A Phase 2, randomized, double-blind, placebo-controlled multi-center trial sub-study for the clinical effects of paridiprubart treatment in hospitalized critically ill patients with COVID-19 ARDS

Abstract

ABSTRACTBackgroundCoronavirus disease 2019 (COVID-19) mortality is predominantly due to acute respiratory distress syndrome (ARDS). There are currently limited treatment options for ARDS, a life-threatening condition with different etiologies, secondary to inflammation-induced lung injury. Paridiprubart is a monoclonal antibody that inhibits Toll-like Receptor 4 (TLR4), a key player in ARDS pathophysiology.MethodsThis was a prespecified sub-study of a randomized, double-blind, placebo-controlled, Phase 2 trial evaluating the efficacy and safety of paridiprubart in COVID-19 patients with ARDS receiving invasive mechanical ventilation and additional organ support. Efficacy outcomes were 28- and 60-day all-cause mortality, and improvement in COVID-19 severity and ventilation-free days at 28-days post-treatment.ResultsThirteen (13) and twenty (20) patients received paridiprubart and placebo, respectively. The groups were comparable for demographics and baseline parameters, except for higher kidney failure incidence and use of immune modulators and antivirals, and lower corticosteroids use in the paridiprubart group. Mortality at 28-days post-treatment was 7.7% (1/13) in the paridiprubart group versus 40.0% (8/20) for placebo (OR=0.125; 95% CI, 0.013-1.160; P=0.067; P[bootstrap]=0.011). 60-day mortality was 23.1% (3/13) in paridiprubart-treated patients and 45.0% (9/20) in placebo patients (OR=0.367; 95% CI, 0.077-1.749; P=0.208; P[bootstrap]=0.162). Mean survival time was 55.78 days for paridiprubart recipients compared to 41.44 days for placebo patients (HR=0.386; 95% CI, 0.077-1.436; P=0.156; P[bootstrap]=0.083). Although not statistically significant, results for other efficacy measures favored paridiprubart. Incidence of adverse events was similar in both groups.ConclusionsIn COVID-19 patients with ARDS requiring invasive ventilation and organ support, paridiprubart was efficacious in preventing mortality and improving clinical outcomes, with no safety concerns.