A Randomized, Double-Blind, Sham Controlled, Stratified, Pivotal Efficacy and Safety Study of the EmitBio RD-X19 Treatment Device in Individuals 40 Years of Age and Older With Mild COVID-19 in the At-Home Setting
Phase: NA
Conditions: COVID-19
Sponsor: EmitBio Inc.

 
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1
  
CLINICAL TRIAL PROTOCOL 
 
A Randomized, Double-Blind, Sham Controlled, Stratified, Pivotal Efficacy and Safety 
Study of the EmitBio RD-X19 Treatment Device in Individuals 40 Years of Age and 
Older with Mild COVID-19 in the At-Home Setting 
 
Protocol Number: EB-P30-01 Version 3.1 
 
Investigational Device: EmitBio RD-X19 
 
 
Specific Indication: Treatment of Mild COVID-19 in Individuals ≥40 years of age 
 
Target Respiratory Disease Pathogen and Disease: SARS-CoV-2, mild COVID-19 
 
 
 
 
 
Name and Address of Sponsor:            
Name and Address of CRO: 
 
 
EmitBio Inc.                                                  IQVIA MedTech    
 
                                                      
615 Davis Drive, Suite 800  
            2400 Ellis Road 
Morrisville, NC 27560                                Durham, NC 27703 
 
 
Tel: + 1 (843) 540-3569 
                       Tel:  + 1 (866) 267-4479 
 
 
 
 
 
 
 
 
GCP Statement: This trial will be performed in compliance with (c)GCP. 
The information in this document is confidential and is proprietary to EmitBio Inc and/or 
KnowBio LLC. It is understood that information in this document shall not be used other than 
for the direct purpose of executing this protocol without the expressed written permission of 
EmitBio Inc or KnowBio LLC. 
 

 
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Signatures of the following individuals indicate that all agree this version is final. 
 
 
 
_______________________________ 
 
__________________         
Kiernan DeAngelis, MD 
 
Date 
Chief Medical Officer  
EmitBio Inc 
 
 
______________________________ 
 
__________________  
 
Tammy Carrea  
 
Date 
VP Quality, Regulatory, and Clinical Affairs 
EmitBio Inc 
 
 
 
______________________________ 
 
__________________    
Marla Mills-Wilson 
 
Date 
Director Clinical Operations/Project Lead 
 
 
 
_______________________________ 
 
 __________________  
 
Jonathan Smith, PhD 
 
Date 
Independent Study Statistician 
Adaptive Plus, LLC 
 
 
 
_______________________________ 
 
__________________ 
John Demos, JD 
 
Date 
General Counsel 
KnowBio Inc. 
 
 
 
_______________________________ 
 
__________________  
 
Crystal Perez (or signatory) 
 
Date 
Project Lead 
IQVIA 
 
 

 
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1.0 INSTITUTIONAL STATEMENT OF COMPLIANCE 
Each institution engaged in this research will hold a current Federal Wide Assurance 
(FWA) issued by the Office of Human Research Protection (OHRP), and/or will be guided 
by the review and deliberations of an Institutional Review Board (IRB)/Independent or 
Institutional Ethics Committee (IEC) that must be registered with OHRP as applicable to 
the research. 
 
The study will be carried out in accordance with the following as applicable: 
• United States (US) Code of Federal Regulations (CFR) 45 CFR Part 46: Protection of 
Human Subjects 
• Food and Drug Administration (FDA) Regulations: 21 CFR Part 50 (Protection of 
Human Subjects), 21 CFR Part 54 (Financial Disclosure by Clinical Investigators), 21 
CFR Part 56 (IRBs), 21 CFR Part 11, and 21 CFR 812 (Investigational Device 
Exemptions) 
• The International Council for Harmonization (ICH) of Technical Requirements for 
Registration of Pharmaceuticals for Human Use (ICH) E6(R2) Good Clinical Practice 
(GCP), and the Belmont Report: Ethical Principles and Guidelines for the Protection of 
Human Subjects of Research, Report of the National Commission for the Protection of 
Human Subjects of Biomedical and Behavioral Research 
• Any additional applicable Federal, State, and Local Regulations and Guidance

 
 
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2.0 INVESTIGATOR’S AGREEMENT 
This signature provides the necessary assurance that this study will be conducted according to all 
stipulations of the protocol, including statements regarding confidentiality, and according to local 
legal and regulatory requirements, US federal regulations, and ICH E6(R2) GCP guidelines. 
 
 
Principal Investigator Signature: 
 
 
 
Name: ____________________________________ 
 
 
Signed: ____________________________________ 
 
Date: ___________________ 
 
 
 
                           
 
Site Name and Address: 
 
 
 
 
 
 
 

 
 
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3.0 TABLE OF CONTENTS 
 
Contents 
1.0 INSTITUTIONAL STATEMENT OF COMPLIANCE ..................................................... 3 
2.0 INVESTIGATOR’S AGREEMENT ..................................................................................... 4 
3.0 TABLE OF CONTENTS ........................................................................................................ 5 
4.0 PROTOCOL INTRODUCTION ........................................................................................... 8 
4.1 BACKGROUND ......................................................................................................................... 8 
4.2 STUDY GOALS ....................................................................................................................... 13 
4.3 STUDY DESIGN ...................................................................................................................... 14 
4.4 STUDY POPULATION .............................................................................................................. 16 
4.5 OBJECTIVES AND ENDPOINTS ................................................................................................ 18 
4.6 INCLUSION AND EXCLUSION CRITERIA .................................................................................. 19 
4.6.1 Inclusion Criteria ........................................................................................................... 19 
4.6.2 Exclusion Criteria .......................................................................................................... 20 
4.7 STUDY SCHEDULE OF ACTIVITIES ......................................................................................... 22 
5.0 PROTOCOL .......................................................................................................................... 24 
5.1 BACKGROUND AND STUDY RATIONALE ................................................................................ 24 
5.2 RISKS AND BENEFITS ............................................................................................................ 24 
5.2.1  Potential Risks (Anticipated Device Related Adverse Events) .................................... 24 
5.2.2  Potential Benefits .......................................................................................................... 25 
6.0 STUDY DESIGN DETAIL ................................................................................................... 26 
6.1 SCIENTIFIC RATIONALE FOR THE STUDY ............................................................................... 27 
6.1.1 Justification for Dose ..................................................................................................... 27 
6.2 STUDY VOLUNTEER SELECTION, RETENTION & COMPENSATION .......................................... 28 
6.2.1 Recruitment ................................................................................................................... 28 
6.2.2 Retention ........................................................................................................................ 29 
6.2.3 Compensation Plan for Subjects .................................................................................... 29 
6.2.4 Costs .............................................................................................................................. 29 
7.0 STUDY DEVICE ................................................................................................................... 30 
7.1 REGULATORY CONSIDERATIONS ........................................................................................... 30 
7.1.1 Preliminary Regulatory Pathway for EmitBio RD-X19 ................................................ 30 
7.1.2 Proposed Label Claim/Indication for Use: .................................................................... 31 
7.1.3 Medical Device Quality System: ................................................................................... 31 
7.2 STUDY DEVICE AND USE ....................................................................................................... 31 
7.2.1 Device Description ........................................................................................................ 31 
7.3 USE / STORAGE & MAINTENANCE / ACCOUNTABILITY .......................................................... 32 
7.3.1 Acquisition and Accountability ..................................................................................... 32 
7.3.2 Device Storage and Maintenance .................................................................................. 32 
7.3.3 Preparation for Use ........................................................................................................ 32 

 
 
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7.4 MEASURES TO MAXIMIZE STUDY SUBJECT COMPLIANCE ..................................................... 32 
7.5 DEVICE DISCONTINUATION ................................................................................................... 33 
7.5.1 Study Pausing Criteria ................................................................................................... 33 
7.5.2 Study Stopping Criteria ................................................................................................. 34 
7.5.3 Investigator Decision to Discontinue Subject Use of Device ....................................... 34 
7.5.4 Follow-up of Study Subjects Who Discontinue Device Use ......................................... 35 
8.0 STUDY ASSESSMENTS AND PROCEDURES ................................................................ 35 
8.1 SCREENING ASSESSMENTS .................................................................................................... 35 
8.1.1 Screening Procedures .................................................................................................... 35 
8.2 ENROLLMENT PROCESS ......................................................................................................... 39 
8.3 DAY 1 DEVICE ASSIGNMENT, TRAINING, AND TREATMENT .................................................. 40 
8.3.1 Split Treatment .............................................................................................................. 40 
8.4 PROCEDURES FOR CLINICALLY SIGNIFICANT FINDINGS ......................................................... 42 
8.5 BIO-SPECIMEN COLLECTION .................................................................................................. 42 
8.6 SAFETY AND OTHER ASSESSMENTS ...................................................................................... 42 
8.6.1 Definition of Treatment Emergent Adverse Event (TEAE) .......................................... 46 
8.6.2 Solicited Treatment Emergent Adverse Events – Reactogenicity ................................. 46 
8.6.3 Unsolicited Treatment Emergent Adverse Events ......................................................... 47 
8.6.4 Treatment Emergent Adverse Event Reporting ............................................................. 47 
8.6.5 Definition of a Serious Adverse Event (SAE) ............................................................... 47 
8.6.6 Serious Adverse Event Reporting .................................................................................. 48 
8.6.7 Regulatory Reporting of Device-related AEs ................................................................ 48 
8.6.8 Classification of a Treatment Emergent Adverse Event ............................................... 48 
8.6.9 Severity of Treatment Emergent Adverse Events ......................................................... 49 
8.6.10 Relationship to Study Intervention/Investigational Device ......................................... 49 
8.6.11 Time Period and Frequency for Event Assessment and Follow-Up ............................ 50 
8.6.12 Treatment Emergent Adverse Event Reporting to Study Subjects .............................. 50 
8.7 REPORTING SUMMARY .......................................................................................................... 50 
8.8 PREGNANCY REPORTING ....................................................................................................... 51 
9.0 STATISTICAL CONSIDERATIONS ................................................................................. 51 
9.1 PRIMARY ENDPOINT AND KEY SECONDARY ENDPOINT......................................................... 51 
9.2 POWER AND SAMPLE SIZE: .................................................................................................... 52 
9.3 ANALYSIS POPULATIONS:...................................................................................................... 52 
9.4 STATISTICAL ANALYSES ....................................................................................................... 53 
9.4.1 Efficacy Analyses .......................................................................................................... 53 
9.4.2 Safety Analyses ............................................................................................................. 56 
9.4.3 Interim Analysis ............................................................................................................ 57 
10.0 OPERATIONAL CONSIDERATIONS AND SUPPORTING DOCUMENTS ............ 57 
10.1 ETHICAL CONSIDERATIONS ................................................................................................. 57 
10.1.1 Informed Consent Process ........................................................................................... 57 
10.1.2 Confidentiality and Privacy ......................................................................................... 59 
10.2 CLINICAL MONITORING ....................................................................................................... 59 
10.3 QUALITY SYSTEM ............................................................................................................... 59 
10.4 DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES ................................................ 59 
10.5 DCT (DECENTRALIZED TEAM) RESPONSIBILITIES .............................................................. 60 

 
 
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10.6 SPONSOR RESPONSIBILITIES ................................................................................................ 60 
10.7 SOURCE DOCUMENTS .......................................................................................................... 61 
10.8 STUDY RECORD RETENTION ............................................................................................... 61 
10.9 PROTOCOL DEVIATIONS AND VIOLATIONS .......................................................................... 62 
10.10 PUBLICATION AND DATA SHARING POLICY ...................................................................... 62 
10.11 CONFLICT OF INTEREST POLICY ........................................................................................ 62 
10.12 RESEARCH RELATED INJURIES .......................................................................................... 62 
11.0 REFERENCES .................................................................................................................... 64 
12.0 DEFINITIONS..................................................................................................................... 67 
13.0 APPENDICES ..................................................................................................................... 70 
Appendix 1 RD-X19 Investigational Device Manual (Instructions for Use) ...................... 70 
 
 
 
 

 
 
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4.0 PROTOCOL INTRODUCTION 
4.1 Background 
In December 2019, the Wuhan Municipal Health Committee identified an outbreak of viral 
pneumonia cases of unknown origin. Severe acute respiratory syndrome coronavirus type 2 (SARS-
CoV-2) was shortly thereafter identified as the etiological agent for Coronavirus Disease 2019 
(COVID-19). Recent reports demonstrate that viral load strongly correlates with disease severity, 
progression, and mortality in SARS-CoV-2-infected humans [1], and a higher number of health 
risk factors is associated with higher viral load. Many of the tissues  and glands in the oral cavity 
have been documented to have high levels of ACE-2 and TMPRSS2 expression, highlighting the 
importance of the oral cavity in understanding both disease progression and oral-lung transmission 
via aspiration [2,3]. 
There are currently no FDA authorized or approved therapies that directly target early (i.e., within 
3 days of symptom appearance) mild COVID-19 in the absence of risk factors for progression to 
severe disease, nor are there treatments directed locally to SARS-CoV-2 that is resident in the upper 
respiratory tract or oral cavity. Systemically administered antivirals, antibody therapies and 
convalescent plasma have shown clinical evidence of nasopharyngeal viral load reductions and 
improved clinical outcomes in non-hospitalized populations [4–6]. However, subsequent 
Emergency Use Authorizations have restricted these therapies only to individuals at increased risk 
for severe disease and hospitalization. All immune-based therapies require intravenous 
administration. The diversity of genetic variants of concern is increasing and new variants have 
demonstrated enhanced transmissibility and resistance to existing antibody therapies and 
immunological circumvention of current vaccines [7–9]. Rapidly occurring genetic mutations in 
SARS-CoV-2, especially in the crucial spike protein ligand to the ACE-2 receptor, are giving rise 
to a plethora of new viral phenotypes, some of which are highly transmissible and show patterns 
of increased virulence. Regulatory authorization of potent antivirals such as nirmatrelvir/ritonavir 
(Paxlovid) and, to a lesser extent, molnupiravir have been a welcome addition to the treatment of 
individuals with COVID-19 in the outpatient setting. However, these therapies are only indicated 
for use in individuals with risk factors for progression to more severe forms of disease and there 
is a growing awareness, and likely prevalence, of COVID-19 symptoms and SARS-CoV-2 
rebound associated with the use of these antivirals [10,11]. These existing limitations underscore 
the need for innovative therapeutic countermeasures that can be made widely available in an 
equitable fashion and directly address the issue of emerging variants. 
 
