Phase I/II Safety, Dose Finding & Antiviral Activity of RD-X19 in Mild/Moderate Outpatient COVID-19

Study Overview
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Brief Summary
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This randomized, Phase I/II feasibility study will evaluate the safety and efficacy of the RD-X19 device in SARS-CoV-2 infected individuals with uncomplicated COVID-19.

Detailed Description
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This is a randomized, sham-controlled dose escalation and bioeffect study. The primary goal of the study is to evaluate the safety of the RD-X19 device in SARS-CoV-2 infected individuals with outpatient COVID-19 and to assess the reduction of SARS-CoV-2 viral load in each dose group compared to sham controls. The primary safety measure is absence of device-related serious adverse events or patterns of severity ≥2 device-related adverse events. Safety and tolerability (local reactogenicity) will be assessed actively on each clinic visit by review of potential adverse events (AEs) and targeted physical examination, as required. Metabolic, liver, kidney and hematological laboratory evaluations will be performed at baseline and at Day 8 or early termination (and potentially during unscheduled) clinic visits. Methemoglobin assessments will be performed at baseline and Day 8. Various efficacy assessments will explore the impact of RD-X19 treatment on the reduction in log10 SARS-CoV-2 viral load and alleviation of symptoms associated with COVID-19. Both the magnitude of reduction as a function of dose as well as time to clearance will be assessed.

Official Title
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Phase I/II Randomized, Dose Escalation Study to Evaluate the Safety and Antiviral Activity of the RD-X19 Device in SARS-CoV-2 Infected Individuals With Uncomplicated COVID-19

Conditions
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COVID19

Intervention / Treatment
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* Device: RD-X19


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Positive for SARS-CoV-2 antigen via nasal swab at or within the past 24 hours of the screening visit detected using an FDA authorized SARS-CoV-2 antigen test. Onset of signs and symptoms consistent with COVID-19* no longer than within the past 3 days* and have either a) a fever of at least 100 °F or b) at least two moderate or severe symptoms (cough, sore throat, nasal congestion, headache, chills/sweats, muscle or joint pain, fatigue, and nausea) at the time of screening. Provides written informed consent prior to initiation of any study procedures. Be able to understand and agrees to comply with planned study procedures and be available for all study visits. Agrees to the collection of nasopharyngeal swabs, oropharyngeal swabs, oral saliva specimen collection and venous blood specimens per protocol. Agrees to refrain from using oral antiseptics (e.g. hydrogen peroxide rinse, Listerine) or mouthwashes of any kind during the study. Male or non-pregnant female, 18 to 65 years of age, inclusive, at time of enrollment. No uncontrolled disease process (chronic or acute), other than COVID-19 signs and symptoms*. 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 urine pregnancy test at screening. Any medical disease or condition that, in the opinion of the site Principal Investigator (PI) or appropriate sub-investigator, precludes study participation. Presence of self-reported or medically documented uncontrolled significant medical or psychiatric condition(s) other than COVID-19. Reports a recent positive test result (within the past 6 months) for hepatitis B surface antigen, hepatitis C virus antibody, or HIV-1 antibodies at screening. Has a history of alcohol abuse or other recreational drug (excluding cannabis) use within 1 month of Study Day 1. COVID-19 signs associated with acute respiratory distress or imminent serious medical outcomes. ^^ BMI ≥36 Subjects living (e.g., siblings, spouses, relatives, roommates) in the same household cannot be enrolled. Has participated in another investigational study involving any intervention for SARS-CoV-2/COVID- 19 within the past 6 months or any clinical trial with interventional investigational product within 30 days of screening. Currently enrolled in or plans to participate in another clinical trial with an interventional investigational agent that will be received during the studyperiod. History of hospitalization within the past 60 days. History of systemic antiviral therapies within the past 30 days. History of oral corticoid steroid use within the past 14 days or steroid injection within the past 6 months. Active use of nasal or inhalable steroids is also exclusionary. Topical steroids are not exclusionary. Has a history of hypersensitivity or severe allergic reaction (e.g., anaphylaxis, generalized urticaria, angioedema, other significant reaction) to nitrites, nitrates, or sun exposure. Has any oral abnormality (e.g. ulcer, oral mucositis, gingivitis) that in the opinion of the investigator would interfere with device use, or 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: The study will be conducted as a randomized, double-blind, sham-controlled study in SARS-CoV-2 infected individuals with outpatient COVID-19. Subjects will be randomized 2:1 RD-X19 to Sham Device treatment arms.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RD-X19 Device<br>Experimental device that uses safe electromagnetic energy to stimulate the proximal repository of respiratory tract infectious disease pathogens. | Device: RD-X19<br>* Experimental device that uses safe electromagnetic energy to stimulate the proximal repository of respiratory tract infectious disease pathogens.<br>|
| Sham Comparator: Sham Device<br>Investigational device that uses safe electromagnetic energy to target the oropharynx but at energy levels with a lower inactivation potential against SARS-CoV-2 in vitro. | Device: RD-X19<br>* Experimental device that uses safe electromagnetic energy to stimulate the proximal repository of respiratory tract infectious disease pathogens.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Safety Measure | Number of Participants with device-related serious adverse events or any patterns of severity ≥2 device-related adverse events in the same SOC grouping of Preferred Terms based on Medical Dictionary for Regulatory Activities (MedDRA) coding, as determined throughout the course of the study. | Baseline thru Day 8 | 
| Primary Efficacy Measure | Time weighted average change in viral load from baseline by RT-qPCR from Day 1 to Day 8. | Baseline to Day 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Subjects Demonstrating Clearance of Viral Infection | Proportion of subjects demonstrating clearance of viral infection, defined as a negative test via RT-qPCR on Day 8/ET. | Days 1, 3, 5 and 8 | 
| Median Time to Alleviation of Symptoms | Median time to alleviation of symptoms as measured by the time when all eight symptoms (cough, sore throat, nasal congestion, headache, chills/sweats, muscle or joint pain, fatigue, and nausea) had been assessed by the subject as none (0) or mild (1). | Daily through day 8 |