Efficacy and Safety of Danirixin (GSK1325756) Co-administered With Standard-of-Care Antiviral (Oseltamivir): A Phase 2b, Global, Randomized Study of Adults Hospitalized With Influenza

Background: Excessive neutrophil migration has been correlated with influenza symptom severity. Danirixin (GSK1325756), a selective and reversible antagonist of C-X-C chemokine receptor 2, decreases neutrophil activation and transmigration to areas of inflammation. This study evaluated the efficacy and safety of intravenous (IV) danirixin co-administered with oseltamivir for the treatment of adults hospitalized with influenza.

Methods: In this phase 2b, double-blind, 3-arm study (NCT02927431), influenza-positive participants were randomized 2:2:1 to receive danirixin 15mg intravenously (IV) twice daily (bid) + oral oseltamivir 75mg bid (OSV), danirixin 50mg IV bid + OSV, or placebo IV bid + OSV, for up to 5 days. The primary endpoint was time to clinical response (TTCR).

Results: In total, 10 participants received study treatment (danirixin 15mg + OSV, n = 4; danirixin 50mg + OSV, n = 4; placebo + OSV, n = 2) before the study was terminated early due to low enrollment. All participants achieved a clinical response. Median (95% confidence interval) TTCR was 4.53 days (2.95, 5.71) for danirixin 15mg + OSV, 4.76 days (2.71, 5.25) for danirixin 50mg + OSV, and 1.33 days (0.71, 1.95) for placebo + OSV. Adverse events (AEs) were generally of mild or moderate intensity; no serious AEs were considered treatment-related. Interleukin-8 levels increased in nasal samples (using synthetic absorptive matrix strips) and decreased serum neutrophil-elastase-mediated degradation of elastin decreased in danirixin-treated participants, suggesting effective target engagement.

Conclusions: Interpretation of efficacy results is restricted by the low participant numbers. The safety and tolerability profile of danirixin was consistent with previous studies.

Clinical trial information: The registration data for the trial are in the ClinicalTrials.gov database, number NCT02927431, and in the EU Clinical Trials Register (https://www.clinicaltrialsregister.eu/) as GSK study 201023, EudraCT 2016-002512-40. Anonymized individual participant data and study documents can be requested for further research from www.clinicalstudydatarequest.com.