Evaluation of the RD-X19 Treatment Device in Individuals With Mild COVID-19

This is a randomized, double-blind, sham controlled, stratified, pivotal efficacy and safety study of the EmitBio RD-X19 device in individuals age 40 and older with mild COVID-19 (as defined by NIH and FDA) in the at-home setting. Study subjects will self-administer treatment twice daily, 5 minutes per treatment for 7 consecutive days. Subjects will remain on study for a total of 14 study days (± 2 days) for treatment and follow-up. Neither study subject nor clinical trial personnel will be aware of the subject's treatment assignment. Clinical safety and efficacy outcomes will be assessed via self-assessed signs and symptoms (e-diary entries twice a day during the entire study period) with daily study staff checks, including home visits, and/or clinic visits for objective clinical assessments (vital signs, targeted physical exams, oropharyngeal exams) on study days 1, 5, 8 and 14.

The primary goal of the study is to evaluate the safety and efficacy of the RD-X19 treatment device to provide sufficient evidence to FDA to justify the authorization and/or approval of the device for treatment of subjects with mild COVID-19, age 40 and older in the home setting. Every attempt will be made to continue to follow safety in any study subject choosing to terminate the study early and all study subjects who progress to moderate or more severe forms of COVID-19 will be immediately referred for appropriate medical care. Medically necessary care of study participants will always take precedence over research.

Inclusion criteria

• Positive for SARS-CoV-2 as detected using an FDA authorized SARS-CoV-2 antigen test at the screening/baseline visit.
• Negative for Influenza A and B antigen using an FDA-authorized rapid diagnostic test.
• At least two moderate or greater COVID-19 signs and symptoms from the following list: cough, sore throat, nasal congestion, headache, chills and/or sweats, myalgia, fatigue, nausea (with or without vomiting) or one moderate or greater symptom and fever (temperature ≥ 100.5 degrees F).
• Time from appearance of first COVID-19 sign or symptom to screening must be 72 hours or less.
• Males or females, including pregnant and fecund females, 40 years of age and older on the date of enrollment.
• BMI <40
• Provides written informed consent prior to initiation of any study procedures.
• Be able to understand and agrees to fully comply with defined and described study procedures and be available for all study visits for the entire study duration.
• Agrees to collection of a nasopharyngeal swab for qPCR at baseline for the purposes of assessing viral burden as a potential covariate in data analyses and for genetic sequencing to characterize the predominant SARS-CoV-2 variants present in the study population.
• Agrees to perform self-diagnostic home testing twice a day, separated by ≥ 6 hours for the entire length of the study.
• Agrees to restrict medications used for symptomatic relief of signs and symptoms of COVID-19 during the study period, and, if used, to report ALL such medications (including home remedies) to the study staff.
• Agrees to avoid the use of oral rinses and toothpastes containing alcohol-based compounds (e.g. Eucalyptol, Menthol, Thymol, Phenol) and/or Salicylates during the study period. Oral rinses, breath fresheners and toothpaste not containing these compounds are allowed.
• Agrees to avoid nasal and sinus saline lavage during the study period.
• No uncontrolled disease process (chronic or acute), other than COVID-19 signs and symptoms (See section 8.1.1 - General Screening)*.
• No physical or mental conditions or attributes at the time of screening, which in the opinion of the PI, will prevent full adherence to, and completion of, the protocol.

Exclusion criteria

• Positive for Influenza A and B antigen using an FDA-authorized rapid diagnostic test.
• Individuals < age 40 on study day 1.
• Individuals who are symptomatic for COVID-19 for more than 72 hours on study day 1.
• COVID-19 signs associated with moderate or greater disease with evidence of lower respiratory involvement including shortness of breath (SOB) at rest or as determined by an exertional SOB protocol, SpO2 ≤94, respiratory rate ≥20 breaths per minute, heart rate ≥90 beats per minute, or abnormal pulmonary imaging.
• Any medical disease or condition that, in the opinion of the site Principal Investigator (PI) or appropriate sub-investigator, precludes study participation.
• History of use of a rescue inhaler for uncontrolled asthma within one month of study day 1.
• History of recurrent alcohol intoxication or other recreational drug use (excluding medically prescribed cannabis) within one month of study day 1.
• History of use, within one month of study day 1, of any FDA-authorized treatment for COVID-19. Use of non-approved putative therapies for COVID-19 (hyroxycholorquine, ivermectin, azithromycin) must be discontinued prior to enrollment in the study.
• History of any systemic antiviral therapies within one month of study day 1.
• History of oral or parenteral corticosteroid use within one month of study day 1. Active use of nasal or inhalable steroids is also exclusionary. Topical steroids are not exclusionary.
• History of any chronic medical condition that has required adjustments to the type, dose or schedule of medical treatments within one month of study day 1.
• Requirement to use narcotic medication for analgesia.
• History of vasomotor rhinitis with or without post-nasal drip within one month of study day 1.
• History of hypersensitivity or severe allergic reaction (e.g., anaphylaxis, generalized urticaria, angioedema, other significant reaction) to sun exposure.
• Presence of any oral abnormality (e.g., including, but not limited to, ulcer, oral candidiasis, oral mucositis, symptomatic gingivitis, history of frequent recurrent aphthous ulcers, burning mouth syndrome, dry mouth syndrome, a disease that can result in xerostomia (e.g., Sjogren's syndrome), Temporomandibular Joint Syndrome, or other oral disorder that in the opinion of the investigator would interfere with device use and evaluation.
• Any intra-oral metal body piercings that cannot be removed for the duration of the study. Metal orthodontia is permitted as braces will be covered by the device mouthpiece.
• Any individual without teeth or with a dental malformation that precludes directed use of the device as intended.
• Currently enrolled in or plans to participate in another clinical trial with a therapeutic investigational agent for any medical indication that will be received during the study period.