Bacteremia Due to Staphylococcus Aureus, Endocarditis Infective, Left Sided Infective Endocarditis (Disorder), Right Sided Infective Endocarditis (Disorder)
Conditions
Keywords
Staphylococcus aureus bacteremia, left-sided endocarditis, right-sided endocarditis, SAB
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).
Interventions
DRUGTonabacase (LSVT-1701)
4.5 or 6.0 mg/kg IV once daily for 4 days
Sponsors
Lysovant
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Sequential ascending-dose
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of treatment-emergent adverse events coded per the Medical Dictionary of Regulatory Activities (MedDRA) v.24.0 [norm] | Up to Day 90±14 |
| Changes in 12-lead electrocardiogram (ECG) | Day 1 and Day 2 |
| 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area under the concentration-time curve (AUC) of LSVT-1701 | Day 4 | — |
| Maximum plasma concentration (Cmax) 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| Mortality attributable to SAB | Day 14 and Day 28 | — |
| 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. |
| All-cause mortality | Day 14 and Day 28 | — |
Countries
United States
Outcome results
None listed