The technology utilized by the RD-X19 device (dosing oral tissues with 425 nm light) has been 
repeatedly demonstrated to provide high-level viral inactivation of SARS-CoV-2 in multiple, 
consistent, expert-laboratory in vitro studies. There are multiple mechanisms of action by which 425 
nm light doses reduce SARS-CoV-2 viral load, including (1) direct cell-free inactivation of virus 

 
 
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and (2) inhibiting replication of cell-associated SARS-CoV-2 by enhancing the innate immune 
response. Unlike the adaptive immunity induced or provided by vaccines or monoclonal antibodies, 
425 nm light dosing is not antigen-specific, antigen-directed, or antigen-dependent. RD-X19 has 
resulted in the inactivation of all SARS-CoV-2 variants of concern tested to date, including Delta 
and Omicron. This technology presents an unprecedented opportunity for mitigating the threat posed 
by current SARS-CoV-2 variants as well as novel pre-emergent coronavirus strains.  
EmitBio’s first-in-man (FIM) (NCT04557826) study evaluated the acute safety and tolerability of 
the RD-X19 device in 25 healthy volunteers. There were no unscheduled clinic visits or adverse 
events requiring unscheduled medical evaluation or medical care during the study.  No Serious 
Adverse Events (SAEs) were observed during the study. No Treatment Emergent Adverse Events 
(TEAEs) based on laboratory findings were observed during the study.  No significant elevations in 
methemoglobin over baseline levels were observed during the study period. Solicited reactogenicity 
and TEAEs for this study included illumination site pain, erythema, edema/induration, headache, 
difficulty swallowing, nausea, fever, and chills and/or sweats.  No TEAEs required medical 
intervention or alteration to the study subject’s participation in the trial. No study subject withdrew 
from the trial because of a TEAE.  All TEAEs were of short duration, with resolution typically 
reached the same day or within 24 hours.  In summary, the trial demonstrated no evidence of risk 
when the EmitBio RD-X19 (delivering a nominal dose of 9 J/cm2 twice daily (BID) for 14 days) 
was used as intended in an at-home environment.  
Following the FIM study, EmitBio conducted an early feasibility randomized, sham-controlled, 
double-blind safety, tolerability and bioeffect study evaluating the RD-X19 device vs. Sham control 
(EB-P12-01 – 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 (NCT04662671) [12]). In summary, a total of 31 study subjects were randomized 2:1 into RD-
X19 treatment vs. Sham control groups in this randomized controlled trial (RCT). The protocol was 
open to individuals diagnosed positive by an FDA-authorized SARS-CoV-2 antigen test performed 
within 24 hours of enrollment with the presence of two or more COVID-19 signs and symptoms of 
≥ moderate severity (using guidance applied to severity grading of Adverse Events (AEs)) with 
initial symptom onset 72 hours or less prior to study enrollment. The listing of inclusion and 
exclusion criteria can be found in the ClinicalTrials.gov reference above. 
 
Primary safety analyses returned the following results: no SAEs, no medically attended or device-
related TEAEs (all TEAEs captured were the appearance or worsening of COVID-19 related signs 
or symptoms). All TEAEs were attributed to COVID-19, and, notably, there were no local site 
reactions including no changes within the oral cavity indicative of pathology reflecting clinically 
meaningful potential changes to the oral microbiome. The device was completely safe and 
exceptionally well-tolerated in this study. 
 
Bioeffects (efficacy) included evaluation of reductions in the mean log10 salivary viral load from 
baseline through study day 8 via RT-qPCR and time to sustained resolution of COVID-19 signs 

 
 
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and symptoms, defined as all COVID-19 signs or symptoms graded as 0 (absent) or 1 (mild) with 
no reoccurrence of any sign or symptom of severity score >1 after resolution was achieved.   
 
The EmitBio RD-X19 was safe, reduced salivary viral load 100-fold after 4 days of treatment at 
study day 5 and 1000-fold (99.9%) at study day 8 – a full 72 hours after the completion of treatment.  
In our study, the median time to sustained COVID-19 symptom resolution was achieved 57 hours 
faster in the RD-X19 treated group than in the sham control group, a result that is both clinically 
meaningful and statistically significant. No study volunteer required medical intervention other than 
self-medication with OTC remedies. There were no study subjects that discontinued participation. 
 
Building on the positive results from previous trials, EmitBio conducted a larger randomized, sham-
controlled, dose-finding study of the RD-X19 device in subjects with mild to moderate COVID-19 
(NCT04966013).  Previous preclinical work in human tissue models showed that dosing with 32 
J/cm2 of 425 nm light twice daily for three days reduced Beta and Delta virus titers by up to 99.99% 
and induced no cytotoxicity in time-matched, uninfected well-differentiated human large airway 
epithelial cell cultures.  Accordingly, the EB-P20-01 trial aimed to demonstrate the feasibility of 
ascending 24 J/cm2 and 32 J/cm2 BID dose cohorts. In total, 241 potential subjects were assessed 
for inclusion eligibility and 216 were enrolled from 9 clinical study sites in the United States.  This 
trial included subjects who were infected with SARS-CoV-2 for the first time, previously infected, 
and/or with breakthrough infections who were previously vaccinated. In addition to assessing the 
treatment benefit in subjects with both mild and moderate COVID-19, genetic sequencing confirms 
this trial enrolled subjects infected with Delta and Omicron variants.  During the course of the study, 
no predefined safety signals as outlined in the study pausing or stopping criteria were observed.  
Treatment of Cohort B with 32 J/cm2 twice daily dosing was considered safe and well tolerated. 
Under 21 CFR 812.3(m), the RD-X19 does not meet any of the below criteria that define a 
Significant Risk (SR) device:  
• Is intended as an implant and presents a potential for serious risk to the health, safety, or 
welfare of a subject; - The RD-X19 is neither intended as an implant nor does it present a 
potential for serious risk to health, safety, or welfare of a subject.   
• Is purported or represented to be for use supporting or sustaining human life and presents a 
potential for serious risk to the health, safety, or welfare of a subject; - The RD-X19 does 
not present a potential for serious risk to health, safety, or welfare of a subject.   
• Is for a use of substantial importance in diagnosing, curing, mitigating, or treating disease, 
or otherwise preventing impairment of human health and presents a potential for serious 
risk to the health, safety, or welfare of a subject; - The RD-X19 does not present a potential 
for serious risk to health, safety, or welfare of a subject.   
• Otherwise presents a potential for serious risk to the health, safety, or welfare of a subject.  
- The RD-X19 does not present a potential for serious risk to health, safety, or welfare of a 
subject.   
 

 
 
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In addition to the above, the risks identified, mitigation measures and control strategies in 
combination with a review of all available nonclinical and clinical safety information have 
confirmed the company’s conclusion that the RD-X19 operating at the proposed dose levels is a 
Nonsignificant Risk (NSR) device.  
 
Through three clinical trials, institutional review boards have agreed with EmitBio’s 
characterization of RD-X19 as an NSR device.  The safety data from those trials has thus far further 
demonstrated the very low-risk nature of the device.   
 
EmitBio therefore intends to continue the experimental investigation and development of RD-X19 
as a NSR device and will not apply for an Investigational Device Exemption prior to this proposed 
study. 
 
The Mechanisms of Action (MOA) of RD-X19 are through both direct and indirect antiviral effects. 
RD-X19 reduces cell-free SARS-CoV-2 titer by as much as 99.99% and inhibits cell-associated 
viral titer by 99.9% when measured at 24 hours after a single treatment in vitro. One of the putative 
antiviral mechanism involves upregulation of  reactive oxygen species (ROS) and nitric oxide (NO) 
in epithelial cells. NO production occurs via both a 425 nm light-induced increase in nitric oxide 
synthases (NOSs) and stimulation of the instantaneous release of the body’s bound stores of NO. It 
is hypothesized that photoimmunomodulation of the respiratory epithelium also signals additional 
effector cells of the innate immune system. The innate immune effectors include natural killer (NK) 
cells, monocytes, additional macrophages, and dendritic cells (professional antigen-presenting 
cells) that rapidly proliferate and swarm the infecting virus. The technology utilized by RD-X19 
has been repeatedly demonstrated to provide high-level viral inactivation in multiple, consistent, 
expert-laboratory in vitro studies. The direct cell-free inactivation of virus by visible blue light 
presents a transformational opportunity for therapy that is not antigen-directed or antigen-specific, 
unlike adaptive immunity induced or provided by vaccines and monoclonal antibodies. 
EmitBio will continue efforts to understand the detailed mechanisms of action that inactivate SARS-
CoV-2 and inhibit its replication during and after application of RD-X19. Preliminary results indicate 
that 425 nm light simultaneously acts on the SARS-CoV-2 spike, nucleocapsid, and RNA. Thus, this 
technology presents an unprecedented opportunity for protection that is not antigen-directed or  
antigen-specific, with a high likelihood of mitigating the threat posed by current SARS-CoV-2 
variants as well as novel pre-emergent coronavirus strains. 425 nm light has inactivated all SARS-
CoV-2 variants tested to date, including WA1, Alpha, Beta, Gamma, Delta, and Omicron (B.1.1.529 
and BA.2), the Lambda variant, and early variant strains from California and New York [13]. 
Currently, the predominant circulating strains – Omicron subvariants BA.4 and BA.5 – are highly 
communicable and are responsible for substantial morbidity and mortality, especially among 
individuals with risk factors for progression to severe COVID-19.  What has not been well-
characterized is the effect of COVID-19 risk factors on disease pathogenesis and outcomes among 
individuals who have upper airway COVID-19 at presentation to the health care system, or who never 
present to the health care system because they manage their COVID-19 at home. Multiple published 

 
 
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sources of evidence are unequivocal in their finding that age is a critical risk factor for disease 
progression, the development of long COVID and the occurrence of post-COVID sequelae such as 
chronic pulmonary disease, including interstitial pulmonary fibrosis. EmitBio desires to initially target 
the use of RD-X19 to those who will most benefit from its use. 
As shown in Table 1. below and as reported previously by others [14–17], among individuals meeting 
the FDA/NIH definition of mild COVID-19, age is a strong prognostic factor for time to COVID-19 
symptom resolution, with subjects 40 years or older having substantially increased times to sustained 
symptom resolution. 
 
Table 1. Age is a prognostic factor for time to COVID-19  
symptom resolution in sham treated subjects with mild COVID-19. 
Age 
category 
Sham median time to 
sustained symptom resolution 
(hours) 
18-29 
89.9 
30-39 
85.4 
40-49 
170.3 
50-65 
241.2 
 
In view of the above findings, in this pivotal trial we plan to enroll  subjects with mild COVID-19 
who are age 40 or older, as described in detail below.  
 
 
 

 
 
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4.2 Study Goals 
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 by, (a) self-
assessed signs and symptoms (e-diary entries twice a day during the entire study period), (b) televisits 
for all at home study treatments, (c) remote study staff checks on days 8-14 and, (d) clinic visits on 
study days 1, 5, 8, and 14 for objective clinical assessments (vital signs, targeted physical exams, 
oropharyngeal exams). 
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 continute 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. 
 
