Safety, tolerability, bioavailability, and biological activity of
inhaled interferon-α2b in healthy adults: The IN2COVID phase 1
randomized trial
Abstract
Aim: Interferons (IFNs) have been identified as a potential treatment
alternative for Coronavirus Disease 19 (COVID-19). This study assessed
the safety, tolerability, bioavailability, and biological activity of
inhaled interferon-α2b (IFN-α2b) in healthy adults. Methods: A
double-blind, randomized, phase 1 clinical trial was conducted with two
cohorts of healthy subjects aged 18-50 years old. The first cohort
received 2.5 MIU of inhaled IFN-α2b twice daily for 10 days (n=6) or
placebo (n=3); the second cohort received 5.0 MIU of inhaled IFN-α2b 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 the
participant´s treatment acceptability. Bioavailability and biological
activity were measured from serum IFNα levels and real-time quantitative
PCR of interferon-induced genes in blood before and after treatments.
Results: Exposure to inhaled IFN-α2b at 2.5 MIU or 5 MIU doses did not
produce 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.
All adverse events were mild or moderate and did not require medical
care. Participants reported very high tolerability. A dose-dependent
mild increase in serum IFN-α concentrations and an increase in serum RNA
expression of IFN-induced genes were observed after treatment.
Conclusion: Inhaled IFN-α2b was safe, well-tolerated, and induced
systemic biological activity in healthy subjects.