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

Study Overview
=================
Brief Summary
-----------------
This is a randomized, sham controlled, dose finding study of the EmitBio RD-X19 device in individuals with symptomatic COVID-19 in the outpatient setting.

Detailed Description
-----------------
This is a randomized, sham controlled, dose finding study of the EmitBio RD-X19 device in individuals with symptomatic COVID-19 in the outpatient setting. Study subjects will self-administer treatment twice daily for 7 days with a one-week follow-up period at Day 14 (+/- 2 days) and will not be aware of which treatment group to which they have been randomized. Clinical outcomes will be assessed via patient reported outcomes (questionnaire and diary cards) and virologic outcomes will be assessed post baseline on Days 3, 5, 8, and 14 via biospecimen collection. The primary goal of the study is to evaluate multiple doses of the RD-X19 treatment device and establish evidence for safety and efficacy for each of the RD-X19 doses compared to sham in SARS-CoV-2 infected individuals with outpatient COVID-19. The primary efficacy outcome is time to sustained symptom resolution. Other clinical and microbiological outcomes will also be assessed. Safety and tolerability (local reactogenicity) will be assessed actively and study subject diary card data recorded at each clinic visit by review of potential treatment emergent adverse events (TEAEs) and targeted oral and physical examinations. Volunteers will be instructed to contact designated clinical trial staff for AEs of a medically-urgent nature as soon as is practically possible and to seek immediate medical care, if needed. Study subjects who experience progression of disease to a grade 3 severity score (e.g SpO2 ≤ 93%, or respiratory rate ≥30/ minute on room air) will be instructed to urgently seek medical care at their nearest Urgent Care or Emergency Department. Study subjects who progress to severe acute respiratory distress syndrome with substantial risk for mortality without immediate medical intervention will be referred directly by site staff to their closest hospital. All study subjects who are hospitalized will be tracked to assess time to hospital discharge or death; the time and date of these events will be captured as part of the trial data. Metabolic, liver, kidney and hematological laboratory evaluations will be performed at baseline and at Day 14 or early termination (and potentially during unscheduled) clinic visits. Methemoglobin assessments will be performed at baseline and Day 14.

Official Title
-----------------
A Phase II, Randomized, Sham Controlled Dose Finding Study of the RD-X19 Treatment Device in Individuals With Mild to Moderate COVID-19

