Direct Lysis of Staph Aureus Resistant Pathogen Trial of Exebacase

NCT ID: NCT04160468

Last Updated: 2023-11-02

Study Results

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE3

Total Enrollment

259 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-12-20

Study Completion Date

2022-09-09

Brief Summary

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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.

Detailed Description

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Conditions

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Staphylococcus Aureus Bacteremia Staphylococcus Aureus Endocarditis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Exebacase

Group Type EXPERIMENTAL

Exebacase

Intervention Type DRUG

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

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Participants will receive a single IV infusion of placebo in addition to SoCA selected by the investigator.

Interventions

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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.

Intervention Type DRUG

Placebo

Participants will receive a single IV infusion of placebo in addition to SoCA selected by the investigator.

Intervention Type DRUG

Eligibility Criteria

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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)
Minimum Eligible Age

12 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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ContraFect

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Cf 301-105

Birmingham, Alabama, United States

Site Status

CF-301-105 Study Site

Orange, California, United States

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Sacramento, California, United States

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San Diego, California, United States

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CF-301-105 Investigator Site

Sylmar, California, United States

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Torrance, California, United States

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Hartford, Connecticut, United States

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New Haven, Connecticut, United States

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Washington D.C., District of Columbia, United States

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Washington D.C., District of Columbia, United States

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Gainesville, Florida, United States

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Atlanta, Georgia, United States

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Augusta, Georgia, United States

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Decatur, Georgia, United States

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Idaho Falls, Idaho, United States

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CF-301-105 Investigator Site

Chicago, Illinois, United States

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Glenview, Illinois, United States

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Highland Park, Illinois, United States

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Maywood, Illinois, United States

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Fort Wayne, Indiana, United States

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Kansas City, Kansas, United States

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Baltimore, Maryland, United States

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Baltimore, Maryland, United States

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CF 301-105 Study Site

Boston, Massachusetts, United States

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CF-301-105 Study Site

Burlington, Massachusetts, United States

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Cf 301-105

Worcester, Massachusetts, United States

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Cf 301-105

Detroit, Michigan, United States

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Cf 301-105

Royal Oak, Michigan, United States

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Cf 301-105

Rochester, Minnesota, United States

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Columbia, Missouri, United States

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St Louis, Missouri, United States

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Butte, Montana, United States

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Omaha, Nebraska, United States

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Omaha, Nebraska, United States

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Neptune City, New Jersey, United States

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Newark, New Jersey, United States

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New York, New York, United States

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Valhalla, New York, United States

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Chapel Hill, North Carolina, United States

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Charlotte, North Carolina, United States

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Durham, North Carolina, United States

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Greenville, North Carolina, United States

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Columbus, Ohio, United States

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Cf 301-105

Toledo, Ohio, United States

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Cf 301-105

Allentown, Pennsylvania, United States

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Cf 301-105

Philadelphia, Pennsylvania, United States

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Cf 301-105

Philadelphia, Pennsylvania, United States

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CF 301-105 Investigator Site

West Reading, Pennsylvania, United States

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Cf 301-105

Memphis, Tennessee, United States

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Cf 301-105

Memphis, Tennessee, United States

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Cf 301-105

Nashville, Tennessee, United States

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Cf 301-105

Houston, Texas, United States

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CF-301-105 Study Site

Salt Lake City, Utah, United States

Site Status

Cf 301-105

Burlington, Vermont, United States

Site Status

Cf 301-105

Milwaukee, Wisconsin, United States

Site Status

Countries

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United States

References

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Fowler VG Jr, Das AF, Lipka-Diamond J, Ambler JE, Schuch R, Pomerantz R, Cassino C, Jauregui-Peredo L, Moran GJ, Rupp ME, Lachiewicz AM, Kuti JL, Wise RA, Kaye KS, Zervos MJ, Nichols WG. Exebacase in Addition to Standard-of-Care Antibiotics for Staphylococcus aureus Bloodstream Infections and Right-Sided Infective Endocarditis: A Phase 3, Superiority-Design, Placebo-Controlled, Randomized Clinical Trial (DISRUPT). Clin Infect Dis. 2024 Jun 14;78(6):1473-1481. doi: 10.1093/cid/ciae043.

Reference Type DERIVED
PMID: 38297916 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33910968 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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CF-301-105

Identifier Type: -

Identifier Source: org_study_id

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