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

Primary Purpose

Staphylococcus Aureus Bacteremia, Staphylococcus Aureus Endocarditis

Status
Terminated
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Exebacase
Placebo
Sponsored by
ContraFect
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Staphylococcus Aureus Bacteremia focused on measuring S. aureus bloodstream infection, S. aureus bacteremia, S. aureus right-sided infective endocarditis

Eligibility Criteria

12 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 COVID-19

Sites / Locations

  • Cf 301-105
  • CF-301-105 Study Site
  • Cf 301-105
  • Cf 301-105
  • CF-301-105 Investigator Site
  • Cf 301-105
  • CF-301-105 Study Site
  • Cf 301-105
  • Cf 301-105
  • Cf 301-105
  • Cf 301-105
  • Cf 301-105
  • Cf 301-105
  • Cf 301-105
  • CF-301-105 Study Site
  • CF-301-105 Investigator Site
  • Cf 301-105
  • Cf 301-105
  • Cf 301-105
  • Cf 301-105
  • Cf 301-105
  • Cf 301-105
  • Cf 301-105
  • CF 301-105 Study Site
  • CF-301-105 Study Site
  • Cf 301-105
  • Cf 301-105
  • Cf 301-105
  • Cf 301-105
  • CF-301-105 Study Site
  • Cf 301-105
  • CF-301-105 Study Site
  • Cf 301-105
  • Cf 301-105
  • Cf 301-105
  • Cf 301-105
  • Cf 301-105
  • Cf 301-105
  • Cf 301-105
  • Cf 301-105
  • Cf 301-105
  • CF-301-105 Study Site
  • CF-301-105 Study Site
  • Cf 301-105
  • Cf 301-105
  • Cf 301-105
  • Cf 301-105
  • CF 301-105 Investigator Site
  • Cf 301-105
  • Cf 301-105
  • Cf 301-105
  • Cf 301-105
  • CF-301-105 Study Site
  • Cf 301-105
  • Cf 301-105

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Exebacase

Placebo

Arm Description

Outcomes

Primary Outcome Measures

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.
Treatment-emergent Adverse Events (TEAEs) Through Day 60
Number and percentage of patients with treatment-emergent adverse events (TEAEs)

Secondary Outcome Measures

Full Information

First Posted
November 7, 2019
Last Updated
September 23, 2023
Sponsor
ContraFect
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1. Study Identification

Unique Protocol Identification Number
NCT04160468
Brief Title
Direct Lysis of Staph Aureus Resistant Pathogen Trial of Exebacase
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Terminated
Why Stopped
The independent DSMB recommended that the study be stopped for futility following interim efficacy analysis.
Study Start Date
December 20, 2019 (Actual)
Primary Completion Date
September 9, 2022 (Actual)
Study Completion Date
September 9, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
ContraFect

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Staphylococcus Aureus Bacteremia, Staphylococcus Aureus Endocarditis
Keywords
S. aureus bloodstream infection, S. aureus bacteremia, S. aureus right-sided infective endocarditis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
259 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Exebacase
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Exebacase
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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Participants will receive a single IV infusion of placebo in addition to SoCA selected by the investigator.
Primary Outcome Measure Information:
Title
Clinical Responder Rate at Day 14 in the MRSA Population in the Microbiological Intent-to-treat (mITT) Analysis Set
Description
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.
Time Frame
Day 14
Title
Treatment-emergent Adverse Events (TEAEs) Through Day 60
Description
Number and percentage of patients with treatment-emergent adverse events (TEAEs)
Time Frame
Through Day 60

