Clinical trial NCT05329168: ERAdicate S. Aureus in Patients With Bacteremia and Endocarditis
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
Overall status: WITHDRAWN
Phase: PHASE2
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
Lead sponsor: Lysovant
Sponsor class: INDUSTRY
First posted: 2022-04-14
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Sequential ascending-dose
Primary purpose: TREATMENT

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).


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

Primary outcomes:
measure: Incidence of treatment-emergent adverse events coded per the Medical Dictionary of Regulatory Activities (MedDRA) v.24.0 [norm]
timeFrame: Up to Day 90±14
measure: Incidence of Grade 3 or Grade 4 toxicity according to modified DAIDS criteria version 2.1
timeFrame: Up to 14±4 days after end of SOC antibiotic therapy (up to Day 42)
measure: Changes in 12-lead electrocardiogram (ECG)
timeFrame: Day 1 and Day 2
Secondary outcomes:
measure: Maximum plasma concentration (Cmax) of LSVT-1701
timeFrame: Day 4
measure: Area under the concentration-time curve (AUC) of LSVT-1701
timeFrame: Day 4
measure: Overall clinical response
timeFrame: 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)
measure: Microbiological response rate
timeFrame: Days 3, 5, 7, 14, and up to Day 90
Other outcomes:
measure: Overall clinical response in patients with left-sided endocarditis
timeFrame: Up to Day 14
measure: Overall clinical response in patients with right-sided endocarditis
timeFrame: Up to Day 14
measure: All-cause mortality
timeFrame: Day 14 and Day 28
measure: Mortality attributable to SAB
timeFrame: Day 14 and Day 28
Locations:
city: Butte
country: United States
facility: Lsvt-1701-2001
state: Montana
Study officials:
References: