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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Staphylococcus Aureus Bacteremia, Staphylococcus Aureus Endocarditis

Intervention / Treatment
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* Biological: CF-301
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CF-301<br>Patients will receive a single IV infusion of CF-301 in addition to standard of care (SOC) antibacterial therapy selected by the investigator. | Biological: CF-301<br>* CF-301, 0.25 mg/kg, given as a single 2 hour iv infusion<br>|
| Placebo Comparator: Placebo<br>Patients will receive a single IV infusion of placebo in addition to standard of care (SOC) antibacterial therapy selected by the investigator. | Drug: Placebo<br>* Placebo, given as a single 2 hour iv infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| Microbiological Eradication at Test of Cure (TOC) | Number and percentage of patients with microbiological eradication in the mITT population | TOC between 56-70 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Staphylococcus aureus, bacteremia, staphylococcal endocarditis