Results of a Global Phase 3 Study of Delafloxacin (DLX) Compared to Vancomycin With Aztreonam (VAN) in Acute Bacterial Skin and Skin Structure Infections (ABSSSI)

Background. Delafloxacin (DLX) is an investigational broad-spectrum fluoroquinolone in development for treatment of skin infections. Methods. Multicenter, randomized, double-blind trial of adults with wound, burn, major abscesses, or cellulitis (at least ≥75 cm2 and at least two systemic signs). Patients were randomized 1:1 to receive BID either DLX 300 mg IV or VAN 15 mg/kg IV with aztreonam for 5-14 days. Primary endpoint for FDA was response at 48-72 hours with ≥20% reduction in lesion size. Secondary endpoint was investigator–assessed response based on complete resolution of signs and symptoms (Cure) at the Follow up (FU), Day 14 ± 1, and Late Follow up (LFU), Day 21-28, visits. Results. 660 patients were randomized, of whom 63% were male with a mean age 45.8 yrs. Average lesion size was 307 cm2; 39% of patients had cellulitis, 25% abscesses, 35% wound and 1% burn infections. 19% received a single dose of short-acting antibiotic prior to enrollment. 490 (74%) patients had pathogens identified at baseline. Staphylococcus aureus (324) was the most frequent isolate; 52% (169 of 324) were methicillin-resistant S. aureus (MRSA). Bacteremia was seen in 2% of patients. Efficacy data for the intent-to-treat (ITT) and microbiologically evaluable (ME) populations are presented below: The overall percentage of patients with at least one treatment-emergent adverse event (TEAE) was higher for VAN (59.2) compared to DLX (47.5). The AE incidence by 5% or more of patients was similar across treatment arms, and the most frequent AEs were infection, infusion site extravasation, diarrhea, nausea, and headache. Conclusion. DLX was comparable to VAN in treatment of ABSSSI based on the early objective response as well as investigator-assessed response at FU and LFU. DLX was also comparable to VAN in treating patients with MRSA. DLX appears well tolerated with a lower % of patients with TEAE compared to VAN. Disclosures. S. Cammarata, Melinta Therapeutics: Employee, Salary; J. Gardovskis, Melinta Therapeutics: Investigator, Research support; B. Farley, Melinta Therapeutics: Investigator, Research support; E. Sun, Melinta Therapeutics: Employee, Salary; M. Quintas, Melinta Therapeutics: Employee, Salary; L. Lawrence, Melinta Therapeutics: Employee, Salary; J. Pullman, Melinta Therapeutics: Investigator, Research support