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

Abstract

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-1α and IL-1β, with corresponding inhibition of severe acute respiratory syndromecoronavirus 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).

Efficacy and hazards of 425 nm oral cavity light dosing to inactivate SARS-CoV-2

“…Nevertheless, the existence of multiple FDA-cleared devices with doses and irradiances both inside and slightly outside of this non-hazardous zone supports that the preclinical hazard assessments are broadly consistent with existing work in the field and provides additional support for the safety of new devices operating with doses and irradiances inside the non-hazardous zone. As a specific example, RD-X19 [9] , an oral cavity light-dosing investigational device, is under evaluation for the treatment of COVID-19 in clinical trials [11] at several doses and irradiances. All of the doses and irradiances being tested in the clinic fall within the non-hazardous region defined in this study ( Fig.…”

“…In spite of these limitations, we consider the approach presented in this work sufficient to establish that a non-hazardous dose of 425 nm light can serve as the basis for a light-based treatment for infections caused by SARS-CoV-2; however, we recognize that evaluation of potential hazards and predicted efficacy is an ongoing process, and any new candidate potential hazards or limitations to efficacy should be investigated through future preclinical in vitro and ex vivo studies. We also recognize that the ultimate evaluation of the prospective risks and offsetting benefits of any medical technology can only be completed through appropriate clinical trials and note that the 425 nm light doses delivered in both completed (16 J/cm 2 ) and ongoing (24 J/cm 2 and 32 J/cm 2 ) trials have been informed by the work presented here [ 9 , 11 , 12 ].…”

“…As an alternative to virus inactivation with cytotoxic UV wavelengths, delivering precisely-engineered doses of visible (>400 nm) light to the oral cavity has emerged as a promising approach for in situ SARS-CoV-2 inactivation. In particular, data from several groups suggests that 425 nm light doses inhibit the replication of SARS-CoV-2 in both cell lines (Vero E6) and in well-differentiated human large airway epithelial models (MatTek EpiAirway), and in a 31 subject, randomized, double-blind, sham-controlled early feasibility clinical trial it was observed that twice-daily dosing of the oropharynx and surrounding tissues with 16 J/cm 2 doses of 425 nm light reduced the mean time to COVID-19 symptom resolution by 57 hours with a corresponding reduction in viral load in saliva [8] , [9] , [10] . Further, another clinical trial is ongoing whose objective is to confirm the results of the 31-subject trial in a larger population and for two different light doses (24 J/cm 2 and 32 J/cm 2 ) [11] .…”

“…Previously, in vitro hazard assessments established that antiviral 425 nm light doses up to 60 J/cm 2 doses are not cytotoxic in cell lines (Vero E6) and that doses up to 32 J/cm 2 are not cytotoxic in well-differentiated human large airway epithelial cells [10] . Further, in the 16 J/cm 2 early feasibility trial, there were no application site reactions and no device-related serious adverse events reported [ 9 , 11 , 12 ]. Although these prior hazard assessments [ 10 , 13 ] and initial clinical safety analyses are necessary steps toward the development of acute oral cavity light-dosing devices, continuing to evaluate potential hazards (through preclinical studies) and clinical safety (through clinical trials) is necessary, particularly for the novel application of photomedicine in the oral cavity for which there is limited clinical precedent.…”

“…In turn, it is shown that a 425 nm light dose established as non-hazardous using this process inactivates SARS-CoV-2 in vitro in artificial saliva. Finally, these results are presented in the context of existing FDA-cleared oral cavity light dosing devices as well as ongoing work using acute 425 nm light dosing of through the oral cavity to treat COVID-19 [9] .…”