C1. Clinical trials (abstracts submitted to C1 should choose a secondary category that describes the subject matter of the trial)
Oral Abstract Submission
Alexey Ruzin, PhD
Disclosure: AstraZeneca: Employee, Shareholder
Innovative Medicines Initiative (IMI): Other Financial or Material Support, IMI grant # 115523, composed of European Union 7th Framework Programme FP7/2007-2013 and EFPIA in-kind contributions
Background : Staphylococcus aureus (SA) pneumonia imposes significant morbidity and mortality in mechanically ventilated, intensive care unit (MV ICU) patients despite best clinical care. We assessed efficacy, PK, AT-neutralizing antibodies (AT NAbs), and safety of suvratoxumab (suvra) in MV ICU subjects in the placebo-controlled, randomized Phase 2 SAATELLITE study (NCT02296320; EudraCT 2014-001097-34).
Methods : Subjects with PCR-confirmed SA colonization of the lower respiratory tract were randomized to either a single intravenous infusion of 5000 mg suvra (n=96) or placebo (n=100) and followed for 190 days post dose. Efficacy endpoints were Endpoint Adjudication Committee-determined relative risk reduction (RRR) of SA pneumonia incidence in suvra vs. placebo recipients within 30 days post dose (primary endpoint, tested at 2-sided α=0.1), incidence of all-cause pneumonia, and all-cause pneumonia or death. Serum suvra PK and levels of AT NAbs were measured through 90 days post dose and analyzed for statistical correlation. Treatment-emergent adverse events (TEAEs) and serious AEs (SAEs) were assessed through 190 days post dose.
Results : Baseline characteristics were similar between groups. Suvra provided 31.9% RRR in incidence of SA pneumonia vs. placebo (17.7% vs 26%; P=0.166), 30% RRR (P=0.146) in incidence of all-cause pneumonia, and 23% RRR (P=0.164) in incidence of all-cause pneumonia or death. Suvra reduced mean hospital stay and ICU duration by 3.0 and 2.4 days, resp. vs. placebo. Mean serum±SD suvra level was 296±131 µg/ml at 30 days post dose. Serum AT NAb±SD levels reached 156.03±72.48 IU/mL at 2 days post dose, declining slowly to 33.74±16.04 IU/mL by 90 days post dose. AT NAbs correlated with PK (r2=0.7), thereby confirming functional activity of suvra over time. Proportion of subjects with TEAEs or SAEs were similar between groups: ≥1 TEAE (93.8% suvra; 93.0% placebo); ≥1 serious and/or ≥grade 3 severity SAE (66.7% suvra; 58.0% placebo).
Conclusion : A single intravenous dose of suvra produced a trend toward reduced incidence of SA pneumonia, health resource savings, sustained functional exposure in serum, and an acceptable safety profile. These results support continued development of suvra in MV ICU patients.