NCT04160468

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.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
259

participants targeted

Target at P50-P75 for phase_3

Timeline
Completed

Started Dec 2019

Typical duration for phase_3

Geographic Reach
1 country

55 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 7, 2019

Completed
6 days until next milestone

First Posted

Study publicly available on registry

November 13, 2019

Completed
1 month until next milestone

Study Start

First participant enrolled

December 20, 2019

Completed
2.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 9, 2022

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 9, 2022

Completed
1.1 years until next milestone

Results Posted

Study results publicly available

October 18, 2023

Completed
Last Updated

November 2, 2023

Status Verified

October 1, 2023

Enrollment Period

2.7 years

First QC Date

November 7, 2019

Results QC Date

September 23, 2023

Last Update Submit

October 17, 2023

Conditions

Keywords

S. aureus bloodstream infectionS. aureus bacteremiaS. aureus right-sided infective endocarditis

Outcome Measures

Primary Outcomes (2)

  • 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

Study Arms (2)

Exebacase

EXPERIMENTAL
Drug: Exebacase

Placebo

PLACEBO COMPARATOR
Drug: Placebo

Interventions

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.

Exebacase

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

Placebo

Eligibility Criteria

Age12 Years+
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (55)

Cf 301-105

Birmingham, Alabama, 35294, United States

Location

CF-301-105 Study Site

Orange, California, 92868, United States

Location

Cf 301-105

Sacramento, California, 95817, United States

Location

Cf 301-105

San Diego, California, 92037, United States

Location

CF-301-105 Investigator Site

Sylmar, California, 91342, United States

Location

Cf 301-105

Torrance, California, 90502, United States

Location

CF-301-105 Study Site

Hartford, Connecticut, 06102, United States

Location

Cf 301-105

New Haven, Connecticut, 06510, United States

Location

Cf 301-105

Washington D.C., District of Columbia, 20010, United States

Location

Cf 301-105

Washington D.C., District of Columbia, 20037, United States

Location

Cf 301-105

Gainesville, Florida, 32608, United States

Location

Cf 301-105

Atlanta, Georgia, 30322, United States

Location

Cf 301-105

Augusta, Georgia, 30912, United States

Location

Cf 301-105

Decatur, Georgia, 30033, United States

Location

CF-301-105 Study Site

Idaho Falls, Idaho, 83404, United States

Location

CF-301-105 Investigator Site

Chicago, Illinois, 60637, United States

Location

Cf 301-105

Glenview, Illinois, 60026, United States

Location

Cf 301-105

Highland Park, Illinois, 60035, United States

Location

Cf 301-105

Maywood, Illinois, 60153, United States

Location

Cf 301-105

Fort Wayne, Indiana, 46804, United States

Location

Cf 301-105

Kansas City, Kansas, 66160, United States

Location

Cf 301-105

Baltimore, Maryland, 21201, United States

Location

Cf 301-105

Baltimore, Maryland, 21224, United States

Location

CF 301-105 Study Site

Boston, Massachusetts, 02215, United States

Location

CF-301-105 Study Site

Burlington, Massachusetts, 01805, United States

Location

Cf 301-105

Worcester, Massachusetts, 01605, United States

Location

Cf 301-105

Detroit, Michigan, 48202, United States

Location

Cf 301-105

Royal Oak, Michigan, 48073, United States

Location

Cf 301-105

Rochester, Minnesota, 55905, United States

Location

CF-301-105 Study Site

Columbia, Missouri, 65212, United States

Location

Cf 301-105

St Louis, Missouri, 63110, United States

Location

CF-301-105 Study Site

Butte, Montana, 59701, United States

Location

Cf 301-105

Omaha, Nebraska, 68124, United States

Location

Cf 301-105

Omaha, Nebraska, 68198, United States

Location

Cf 301-105

Neptune City, New Jersey, 07753, United States

Location

Cf 301-105

Newark, New Jersey, 07102, United States

Location

Cf 301-105

New York, New York, 10029, United States

Location

Cf 301-105

Valhalla, New York, 10595, United States

Location

Cf 301-105

Chapel Hill, North Carolina, 27599, United States

Location

Cf 301-105

Charlotte, North Carolina, 28203, United States

Location

Cf 301-105

Durham, North Carolina, 27710, United States

Location

CF-301-105 Study Site

Greenville, North Carolina, 27834, United States

Location

CF-301-105 Study Site

Columbus, Ohio, 43210, United States

Location

Cf 301-105

Toledo, Ohio, 43608, United States

Location

Cf 301-105

Allentown, Pennsylvania, 18103, United States

Location

Cf 301-105

Philadelphia, Pennsylvania, 19104, United States

Location

Cf 301-105

Philadelphia, Pennsylvania, 19107, United States

Location

CF 301-105 Investigator Site

West Reading, Pennsylvania, 19611, United States

Location

Cf 301-105

Memphis, Tennessee, 38103, United States

Location

Cf 301-105

Memphis, Tennessee, 38105, United States

Location

Cf 301-105

Nashville, Tennessee, 37232, United States

Location

Cf 301-105

Houston, Texas, 77030, United States

Location

CF-301-105 Study Site

Salt Lake City, Utah, 84108, United States

Location

Cf 301-105

Burlington, Vermont, 05401, United States

Location

Cf 301-105

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (2)

  • 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.

  • 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.

MeSH Terms

Interventions

exebacase

Results Point of Contact

Title
Medical Director
Organization
ContraFect

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 7, 2019

First Posted

November 13, 2019

Study Start

December 20, 2019

Primary Completion

September 9, 2022

Study Completion

September 9, 2022

Last Updated

November 2, 2023

Results First Posted

October 18, 2023

Record last verified: 2023-10

Locations