 
 

 
 
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4.3 Study Design 
Subjects will provide written informed consent prior to initiating any screening procedures.  Subjects 
meeting all screening criteria will be eligible for enrollment and randomization into the study.  
Subjects with COVID-19 disease with signs and symptoms reported more than 72 hours from onset 
will be given instructions to see their primary care provider, urgent care or emergency treatment in 
accordance with current standards of medical practice. 
This pivotal efficacy and safety registration trial will initially randomize 326 volunteers total at a 
1:1 ratio into RD-X19 treatment and sham treatment groups. Sample size calculations are described 
more fully in Section 9.2, Power and Sample Size. The study population and inclusion/exclusion 
criteria are defined fully in Section 4.4, Study Population, and Inclusion/Exclusion Criteria, 4.6 
respectively. Briefly, enrollment requires subjects to be age 40 or older on the date of enrollment, 
have a positive COVID-19 test with time since symptom onset of 72 hours or less, and to meet the 
definition of mild COVID-19 described in Section 4.4, Study Population. Subjects will be stratified 
by age (age categories 40-49 and ≥50) and baseline disease severity score (< 1.25, ≥ 1.25). The 
baseline disease severity score is defined as the sum of the eight individual scores divided by eight.  
The primary endpoint will be time to sustained resolution of COVID-19 signs and symptoms without 
subsequent symptom recurrence or disease progression until the end of the study. Resolution of 
COVID-19 signs and symptoms is defined as the earliest time when cough, sore throat, nasal 
congestion, headache, chills and/or sweats, myalgia, fatigue, and nausea (with or without vomiting) 
have been assessed by the subject as absent (0) or mild (1) and temperature is less than 100.5 °F. 
Sustained resolution of COVID-19 signs and symptoms is achieved when all signs and symptoms 
remain at this level for five consecutive assessments (corresponding to an approximate 48-hour 
period). After sustained resolution is achieved, symptom recurrence is defined as having three or 
more consecutive assessments (corresponding to an approximately 24-hour period) where two or 
more of the nine signs and symptoms do not meet the resolution condition. “Disease progression” is 
defined as having evidence of involvement of the lower respiratory tract: shortness of breath (defined 
as respiratory rate of 20 or more breaths per minute) and SpO2 <96% (both ascertained from the 
average of three replicate assessments) and/or respiratory distress requiring pulmonary imaging that 
demonstrates COVID-19 pneumonia.  
The key secondary virological endpoint will be the time to the first of two consecutive negative 
SARS-CoV-2 antigen tests (with a minimum time between tests of 6 hours) without subsequent 
virological rebound, during the subjects' remaining time on study. Virological rebound (after having 
achieved two such consecutive negative tests) is defined as having two or more positive tests out of 
three consecutive assessments (corresponding to an approximately 24-hour period).  
Safety and tolerability (local reactogenicity) will be assessed as numbers and proportions of 
documented Treatment Emergent Adverse Events (TEAEs). Adverse Events (AEs) are any untoward 
medical occurrence, unintended disease or injury, or untoward clinical signs (including abnormal 
laboratory findings) in subjects, whether or not related to the investigational medical device and 
whether anticipated or unanticipated. TEAEs are adverse events (AEs) that either start after initial 

 
 
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treatment, or which are present prior to treatment initiation but which increase in severity after 
treatment. No AEs that are not TEAEs are expected in this study since the time between enrollmen 
t and first treatment is very brief. TEAEs will be determined by self-assessment and reported to 
decentralized team members during televisits. These unsolicited TEAEs will be reported by the 
decentralized team members to the clinical site staff. TEAEs will also be captured objectively by 
clinic staff during physical and oropharyngeal examinations on study days 5, 8 and 14, or during 
early termination. Volunteers will be instructed to contact designated clinical trial staff for TEAEs 
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 moderate severity will be 
instructed to seek care from their primary care provider or an urgent care center and will be advised 
to request a pulmonary imaging study (preferrably CT) as part of their healthcare evaluation to 
document the presence and extent, or absence, of COVID-19 pneumonia. Study subjects who 
progress to severe disease will be instructed to seek urgent medical care at their nearest Emergency 
Department.  All study subjects who require a medically-attended visit will be asked to provide the 
results of their evaluations to study staff to assess whether COVID-19 progression has occurred. 
Study subjects who are hospitalized will be tracked to assess the date and time of hospital admission 
to discharge or death and these events will be captured as part of the trial data.   
Previous clinical trials of RD-X19 have demonstrated very infrequent, transient and mild device-
related TEAEs. In the unexpected event that device-related SAEs or patterns of device-related 
TEAEs are observed, the Sponsor’s Medical Monitor/Chief Medical Officer will immediately 
consult with and refer these data to the Independent Medical Monitor for review and 
recommendations.   
Assessments of safety and clinical outcomes will occur as outlined in Section 4.7, Study Schedule 
of Activities, below.  A clinic-based visit will occur at baseline (Day 1) with subsequent  clinic visits 
on study days 5 (±1), 8 (±1) and 14 (±2). Televisits will occur on days 1-7. Direct observation of 
each treatment will occur either during the clinic or televisit, depending on the study day. Subjects 
should plan to bring devices and supplies with them to the clinic. 
Subject safety will be monitored throughout the study by the Site Investigators, supported by regular 
review by the Sponsor’s Medical Monitor/Chief Medical Officer (CMO) with pre-specified pausing 
and stopping criteria (see Section 7.5, Device Discontinuation). 
As described in Section 9.4.3, Interim Analysis,  a blinded sample size review will be carried out by 
an independent statistician based on the first 164 randomized subjects. Briefly, if the pooled 
proportion of subjects with an event for the primary endpoint is less than assumed, then to maintain 
the power of the study the total number of randomized subjects will be increased; subject to a cap of 
380 subjects. 
 
 

 
 
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4.4 Study Population 
The study population is subjects age 40 and older with a positive COVID-19 test who meet the 
definition of mild COVID-19 below and have time since symptom onset of 72 hours or less.   
Categorization of COVID-19 disease severity will be defined as follows: 
Mild COVID-19 
• Positive testing by an FDA-authorized SARS-CoV-2 diagnostic test, AND  
• Symptoms of mild illness with COVID-19 that could include fever, cough, sore throat, 
nasal congestion (including rinorrhea), headache, muscle or joint pain, fatigue, 
unexplained chills and/or sweats, nausea (with or without vomiting) or other non-
respiratory symptoms that may alter daily living (e.g. loss of taste or smell), AND  
• Do not have dyspnea, abnormal chest imaging, or any other clinical signs indicative of 
Moderate or Severe COVID-19, AND  
• Have a mean respiratory rate of <20 breaths/minute and mean heart rate of <90 
beats/minute 
Moderate COVID-19 
• Positive testing by an FDA-authorized SARS-CoV-2 diagnostic test, AND 
o The symptoms of mild WITH:  
o Clinical signs suggestive of lower airway involvement such as resting respiratory 
rate  ≥20 but <30 breaths per minute, imaging indicating lower respiratory disease 
involving <50% of the lung tissue, or clinical signs suggestive of moderate illness 
with COVID-19 such as heart rate ≥ 90 but < 125 beats per minute, and oxygen 
saturation (SpO2) ≥94% on room air at sea level. 
Severe COVID-19 
• Positive testing by an FDA authorized SARS-CoV-2 diagnostic test, AND 
o The symptoms of moderate illness WITH: 
o Clinical signs indicative of severe systemic illness, such as resting respiratory rate 
≥ 30 per minute, heart rate ≥ 125 per minute, lung infiltrates involving > 50% of 
the lung tissue, or SpO2 <94% on room air at sea level. 
 
 
 
 
 

 
 
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4.4.1. Symptom Severity Grading 
Guidance to study subjects for severity grading of COVID-19 signs and symptoms will be based 
on definitions used for severity grading TEAEs and a severity scoring card will be provided to 
study subjects at their screening and enrollment visit: 
• 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.  
• Fever will be severity scored as dichotomous: ≥100.50F (fever) vs <100.50F (afebrile) 
 
 

 
 
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4.5 Objectives and Endpoints 
OBJECTIVES 
ENDPOINTS 
(OUTCOME MEASURES) 
Safety Assessments 
• Device-related Serious Adverse 
Events (SAEs) and Treatment 
Emergent Adverse Events (TEAEs) 
characterized by Medical Dictionary 
for Regulatory Affairs (MedDRA) 
System Order Classified (SOC) 
Preferred Terms (PTs), including 
local site reactions. 
• Collection of all TEAEs reported 
from study subjects’ daily diary 
entries or in-office visits and via 
monitoring for application site 
reactions during clinic visits by 
investigators’ 
examination 
of 
intraoral pathology. MedDRA SOC 
PT-defined 
TEAEs 
will 
be 
established 
and 
evaluated 
individually and collectively for 
severity and attribution. TEAEs will 
be presented in tables, and listings. 
 
Primary Outcome Assessment 
• Sustained resolution of COVID-19 
signs and symptoms. 
• Time to sustained resolution of 
COVID-19 signs and symptoms 
without subsequent symptom 
recurrence or disease progression 
until the end of the study (as 
described in Section 4.3, Study 
Design).  
Secondary Outcome Assessment 
 
• Time to first of two consecutive 
negative antigen tests 
• [Key] Time to the first of two 
consecutive negative SARS-
CoV-2 antigen tests without 
subsequent virological rebound.  
 
 
 

 
 
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4.6 Inclusion and Exclusion Criteria 
4.6.1 Inclusion Criteria 
A subject must meet all the following criteria to be eligible for inclusion in this study: 
1. Positive for SARS-CoV-2 as detected using an FDA authorized SARS-CoV-2 antigen test at 
the screening/baseline visit.  
2. Negative for Influenza A and B antigen using an FDA-authorized rapid diagnostic test. 
3. 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 F). 
4. Time from appearance of first COVID-19 sign or symptom to screening must be 72 hours or 
less. 
5. Males or females, including pregnant and fecund females, 40 years of age and older on the 
date of enrollment. 
6. BMI <40. 
7. Provides written informed consent prior to initiation of any study  procedures. 
8. 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. 
9. 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. 
10. Agrees to perform self-diagnostic home testing twice a day, separated by ≥ 6 hours for the 
entire length of the study. 
11. 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. 
12. 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. 
13. Agrees to avoid nasal and sinus saline lavage during the study period. 
14. No uncontrolled disease process (chronic or acute), other than COVID-19 signs and 
symptoms (See section 8.1.1 – General Screening)*.  
15. No physical or mental conditions or attributes at the time of screening, which in the opinion 

 
 
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of the PI, will prevent full adherence to, and completion of, the protocol. 
 
4.6.2 Exclusion Criteria 
A subject with any of the following criteria will be excluded from participation in this study: 
1. Positive for Influenza A and B antigen using an FDA-authorized rapid diagnostic test. 
2. Individuals < age 40 on study day 1. 
3. Individuals who are symptomatic for COVID-19 for more than 72 hours on study day 1. 
4. 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. 
5. Any medical disease or condition that, in the opinion of the site Principal Investigator (PI) or 
appropriate sub-investigator, precludes study participation. 
6. History of use of a rescue inhaler for uncontrolled asthma within one month of study day 1.  
7. History of recurrent alcohol intoxication or other recreational drug use (excluding medically 
prescribed cannabis) within one month of study day 1. 
8. 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. 
9. History of any systemic antiviral therapies within one month of study day 1. 
10. 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. 
11. 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. 
12. Requirement to use narcotic medication for analgesia. 
13. History of vasomotor rhinitis with or without post-nasal drip within one month of study day 1. 
14. History of hypersensitivity or severe allergic reaction (e.g., anaphylaxis, generalized urticaria, 
angioedema, other significant reaction) to sun exposure.  
15. 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.  

 
 
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16. 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. 
17. Any individual without teeth or with a dental malformation that precludes directed use of the device 
as intended. 
18. 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.

