Safety and Efficacy of Dupilumab for the Treatment of Hospitalized Patients With Moderate to Severe Coronavirus Disease 2019: A Phase 2a Trial

Abstract

Background: Based on studies implicating the type 2 cytokine interleukin 13 (IL-13) as a potential contributor to critical coronavirus disease 2019 (COVID-19), this trial was designed as an early phase 2 study to assess dupilumab, a monoclonal antibody that blocks IL-13 and interleukin 4 signaling, for treatment of inpatients with COVID-19.

Methods: We conducted a phase 2a randomized, double-blind, placebo-controlled trial (NCT04920916) to assess the safety and efficacy of dupilumab plus standard of care vs 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 2 deaths in the dupilumab group compared with 5 deaths in the placebo group (60-day survival: 89.5% vs 76.2%; adjusted hazard ratio [HR], 0.05 [95% confidence interval {CI}, .004-.72]; P = .03). Among subjects who were not in the intensive care unit (ICU) at randomization, 3 subjects in the dupilumab arm were admitted to the ICU compared to 6 in the placebo arm (17.7% vs 37.5%; adjusted HR, 0.44 [95% CI, .09-2.09]; P = .30). Last, 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.

Clinical trials registration: NCT04920916.

Keywords: COVID-19; IL-13; SARS-CoV-2; dupilumab; type 2 immunity.

© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.

Figures

Figure 1.

Kaplan-Meier survival curves depicting 60-day mortality between the 2 treatment groups. Adjusted P value indicative of adjustment for sex and time-varying ventilation in the Cox regression. Patient study visits occurred within an allotted range of exact study days, and therefore the number at risk in the table is representative of patient data availability up until those exact days (ie, if study visit was conducted on day 59 and no event had occurred, then the subject was included in the at-risk pool up until day 59 but not in that for day 60).

Figure 2.

Kaplan-Meier curve depicting need for escalation to intensive care over the 60-day study period. Patients already admitted to the intensive care unit on day of enrollment (n = 7) were excluded from analysis. Patient study visits occurred within an allotted range of exact study days and therefore the number at risk in the table is representative of patient data availability up until those exact days (ie, if study visit was conducted on day 59 and no event had occurred, then the subject was included in the at-risk pool up until day 59 but not in that for day 60).