Safety and Efficacy of Dupilumab for the Treatment of Hospitalized Patients with Moderate to Severe COVID 19: A Phase IIa Trial

Abstract Background Based on studies implicating the type 2 cytokine interleukin (IL)-13 as a potential contributor to critical COVID-19, this trial was designed as an early phase II study to assess dupilumab, a monoclonal antibody that blocks IL-13 and IL-4 signaling, for treatment of inpatients with COVID-19. Methods We conducted a phase IIa randomized double-blind placebo-controlled trial (NCT04920916) to assess the safety and efficacy of dupilumab plus standard of care versus placebo plus standard of care in mitigating respiratory failure and death in those hospitalized with COVID-19. Results Forty eligible subjects were enrolled from June to November of 2021. There was no statistically significant difference in adverse events nor in the primary endpoint of ventilator free survival at day 28 between study arms. However, for the secondary endpoint of mortality at day 60, there were two deaths in the dupilumab group compared five deaths in placebo (60-day survival 89.5% vs 76.2%, adjusted HR 0.05, 95% CI: 0.004- 0.72, p = 0.03). Among subjects who were not in the ICU at randomization, three subjects in the dupilumab arm were admitted to the ICU compared to six in the placebo (17.7% vs. 37.5%; adjusted HR 0.44, 95% CI: 0.09-2.09, p = 0.30). Lastly, we found evidence of type 2 signaling blockade in the dupilumab group through analysis of immune biomarkers over time. Conclusions Although the primary outcome of day 28 ventilator-free survival was not reached, adverse events were not observed and survival was higher in the dupilumab group by day 60.