Safety, Efficacy and Pharmacokinetics of CF-301 vs. Placebo in Addition to Antibacterial Therapy for Treatment of S. Aureus Bacteremia

Staphylococcus Aureus Bacteremia Clinical Trial

Official title:

A Multicenter, Double-Blind, Randomized, Comparative Study of the Safety, Tolerability, Efficacy, and Pharmacokinetics of CF-301 vs. Placebo in Addition to Standard-of-Care Antibacterial Therapy for the Treatment of Adult Patients With Staphylococcus Aureus Bloodstream Infections (Bacteremia) Including Endocarditis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03163446
• Other study ID #: CF-301-102
• Status: Completed
• Phase: Phase 2
• Start date: May 23, 2017
• Est. completion date: March 7, 2019

Study information

• Verified date: September 2021
• Source: ContraFect
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the safety, tolerability, efficacy and pharmacokinetics (PK) of CF-301 in addition to background standard of care (SOC) antibacterial therapy for the treatment of Staphylococcus aureus (S. aureus) bloodstream infections (bacteremia), including endocarditis in adults. Patients will be randomized to receive a single intravenous dose of CF-301 or placebo in addition to SOC antibacterial therapy. Patients will be prescribed standard of care antibiotics selected by the investigators based on their professional experience, practice guidelines and local antibiotic susceptibility information for the treatment of S. aureus bacteremia. CF-301 is a lysin and member of a new class of targeted protein-based antimicrobials that has demonstrated activity against S. aureus in laboratory (in vitro) and animal studies, alone and in addition to conventional antibiotics.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 121
• Est. completion date: March 7, 2019
• Est. primary completion date: March 7, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• male or female, 18 years or older
• blood culture positive for S. aureus
• at least one sign or symptom attributable to S. aureus bacteremia
• known or suspected complicated S. aureus BSI and/or endocarditis by Modified Duke Criteria
• patient is not pregnant or breastfeeding and is not of reproductive potential or agrees to use contraception if of reproductive potential.

Exclusion Criteria:

• patient previously received CF-301.
• treatment with any potentially effective (anti-staphylococcal) systemic antibiotic for more than 72 hours within 7 days before randomization.
• presence of any removable infection source that will not be removed or debrided within 72 hours after randomization.
• brain abscess or meningitis.
• community acquired pneumonia or known polymicrobial bacteremia

Related Conditions & MeSH terms

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

Intervention

Biological:
• CF-301
CF-301, 0.25 mg/kg, given as a single 2 hour iv infusion

Drug:
• Placebo
Placebo, given as a single 2 hour iv infusion

Locations

Country	Name	City	State
Belgium	CF-301-102 Study Site #2	Brussels
Belgium	CF301-102 Study Site	Brussels
Belgium	CF301-102 Study Site	Edegem
Belgium	CF301-102 Study Site	Ghent
Belgium	CF301-102 Study Site	Leuven
Bulgaria	CF301-102 Study Site	Ruse
Bulgaria	CF301-102 Study Site	Sofia
Chile	CF-301-102 Study Site	Santiago
Chile	CF-301-102 Study Site	Viña Del Mar
Czechia	CF301-102 Study Site	Brno
Czechia	CF301-102 Study Site	Prague
Czechia	CF301-102 Study Site #2	Prague
France	CF301-102 Study Site	Limoges
France	CF301-102 Study Site	Lyon
France	CF301-102 Study Site	Paris
France	CF301-102 Study Site	Toulon
Germany	CF-301-102 Study Site	Berlin
Germany	CF-301-102 Study Site #2	Berlin
Germany	CF-301-102 Study Site	Cologne
Germany	CF-301-102 Study Site	Freiburg
Greece	CF301-102 Study Site	Athens
Greece	CF301-102 Study Site #3	Athens
Greece	Study Site #2	Athens
Greece	CF301-102 Study Site	Larissa
Guatemala	CF-301-102 Study Site	Guatemala City
Guatemala	CF-301-102 Study Site	Santa Rosita
Israel	CF301-102 Study Site	Be'er Sheva
Israel	CF301-102 Study Site	Nazareth
Israel	CF301-102 Study Site	Safed
Israel	CF301-102 Study Site	Tel HaShomer
Italy	CF301-102 Study Site	Bergamo
Italy	CF-301-102 Study Site	Busto Arsizio
Italy	CF-301-102 Study Site	Genoa
Russian Federation	CF-301-102 Study Site	Krasnodar
Russian Federation	CF-301-102 Study Site	Moscow
Russian Federation	CF-301-102 Study Site	St. Pertersburg
Russian Federation	CF-301-102 Study Site #2	St. Petersburg
Spain	Cf301-102	Barcellona
Spain	CF-301-102 Study Site #2	Barcelona
Spain	CF301-102 Study Site	Córdoba
Spain	CF301-102 Study Site	Seville
Spain	CF301-102 Study Site	Terrassa
United Kingdom	CF301-102 Study Site	Chelmsford
United Kingdom	CF301-102 Study Site	Liverpool
United Kingdom	CF-301-102 Study Site	London
United Kingdom	CF301-102 Study Site #2	London
United Kingdom	CF301-102 Study Site	Oxford
United States	CF-301-102 Study Site	Atlanta	Georgia
United States	CF-301-102 Study Site	Augusta	Georgia
United States	CF-301-102 Study Site	Bethlehem	Pennsylvania
United States	CF-301-102 Study Site	Birmingham	Alabama
United States	CF301-102 Study Site	Burlington	Massachusetts
United States	CF301-102 Study site	Butte	Montana
United States	CF301-102 Study Site	Chicago	Illinois
United States	CF-301-102 Study Site	Cleveland	Ohio
United States	Cf-301-102	Columbus	Ohio
United States	CF301-102 Study Site	Columbus	Ohio
United States	CF0301-102 Study Site	Decatur	Georgia
United States	CF-301-102 Study Site	Detroit	Michigan
United States	CF-301-102 Study Site	Englewood	New Jersey
United States	CF-301 Study Site	Idaho Falls	Idaho
United States	CF-301-102 Study Site	Milwaukee	Wisconsin
United States	CF-301-102 Study Site	New Haven	Connecticut
United States	CF-301-102 Study Site	New York	New York
United States	CF-301-102 Study Site	New York	New York
United States	CF-301-102 Study Site	Newark	Delaware
United States	CF-301-102 Study Site	Omaha	Nebraska
United States	CF301-102 Study Site	Omaha	Nebraska
United States	CF301-102 Study Site	Paterson	New Jersey
United States	Cf-301-102	Richmond	Virginia
United States	CF-301-102 Study Site	Roanoke	Virginia
United States	CF301-102 Study Site	Royal Oak	Michigan
United States	CF-301-102 Study Site	Sacramento	California
United States	CF301-102 Study Site	Saint Louis	Missouri
United States	CF-301-102 Study Site	Seattle	Washington
United States	CF301-102 Study Site	Sylmar	California
United States	CF-301 Study Site	Toledo	Ohio
United States	CF-301-102 Study Site	Valhalla	New York

