# 549. A Phase 2a Randomized, Double-Blind, Controlled Trial of the Efficacy and Safety of an Intravenous (IV) Bacteriophage Cocktail (AP-SA02) vs. Placebo in Combination with Best Available Antibiotic Therapy (BAT) in Patients with Complicated Staphylococcus aureus Bacteremia

## TL;DR

A clinical trial found that an intravenous bacteriophage cocktail, when combined with standard antibiotics, improved cure rates and safety in patients with severe Staphylococcus aureus infections.

## Contribution

This is the first phase 2a trial showing clinical efficacy of an IV bacteriophage cocktail in treating complicated S. aureus bacteremia.

## Key findings

- AP-SA02 combined with antibiotics showed higher cure rates at Day 12 compared to placebo (88% vs. 58%).
- No relapses were observed in the AP-SA02 group four weeks post-treatment, while 23-25% relapsed in the placebo group.
- Patients receiving AP-SA02 had faster recovery markers, shorter ICU and hospital stays, and no serious adverse events.

## Abstract

Complicated Staphylococcus aureus bacteremia (SAB) is a serious, common, and frequently lethal infection. Treatment options are complicated by resistance, drug intolerance, or relapse. Novel therapeutics are urgently needed.

We performed a phase 2a randomized, double-blind, controlled trial of the efficacy and safety of an IV bacteriophage cocktail, AP-SA02, q6 hrs x 5 days vs. placebo (2:1 ratio) in combination with BAT in patients with complicated SAB. Clinical response (Table 1) was assessed in the intent-to-treat (ITT) population at Test of Cure (TOC) on Day 12, post-BAT, and End of Study (EOS) four weeks after BAT completion. Safety analysis included data from the Phase 1b trial (n=8).

We enrolled 42 patients from 17 sites (95% US), with 29 randomized to AP-SA02 (A) and 13 to placebo (P). MRSA was the pathogen in 39% of the (A) and 44% (P) groups, respectively. Site of infection and antibiotics used were similar for both arms. (Table 2). Treatment-emergent adverse events (TEAEs) occurred in 6% (2/35) and 0% (0/15) in the (A) and (P) groups, respectively. (Table 3). Day 12 clinical response rates were 88% (21/24) in SA-PA02 vs. 58% (7/12) in the placebo (p = 0.047) as assessed by blinded site investigators (PI), and 83% (20/24) vs. 58% (7/12) as assessed by the blinded Adjudication Committee (AC). At post-BAT and EOS, non-response/relapse rate was 0% and 0% in the (A) group by both PI and AC assessment compared to 23% by AC and 25% PI in the (P) group (p < 0.025, Figure 1). Patients on AP-SA02 had trends toward rapid normalization of C-reactive protein, shorter time to negative blood culture, shorter ICU and hospital stay. (Table 2)

The intravenous bacteriophage cocktail, AP-SA02, combined with BAT, had a higher and earlier cure rate compared to placebo in patients with complicated SAB at day 12, at post BAT, and EOS as assessed by both blinded site investigators and independent adjudicators. AP-SA02 appears safe with clinical efficacy against both MRSA and MSSA and trends toward earlier resolution, shorter hospitalization, and no evidence of relapse 4 weeks post-therapy. Results strongly support proceeding to a Phase III trial of this novel bacteriophage cocktail for SAB.

All Authors: No reported disclosures