ERAdicate S. Aureus in Patients With Bacteremia and Endocarditis (ERASE)
Primary Purpose
Bacteremia Due to Staphylococcus Aureus, Left Sided Infective Endocarditis (Disorder), Right Sided Infective Endocarditis (Disorder)
Status
Withdrawn
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Tonabacase (LSVT-1701)
Sponsored by
About this trial
This is an interventional treatment trial for Bacteremia Due to Staphylococcus Aureus focused on measuring Staphylococcus aureus bacteremia, left-sided endocarditis, right-sided endocarditis, SAB
Eligibility Criteria
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
Sites / Locations
- Lsvt-1701-2001
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Sequential ascending-dose cohort
Arm Description
Sequential ascending-dose cohort
Outcomes
Primary Outcome Measures
Incidence of treatment-emergent adverse events coded per the Medical Dictionary of Regulatory Activities (MedDRA) v.24.0 [norm]
Incidence of Grade 3 or Grade 4 toxicity according to modified DAIDS criteria version 2.1
Changes in 12-lead electrocardiogram (ECG)
Secondary Outcome Measures
Maximum plasma concentration (Cmax) of LSVT-1701
Area under the concentration-time curve (AUC) of LSVT-1701
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.
Microbiological response rate
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05329168
Brief Title
ERAdicate S. Aureus in Patients With Bacteremia and Endocarditis
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
June 2022
Overall Recruitment Status
Withdrawn
Why Stopped
business decision before FPFV; not related to any safety concerns
Study Start Date
May 1, 2022 (Anticipated)
Primary Completion Date
August 17, 2023 (Anticipated)
Study Completion Date
November 1, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Lysovant
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. 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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
Sequential ascending-dose
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Sequential ascending-dose cohort
Arm Type
Experimental
Arm Description
Sequential ascending-dose cohort
Intervention Type
Drug
Intervention Name(s)
Tonabacase (LSVT-1701)
Intervention Description
4.5 or 6.0 mg/kg IV once daily for 4 days
Primary Outcome Measure Information:
Title
Incidence of treatment-emergent adverse events coded per the Medical Dictionary of Regulatory Activities (MedDRA) v.24.0 [norm]
Time Frame
Up to Day 90±14
Title
Incidence of Grade 3 or Grade 4 toxicity according to modified DAIDS criteria version 2.1
Time Frame
Up to 14±4 days after end of SOC antibiotic therapy (up to Day 42)
Title
Changes in 12-lead electrocardiogram (ECG)
Time Frame
Day 1 and Day 2
Secondary Outcome Measure Information:
Title
Maximum plasma concentration (Cmax) of LSVT-1701
Time Frame
Day 4
Title
Area under the concentration-time curve (AUC) of LSVT-1701
Time Frame
Day 4
Title
Overall clinical response
Description
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.
Time Frame
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)
Title
Microbiological response rate
Time Frame
Days 3, 5, 7, 14, and up to Day 90
Other Pre-specified Outcome Measures:
Title
Overall clinical response in patients with left-sided endocarditis
Description
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.
Time Frame
Up to Day 14
Title
Overall clinical response in patients with right-sided endocarditis
Description
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.
Time Frame
Up to Day 14
Title
All-cause mortality
Time Frame
Day 14 and Day 28
Title
Mortality attributable to SAB
Time Frame
Day 14 and Day 28
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
Lsvt-1701-2001
City
Butte
State/Province
Montana
ZIP/Postal Code
59701
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
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ERAdicate S. Aureus in Patients With Bacteremia and Endocarditis
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