Sponsors (1)

Lead Sponsor	Collaborator
ContraFect

Countries where clinical trial is conducted

United States,  Belgium,  Bulgaria,  Chile,  Czechia,  France,  Germany,  Greece,  Guatemala,  Israel,  Italy,  Russian Federation,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Clinical Outcome at Day 14 in MRSA Subgroup	Description of clinical outcome in the MRSA subgroup in the mITT population. Responder (clinical outcome of improvement or response) was defined as survival with improvement or resolution of attributable signs and symptoms, and without new signs or symptoms, new foci of infection, change in antibiotics due to non-response, complications of S. aureus, or further surgery or medical intervention to treat S. aureus.	Day 14
Primary	Incidence of Adverse Events [Safety and Tolerability]	Number and percentage of patients with treatment-emergent adverse events (TEAEs)	Through Day 7, at Test of Cure (TOC) between 56-70 days, and at Day 180
Primary	Clinical Outcome at Day 14	Description of clinical outcome in the Microbiological Intent-to-Treat (mITT) population. Responder (clinical outcome of improvement or response) was defined as survival with improvement or resolution of attributable signs and symptoms, and without new signs or symptoms, new foci of infection, change in antibiotics due to non-response, complications of S. aureus, or further surgery or medical intervention to treat S. aureus.	Day 14
Primary	CF-301 Maximum Plasma Concentration (Cmax)	CF-301 plasma concentrations at specified timepoints.	Pre-dose and at 0.5, 1.5, 2, 2.25, 3, 4, 8, 14, 24, and 48 hours after the start of CF-301 infusion
Primary	CF-301 Area Under the Curve (AUC 0-t)	CF-301 plasma concentrations at specified time points	Pre-dose and at 0.5, 1.5, 2, 2.25, 3, 4, 8, 14, 24, and 48 hours after the start of CF-301 infusion
Secondary	Clinical Outcome at Day 7	Description of clinical outcome in the mITT population. Responder (clinical outcome of improvement or response) was defined as survival with improvement or resolution of attributable signs and symptoms, and without new signs or symptoms, new foci of infection, change in antibiotics due to non-response, complications of S. aureus, or further surgery or medical intervention to treat S. aureus.	Day 7
Secondary	Clinical Outcome at End of Standard of Care Antibacterial Therapy (EOT)	Description of clinical outcome in the mITT population. Responder (clinical outcome of improvement or response) was defined as survival with improvement or resolution of attributable signs and symptoms, and without new signs or symptoms, new foci of infection, change in antibiotics due to non-response, complications of S. aureus, or further surgery or medical intervention to treat S. aureus.	EOT between 28-42 days
Secondary	Clinical Outcome at Test of Cure (TOC)	Description of clinical outcome in the mITT population. Responder (clinical outcome of improvement or response) was defined as survival with improvement or resolution of attributable signs and symptoms, and without new signs or symptoms, new foci of infection, change in antibiotics due to non-response, complications of S. aureus, or further surgery or medical intervention to treat S. aureus.	TOC between 56-70 days
Secondary	Clearance of Bacteremia at Day 7 After CF-301/Placebo Administration	Number and percentage of patients with clearance of bacteremia in the mITT population	Day 7
Secondary	Clearance of Bacteremia at Day 14 After CF-301/Placebo Administration	Number and percentage of patients with clearance of bacteremia in the mITT population	Day 14
Secondary	Microbiological Eradication at End of Standard of Care Antibacterial Therapy (EOT)	Number and percentage of patients with microbiological eradication in the mITT population	EOT between 28-42 days
Secondary	Microbiological Eradication at Test of Cure (TOC)	Number and percentage of patients with microbiological eradication in the mITT population	TOC between 56-70 days