A multicenter, randomized, double-blind, placebo-controlled phase ii trial of intravenous inflammasome inhibitor (NuSepin) for the treatment of COVID-19 patients

Abstract Purpose Here we evaluated whether a novel inflammasome inhibitor targeting GPCR19 (NuSepin) provides greater benefit than placebo in patients with COVID-19 pneumonia. Methods We conducted a double-blind, randomized, placebo-controlled phase ii trial of intravenous NuSepin, which is an NLRP3 inflammasome inhibitor targeting GPCR19, in adults who were hospitalized with COVID-19 pneumoniae in Romania from September 2020 to March 2021. The primary outcome was the time to clinical improvement, defined as a decline of two ordinal scales (OS) from randomization on a six-category OS that ranges from 1 (discharged with normal activity) to 6 (death) (=TTCI_P). In addition, clinical improvement was also assessed by aggregated National Early Warning Score 2 (NEWS2), and TTCI_S was defined by time to NEWS2=0 from randomization, which is maintained for 24 h. Results TTCI_P was different between groups numerically, but not statistically. The median difference in TTCI_S was 3.5 d between the NuSepin group and the placebo group (p = 0.016) in moderate-to-severe patients (with baseline NEWS2 ≥ 5) of the PP set [recovery rate ratio = 2.7, p = 0.02], which favored improved recovery in the NuSepin group. The overall recovery rate ratio was 3.4, which favors the NuSepin group in terms of recovery rate (p = 0.0026) when the effects of covariates (use of anti-viral drugs and baseline NEWS2 ≥ 5) were adjusted. Serious adverse events were reported in a patient who received 0.2 mg/kg NuSepin (4.5%), but this was found to be unrelated to NuSepin treatment. Conclusion Considering that NuSepin has a favorable and tolerable safety profile, clinical improvement of hospitalized moderate-to-severe patients might be achieved with 0.2 mg/kg NuSepin significantly faster than placebo.