ERAdicate S. Aureus in Patients With Bacteremia and Endocarditis

Study Overview
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Brief Summary
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This study evaluates safety and tolerability of endolysin-derived LSVT-1701 (tonabacase) as an add-on to standard of care (SOC) antibiotic therapy for the treatment of patients with complicated Staphylococcus aureus bacteremia (SAB), including left- and right-sided infective endocarditis (IE).

Official Title
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An Open-Label, Multiple-Ascending Dose, Multicenter Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of LSVT-1701 as an Add-on to Standard of Care Antibiotics for the Treatment of Complicated Methicillin-Sensitive and -Resistant Staphylococcus Aureus Bacteremia Including Left- and Right-sided Infective Endocarditis

Conditions
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Bacteremia Due to Staphylococcus Aureus, Left Sided Infective Endocarditis (Disorder), Right Sided Infective Endocarditis (Disorder), Endocarditis Infective

Intervention / Treatment
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* Drug: Tonabacase (LSVT-1701)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age of 18 to 90 years Index blood culture collection within 96 hours prior to enrollment positive for S. aureus Experienced at least one sign or symptom related to SAB within past 96 hours prior to enrollment Known or suspected left- and/or right-sided endocarditis by modified Duke criteria and/or known or suspected complicated SAB Required duration of SOC antibiotic therapy ≤ 42 days Exclusion Criteria: Previous receipt of LSVT-1701 or CF-301 (exebacase) Known hypersensitivity to kanamycin or other aminoglycosides Treatment with any potentially effective (anti-S. aureus) systemic antibiotic for > 96 hours within 7 days before enrollment. Exception: Persistent S. aureus bacteremia after 96 hours of prior appropriate systemic antistaphylococcal antibiotic, and/or resistance to the prior systemic antibiotic Treatment with dalbavancin or oritavancin within the previous 90 days Known or suspected brain abscess or meningitis Community acquired pneumonia, nosocomial pneumonia because of pathogens other than S. aureus, or known polymicrobial bacteremia Presence of an intravascular infection source or extravascular material that cannot be removed within 96 hours after enrollment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 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
Intervention Model: Single Group Assignment
Interventional Model Description: Sequential ascending-dose
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sequential ascending-dose cohort<br>Sequential ascending-dose cohort | Drug: Tonabacase (LSVT-1701)<br>* 4.5 or 6.0 mg/kg IV once daily for 4 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment-emergent adverse events coded per the Medical Dictionary of Regulatory Activities (MedDRA) v.24.0 [norm] |  | Up to Day 90±14 | 
| Incidence of Grade 3 or Grade 4 toxicity according to modified DAIDS criteria version 2.1 |  | Up to 14±4 days after end of SOC antibiotic therapy (up to Day 42) | 
| Changes in 12-lead electrocardiogram (ECG) |  | Day 1 and Day 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum plasma concentration (Cmax) of LSVT-1701 |  | Day 4 | 
| Area under the concentration-time curve (AUC) of LSVT-1701 |  | Day 4 | 
| Overall clinical response | Overall clinical response is defined as survival, resolution or improvement of attributable signs and symptoms, no new attributable signs and symptoms, no new foci of S. aureus infection, no change in antibiotics due to non-response, and no further surgery or medical intervention to treat S. aureus. | Day 7, Day 14, after end of SOC antibiotic therapy (up to Day 42), and at test of cure (TOC; 14 days after the EOT) | 
| Microbiological response rate |  | Days 3, 5, 7, 14, and up to Day 90 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Staphylococcus aureus bacteremia, left-sided endocarditis, right-sided endocarditis, SAB