Conditions
-----------------
COVID19

Intervention / Treatment
-----------------
* Device: RD-X19
* Device: Sham


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria Positive for SARS-CoV-2 as detected using an FDA authorized SARS-CoV-2 antigen test at or within 24 hours of the screening visit. COVID-19 signs and symptoms within 72 hours from symptom onset, including at least two moderate* or greater symptoms from: cough, sore throat, nasal congestion, headache, unexplained chills and/or sweats, myalgia, fatigue, nausea (with or without vomiting). o Alternatively, subjects with the presence of at least one moderate symptom and either a) a fever with an oral temperature of at least 100.5° F or b) shortness of breath/difficulty breathing on exertion (e.g., walking, going up and down stairs) are also eligible for enrollment. BMI <40 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 saliva, nasopharyngeal, and venous blood specimens per protocol. Males or females, 18 to 65 years of age, inclusive. No uncontrolled disease process(es) based on patient reported medical history (chronic or acute), other than direct 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. Symptom scoring is independent from the classification of COVID-19 disease severity at baseline. Guidance to study subjects for grading of signs and symptoms will be based on definitions used for the grading of TEAEs: None (Grade 0): Not present Mild (Grade 1): Symptoms that are usually transient and may require only minimal or no palliative or specific therapeutic intervention and generally do not interfere with the subject's usual activities of daily living. Moderate (Grade 2): Symptoms that are usually alleviated with palliative or specific therapeutic intervention. The symptoms interfere with usual activities of daily living causing discomfort but pose no significant or permanent risk of harm to the study subject. Severe (Grade 3): Events interrupt usual activities of daily living, or significantly effect clinical status, or may require intensive therapeutic intervention. Severe events are usually incapacitating. Exclusion Criteria Positive urine pregnancy test at screening or females who intend to become pregnant during the study. COVID-19 signs associated with severe respiratory distress or imminent serious medical outcomes.^^ ^^Potential Study Subjects Presenting with any of the following should be referred for immediate medical care and are not eligible for the study Fever > 104° F Cough with sputum production Rales and/or rhonchi Difficulty breathing with respiratory distress defined by a respiratory rate ≥30 per minute, heart rate ≥125 per minute, SpO2 ≤93% on room air at sea level or PaO2/FiO2 <300. Persistent pain or pressure in the chest Confusion Any medical disease or condition that, in the opinion of the site Principal Investigator (PI) or appropriate sub-investigator, precludes study participation. Reports a recent positive test result (within the past 6 months) for hepatitis A, hepatitis B or, 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. Currently enrolled in or plans to participate in another clinical trial with a therapeutic investigational agent (e.g., monoclonal antibody, oral protease inhibitor) that will be received during the study period. History of systemic antiviral therapies (e.g., remdesivir) within the past 30 days. History of oral or parenteral corticosteroid use within the past 30 days. 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 sun exposure. Currently undergoing photodynamic therapy (PDT) or photochemotherapy (PUVA) for an unrelated disease or condition that utilizes photosensitizing drugs including but not limited to 5-aminolevulinic acid, Methyl-5-aminolevulinic acid, porfimer sodium, methoxsalen (8-methoxypsoralen), 5-methoxypsoralen, trioxsalen. Has any oral abnormality (e.g., ulcer, oral candidiasis, oral mucositis, gingivitis) that in the opinion of the investigator would interfere with device use and evaluation. Any intra-oral body piercings that cannot be removed and remain 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.

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Volunteers meeting all inclusion criteria and none of the exclusion criteria will be randomized to the RD-X19 treatment arm or the sham treatment arm within each cohort in a 2:1 ratio according to a fixed schedule via a permuted block design.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: RD-X19 Device, Dose A<br>RD-X19. Investigational device that uses safe electromagnetic energy to target the oropharynx. | Device: RD-X19<br>* Investigational device that uses safe electromagnetic energy to target the oropharynx.<br>|
| Active Comparator: RD-X19 Device, Dose B<br>RD-X19. Investigational device that uses safe electromagnetic energy to target the oropharynx. | Device: RD-X19<br>* Investigational device that uses safe electromagnetic energy to target the oropharynx.<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: Sham<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..<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sustained resolution of COVID-19 signs and symptoms | The primary efficacy endpoint is time to sustained resolution of COVID-19 signs and symptoms. | Baseline thru Day 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Medically Attended Visits | Numbers and percentages of study subjects who require medical attention or intervention attributed to COVID-19; | Baseline thru Day 14 | 
| Severe Disease Progression | Numbers and percentages of study subjects who progress to severe disease with respiratory rate >30/minute and/or O2 saturation ≤93% on room air or FiO2 ≥300% with any respiratory distress. | Baseline thru Day 14 | 
| Hospitalizations | Numbers and percentages of study subjects who require hospitalization for severe COVID-19. | Baseline thru Day 14 | 
| Worsening of Disease | Number and percentage of study subjects who experience progression of COVID-19 as defined by an increase of the composite COVID-19 severity score greater than baseline at any point in the study on or after day 3. | Day 3 thru Day 14 | 
| Return to Pre-COVID Health | Numbers and percentages of study subjects on day 8 and day 14 who answer yes to the following patient-reported global impression assessments, a) return to usual health and b) return to usual activities. | Days 8 and 14 | 
| Mean change in nasopharyngeal viral load | Mean change in nasopharyngeal viral load on days 3, 5, 8, and 14. | Days 3, 5, 8 and 14 | 
| Proportion of subjects demonstrating clearance of viral infection | Proportion of subjects demonstrating clearance of viral infection on Days 3, 5, 8 and 14. | Days 3, 5, 8 and 14 |