 
 
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4.7 Study Schedule of Activities  
 
Study Procedures 
Screening, Enrollment & 
Randomization 
Treatment 
(Visit Window) 
Treatment  
(Visit Window) 
Follow Up2,5 
Days 8-14 
(Visit Window) 
At Each Study Day 
Baseline1, 2  
(Day 1 Clinic) 
Day 52 (± 1) 
Days 2, 3, 4, 6, 7                           
 
Day 8 
 (+1) 
Day 
14/ET7 
(±2) 
Informed Consent  
X 
 
 
 
 
SARS-CoV-2 Rapid Antigen & Flu A and B 
Rapid Antigen Tests 
X 
 
 
 
 
SARS-CoV-2 Rapid Antigen Test (Days 1-14) 
X 8 
(1 at home, 1 in clinic) 
X  
(1 at home, 1 in clinic) 
Twice daily 
Nasopharyngeal Swab for qPCR and viral 
sequencing 
X 
 
 
 
 
Medical History & Physical Examination3,4 
X 
X 
Changes Since Last Visit (CSLV) 
 
 
X 
CSLV 
X 
CSLV 
Oropharyngeal Assessment4 
X 
X 
 
 
X 
X 
Urine Pregnancy Test 
X 
 
 
 
X 
Concomitant Medication History/New 
Medications 
X 
X 
Changes Since Last Visit (CSLV) 
 
 
X 
CSLV 
X 
CSLV 
Vital Signs 
X 
 
X 
 
X 
X 
Temp and SpO2 (Twice Daily, Days 1-14) 
X8 
(1 at home, 1 in clinic) 
X 
(1 at home, 1 in clinic) 
X 
X 
(1 at 
home, 1 
in clinic) 
X 
TEAE Assessments4  
X 
X 
 
X 
X 
Demographics, Inclusion / Exclusion Review 
X 
 
 
 
 

 
 
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e-Diary Training  
X 
 
 
 
 
RD-X19 Device Dispensing/Collection  
X 
 
 
X5 
X5 
Treatments 
X 8 
(1 at home, 1 in clinic) 
X  
(1 at home, 1 in clinic) 
Twice Daily 
(Record in e-Diary twice daily) 
 
 
 Televisit By DCT Study Staff 
X (1 Televisit on clinic days) 
X (1 Televisit on clinic days) 
X (2 Televisits on non-clinic days) 
 
 
Investigational Device, RD-X19, Retrieval 
 
 
 
X 
X 
COVID-19 Symptom Assessment (e-Diary 
Completion, Days 1-14) 
X 
 
X 
(1 at home, 1 in clinic) 
Record in e-Diary twice daily, including Temp & SpO2 
Daily QA of e-Diary 
 
1. Must be Clinic-based visit. 
2. Days 1 and 5 have one treatment in the clinic and one at home. Study Days 5(+/-1), 8(+/-1) and 14(+/-2) visits are clinic based. Clinic visits on Study Days 5 and 8 
must be separated by ≥ 48 hours.  
3. Physical Examinations at Baseline (Day 1) and on Day 14 or early termination are full physical examinations. Examinations on study days 5 and 8 are targeted 
examinations based on the assessment of reported or observed TEAEs. 
4. PEs and oropharyngeal assessments, as well as TEAE scoring and attribution, must be performed by appropriately trained and experienced medical personnel. TEAE 
attribution requires medical personnel credentialled to make clinical decisions. 
5. Retrieved by study staff during clinic visit on Day 8 or 14. 
6. SARS-CoV-2 rapid antigen test & Influenza A and B rapid antigen test (separate tests) at baseline (Day 1); SARS-CoV-2 alone thereafter; Baseline counts as SARS-
CoV-2 test #1 for study day1 
7.  Early termination. 
8.   Exception if using Split Treatment on Day 1. See the Split Treatment section

 
 
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5.0 PROTOCOL 
5.1 Background and Study Rationale 
In laboratory studies, the light-dosing technology employed in the RD-X19 device has demonstrated 
the ability, through both direct and intermediate mechanisms, to kill cell-free virus by as much as 
99.99% and inhibit the cell-associated replication of multiple coronaviruses by 99.9% when 
measured at 24 hours after a single light treatment in vitro. The technology utilized by RD-X19 has 
been repeatedly demonstrated to provide dose-dependent antiviral activity in multiple, laboratory in 
vitro models. The mechanism of action via direct cell-free inactivation of virus by 425 nm visible 
blue light and an augmented innate immune response presents a breakthrough opportunity for 
therapy that is not specific pathogen-directed or dependent on antigen-specific adaptive immunity. 
5.2 Risks and Benefits 
5.2.1  Potential Risks (Anticipated Device Related Adverse Events) 
The potential risks of participating in this trial are mild, transient, local reactions as measured in 
previous EmitBio clinical studies. See the Clinical Investigators Brochure for more detail.  
EmitBio has classified RD-X19 as a “Not Significant Risk” (NSR) device per FDA guidelines and 
three IRBs have concurred with this designation; refer to Section 7.1.1, Preliminary Regulatory 
Pathway. 
CAUTION - The light emitted may be harmful to the eyes. Do not stare at the light. Photobiological 
eye safety testing has classified this device as Risk Group 2 - Moderate risk. The blue light emitted 
does not pose an immediate hazard due to aversion response to very bright light sources or due to 
thermal discomfort of prolonged exposures. However, direct illumination of unprotected eyes should 
be avoided. Study staff must ensure volunteers understand to never point the RD-X19 device toward 
their or anyone else's eyes. 
 
A summary of the known and potential risks of the RD-X19 are as follows: 
• 
Depth of insertion beyond recommended depth has the potential to result in pharyngeal 
gag reflex for some study subjects. 
• 
Exposure to blue light may be harmful to the eyes when the device is used incorrectly. 
• 
Exposure of tissues to blue light may cause mild, transient localized oropharyngeal pain, 
erythema, edema, and induration at the illumination site. 
• 
Exposure of tissues to blue light may cause mild transient pain, redness, swelling,  lesion, 
or dryness of the oral mucosa.  
• 
May result in  jaw discomfort when used by individuals with a small oral cavity. 
• 
Extended blue light exposure to eyes may result in worsened headache pain associated 
with chronic migraines and other cerebral vascular disorders associated with headache. 

 
 
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• 
Shining the end of the RD-X19 illumination device directly onto skin from approximately 
1 cm away has the potential to induce mild erythema. 
 
Risks to Privacy 
Subjects will be asked to provide personal health information (PHI). All attempts will be made to 
keep this PHI confidential within the limits of the law. However, there is a chance that unauthorized 
persons will see the subject’s PHI. All study records will be kept in a locked file cabinet or 
maintained in a locked room at the participating clinical trial site(s). Electronic files will be password 
protected. Only people who are involved in the conduct, oversight, monitoring, or auditing of this 
trial will be allowed access to the PHI that is collected. Any publications from this trial will not use 
information that will identify subjects by name. 
Organizations that may inspect and/or copy research records maintained at the participating clinical 
trial site(s) for quality assurance (QA) and data analysis include groups such as the IRB and the 
FDA. 
A description of this clinical trial will be posted on http://www.ClinicalTrials.gov. This web site 
does not include information that can identify subjects. 
There may be other risks, discomforts or side effects that are entirely unknown at this time. 
5.2.2  Potential Benefits 
There are no guaranteed benefits to study participants; however, based on our previous clinical 
studies, we expect to observe benefits including faster resolution of COVID-19 signs and symptoms.  
The use of the EmitBio RD-X19 is intended to alleviate the clinical signs and symptoms associated 
with COVID-19 and to reduce the time to a negative antigen test. There is also the potential for 
benefit to society resulting from insights gained from participation in this, and other similar studies. 
 
 

 
 
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 6.0 STUDY DESIGN DETAIL 
The primary goal of the study is to establish the efficacy and safety of the RD-X19 treatment device 
to treat eligible subjects who have mild COVID-19 with sufficient data to support a regulatory filing 
for authorization and approval by FDA. 
The study population is subjects age 40 or older who have a positive COVID-19 test with time since 
symptom onset of 72 hours or less, and who meet the definition of mild COVID-19 described in 
Protocol Section 4.4, Study Population. The target study population will reflect the underlying 
communities age 40 and over experiencing mild COVID-19, possessing both seropositive and 
seronegative subjects from a mixture of those who have previously had COVID-19, as well as 
vaccinated and unvaccinated subjects. Viral genetic sequencing will be performed in order to 
characterize SARS-CoV-2 variants present in the study population (at the time of protocol writing, 
Omicron sublineages BA.4 and BA.5 are the predominant circulating variants worldwide). 
The targeted number of subjects (N = 326) will be randomized 1:1 per treatment group. This sample 
size has >90% power to detect a clinically meaningful and statistically significant reduction in time to 
sustained resolution of COVID-19 signs and symptoms (without subsequent symptom recurrence or 
disease progression) in active RD-X19 vs Sham treatment groups. Full details on the sample size and 
power calculations are given in Section 9.2, Power and Sample Size. As described in Section 9.4.3, 
Interim Analysis, a blinded sample size review will be carried out by an independent statistician based 
on the first 164 randomized subjects. If the pooled proportion of subjects with an event for the primary 
endpoint is less than assumed, the total number of randomized subjects will be increased to maintain 
the power of the study; subject to a preliminary cap of 380. The number of randomized subjects will 
not be decreased.  
The primary efficacy endpoint will be time to sustained resolution of COVID-19 signs and symptoms 
without subsequent symptom recurrence or disease progression as defined in Study Design, Section 
4.3. 
The key secondary endpoint will be the time to the first of two consecutive negative SARS-CoV-2 
antigen tests without subsequent virological rebound, as defined in Section 4.3, Study Design. 
Subjects will be stratified by age (age categories 40-49 and ≥50) and baseline composite disease 
severity score (< 1.25, ≥1.25). The baseline disease severity score is calculated using the symptom 
severity score data provided by the subject during the baseline/day 1 study visit. Self-assessments 
by study subjects will occur on each study day, with post-baseline assessments conducted by study 
investigators on Day 5 (± 1 day), Day 8 (± 1 day) and Day 14 (± 2 days). Individuals who are 
hospitalized will be tracked until discharge or death and the date and time of these events will be 
captured in the study data.  

 
 
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The presence of TEAEs will be self-assessed by study subjects throughout the study and may be 
reported to the DCT team member during a televisit or to the site Study Coordinator at any time. All 
TEAEs will be evaluated by clinical investigators during clinic visits by targeted physical 
examination, as required, and oropharyngeal examination.  
Pregnancy testing will be performed at screening and at Day 14 or early termination visits.  
Subjects will be instructed to enter data into their e-Diaries twice daily to assess COVID-19 signs 
and symptoms and record the time of treatments. Each assessed COVID-19 symptom will be rated 
on a 4-point scale from none (0) to severe (3) and a summary severity average will be calculated.  
Fever will be assessed dichotomously as present (≥100.50 F) or absent (<100.50 F).  Twice daily oral 
temperatures and oxygen saturation levels (SpO2) will be measured by study-provided thermometers 
and pulse co-oximeters for home use.  Study staff will make personal contact with study participants 
through televisits on each of the first seven (7) days of the study to ensure compliance with the 
treatment regimen and ascertainment and recording of clinical data.  
Study Subject safety will be monitored throughout the study by the Investigator and supported by 
regular review by the Sponsor’s Medical Monitor/Chief Medical Officer and, as needed, by the 
independent Medical Monitor.   
The statistical analysis methods for efficacy and safety data as well as details on the sample size 
calculation are described in Section 9, Statistical Considerations. 
6.1 Scientific Rationale for the Study 
The technology utilized by RD-X19 has been repeatedly demonstrated to provide dose-dependent 
antiviral activity in multiple consistent, expert-laboratory in vitro studies.  The proof-of-concept 
clinical study EB-P12-01, established an effective dose (16 J/cm2, BID) in subjects with mild-to-
moderate COVID-19. The mechanism of action, including the potential to augment innate immunity, 
presents an unprecedented opportunity for treatment that is not specifically antigen-directed or 
dependent with documented activity against SARS-CoV-2 variants which have shown increased 
speed of replication in human tissue.  EB-P20-01 established that there continued to be a high level 
of  safety and tolerability when RD-X19 delivered a dose of 32 J/cm2, BID for 7 consecutive days.  
Subsequent analyses demontrated the utility in individuals 40 years of age and older with mild 
COVID-19 and informed the design of this pivotal trial. 
 6.1.1 Justification for Dose 
In repeated laboratory experiments, including experiments conducted by external third parties with 
bench top LED arrays capable of delivering precise wavelengths, irradiances, and doses of light, it 
has been determined that the visible light emitted by the EmitBio RD-X19 device can provide potent 
antiviral activity against upper respiratory pathogens including SARS-CoV-2. Reduction in cell-free 
virus of ≥1000 fold and inhibition of viral replication of ≥99% have been observed in repeated 
experiments conducted by the sponsor and external expert laboratories.  Dose-dependent effects are 
observed ranging from as little as a single 7.5 J/cm2 exposure up to complete antiviral activity at 30 

 
 
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J/cm2 measured 24 hours and 48 hours after exposure.  Multiple cell types including human 
respiratory epithelial cells and 3D epithelial tissue (oral and tracheal/bronchial tissues) in culture 
show high viability at single doses of visible blue light up to 120 J/cm2 and after several days of 
repeat, twice daily dosing with 32 J/cm2.  These repeated experiments, conducted in multiple labs 
with multiple cell types, along with years of medical use of licensed devices with comparable 
wavelengths, irradiances, and doses, all support the dose and schedule herein. 
6.2 Study Volunteer Selection, Retention & Compensation 
  6.2.1 Recruitment 
Individuals 40 years of age and older are the target for this study. The perspective and experience of 
these individuals is critical to develop a distinctive study brand that optimizes study awareness and 
educational materials that will attract individuals eligible for the study. A Decentralized Clinical Trial 
(DCT) paradigm will reduce burden on study subjects by offering most of the required study 
procedures through televisits.  
Sites and PIs chosen for the studies will be in areas of high population density with well-defined 
community outreach mechanisms. Sites will include a combination of EmitBio’s prior well-qualified 
sites as well as new, well-experienced sites who have been conducting COVID-19 treatment studies 
and are established in their communities. The sites will have access to the desired study population 
as they are the first place to call or visit to receive COVID-19 advice and treatments. Having the 
EmitBio device study available to sites should help maximize the current site’s potential database and 
visits already scheduled to find a study opportunity for their clients. The over-arching goal is to make 
the process of study recruitment as easy as possible for sites by providing them the support they need 
through audio, video and printed materials and educational content for their staff and the individuals 
in their supported communites. Online content (social media post, clinical trial web listing, and 
banner) will be created to post on study site websites. Study fliers will be available at multiple 
community locations, and posters created to hang in key locations to raise awareness of the study. 
Physician referral letters will be sent to notify existing provider networks of the study opportunity 
available for their patients as well. Symptom awareness will be the primary focus of key materials so 
that those with mild COVID-19 will be reminded of the necessity to test and the opportunity to 
participate in a novel treatment study that stresses not needing to take systemic medication. Quick 
reference materials such as a lay language protocol synopsis, eligibility criteria booklet with self-
assessment instructions, study information slides and a principal investigator welcome letter to 
explain the intended use of the materials will be made available.  
Community-based awareness campaigns will proactively reach potential study subjects.  Creative ads 
and messaging with graphics will be developed to appeal to individuals 40 years and older who may 
qualify for the study. All recruitment materials will be translated into Spanish for Hispanic 
communities as needed for the study. Campaign ads will direct interested participants to a central 
website to learn more about the study and complete a brief online pre-screening questionnaire focusing 

