A phase 3 study to evaluate the efficacy and safety of reparixin in severe COVID-19 pneumonia

Abstract

Introduction: The clinical progression of severe coronavirus disease 2019 (COVID-19) is associated with uncontrolled activation of inflammatory cytokines that results in excessive tissue injury, among which is interleukin–8 (IL-8).

Aims: To assess the efficacy and safety of reparixin, an inhibitor of IL-8 receptors, as add-on therapy to the standard of care for severe COVID-19 pneumonia.

Methods: This was a Phase 3, multicenter, randomized, placebo-controlled study in hospitalized adult patients with COVID-19 requiring oxygen support and/or noninvasive ventilation. From February to July 2021, patients were randomized 2:1 to oral reparixin or placebo in addition to the standard of care for up to 21 days or until hospital discharge. The primary endpoint was the proportion of patients alive and free of respiratory failure. This study was funded by Dompé Farmaceutici SpA (ClinicalTrials.gov: NCT04878055).

Results: Of the 278 randomized patients, 185 patients in the reparixin group and 94 patients in the placebo group were included in the primary intention-to-treat analysis. The proportion of patients alive and free of respiratory failure at day 28 was greater in the reparixin group but not statistically significant (n=152 (89.4%) vs. n=71 (85.5%), OR: 1.63, 95% CI: 0.75 - 3.51, p= 0.2). While time to recovery was not different between groups, patients who received reparixin had a lower intensive care unit admission rate. Reparixin was well-tolerated.

Conclusions: This trial did not meet the primary efficacy endpoint due to the low mortality in both arms, yet reparixin showed a promising trend towards limiting disease progression. A confirmatory Phase 3 study is currently underway.