Safety, Tolerability, Bioavailability, and Biological Activity of Inhaled Interferon-& alpha;2b in Healthy Adults: The (INCOVID)-C-2 Phase I Randomized Trial

Background and ObjectivesInterferons have been identified as a potential treatment alternative for coronavirus disease 2019. This study assessed the safety, tolerability, bioavailability, and biological activity of inhaled interferon-& alpha;2b (IFN)-& alpha;2b in healthy adults.MethodsA double-blind, randomized, phase I clinical trial was conducted with two cohorts of healthy subjects aged 18-50 years. The first cohort received 2.5 MIU of inhaled IFN-& alpha;2b twice daily for 10 days (n = 6) or placebo (n = 3); the second cohort received 5.0 MIU of inhaled IFN-& alpha;2b in a similar scheme (n = 6) or placebo (n = 3). The first two doses were administered in an emergency department, then participants completed their treatment at home. Safety was measured through vital signs, new symptoms, and laboratory tests. Tolerability was measured as participants' treatment acceptability. Bioavailability and biological activity were measured from serum IFN & alpha; concentrations and real-time quantitative polymerase chain reaction of interferon-induced genes in blood before and after treatments.ResultsExposure to inhaled IFN-& alpha;2b at 2.5-MIU or 5-MIU doses did not produce statistically significant changes in participant vital signs, or elicit new symptoms, and standard hematological and biochemical blood measurements were comparable to those recorded in individuals who received placebo. A total of 58 adverse events were observed. All were mild or moderate and did not require medical care. All participants reported very high tolerability towards a twice-daily nebulized treatment for 10 days (98.0, 97.0, and 97.0 in the placebo, 2.5-MIU, and 5-MIU groups, respectively, on a 0- to 100-mm visual analog scale). A dose-dependent mild increase in serum IFN-& alpha; concentrations and an increase in serum RNA expression of IFN-induced genes were observed 11 days after treatment (p < 0.05 for all between-group comparisons).ConclusionsInhaled IFN-& alpha;2b was preliminarily safe and well tolerated, and induced systemic biological activity in healthy subjects.