 
 
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on inclusion and exclusion criteria for the study. Recruitment methods will be assessed to determine 
what works and what doesn’t work, with adjustments made accordingly.  
No site will be allowed to randomize more than 15% of the total number of subjects randomized. 
6.2.2 Retention 
Study retention strategies will include education and explanation of the study schedule and procedures 
during screening and enrollment visits and restriction of enrollment to persons who can attend all 
study visits. Contact with study subjects will occur on a twice daily basis on days 1-7 to ensure study 
compliance. The importance of conducting treatments as instructed as well as capturing timely, 
accurate COVID-19 signs and symptoms and TEAE data will be stressed. 
6.2.3 Compensation Plan for Subjects 
Subjects will be compensated for their participation in this trial. Compensation will be ultimately 
subject to local IRB approval. Reimbursements will be disbursed at specific timepoints during the 
study with the total amount contingent on presenting up to date diary card entries and completing 
study procedures through day 14. 
6.2.4 Costs 
There is no cost to subjects for the research tests, procedures/evaluations or study device while taking part 
in this trial. Procedures and treatment for clinical care may be billed to the subject's insurance or third 
party. 
 

 
 
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7.0 STUDY DEVICE 
7.1 Regulatory Considerations 
7.1.1 Preliminary Regulatory Pathway for EmitBio RD-X19 
The Food and Drug Administration (FDA) plays a critical role in protecting the United States 
from threats such as emerging infectious diseases, including the COVID-19 pandemic. To date, 
the agency has utilized various mechanisms to expand access for drugs, grant Emergency Use 
Authorization (EUA) for certain diagnostic and treatment approaches and has issued policies for 
medical devices without premarket notification during the COVID-19 public health emergency. 
Under 21 CFR 812.3(m), the RD-X19 does not meet any of the below criteria that define a 
Significant Risk (SR) device:  
• Is intended as an implant and presents a potential for serious risk to the health, 
safety, or welfare of a subject. The RD-X19 is neither intended as an implant nor 
does it present a potential for serious risk to health, safety, or welfare of a subject.   
• Is purported or represented to be for use supporting or sustaining human life and 
presents a potential for serious risk to the health, safety, or welfare of a subject. The 
RD-X19 does not present a potential for serious risk to health, safety, or welfare of 
a subject.   
• Is for a use of substantial importance in diagnosing, curing, mitigating, or treating 
disease, or otherwise preventing impairment of human health and presents a 
potential for serious risk to the health, safety, or welfare of a subject. The RD-X19 
does not present a potential for serious risk to health, safety, or welfare of a subject. 
• Otherwise presents a potential for serious risk to the health, safety, or welfare of a 
subject. The RD-X19 does not present a potential for serious risk to health, safety, 
or welfare of a subject.   
 
In addition to the above, the risks identified, mitigation measures and control strategies in 
combination with a review of all available nonclinical and clinical safety information have 
confirmed the company’s conclusion that the RD-X19 operating at the proposed fluence levels is a 
Nonsignificant Risk (NSR) device.  
 
Through three clinical trials, institutional review boards have agreed with EmitBio’s 
characterization of RD-X19 as an NSR device.  The safety data from those trials has thus far further 
demonstrated the low-risk nature of the device.   
 

 
 
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EmitBio has implemented a Risk Management process that is compliant with ANSI AAMI ISO 
14971:2019 and, with the guidance of ISO/RT 24971:2020, developed a Risk Management Plan 
specifically for the RD-X19 system. Risk Management activities have been conducted in 
accordance with to the Risk Management Plan and internal Standard Operating procedures, 
including a Hazards Analyis to identify characteristics of the RD-X19 device that could affect 
safety and separate risk analyses that focus on the design and use/misuse related hazards.   
The Sponsor intends to continue development of RD-X19 as a NSR device and conduct this 
clinical study without an Investigational Device Exemption (IDE) application approved by FDA 
prior to initiation.  
Strict safety oversight will provide rapid detection of significant device-related TEAEs warranting 
pausing or halting the trial. See Section 8.5, Safety and Other Assessments, for detailed 
description of study Pausing and Stopping Rules. 
7.1.2 Proposed Label Claim/Indication for Use: 
The EmitBio RD-X19 device is intended for use as a treatment for mild COVID-19 in  subjects 
with positive results of direct SARS-CoV-2 viral testing ages 40 years of age and older who are 
symptomatic for 72 hours or less. 
7.1.3 Medical Device Quality System: 
EmitBio will operate under an established Quality Management System (QMS), with a 
commitment for continuous improvement and effectiveness, in accordance with the requirements 
of the customers and applicable international standards. Specifically, the EmitBio Quality 
Management System is compliant with the requirements of the FDA Quality Systems Regulations 
(QSR). Any device that malfuntions during the trial will be fully evaluated and documented in 
compliance with EmitBio’s QMS. 
7.2 Study Device and Use 
7.2.1 Device Description 
The RD-X19 device is designed to emit visible light to inactivate SARS-CoV-2 and stimulate 
host defenses in the oropharynx and surrounding tissues. The RD-X19 device does this without 
additional photosensitizers or chemical reagents that are typically employed with traditional 
photodynamic therapeutics.  
The device consists of two components: (1) Light Engine, and (2) Light Guide; each designed to 
allow the assembled device to meet specific criteria based on targeted safety and efficacy.   
There are two primary accessories required for use of the device.  The first accessory, the AC 
Adapter, is used for recharging the device.  The AC Adapter is plugged into wall voltage and then 
connected to the device via a USB Cable between device uses.  The user is prompted via indicator 

 
 
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lights when recharging is necessary, in progress, and complete.  The second accessory, the Device 
Storage Base, is used for storing the device between uses. 
7.3 Use / Storage & Maintenance / Accountability 
 7.3.1 Acquisition and Accountability 
The sponsor will provide clinical sites with RD-X19 devices packaged in appropriately labelled 
containers containing all components as well as instructions for use by study participants.  Each 
RD-X19 device will be thermo-labelled on its power unit with a serial number.  Study staff will 
ensure that each device’s serial number (e.g. P30-123) is assigned to a specific study subject and 
the link between device serial number and study subject study number will be maintained on an 
accountability log.  Subjects will be requested to bring their device to the clinic for each scheduled 
visit.  Upon completion of a subject’s treatment regimen in the trial, all RD-X19 devices and 
components must be returned to the study staff and then to the study sponsor. If a RD-X19 device 
should malfunction, study subjects must immediately notify the site staff to obtain a replacement 
device. Site staff will contact the designated randomization and device type key holder and and 
an appropriate device will identified to replace the malfunctioning device.  Malfunctioning 
devices should be stored at the applicable study site and returned to the sponsor at the end of the 
study with the other devices. 
 7.3.2 Device Storage and Maintenance 
All RD-X19 devices will be stored in a locked device storage room at the clinical trial site until 
needed for assignment to an enrolled study volunteer.  Upon acquisition by the study subject, 
devices should be stored in a dry climate-controlled environment in the original container in which 
it was provided.   
The device should be stored securely out of the reach of children who may mistakenly misuse the 
device, especially illumination of eyes – which is always to be avoided. The mouthpiece of the 
device is removable for rinsing with mild soap and warm water.  The power housing may be 
cleaned with a soft cloth that has been dampened in mild dish detergent diluted in water; pieces 
should then be dried with a soft cloth.  The optic of the device can be wiped gently with a dry 
cloth suitable for cleaning optical glasses. 
 7.3.3 Preparation for Use 
Refer to Appendix: RD-X19 Instructions For Use. 
7.4 Measures to Maximize Study Subject Compliance 
Study staff will make direct contact with study subjects via televisits for all at home treatments. 
Throughout the term of the study, study staff will remind subjects of the importance of capturing 
all clinical data within the e-Diary and to report any suspected AEs.  All study subject data with 
be quality assured on a daily basis. 

 
 
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Subjects will receive appropriate compensation for the disruption to normal daily activities 
created by this protocol.   
Additionally, the subjects will be educated on the role of their individual contribution in clinical 
research as it relates to developing a solution for mild COVID-19. 
7.5 Device Discontinuation 
7.5.1 Study Pausing Criteria 
If observations of any potential device-related SAE or patterns of non-resolving device-related 
TEAEs with severity grade 2 or higher in the same System Organ Classification Preferred Term 
(SOC PT) are observed in a single subject, treatment will be discontinued for that subject and 
they will continue with the full study schedule including collection of all data as if they had 
continued to be treated. 
EB-P30-01 enrollment may be paused if any of the following events occur: 
• Any subject experiences a device-related SAE. 
• Any subject experiences laryngospasm, bronchospasm, or anaphylaxis within 2 
hours after treatment. 
• Two (2) or more subjects experience an allergic reaction such as generalized 
urticaria (defined as occurring at three or more body parts) within 72 hours after 
treatment. 
o Potential photo-allergy or phototoxicity to one or more photosensitizing 
drugs in the subject’s medical history should be investigated in all cases.  
See “Medications that Increase Sensitivity to Light: A 1990 Listing 
(Levine 1990).” 
• Three (3) or more subjects experience a Grade 2 or higher TEAE within the same 
SOC PT based on the Medical Dictionary for Regulatory Activities (MedDRA) 
coding, considered to be related to RD-X19. 
 
While the study is paused, a complete review of safety findings will be performed by an 
Independent Medical Monitor at the earliest opportunity and will make a recommendation to the 
Sponsor regarding continuation or termination of all or some of the study subjects and/or the 
overall study protocol.  The Independent Medical Monitor has no affiliation with the design or 
conduct of the trial. The recommendation will be taken under advisement by the study Sponsor 
who has responsibility for any final decision. 
A study volunteer may elect to discontinue participation in the trial at any time. Investigative staff 
will ask the volunteer to return for an early termination evaluation, but they are under no 
obligation to do so. All study subjects must return the RD-X19 device at study termination and 

 
 
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study staff must verify that the device serial number matches the study subject to whom it was 
assigned. 
7.5.2 Study Stopping Criteria 
If ≥2 device-related SAEs or ≥3 device-related severe TEAEs (grade 3) in the same SOC PT are 
observed, further enrollment and treatment will be discontinued. Subjects on trial at the time on 
discontinuation will continue to be followed per protocol. 
7.5.3 Investigator Decision to Discontinue Subject Use of Device 
A subject may be removed from the study for the following reasons post initial device use; 
however, whenever possible the subject should be followed for safety evaluations per protocol: 
• 
Study non-compliance to protocol requirements that in the opinion of the 
participating clinical site PI or appropriate sub-investigator poses an increased risk (e.g., 
missing safety labs) or compromises the validity of the data. 
• 
Lost to follow-up. A subject will be considered lost to follow-up if he or she fails to 
appear for a follow-up assessment. Extensive effort (i.e., generally three documented 
contact attempts via telephone calls, e-mail, etc., made on separate occasions) will be 
made to locate or recall the subject, followed by a couriered delivery of study documents 
to the subject's home address to determine the subject’s health status. These efforts will 
be documented in the subject’s study file. 
• 
Medical disease or condition, or new clinical finding(s) for which continued 
participation, in the opinion of the participating clinical site PI or appropriate sub- 
investigator, might compromise the safety of the subject, interfere with the subject’s 
successful completion of this study, or interfere with the evaluation of safety. 
• 
If any TEAE, clinical laboratory abnormality or situation occurs such that continued 
participation in the study would not be in the best interest of the subject. 
• 
The occurrence of a SAE. 
• 
 If the subject is using the device in any manner inconsistent with instructions and 
protocol directives and procedures. 
 
If the subject agrees, every attempt will be made to follow all TEAEs through resolution or 
stabilization. 
Subjects who withdraw or are lost to follow-up after signing the informed consent form (ICF) and 
use the RD-X19 device will not be replaced. Subjects who withdraw or are withdrawn from this 
study after signing the ICF during screening but before randomization will be replaced. 
The reason for subject discontinuation or withdrawal from the study will be recorded on the 
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7.5.4 Follow-up of Study Subjects Who Discontinue Device Use 
Discontinuation of study device use does not constitute discontinuation from the study, and the 
study procedures should be completed as indicated by the Study Schedule of Activities. If a 
clinically significant finding is identified, including, but not limited to, changes from baseline 
(Day 1), after enrollment, the participating clinical trial site PI or qualified designee will determine 
if any change in subject management is needed. Any new clinically relevant finding will be 
reported as a TEAE. 
 
