A Phase I Study of the EmitBio™ RD19 Device to Prevent SARS-CoV-2 and COVID-19

Respiratory Tract Infections Clinical Trial

Official title:

A Phase I Open Label, First-in-Man Acute Safety, Tolerability and Acceptability Study of the EmitBio™ RD19 Device to Prevent SARS-CoV-2 Infection and COVID-19 Disease

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04525976
• Other study ID #: RD19-01-3Q20
• Status: Not yet recruiting
• Phase: N/A
• Start date: August 31, 2020
• Est. completion date: October 1, 2020

Study information

• Verified date: August 2020
• Source: KNOWBio Inc.
• Contact: John G McNeil, MD MPH PHD
• Phone: 843.540.3550
• Email: jmcneil[@]emitbio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This first-in-man (FIM) phase I study will evaluate the acute safety, tolerability, and device acceptability for use among 25 healthy volunteers between the age of 18 and 45.

Safety and tolerability (local reactogenicity) will be assessed actively at screening (baseline set), and study days 1, 7 and 14, and on non-clinic visit days by collection of these data by history during clinic visits via a memory aid (diary cards).

Metabolic, liver and kidney safety laboratory evaluations, as well as urinalysis, will be performed at screening and at Day 14 or early termination (and potentially during unscheduled) clinic visits. Hematological safety assessments will be performed at all visits.

Description:

This first-in-man (FIM) phase I study will evaluate the acute safety, tolerability, and device acceptability for use among 25 healthy volunteers between the age of 18 and 45. Based on the results of numerous preclinical studies, a single dose (5 joules/cm2) and schedule (twice a day, separated by at least 4 hours, preferably 8 to 12 hours apart) will be evaluated.

Safety and tolerability (local reactogenicity) will be assessed actively at the following study days: screening (baseline set), 1, 7 and 14, and on non-clinic visit days by collection of these data by history during clinic visits via a memory aid (diary cards). Volunteers will be encouraged to promptly contact designated clinical trial staff or the one of the Sponsor's Emergency Response Team for AEs of a medically urgent nature.

A Comprehensive Metabolic Panel, as well as CBC with differential, urinalysis, and pregnancy testing will be performed at screening and at Day 14 or early termination (and potentially during unscheduled) clinic visits. Hematological safety assessments (evaluation of methemoglobinemia) will be performed at all visits.

Study volunteers will be asked to immediately contact the clinical coordinator and/or the PI in all instances where they experience an AE of greater than moderate intensity. Volunteers will be instructed to report to the clinical trial unit for an unscheduled visit or to seek the appropriate level of medical care based on the nature of their AE/SAE. In all such instances, all relevant information pertaining to these significant medical events will be captured on the appropriate e-CRFs.

Hematology safety laboratory evaluations will be performed at screening, as well during all scheduled clinic visits. Laboratory assessments may be part of the evaluation of medically attended AE evaluation and for all SAEs.

Upon ratification of the CTA, the site will begin pre-recruitment outreach efforts of potential volunteers within M3-WRA's database to ascertain "interest in general" in this study. Official recruitment which may include fliers, letters, telephone calls, etc. and specific recruitment of potential subjects who have previously participated in other clinical studies conducted at the site will occur only after formal IRB approval. Other forms and/or mechanisms of recruitment may also be used. The IRB will approve the recruitment process and all materials prior to use.

Schedule of assessments can be found in Section 1.2, Schedule of Activities (Table 3).

3.2 Objectives and Outcomes OBJECTIVES ENDPOINTS (OUTCOME MEASURES) Primary

• Evaluation of the acute safety of the EmitBio™ RD19 device. • Frequency, grade and attribution of each incident local and systemic AE during the 14day study period.

• Frequency and attribution of any incident SAEs during the 14 \day study period. Secondary

• Evaluation of the acceptability of the EmitBio™ RD19 device. • Ease of use, clarity of user instructions, & compliance with per protocol schedule and, if out of compliance, reason(s) for noncompliance.

3.3 Scientific Rationale for Study Design The EmitBio™ RD19 device is designed to place a protective countermeasure in the hands of at population-risk individuals in order to reduce the incidence of SARS-CoV-2 and COVID-19. At population-risk individuals are those living where community-transmission of SARS-CoV-2 is likely to occur and where community transmission is actively occurring. Through the identified mechanisms of virus killing and inhibition of virus replication, the RD19 device is expected to reduce SARS-CoV-2 viral load which in combination with other lifestyle measures, may help reduce the incidence of SARS-CoV-2 infection. This type of active protection is urgently needed for high-risk individuals (e.g. individuals exposed to a known infected person and healthcare workers and eldercare facility staff exposed to SARS-CoV-2 infected / COVID-19 patients and residents, respectively). The RD19 device has been engineered with the intent to help curb community transmission of SARS-CoV-2, thereby reducing the incidence of COVID-19. The CDC estimates that 40% of secondary coronavirus transmission occurs before people feel ill, highlighting the need for a broadly distributed protective countermeasure.

The RD19 optical illumination device is inserted into the mouth to shine light on the proximal repository for respiratory tract pathogens in the pharynx. The RD19 device uses a precise color of visible blue light (absent of UV light) to stimulate host defense and eliminate invading pathogens. This color of blue light has been found to both stimulate the instantaneous release of the body's reserves of nitric oxide and to increase endogenous production of nitric oxide in barrier epithelial cells. This naturally produced nitric oxide is substantially elevated over background levels and promotes innate immune responses capable of disrupting SARS-CoV-2 infection and inhibit viral replication of human coronaviruses. In addition to its direct antiviral activity, nitric oxide is an important pro-inflammatory cell signal to elicit induction and recruitment of other innate immune effectors, including NK cells, neutrophils, and macrophages.

