ERASE: ERAdicate S. Aureus in Patients With Bacteremia and Endocarditis

Sponsor

Lysovant (Industry)

Overall Status

Withdrawn

CT.gov ID

NCT05329168

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Bacteremia Due to Staphylococcus Aureus Left Sided Infective Endocarditis (Disorder) Right Sided Infective Endocarditis (Disorder) Endocarditis Infective	Drug: Tonabacase (LSVT-1701)	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

Sequential ascending-doseSequential ascending-dose

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

May 1, 2022

Anticipated Primary Completion Date :

Aug 17, 2023

Anticipated Study Completion Date :

Nov 1, 2023

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: Sequential ascending-dose cohort

Sequential ascending-dose cohort

Drug: Tonabacase (LSVT-1701)

4.5 or 6.0 mg/kg IV once daily for 4 days

Outcome Measures

Primary Outcome Measures

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

Maximum plasma concentration (Cmax) of LSVT-1701 [Day 4]
Area under the concentration-time curve (AUC) of LSVT-1701 [Day 4]
Overall clinical response [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)]
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.
Microbiological response rate [Days 3, 5, 7, 14, and up to Day 90]

Other Outcome Measures

Overall clinical response in patients with left-sided endocarditis [Up to Day 14]
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.
Overall clinical response in patients with right-sided endocarditis [Up to Day 14]
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.
All-cause mortality [Day 14 and Day 28]
Mortality attributable to SAB [Day 14 and Day 28]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 90 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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