medRxiv. 2022 Apr 5:2022.03.30.22273194. doi: 10.1101/2022.03.30.22273194. Preprint.
BACKGROUND: A profound need remains to develop further therapeutics for treatment of those hospitalized with COVID-19 to prevent respiratory decline or death. Based on data implicating the type 2 cytokine interleukin (IL)-13 as a significant factor leading to critical COVID-19, this trial was designed to assess the safety and efficacy of dupilumab, a monoclonal antibody that blocks IL-13 and IL-4 signaling, in those hospitalized with COVID-19.
METHODS: We conducted a phase IIa randomized double-blind placebo-controlled trial 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. Subjects were followed prospectively for 60 days, with collection of clinical outcomes, adverse events and immunologic biomarkers at multiple time points throughout the study period. The primary endpoint was the proportion of patients alive and free of invasive mechanical ventilation at 28 days analyzed in logistic regression.
RESULTS: Forty eligible subjects were enrolled from June 23, 2021 through November 11, 2021. There was no difference in adverse events nor in proportion of patients alive and free of mechanical ventilation at day 28 between study treatment groups. However, for the secondary endpoint of mortality at day 60, subjects randomized to dupilumab had a higher survival rate: 89.5% of subjects in the dupilumab group were alive compared to 76.2% in the placebo group (adjusted HR 0.05, 95% CI: 0.0-0.72, p=0.03). There was a trend toward reduction in ICU admission in the dupilumab group compared to the placebo group (33.3% vs 66.7%; adjusted HR 0.44, 95% CI: 0.09-2.09, p=0.30). Lastly, we saw downstream evidence of IL-4 and IL-13 signaling blockade through analysis of immune biomarkers at multiple study time points.
CONCLUSIONS: Dupilumab was well tolerated and improved 60-day survival in patients hospitalized with moderate to severe COVID-19. Blockade of type 2 immunity offers promise as a novel treatment for COVID-19.