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
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)
Facility Information:
Facility Name
Cf 301-105
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
CF-301-105 Study Site
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
Cf 301-105
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
Cf 301-105
City
San Diego
State/Province
California
ZIP/Postal Code
92037
Country
United States
Facility Name
CF-301-105 Investigator Site
City
Sylmar
State/Province
California
ZIP/Postal Code
91342
Country
United States
Facility Name
Cf 301-105
City
Torrance
State/Province
California
ZIP/Postal Code
90502
Country
United States
Facility Name
CF-301-105 Study Site
City
Hartford
State/Province
Connecticut
ZIP/Postal Code
06102
Country
United States
Facility Name
Cf 301-105
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06510
Country
United States
Facility Name
Cf 301-105
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Facility Name
Cf 301-105
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20037
Country
United States
Facility Name
Cf 301-105
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32608
Country
United States
Facility Name
Cf 301-105
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Cf 301-105
City
Augusta
State/Province
Georgia
ZIP/Postal Code
30912
Country
United States
Facility Name
Cf 301-105
City
Decatur
State/Province
Georgia
ZIP/Postal Code
30033
Country
United States
Facility Name
CF-301-105 Study Site
City
Idaho Falls
State/Province
Idaho
ZIP/Postal Code
83404
Country
United States
Facility Name
CF-301-105 Investigator Site
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Cf 301-105
City
Glenview
State/Province
Illinois
ZIP/Postal Code
60026
Country
United States
Facility Name
Cf 301-105
City
Highland Park
State/Province
Illinois
ZIP/Postal Code
60035
Country
United States
Facility Name
Cf 301-105
City
Maywood
State/Province
Illinois
ZIP/Postal Code
60153
Country
United States
Facility Name
Cf 301-105
City
Fort Wayne
State/Province
Indiana
ZIP/Postal Code
46804
Country
United States
Facility Name
Cf 301-105
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
Cf 301-105
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Cf 301-105
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21224
Country
United States
Facility Name
CF 301-105 Study Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
CF-301-105 Study Site
City
Burlington
State/Province
Massachusetts
ZIP/Postal Code
01805
Country
United States
Facility Name
Cf 301-105
City
Worcester
State/Province
Massachusetts
ZIP/Postal Code
01605
Country
United States
Facility Name
Cf 301-105
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
Cf 301-105
City
Royal Oak
State/Province
Michigan
ZIP/Postal Code
48073
Country
United States
Facility Name
Cf 301-105
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
CF-301-105 Study Site
City
Columbia
State/Province
Missouri
ZIP/Postal Code
65212
Country
United States
Facility Name
Cf 301-105
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
CF-301-105 Study Site
City
Butte
State/Province
Montana
ZIP/Postal Code
59701
Country
United States
Facility Name
Cf 301-105
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68124
Country
United States
Facility Name
Cf 301-105
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198
Country
United States
Facility Name
Cf 301-105
City
Neptune
State/Province
New Jersey
ZIP/Postal Code
07753
Country
United States
Facility Name
Cf 301-105
City
Newark
State/Province
New Jersey
ZIP/Postal Code
07102
Country
United States
Facility Name
Cf 301-105
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Cf 301-105
City
Valhalla
State/Province
New York
ZIP/Postal Code
10595
Country
United States
Facility Name
Cf 301-105
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
Cf 301-105
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28203
Country
United States
Facility Name
Cf 301-105
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
CF-301-105 Study Site
City
Greenville
State/Province
North Carolina
ZIP/Postal Code
27834
Country
United States
Facility Name
CF-301-105 Study Site
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Cf 301-105
City
Toledo
State/Province
Ohio
ZIP/Postal Code
43608
Country
United States
Facility Name
Cf 301-105
City
Allentown
State/Province
Pennsylvania
ZIP/Postal Code
18103
Country
United States
Facility Name
Cf 301-105
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Cf 301-105
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
CF 301-105 Investigator Site
City
West Reading
State/Province
Pennsylvania
ZIP/Postal Code
19611
Country
United States
Facility Name
Cf 301-105
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38103
Country
United States
Facility Name
Cf 301-105
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38105
Country
United States
Facility Name
Cf 301-105
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
Cf 301-105
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
CF-301-105 Study Site
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84108
Country
United States
Facility Name
Cf 301-105
City
Burlington
State/Province
Vermont
ZIP/Postal Code
05401
Country
United States
Facility Name
Cf 301-105
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
33910968
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.
Results Reference
derived

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Direct Lysis of Staph Aureus Resistant Pathogen Trial of Exebacase

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