ERAdicate S. Aureus in Patients With Bacteremia and Endocarditis

NCT05329168 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: LSVT-1701-2001
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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).

Conditions

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

Keywords

Staphylococcus aureus bacteremia; left-sided endocarditis; right-sided endocarditis; SAB

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (4)

• 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)

• Microbiological response rate

  Days 3, 5, 7, 14, and up to Day 90

Other Outcomes (4)

• Overall clinical response in patients with left-sided endocarditis

  Up to Day 14

• Overall clinical response in patients with right-sided endocarditis

  Up to Day 14

• All-cause mortality

  Day 14 and Day 28

Study Arms (1)

Sequential ascending-dose cohort

EXPERIMENTAL

Sequential ascending-dose cohort

Drug: Tonabacase (LSVT-1701)

Interventions

Tonabacase (LSVT-1701) DRUG

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

Sequential ascending-dose cohort

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Lysovant: lead

Study Sites (1)

Lsvt-1701-2001

Butte, Montana, 59701, United States

Location

MeSH Terms

Conditions

Endocarditis

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Sequential ascending-dose

Study Record Dates

• First Submitted: March 23, 2022
• First Posted: April 14, 2022
• Study Start: May 1, 2022
• Primary Completion: August 17, 2023
• Study Completion: November 1, 2023
• Last Updated: June 30, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)