8.0 STUDY ASSESSMENTS AND  PROCEDURES 
8.1 Screening Assessments 
8.1.1 Screening Procedures 
Subjects will provide written informed consent prior to initiating any screening procedures.  At 
the screening visit, and prior to any other study-related activities, designated study personnel will 
provide the subject with detailed study information and will obtain written informed consent.  
Subject numbers will be assigned with the three-digit numerical site number beginning with 
numbers greater than three hundred (e.g. 301) followed by an alphanumeric protocol identifier 
(P30) and finally a three digit unique numerical identifier assigned with each new subject (e.g. 
001). 
Example Subject Number: 301-P30-001 
8.1.2 COVID-19  and Influenza A and B Screening 
Individuals who identify with symptoms associated with mild COVID-19 present for 72 hours or 
less will be tested for the presence of SARS-CoV-2 and Influenza A or B using FDA-authorized 
rapid antigen diagnostic tests.  These systems allow for rapid detection of SARS-CoV-2 and 
Influenza A and B via laminar flow immunoassays for the direct and qualitative detection of target 
antigens.  All potential study subjects must be tested, regardless if they have a documented recent 
positive PCR or antigen test results for SARS-CoV-2. 
Study volunteers will self-assess their COVID-19 symptoms as none (0), mild (1), moderate (2), 
or severe (3) during screening as part of a disease assessment questionnaire per guidance provided 
in protocol section 4.4.1, Symptom Severity Grading. Eligible subjects for enrollment must 
present with mild COVID-19 and test negative for Influenza A and B, and have at least two 
moderate or severe symptoms (cough, sore throat, nasal congestion, headache, chills and/or 
sweats, myalgia, fatigue, nausea (with or without vomiting) or at least one moderate symptom 
and an oral temperature of  ≥ 100.5 F are also eligible for enrollment.  All eligible subjects must 
have had the onset of sign/symptoms ≤72 hours prior to consenting. 

 
 
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• 
Potential subjects with any evidence of lower airway involvement, including 
shortness of breath either at rest on upon exertion, are ineligible for the study 
and should be referred to their primary care provider or urgent care center. 
• 
Potential subjects with COVID-19 signs and symptoms reported more than 72 
hours from onset are ineligible for the study and should be referred to their 
primary care provider or urgent care center. 
• 
Potential subjects will also be asked to report if they have been previously 
diagnosed with COVID-19 via an FDA-approved diagnostic test and whether 
or not they report that they have been previously vaccinated against COVID-
19. The date(s) of prior COVID-19 diagnoses and the number and approximate 
dates of COVID-19 vaccinations and the vaccine manufacturer will be 
documented.  Asking potential subjects to bring the CDC (or national 
equivalent, if such exists for non-US subjects) COVID-19 vaccination card will 
ease the time and burden of this task.  
• 
All vital sign measurements (HR, BP, RR, SpO2%), should be assessed as three 
measures over a 10-minute period and the average value should be captured for 
the purposes of this clinical trial.  
• 
A complete COVID-19 disease assessment will include vital signs recorded as 
part of general screening.  
• 
Subjects will be asked to assess their loss of taste and loss of smell (binary 
assessments at each assessment*). and pose the following patient-reported 
global impression assessments on Days 5, 8 and 14: 
a) In the past 24 hours, have you returned to your usual health (before your COVID-
19 illness)? Yes or No 
b) In the past 24 hours, have you returned to your usual activities (before your 
COVID-19 illness)? Yes or No 
*COVID-related loss of sense of taste and loss of sense of smell are well 
understood to normalize over a prolonged period of time given the neurological 
etiology, long after SARS-CoV-2 has been eliminated from the body. As these 
signs of COVID-19 have been reported to vary with each variant, this information 
is being collected for informational purposes and will be assessed only as part of 
the qualitative patient reported global assessment and will not be included as a 
component of the primary efficacy endpoint. 
 

 
 
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8.1.3 General Screening 
Some or all of the following assessments are performed during the screening visit to determine 
eligibility requirements as specified in the inclusion and exclusion criteria: 
o Obtain subject-reported medical history focusing on conditions per protocol exclusion 
criteria and those associated with an increased risk of progression of COVID-19 
(Asthma, Cancer, Cerebrovascular Disease, Chronic Kidney or Liver Disease, 
Chronic Lung Disease, Tuberculosis, Diabetes Mellitus, Hypertension, Heart Disease, 
Recent Pregnancy, Immune Deficiency, Smoking, Physical Activity level, Mood 
Disorders). It is particularly important to capture and document medical conditions 
that include signs and symptoms of COVID-19 but that are not due to the current 
episode of COVID-19. 
o History of exposure to someone with COVID-19 or participation in an event that poses 
a significant risk of exposure to SARS-CoV-2 (commercial flight, major sporting or 
entertaining events, etc) over the past two weeks, including start and end dates. 
o Review all pre-study medications, vitamins, supplements, and therapies up to 14 days 
prior to the start of screening that could impact the use of, or response to, the device 
and record on the appropriate source document.  The use of any medications to treat 
any of the COVID-19-related symptoms (e.g., analgesics, antipyretics, decongestants) 
should be recorded and the name of medication, dose, dosage form, and date and 
time(s) of administration should be reported.   Antibiotics are not indicated as a 
treatment for COVID-19 and use of antibiotics (e.g. tetracycline, azithromycin) for 
this purpose should be documented accordingly.  Individuals receiving antibiotics for 
treatment of COVID-19 must discontinue use prior to study enrollment and this 
information should be documented.  Individuals should be informed not to take 
antibiotics or other medications purported to treat COVID-19 (such as 
hydroxychloroquine or ivermectin) or known to treat COVID-19 (such as 
nirmatrelvir/ritonavir or molnupiravir) during their participation in the study. 
Antibiotic treatment of a bacterial infection during screening is a protocol exclusion 
because of the existence of an active concurrent disease. During the study, the decision 
to prescribe antibiotics for bacterial infections is a clinical decision that should be 
made by a licensed medical care provider outside of the protocol. Likewise, FDA 
authorized COVID-19 therapies for progressed COVID-19 are, of course, both 
appropriate and necessary when medically indicated but will result in study subjects 
being right censored for the efficacy analysis. These subjects will continue to be 
followed, per protocol, for safety assessments. Such use, and the reason for such use, 
will be documented. Study subjects will be requested to refrain from use of 
medications to treat COVID-19 symptoms. Any such use should be recorded on the 
concomitant medication form along with reason for use. The requirement to use 
narcotics for analgesia is prohibited and exclusionary. The use of acetaminophen (two 

 
 
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500mg tablets every 4-6 hours) as an antipyretic is allowed, but must be captured as a 
concomitant medication, if used. 
o Medications to treat chronic medical disorders must not be in a period of adjustment 
or alteration within 30 days prior to enrollment.  If medications have been adjusted 
within the past 30 days, or are currently being adjusted, this constitutes a chronic 
medical condition not under adequate control and is exclusionary. 
o Measure oxygen saturation at rest via pulse oximeter. Oxygen saturation at rest should 
be measured after the study subject has been in a sitting position for 5 minutes. Hands 
should be warm and resting in the lap.  Any fingernail polish must be removed prior 
to obtaining readings. Readings are taken three times over a 10 minute period and the 
average value recorded. This procedure should be used by study subjects during self-
assessments at home. 
o Measure vital signs (HR, BP, RR, and oral temperature) and height and weight for 
determination of BMI. Vital signs at rest should be measured after the study subject 
has been in a sitting position for 5 minutes. Readings are taken three times over a 10 
minute period and the average value recorded. RR and HR should be measured over 
a full 60 second period. This procedure should be used by study subjects during self-
assessments at home. 
o Assess dyspnea on exertion: have potential study subject walk in place for 30 seconds; 
have the subject sit down and wait 30 seconds and measure RR and oxygen saturation. 
If RR ≥ 20/min and SpO2 < 96%, then individual is excluded from the study. 
o Perform full physical examination which will include assessments of the following 
organs and organ systems: skin, head, ears, eyes, nose, and throat (HEENT), neck, 
lungs, heart, liver, spleen, abdomen, extremities, lymph nodes (axillary and cervical), 
and nervous system. 
o Obtain urine for pregnancy testing in fecund females 
o Review inclusion and exclusion criteria. For clarification, subjects who are 
participating in other diagnostic or observational clinical studies are not prohibited 
from participation based on the exclusion criteria, “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.” 
 
The overall eligibility of the individual to participate in the study will be assessed once all 
screening values are available. The screening process can be suspended prior to complete 
assessment at any time if exclusions are identified by the study team. 
Individuals with a diagnosis of COVID-19 severity greater than mild or, signs and symptoms 
present for more than 72 hours are not eligible for enrollment.   

 
 
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Individuals who qualify for inclusion will be immediately randomized for their day 1 visit. 
BP, pulse, and respiration should be measured 3 times over an approximate 10 minute period.  
The average of the 3 measurements constitutes the value to be captured on the e-CRF an EDC. It 
is important that BP cuffs and sphygnomonometers are adequately sized and calibrated. 
An individual may be re-screened if a protocol eligibility criterion, that is not met at the initial 
time of screening, will be met by rescreening of all assessments within the next 24 hours using 
the same subject number, provided their number of days since symptom onset remains 72 hours 
or less. 
No individual may be screened more than twice due to a screening failure result as defined above. 
Individuals will be provided the results of any screening abnormality necessitating follow-up with 
their primary care provider. 
8.2 Enrollment Process 
The enrollment process occurs in the following order: Pre-screen, Consent, Enroll, Screen,  
Randomize or Exclude, Train, Treat, Follow-up. 
 
Pre-screening is optional. Pre-screening may be an informal process to verify age, SARS-CoV-2 
test results performed independently by the subject, COVID-19 symptoms, and the onset of 
symptoms within the past 72 hours. If a subject appears eligible and interested, the subject is 
consented and considered as officially enrolled. The subject is assigned a subject identification 
number. 
 
Pre-screening may also be a formal process whereby COVID-19 testing is performed at the clinic 
to aid in confirming eligibility. In this instance, a pre-screen or testing informed consent is 
required. (Clinical sites are responsible for developing pre-screen informed consent forms and 
submission to the IRB for approval.) If a subject appears eligible based on pre-screen results, the 
subject is consented again and considered as officially enrolled. The subject is assigned a subject 
identification number. 
 
Following consent, formal screening occurs. The data collected during screening sets baseline 
values. Screening occurs on Day 1, therefore Screening/Baseline = Day 1. During screening, 
subjects complete a self assessment of COVID-19 symptoms guided by the site utilizing a grading 
reference that mimicks what the subjects see in their e-diaires. The data from this self assessment 
is recorded by the clinical site on source documents. The result of this assessment is auto-
calculated in EDC as the composite baseline symptom severity score which is used along with age 
(40-49 or ≥50) as stratifying factors for randomization. Following completion of all screening 
evaluations, the site will use this data to determine eligibility using the inclusion/exclusion criteria. 
If the subject meets the inclusion/exclusion criteria, they are eligible for randomization. If the 
subject fails the screening process, they are considered a screen failure. A study exit form is 
completed for all subjects who received a subject ID number. 
 
Subject data is entered into the RMP (Research Management Platform) EDC system in order to 
receive randomization to either the active or sham investigational device. Once randomized, the 

 
 
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subject receives a nasopharyngeal swab for a qPCR test and viral sequencing. Additional 
information about the subject’s COVID-19 exposure and history are recorded. As applicable, a 
pregnancy test is performed.  
 
Following randomization, the subject is dispensed the assigned device and trained on the use of 
the device.  
8.3 Day 1 Device Assignment, Training, and Treatment 
On Day 1, subjects will be assigned either the active or sham device. Training will be provided 
to the subject on the use of the device. 
Other materials will be dispensed to subjects as well including the following: 
-SpO2 Monitor 
-Thermometer 
-SARS-CoV-2 Rapid Antigen Tests 
-500mg Acetaminophen to be used as needed for fever based on PI discretion(must be 
documented as a concomitant medication if used) 
- Mobile phone, if necessary the subject is assigned a mobile device to record their self 
assessments.  
The subject is assisted with downloading the eCOA application called Study Hub (electronic 
mobile app designed as an e-Diary) and trained on how to enter data. A training entry is 
completed. 
Subjects are trained on how to perform daily at home assessments.  
Of note, on Day 1, subjects must receive the first in clinic treatment by 1700 hours so that the 
second at home treatment occurs after 2300 hours but in time to complete the e-diary and televisit 
before 2400 hours. The e-diary will not allow entries for Day 1 past 2400 hours. The time for the 
Day 1 PM  televisit, as well as for the Day 5 clinic visit, will be scheduled by clinic staff during 
the Day 1 clinic visit. 
Subjects will be advised of the importance of a minimum of 6 hours between the twice daily 
treatments and should understand that their treatments will be observed either during their clinic 
or televisits depending on the study day.  
At least 30 minutes after the first in clinic treatment, a physical examination of the oropharynx 
and surrounding tissue will be performed and subjects will be asked to report any local site 
reactions post the RD-X19 treatment. All solicited local site reactions are considered to be device-
related TEAEs and an adverse event form should be completed. Any other unanticipated adverse 
events are also recorded as applicable. 
8.3.1 Split Treatment 
In the event that a subject is enrolled late in the day on Day 1 and does not complete the first 
treatment by 1700 hours such that the second treatment on Day 1 cannot be completed by 2300 
hours, the subject’s first treatment will be on Day 1 PM and the second treatment and televisit will 

 
 
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occur on Day 2 AM. Thereafter, am/morning and pm/evening treatments will continue until the 
14th treatment with the final treatment on Day 8.  
 
