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
Overview
- Phase
- Phase 2
- Intervention
- CF-301
- Conditions
- Staphylococcus Aureus Bacteremia
- Sponsor
- ContraFect
- Enrollment
- 121
- Locations
- 11
- Primary Endpoint
- Clinical Outcome at Day 14
- Status
- Completed
- Last Updated
- 4 years ago
Overview
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.
Investigators
Eligibility Criteria
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-
- •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
Arms & Interventions
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.
Intervention: CF-301
Placebo
Patients will receive a single IV infusion of placebo in addition to standard of care (SOC) antibacterial therapy selected by the investigator.
Intervention: Placebo
Outcomes
Primary Outcomes
Clinical Outcome at Day 14
Time Frame: 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)
Time Frame: 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]
Time Frame: 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)
Time Frame: 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 Outcomes
- Clinical Outcome at Test of Cure (TOC)(TOC between 56-70 days)
- Microbiological Eradication at Test of Cure (TOC)(TOC between 56-70 days)
- Clinical Outcome at End of Standard of Care Antibacterial Therapy (EOT)(EOT between 28-42 days)
- Clearance of Bacteremia at Day 14 After CF-301/Placebo Administration(Day 14)
- Microbiological Eradication at End of Standard of Care Antibacterial Therapy (EOT)(EOT between 28-42 days)
- Clinical Outcome at Day 7(Day 7)
- Clearance of Bacteremia at Day 7 After CF-301/Placebo Administration(Day 7)