ERAdicate S. Aureus in Patients With Bacteremia and Endocarditis

Endocarditis Infective Clinical Trial

— ERASE  

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT05329168
• Other study ID #: LSVT-1701-2001
• Status: Withdrawn
• Phase: Phase 2
• Start date: May 1, 2022
• Est. completion date: November 1, 2023

Study information

• Verified date: June 2022
• Source: Lysovant
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: November 1, 2023
• Est. primary completion date: August 17, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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

Related Conditions & MeSH terms

• Bacteremia
• Bacteremia Due to Staphylococcus Aureus
• Disease
• Endocarditis
• Endocarditis Infective
• Endocarditis, Bacterial
• Staphylococcal Infections

Intervention

Drug:
• Tonabacase (LSVT-1701)
4.5 or 6.0 mg/kg IV once daily for 4 days

Locations

Country	Name	City	State
United States	Lsvt-1701-2001	Butte	Montana

Sponsors (1)

Lead Sponsor	Collaborator
Lysovant

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Overall clinical response in patients with left-sided endocarditis	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.	Up to Day 14
Other	Overall clinical response in patients with right-sided endocarditis	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.	Up to Day 14
Other	All-cause mortality		Day 14 and Day 28
Other	Mortality attributable to SAB		Day 14 and Day 28
Primary	Incidence of treatment-emergent adverse events coded per the Medical Dictionary of Regulatory Activities (MedDRA) v.24.0 [norm]		Up to Day 90±14
Primary	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)
Primary	Changes in 12-lead electrocardiogram (ECG)		Day 1 and Day 2
Secondary	Maximum plasma concentration (Cmax) of LSVT-1701		Day 4
Secondary	Area under the concentration-time curve (AUC) of LSVT-1701		Day 4
Secondary	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)
Secondary	Microbiological response rate		Days 3, 5, 7, 14, and up to Day 90