The 14th treatment on Day 8 may or may not occur in the clinic depending on the scheduling of 
the Day 8 follow up visit. The site clinical staff must determine whether the Day 8 treatment will 
be in clinic or via televisit and convey to the DCT staff. The DCT staff cannot make decisions on 
treatment or clinic visits; they are only responsible for televisits and televisit scheduling. 
 
A split schedule will occur as follows: 
  
Treatment 1 
Day 1 PM 
Treatment Diary Only 
In RMP: 
-COVID-19 Symptom Assessment  
-Temperature and Oxygen  
-Antigen Test   
-Treatment Administration  
Treatment 2 Diary 
Day 2 AM  
COVID-19 Symptom Assessment  
Temperature and Oxygen  
Antigen Test   
Treatment Administration  
Treatment 3 Diary 
Day 2 PM 
COVID-19 Symptom Assessment  
Temperature and Oxygen  
Antigen Test   
Treatment Administration  
Treatment 4 Diary 
Day 3 AM 
COVID-19 Symptom Assessment  
Temperature and Oxygen  
Antigen Test  
Treatment Administration  
Treatment 5 Diary 
Day 3 PM 
COVID-19 Symptom Assessment  
Temperature and Oxygen  
Antigen Test 
Treatment Administration  
Treatment 6 Diary 
Day 4 AM 
COVID-19 Symptom Assessment  
Temperature and Oxygen  
Antigen Test  
Treatment Administration  
Treatment 7 Diary 
Day 4 PM 
COVID-19 Symptom Assessment  
Temperature and Oxygen  
Antigen Test   
Treatment Administration  
Treatment 8 Diary 
Day 5 AM 
COVID-19 Symptom Assessment  
Temperature and Oxygen  
Antigen Test   
Treatment Administration  
Treatment 9 Diary 
Day 5 PM 
COVID-19 Symptom Assessment  
Temperature and Oxygen  
Antigen Tes  
Treatment Administration  
Treatment 10 Diary 
Day 6 AM 
COVID-19 Symptom Assessment  
Temperature and Oxygen  
Antigen Test  
Treatment Administration  
Treatment 11 Diary 
Day 6 PM 
COVID-19 Symptom Assessment  

 
 
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Temperature and Oxygen  
Antigen Test  
Treatment Administration  
Treatment 12 Diary 
Day 7 AM 
COVID-19 Symptom Assessment  
Temperature and Oxygen  
Antigen Tes  
Treatment Administration  
Treatment 13 Diary 
 
Day 7 PM 
COVID-19 Symptom Assessment  
Temperature and Oxygen  
Antigen Test  
Treatment Administration  
Treatment 14 Diary 
Day 8 AM or PM 
COVID-19 Symptom Assessment  
Temperature and Oxygen  
Antigen Test 
Treatment Administration 
Treatment 14 on Day 8 may occur either in the clinic or by 
televisit, thereafter all e-Diary entries are completed by the 
study subject without a televisit 
Clinic Check 
Day 8  
Morning and Afternoon 
Diaries 
Days 8 -14 
COVID-19 Symptom Assessment  
Temperature and Oxygen  
Antigen Test   
Return mobile device 
 
8.4 Procedures for Clinically Significant Findings 
If in the judgement of the PI any finding poses a previously unknown risk to an individual or leads 
to a diagnosis of a disease or condition that would have disqualified the individual for enrollment, 
the study subject will be withdrawn from the study immediately.   
All clinically significant findings that occur post randomization and after the first use of the RD-
X19 device will be considered TEAEs. 
8.5 Bio-specimen Collection 
A single nasopharyngeal swab and sample will be collected at the baseline (Day 1) visit to assess 
quantitative viral load and for genetic sequencing in a subset of samples. 
Twice daily swabs of the nares will be taken by study subjects to assess the presence or absence 
of SARS-CoV-2 antigen. This is a FDA-authorized home diagnostic test that involves little to no 
discomfort and takes approximately 15-20 minutes to complete. 
8.6 Safety and Other Assessments 
Study procedures are specified in protocol Section 4.6, Schedule of Activities. A study clinician, 
licensed to make medical diagnoses as the participating clinical site PI or appropriate sub-
investigator, will be responsible for all study-related medical decisions. 
o Medical history: 

 
 
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o A complete medical history will be obtained by interview of subjects 
at the screening visit. Subjects will be queried regarding a history of 
significant medical disorders of the head, ears, eyes, nose, throat, 
mouth, cardiovascular system, lungs, gastrointestinal tract, liver, 
pancreas, kidney, urologic system, nervous system, blood, lymph 
nodes, endocrine system, musculoskeletal system, skin, and 
genital/reproductive tract. A history of any allergies, cancer, 
immunodeficiency, psychiatric illness, substance abuse, and 
autoimmune disease will be solicited. 
o At all subsequent visits, an interim medical history will be obtained 
by interview of subjects and any changes since the previous clinic 
visit will be noted. The interim medical history should include an 
assessment for new medical conditions and symptoms starting since 
initiating treatment that are suggestive of a TEAE. 
o Physical examination: 
o A full physical examination will be performed at the screening visit 
and on study day 14, and a symptom-directed (targeted) physical 
examination will be performed if  indicated on study days 5 and 8 or 
at any time an unscheduled visit is required. 
▪ A full physical examination will include assessments of the 
following organs and organ systems: skin, HEENT, neck, 
lungs, heart, liver, spleen, abdomen, extremities, lymph nodes 
(axillary and cervical), and nervous system. 
▪ Height and weight will be measured, and BMI calculated, at 
the screening visit only. 
o A symptom-directed (targeted) physical examination will be 
performed if indicated during other scheduled clinical site visits. 
▪ Targeted physical examinations will primarily focus on 
assessment of signs and symptoms starting since initiating 
treatment that are suggestive of TEAEs and an examination 
of the oropharynx. Interim or unscheduled physical 
examinations will be performed at the discretion of the 
participating clinical site PI or appropriate sub-investigator, if 
necessary, to evaluate TEAEs. 
o Subjects will be observed in the clinic for at least 30 minutes post the 
first RD-X19 illumination. The oropharynx and surrounding tissues 
will be examined. Reactogenicity assessments will be performed on 

 
 
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Day 1 in the clinic and on days 5, 8, and 14 during clinic evaluations. 
Interim or unscheduled targeted physical examinations will be 
performed, if necessary, to evaluate potential TEAEs. 
o Vital signs:  
Vital sign measurements will include systolic and diastolic BP, HR, 
breaths per minute, oral temperature and oxygen saturation via a 
pulse co-oximeter. BP, pulse and respirations and oxygen saturation 
will be assessed as previously described. Subjects must not eat or 
drink anything hot or cold within 10 minutes prior to taking their oral 
temperature or using the RD-X19 device. All subjects will be issued 
thermometers and small pulse oximeters to measure oral temperature 
and O2 saturation on a twice daily basis and record the results on their 
diary card. 
o Urine pregnancy test will be performed locally by the site laboratory 
at the screening visit. Results will be recorded as study data and 
referrals made for serological confirmation and follow-up as 
required. 
o e-Diaries: Subjects will be instructed to fill out e-Diaries twice daily 
to assess their COVID-19 signs and symptoms and record the number 
of treatments completed.  Each of the eight symptoms will be rated 
on a 4-point scale from none (0) to severe (3). Temperature and 
oxygen saturation will also be measured and recorded via devices 
provided by site personnel and taken home by the subject.  Televisit 
contact will be made by with subjects by the decentralized study staff 
during the home  treatments on days 1-7. Observation of use of the 
device and recording of study data should be timed to coincide with 
the study subject encounter. Daily contact with study subjects will 
enhance safety monitoring and reinforce adherence to at-home study 
procedures. 
o 
COVID-19 Severity Progression 
o There is a risk that subjects with mild COVID-19 may progress to 
moderate or more severe disease while on study.  In such cases, 
appropriate medical referrals for evaluation and treatment outside of 
the protocol will be made. 
o Medically attended visits as a result of COVID-19 will be classified 
into the following categories:  
1) those who require medical attention attributed to any 
severity of COVID-19;  

 
 
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2) those who require medical attention attributed to any 
SAE; 
3) Those who progress to moderate disease indicated by new 
onset shortness of breath (respiratory rate ≥20/minute) 
and SpO2 of < 96% confirmed by pulmonary imaging or 
lower airway disease diagnosed by pulmonary imaging 
involving < 50% of lung parenchyma; 
4) Those who progress to severe disease with respiratory rate 
>30/minute and/or O2 saturation ≤93% on room air or 
lower airway disease confirmed by pulmonary imaging 
involving ≥ 50% of lung parenchyma; 
5) Those who require hospitalization for severe COVID-19; 
6) Those who require endotracheal ventilation or ECMO 
with or without the use of solumedrol; and 
7) Those who die. 
o 
Subjects with a primary care, urgent care, or emergency room visit 
that are not hospitalized as a result of their medical consultation, may 
continue treatment with the investigational device and should attend 
regularly scheduled follow up visits per protocol.  Subjects that are 
admitted to the hospital should discontinue all treatment in lieu of 
standard of care for severe/critical COVID-19 illness or other SAEs. 
Such subjects’ endpoint data will be right censored as specified in the 
Statistical Analysis Plan (SAP). 
o Subjects who are treated with any FDA-authorized COVID-19 
therapy will discontinue treatment but will continue to be followed 
per protocol. Such subjects’ endpoint data will be right censored as 
specified in SAP. 
o Subjects who first reach clinical resolution on or after study day 11 
should be scheduled for their day 14 visit, which has a +/- 2 day 
window, so that a total of five consecutive visits (including the first 
resolution visit) are captured where resolution may be observed thus 
allowing the primary clinical sustained resolution endpoint to be met. 
Under no circumstances, however, may a study subject be scheduled 
for their day 14 visit beyond study day 16. 

 
 
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8.6.1 Definition of Treatment Emergent Adverse Event (TEAE) 
Adverse Events (AEs) are any untoward medical occurrence, unintended disease or injury, or 
untoward clinical signs (including abnormal laboratory findings) in subjects, whether or not 
related to the investigational medical device and whether anticipated or unanticipated. TEAEs are 
adverse events (AEs) that either start after initial treatment, or which are present prior to treatment 
initiation but which increase in severity after treatment. No AEs that are not TEAEs are expected 
in this study since the time between enrollment and first treatment is very brief.  
Any medical condition that is present at the time that the subject is screened will be captured as 
part of the study subject’s baseline medical history and will serve as the basis for capturing AEs 
that are treatment-emergent based on worsening severity.  
TEAEs can be further divided into solicited TEAEs and unsolicited TEAEs. Solicited TEAEs are 
those for which the study team will specifically query the subject whether they occurred. 
Unsolicited TEAEs are those events that the subject report occurring without being queried about 
the specific event. 
All TEAEs will be assessed for severity and relationship to study intervention/investigational 
device. Reporting of all TEAEs, solicited and unsolicited, will occur during the period from study 
device administration on Day 1 through Day 14 or until an early termination visit. 
All TEAEs, solicited and unsolicited, will be captured on the appropriate source documents and 
e-CRFs. Information to be collected for TEAEs includes event description, date of onset, 
assessment of severity, relationship to study product and alternate etiology (assessed only by those 
with the training and authority to make a diagnosis such as the participating clinical site PI or 
appropriate sub-investigator), date of resolution, seriousness, and outcome. All TEAEs will be 
documented regardless of relationship. 
TEAEs will be followed to resolution or stabilization. 
8.6.2 Solicited Treatment Emergent Adverse Events – Reactogenicity 
Solicited TEAEs are anticipated TEAEs for which consistent collection of information is desired. 
Study clinicians will follow and collect resolution information for any reactogenicity symptoms 
that are not resolved during the active study period. 
Solicited TEAEs (i.e., reactogenicity) will be collected by direct questioning of study subjects and 
recorded on the appropriate source document and e-CRF during the entire course of the study. 
For this study, solicited TEAEs include: 
• 
Illumination site Pain 
• 
Illumination site Erythema 
• 
Illumination site Edema/Induration 
• 
Any other pain, redness, swelling or lesion of the oral mucosa 

 
 
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8.6.3 Unsolicited Treatment Emergent Adverse Events 
All TEAEs 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 must 
be recorded on the appropriate source document and e-CRF. 
Unsolicited AEs of all severities will be reported during the entire course of the study. 
8.6.4 Treatment Emergent Adverse Event Reporting 
Information on all TEAEs should be recorded on the appropriate source document and e-CRF. 
All clearly related signs, symptoms and results of diagnostic procedures performed because of an 
TEAE should be grouped together and recorded as a single diagnosis.  
8.6.5 Definition of a Serious Adverse Event (SAE) 
An SAE is defined in 21 CFR 312.32 as follows: “An AE is considered serious if, in the view of 
either the participating clinical site PI or appropriate sub-investigator or the sponsor, it results in 
any of the following outcomes: 
• Death, 
• A life-threatening adverse event, 
• Inpatient hospitalization or prolongation of existing hospitalization, 
• A persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions, or 
• A congenital anomaly or birth defect. 
 
