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

Phase 2

Completed

• Conditions: Staphylococcus Aureus Bacteremia; Staphylococcus Aureus Endocarditis
• Interventions: Biological: CF-301; Drug: Placebo

• Registration Number: NCT03163446
• Lead Sponsor: ContraFect

Brief 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-05-15
• Study First Submitted QC: 2017-05-19
• Study Start: 2017-05-23
• Study First Posted: 2017-05-23
• Primary Completion: 2019-03-07
• Study Completion: 2019-03-07
• Results First Submitted: 2021-08-11
• Status Verified: 2021-09
• Results First Submitted QC: 2021-09-10
• Last Update Submitted: 2021-09-10
• Results First Posted: 2021-10-08
• Last Update Posted: 2021-10-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 121

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CF-301	CF-301	Patients will receive a single IV infusion of CF-301 in addition to standard of care (SOC) antibacterial therapy selected by the investigator.
Placebo	Placebo	Patients will receive a single IV infusion of placebo in addition to standard of care (SOC) antibacterial therapy selected by the investigator.

Primary Outcome Measures

Name	Time	Method
Clinical Outcome at Day 14	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.
CF-301 Maximum Plasma Concentration (Cmax)	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	CF-301 plasma concentrations at specified timepoints.
Incidence of Adverse Events [Safety and Tolerability]	Through Day 7, at Test of Cure (TOC) between 56-70 days, and at Day 180	Number and percentage of patients with treatment-emergent adverse events (TEAEs)
CF-301 Area Under the Curve (AUC 0-t)	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	CF-301 plasma concentrations at specified time points

Secondary Outcome Measures

Name	Time	Method
Clinical Outcome at Test of Cure (TOC)	TOC between 56-70 days	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.
Microbiological Eradication at Test of Cure (TOC)	TOC between 56-70 days	Number and percentage of patients with microbiological eradication in the mITT population
Clinical Outcome at End of Standard of Care Antibacterial Therapy (EOT)	EOT between 28-42 days	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.
Clearance of Bacteremia at Day 14 After CF-301/Placebo Administration	Day 14	Number and percentage of patients with clearance of bacteremia in the mITT population
Microbiological Eradication at End of Standard of Care Antibacterial Therapy (EOT)	EOT between 28-42 days	Number and percentage of patients with microbiological eradication in the mITT population
Clinical Outcome at Day 7	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.
Clearance of Bacteremia at Day 7 After CF-301/Placebo Administration	Day 7	Number and percentage of patients with clearance of bacteremia in the mITT population

Trial Locations

Locations (11)

Study Site #2; 🇬🇷 Athens, Greece

CF301-102 Study site; 🇺🇸 Butte, Montana, United States

CF-301-102 Study Site; 🇬🇧 London, United Kingdom

CF0301-102 Study Site; 🇺🇸 Decatur, Georgia, United States

CF301-102 Study Site; 🇬🇧 Oxford, United Kingdom

CF-301 Study Site; 🇺🇸 Toledo, Ohio, United States

CF-301-102 Study Site #2; 🇪🇸 Barcelona, Spain

Cf-301-102; 🇺🇸 Richmond, Virginia, United States

CF301-102 Study Site #3; 🇬🇷 Athens, Greece

Cf301-102; 🇪🇸 Barcellona, Spain

CF301-102 Study Site #2; 🇬🇧 London, United Kingdom