A randomized, controlled, feasibility study of RD-X19 in subjects with mild-to-moderate COVID-19 in the outpatient setting

The RD-X19 is an investigational, handheld medical device precisely engineered to emit blue light through the oral cavity to target the oropharynx and surrounding tissues. At doses shown to be noncytotoxic in an in vitro three-dimensional human epithelial tissue model, the monochromatic visible light delivered by RD-X19 results in light-initiated expression of immune stimulating cytokines IL-1 alpha and IL-1 beta, with corresponding inhibition of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) replication. A single exposure of 425 nm blue light at 60 J/cm(2) led to greater than 99% reductions against all SARS-CoV-2 strains tested in vitro, including the more transmissible (Alpha) and immune evasive (Beta) variants. These preclinical findings along with other studies led to a randomized, double-blind, sham-controlled early feasibility study using the investigational device as a treatment for outpatients with mild to moderate coronavirus disease 2019 (COVID-19). The study enrolled 31 subjects with a positive SARS-CoV-2 antigen test and at least two moderate COVID-19 signs and symptoms at baseline. Subjects were randomized 2:1 (RD-X19: sham) and treated twice daily for 4 days. Efficacy outcome measures included assessments of SARS-CoV-2 saliva viral load and clinical assessments of COVID-19. There were no local application site reactions and no device-related adverse events. At the end of the study (day 8), the mean change in log(10) viral load was -3.29 for RD-X19 and -1.81 for sham, demonstrating a treatment benefit of -1.48 logs (95% confidence internal, -2.88 to -0.071, nominal p = 0.040). Among the clinical outcome measures, differences between RD-X19 and sham were also observed, with a 57-h reduction of median time to sustained resolution of COVID-19 signs and symptoms (log rank test, nominal p = 0.044). Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC? Visible blue light (400-470 nm) has previously been demonstrated to inhibit coronavirus replication in cultured cells and eliminate severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) from infected human epithelial tissue in a laboratory setting. WHAT QUESTION DID THIS STUDY ADDRESS? Can precisely engineered doses of visible light inhibit replication of SARS-CoV-2 variants in a laboratory setting and lead to reductions of SARS-CoV-2 viral load in saliva in patients with coronavirus disease 2019 (COVI-19)? WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE? In this randomized, double--blind, sham-controlled, early feasibility study, light administered in the outpatient setting by the investigational RD-X19 device twice daily over 4 days resulted in clinically meaningful differences in both mean change in SARS-COV-2 viral load by day 8 (-1.48 log10, nominal p = 0.040) and median time to sustained symptom resolution (57-h advantage, nominal p = 0.044) compared to sham. Unlike the photodamage known to be caused by UV light, photobiomodulation via 425 nm blue light exhibited no cytotoxicity in oral mucosal tissues in vitro and no device-related application site adverse events in the clinic. HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE? Self-administered visible light therapy in the outpatient setting may be capable of interrupting SARS-CoV-2 disease pathology (through inactivation of virus and/or stimulation of host immune response) and useful as a treatment for mild to moderate COVID-19. These nonclinical and clinical findings help to inform dosing schedules for the optimal use of light as a therapeutic in future clinical trials.