3.4 Justification for Dose In repeated experiments, including experiments conducted by third party external laboratories, it has been determined that the light emitted by the EmitBio™ RD19 device provides for potent antiviral activity against SARS-CoV-2. Reductions in viral infectivity of host cells >90% have been observed after a single illumination at an energy level of 7.5 joules/cm2. Separately, the yield of replicating SARS-CoV-2 virus in infected cells is inhibited by 50% at range of 9 - 15 J/cm2. Dosing twice a day (total of 15 J/cm2) also allows endogenous nitric oxide levels to be elevated to an extent and for a time period expected to result in high level antiviral effects.

4. STUDY POPULATION Twenty-five (25) males and non-pregnant females, 18 to 45 years of age inclusive, who are in good health and meet all eligibility criteria will be enrolled. The target population should reflect the community at large. The estimated time from initiation of enrollment to completion of the day 1 visit for the last subject enrolled is one week.

Subject Inclusion and Exclusion Criteria must be confirmed by a study clinician, licensed to make medical diagnoses and signatory to The Statement of Compliance as the site PI. Exemptions will be only be granted on Subject Inclusion or Exclusion in rare instances and based on the approval of the Sponsor's Chief Medical Officer.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 25
• Est. completion date: October 1, 2020
• Est. primary completion date: September 17, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

1. Provides written informed consent prior to initiation of any study procedures.

2. Agrees to comply with planned study procedures and be available for all study visits.

3. Agrees to the collection of venous blood per protocol.

4. Male or non-pregnant female, 18 to 45 years of age, inclusive, at time of enrollment.

5. Body Mass Index 18-35 kg/m2, inclusive, at screening.

6. Woman of childbearing potential must have a negative urine pregnancy test within 7 days prior to study initiation.

7. Oral temperature is less than 100.0°F (37.8°C).

8. Pulse no greater than 90 beats per minute.

9. Systolic BP is 85 to 150 mmHg and Diastolic BP = 90 mmHg, inclusive.

10. Clinical screening laboratory evaluations are within acceptable normal reference ranges at the clinical laboratory being used.

Exclusion Criteria:

1. Positive urine pregnancy test at screening.

2. Has any medical disease or condition that, in the opinion of the site PI or appropriate sub- investigator, precludes study participation.

3. Plans to travel away from the study site area during the term of study to a location or in a manner that may interfere with full completion of the study per protocol.

4. Presence of self-reported or medically documented significant medical or psychiatric condition(s).

5. Has an acute illness, as determined by the site PI or appropriate sub-investigator, with or without fever [oral temperature >38.0°C (100.4°F)] within 72 hours of study day 1.

6. Reports a recent positive test result for hepatitis B surface antigen, hepatitis C virus antibody, or HIV-1 antibodies at screening.

7. Currently enrolled in or plans to participate in another clinical trial with an interventional investigational agent that will be received during the study period.

8. Has a history of hypersensitivity or severe allergic reaction (e.g., anaphylaxis, generalized urticaria, angioedema, other significant reaction) to nitrates, nitrites or sun exposure.

9. Chronic use (more than 10 continuous days) of any medications that may be associated with impaired immune responsiveness or oral irritation.

10. Has any blood dyscrasias or significant disorder of coagulation.

11. Has a history of alcohol abuse or other recreational drug (excluding cannabis) use within 1 month of Study Day 1.

12. Has any oral abnormality that 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.

13. Receipt of any other SARS-CoV-2 or COVID19 experimental coronavirus investigational product at any time prior to or during the study.

Related Conditions & MeSH terms

• Infection
• Respiratory Tract Infections

Intervention

Device:
• EmitBio™ RD19
The EmitBio™ RD19 device emits visible blue light to stimulate host defenses (as explained below) to eliminate invading pathogens in the oropharynx and surrounding tissues. Selected wavelengths of blue light upregulate the sustained production of nitric oxide in epithelial tissue through increase of nitric oxide synthases (NOSs) and stimulate the instantaneous release of the body's bound stores of nitric oxide.

Locations

Country	Name	City	State
United States	Carolina Phase I	Raleigh	North Carolina

Sponsors (3)

Lead Sponsor	Collaborator
KNOWBio Inc.	M3-Wake Research Associates Carolina Phase I Clinical Trial Unit, TAB Clinical LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Solicited and Unsolicited Adverse Events - Acute Safety	Solicited and Unsolicited AEs will be ascertained daily using a diary card and recorded on the appropriate e-CRF forms during the entire course of the study.; For this study, solicited AEs include: Illumination site Pain; Illumination site Erythema; Illumination site Edema/Induration; Headache; Difficulty swallowing; Nausea; Fever; Chills; Unsolicited Adverse Events are any AEs spontaneously reported by the subject and/or in response to an open question from study staff or revealed by observation, physical examination or other diagnostic procedures.; All AEs will document onset and duration and will be graded for severity and relationship to the study device.	Screening followed by 14 consecutive days of RD19 device use per protocol
Secondary	Compliance with RD19 use	The degree of compliance with protocol-directed use of RD19 will be assessed as a percentage of #uses divided by total of 28 prescribed uses. Subjects will be asked to provide a reason for any missed use(s).	14 consecutive days of RD19 device use per protocol