermont, United States, 05401
      • Cf 301-105
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Cf 301-105

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Participants will receive a single IV infusion of placebo in addition to SoCA selected by the investigator.
Experimental: Exebacase	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.

What is the study measuring?

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

Secondary Outcome Measures

Outcome Measure	Time Frame
Clinical responder rate at Day 14 in all S. aureus patients	Day 14
30-day survival in the MRSA population	Through Day 30
Clinical responder rate at Day 60 in the MRSA population	Day 60
Clinical responder rate at Day 60 in all S. aureus patients	Day 60
Clinical responder rate at Day 60 in right-sided IE patients (all S. aureus and MRSA populations)	Day 60

Collaborators and Investigators

• Sponsor: ContraFect

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2019
• Primary Completion (Actual): September 9, 2022
• Study Completion (Actual): September 9, 2022

Study Registration Dates

• First Submitted: November 7, 2019
• First Submitted That Met QC Criteria: November 8, 2019
• First Posted (Actual): November 13, 2019

Study Record Updates

• Last Update Posted (Actual): November 2, 2023
• Last Update Submitted That Met QC Criteria: October 17, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: S. aureus bloodstream infection; S. aureus bacteremia; S. aureus right-sided infective endocarditis
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Sepsis; Bacteremia; Endocarditis; Staphylococcal Infections
• Other Study ID Numbers: CF-301-105

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No