Randomized, Double-Blind, Placebo-Controlled Study of the Safety, Tolerability, and Clinical Effect of Danirixin in Adults With Acute, Uncomplicated Influenza

Grace Roberts, Shuguang Chen, Phillip Yates, Anuradha Madan, Jill Walker, Michael L Washburn, Andrew J Peat, Gary Soucie, Edward Kerwin, Sumita Roy-Ghanta, Grace Roberts, Shuguang Chen, Phillip Yates, Anuradha Madan, Jill Walker, Michael L Washburn, Andrew J Peat, Gary Soucie, Edward Kerwin, Sumita Roy-Ghanta

Abstract

Background: Danirixin (DNX), a selective and reversible CXC chemokine receptor 2 antagonist, inhibits neutrophil transmigration and activation. This study assessed the safety, tolerability, and clinical effect of DNX with and without oseltamivir (OSV) in adults with acute, uncomplicated influenza.

Methods: This was a placebo-controlled, double-blind, Phase IIa study. Participants (18-64 years) with influenza-like symptoms (onset ≤48 hours) and positive influenza rapid antigen test were randomized 2:1:2:1 to DNX, placebo, DNX+OSV, or OSV (75 mg each, administered twice daily for 5 days) and followed for 28 days. Primary endpoints included frequency of adverse events (AEs) and serious AEs (SAEs). The effect of DNX on virologic response and clinical effect on influenza symptoms were secondary endpoints.

Results: A total of 45 participants were enrolled, 35 of whom were confirmed influenza positive by polymerase chain reaction analysis. The highest incidence of AEs was in the placebo group (4 of 7, 57%), followed by the DNX+OSV (7 of 16, 44%), DNX (3 of 15, 20%), and OSV (0 of 7, 0%) groups. One SAE (T-wave abnormality) was reported in the DNX group (unrelated to treatment). No differences in viral load assessments were observed among treatment groups.

Conclusions: Danirixin treatment was well tolerated and did not impede viral clearance.

Keywords: CXC chemokine receptor 2 (CXCR2) antagonist; danirixin (DNX); influenza; outpatient; safety.

Figures

Figure 1.
Figure 1.
Study design. BID, twice daily; DNX, danirixin; OSV, oseltamivir; PBO, placebo; RAT, rapid antigen test.
Figure 2.
Figure 2.
Summary of patient disposition. DNX, danirixin; IPP, influenza positive population; OSV, oseltamivir; PBO, placebo; SP, safety population.
Figure 3.
Figure 3.
Median plot of absolute neutrophil count by visit (safety population). Bars represent interquartile ranges. DNX, danirixin; OSV, oseltamivir; PBO, placebo.

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