Important medical events that may not result in death, are not immediately life-threatening, or 
require hospitalization may be considered serious when, based upon appropriate medical 
judgment, they may jeopardize the subject and may require medical or surgical intervention to 
prevent one of the outcomes listed in this definition. An example of such a medical event would 
be an allergic bronchospasm requiring intensive treatment in an emergency room or at home to 
prevent the development of one of the definitions above. 
“Life-threatening” refers to an AE that at occurrence represents an immediate risk of death to a 
subject. It does not include an adverse event or suspected adverse reaction that, had it occurred in  
more severe form, might cause death. Similarly, a hospital admission for an elective procedure is 
not considered an SAE. 
All SAEs will be assessed for severity and relationship to study intervention. All SAEs will be 
recorded on the appropriate SAE e-CRF. 

 
 
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All SAEs will be followed through resolution or stabilization by a study clinician, licensed to 
make medical diagnoses and listed as the participating clinical site PI or appropriate sub-
investigator. 
All SAEs will be reviewed and evaluated by the Sponsor and will be reported according to the 
Reporting Requirements. This report will include severity, association with the study device, 
action(s) taken, and outcome. 
8.6.6 Serious Adverse Event Reporting 
Any TEAE that meets a protocol-defined criterian as an SAE must be reported immediately 
(within 24 hours of site awareness) using the electronic data collection tool, eCRF.  Investigators 
must report all Safety Events (AEs, SAEs and Device Deficiencies) via the Electronic Data 
Capture (EDC) system. If the electronic system is unavailable, then the site will use the paper 
SAE data collection tool to report the event within 24 hours and send to the IQVIA MedTech 
Safety management team by email: Emitbio@iqvia.com. 
Other supporting documentation of the event may be requested by EmitBio’s Medical Monitor 
and should be provided as soon as possible. The Sponsor Medical Monitor will review and assess 
the SAE for regulatory reporting and potential impact on study subject safety and protocol 
conduct. 
At any time after completion of the study, if the participating clinical site PI or appropriate sub-
investigator becomes aware of an SAE that is suspected to be related to study product, the 
participating clinical site PI or appropriate sub-investigator will report the event to the U.S Food 
and Drug Administration using MedWatch, FDA’s Safety Information and Adverse Event 
Reporting Program. 
8.6.7 Regulatory Reporting of Device-related AEs 
EmitBio Inc. will report to the FDA any unanticipated device-related TEAEs and SAEs as soon 
as possible, but in no case later than 10 working days after the sponsor’s initial receipt of the 
information.  
Relevant follow-up information to the safety report will be submitted as soon as the information 
is available. Upon request from FDA, EmitBio will submit to the FDA any additional data or 
information that the agency deems necessary. 
SAEs that are not considered related to RD-X19 will not be reported to the FDA. 
8.6.8 Classification of a Treatment Emergent Adverse Event 
The determination of seriousness, and causality will be made by an on-site investigator who is 
qualified (licensed) to diagnose TEAE information, provide a medical evaluation of TEAEs and 
classify TEAEs based upon medical judgment. This includes, but is not limited to, physicians, 
physician assistants and nurse practitioners.  

 
 
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8.6.9 Severity of Treatment Emergent Adverse Events 
All TEAEs will be assessed for severity according to the toxicity grading scale of mild, moderate, 
and severe.. 
The following guidelines will be used to describe severity: 
• Mild (Grade 1): Events that are usually transient and may require only minimal or no 
treatment or therapeutic intervention and generally do not interfere with the subject’s 
usual activities of daily living. 
• Moderate (Grade 2): Events that are usually alleviated with additional specific therapeutic 
intervention. The event interferes with usual activities of daily living, causing discomfort 
but poses no significant or permanent risk of harm to the research subject. 
• Severe (Grade 3): Events interrupt usual activities of daily living, or significantly affects 
clinical status, or may require intensive therapeutic intervention. Severe events are 
usually incapacitating. 
 
TEAEs characterized as intermittent require documentation of onset and duration of each episode. 
A TEAE is not counted as a separate or new TEAE if at the next clinic visit, the TEAE is persistent 
at the same of lesser severity level.  It shall be recorded as a new TEAE if it worsens in severity.  
The same TEAE verbatim term with a worsened severity score will be documented as an 
independent event, including start and stop dates.  The start and stop date of each reported TEAE 
will be recorded on the appropriate e-CRF.  All device-related grade ≥2 TEAEs (any grade greater 
than mild is considered unanticipated) will be reported.  
See SAE source document for information to be submitted. 
8.6.10 Relationship to Study Intervention/Investigational Device 
For each reported adverse event, the participating clinical site PI or qualified designee must assess 
the relationship of the event to the study device using the following guidelines: 
• Related – The AE is known to occur with the study intervention, there is a reasonable 
possibility that the study intervention caused the AE, or there is a close temporal relationship 
between the study intervention and event. Reasonable possibility means that there is evidence 
to suggest a causal relationship between the study intervention and the AE. 
• Not Related – There is not a reasonable possibility that the administration of the study 
intervention caused the event, there is no temporal relationship between the study intervention 
and event onset, or an alternate etiology has been established. 

 
 
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8.6.11 Time Period and Frequency for Event Assessment and Follow-Up 
Solicited and Unsolicited TEAEs will be recorded by clinical trial staff for the entire duration 
of the study, beginning after device administration and through day 14 (±2 days) or an early 
termination visit. 
8.6.12 Treatment Emergent Adverse Event Reporting to Study Subjects 
The Sponsor will ensure all device-attributed TEAEs and SAEs are reported to participants in the 
study to better inform them of the potential risks vs. benefits of participation. 
 8.7 Reporting Summary 
 
Report 
Time to Report 
Responsibility 
Report To 
Unanticipated (in terms of 
nature, severity (> 2), or 
degree of incidence) Adverse 
Device-Related Event 
including Serious 
Unanticipated Adverse 
Device Events [21 CFR 
812.150] 
Within 10 working days after 
becoming aware 
Investigator 
CRO/Sponsor 
IRB 
Unanticipated Adverse 
Device-Related Event 
including Serious 
Unanticipated Adverse 
Device-Related Events – 
Results of Evaluation 
[21 CFR 812.150] 
Within 10 working days after 
becoming aware 
File as an IDE report to FDA 
Sponsor 
FDA 
IRBs, all 
Investigators, all 
TEAE - unsolicited 
Within 24 hours of becoming 
aware 
DCT 
Investigator 
SAEs or TEAEs that are 
unanticipated, including a 
change in severity (> 2), and 
are treatment/device related 
Within 10 working days after 
becoming aware 
Investigator 
CRO/Sponsor 
IRB 
SAEs or TEAEs that are 
unanticipated, including a 
change in severity (> 2), and 
are treatment/device related 
Within 10 working days after 
becoming aware 
File as an IDE report to FDA 
Sponsor 
FDA 
IRBs, all 
Investigators, all 
Use of Investigational Device 
Without Informed Consent 
[21 CFR 812.150] 
Within 5 working days of the 
device use 
Investigator 
CRO/Sponsor 
IRB 

 
 
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Use of Investigational Device 
Without Informed Consent 
[21 CFR 812.150] 
Within 5 working days of 
becoming aware 
Sponsor 
FDA 
Unapproved protocol 
deviations/violations (an 
accidental or unintentional 
change to the IRB-approved 
protocol) – Major Deviation 
Within 10 business days from 
the time of identification of 
the unplanned or 
unintentional protocol 
deviation/violation 
Investigator 
IRB 
Deviations from the 
investigational plan to protect 
the life or physical well-being 
of a subject in an emergency. 
[21 CFR 812.150] 
Within 5 working days of the 
emergency 
Investigator 
IRB 
CRO/Sponsor 
 
 
8.8 Pregnancy Reporting 
All positive urine pregnancy tests will be recorded during screening and at the end of the study or 
early termination in the study. Women who screen positive for pregnancy will be encouraged, if 
not already scheduled or completed,  to see their primary health care provider or obstetrician  for 
a serological confirmatory test and to be followed thereafter by their obstetrician per best practice 
guidelines. 
Pregnant women and women who may become pregnant during the study will be permitted to 
participate in the study since RD-X19 presents no possible exposure or hazard to germline cells 
or developing embryo or fetus. 
9.0 STATISTICAL CONSIDERATIONS 
9.1 Primary Endpoint and Key Secondary Endpoint 
Primary Endpoint 
The primary endpoint will be time to sustained resolution of COVID-19 signs and symptoms without 
subsequent symptom recurrence or disease progression until the end of the study.  
Resolution of COVID-19 signs and symptoms is defined as cough, sore throat, nasal congestion, 
headache, chills and/or sweats, myalgia, fatigue, and nausea (with or without vomiting) having been 
assessed by the subject as absent (0) or mild (1) and temperature is less than 100.5 °F.  
Sustained resolution of COVID-19 signs and symptoms is achieved when all signs and symptoms 
are resolved for five consecutive assessments (corresponding to an approximately 48-hour period). 

 
 
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 After sustained resolution is achieved, symptom recurrence is defined as having three or more 
consecutive assessments (corresponding to an approximately 24-hour period) where two or more of 
the nine signs and symptoms do not meet the resolution condition.  
“Disease progression” is defined as having evidence of involvement of the lower respiratory tract: 
shortness of breath (defined as respiratory rate of 20 or more breaths per minute) and SpO2 < 96% 
(both ascertained from the average of three replicate assessments) and/or pulmonary imaging 
demonstrating COVID-19 pneumonia. 
Key Secondary Endpoint: 
The key secondary endpoint will be time to the first of two consecutive negative SARS-CoV-2 antigen 
tests (with a minimum time between tests of 6 hours) without subsequent virological rebound during 
the subject’s remaining time on study.  Virological rebound (after having achieved two such 
consecutive negative tests) is defined as having two or more positive tests out of three consecutive 
assessments. 
9.2 Power and Sample Size: 
For Mild subjects (including the additional requirement that baseline heart rate < 90, as in the FDA 
definition of mild COVID-19 [18]) age 40 or older in the EB-P20-01 trial, the hazard ratio in the 
full analysis set (FAS) was 0.62. Assuming an overall type 1 error of 0.025 one-sided a total of 228 
events for the primary endpoint gives 95% power for this hazard ratio of 0.62 and also gives 90% 
power for a hazard ratio of 0.65, as well as 80% power for a hazard ratio of 0.69. 
A total of 326 subjects will be initially randomized 1:1 (to RD-X19 and Sham) and this will give 
approximately 228 events assuming that 90% of RD-X19 subjects and 50% of Sham subjects will 
have the event. Section 9.4.3, Interim Analysis, describes a blinded sample size review that will be 
carried out based on the pooled event rate, after which the number of randomized subjects could 
potentially be increased. 
9.3 Analysis Populations: 
Three analysis populations are defined as follows: 
• 
Full Analysis Set (FAS) which will consist of all randomized subjects. This population will 
be the primary analysis population for all efficacy endpoints. Subjects will be analyzed on 
the basis of the treatment to which they were randomized. 
• 
Safety Population which will consist of all randomized subjects who received any study 
treatment. This population will be the primary analysis population for all safety analyses. 
Subjects will be analyzed on the basis of the treatment that they received. 
• 
Per Protocol (PP) Population will exclude from the FAS: (i) study subjects who experienced 
one or more of a pre-specified subset of major protocol deviations/protocol violations while 
on study, and (ii) subjects who did not meet certain pre-specified criteria concerning number 
of treatments received. The full list of reasons for exclusion from the FAS population will 

 
 
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be defined in the Statistical Analysis Plan prior to unblinding. Protocol deviations are not 
exclusionary for the PP population. Major deviations/violations will be defined within the 
Statistical Analysis Plan prior to unblinding. 
• 
Protocol deviations/violations are defined in the Definitions Section. 
9.4 Statistical Analyses 
9.4.1 Efficacy Analyses 
Details on Derivation of the Primary Endpoint 
The primary endpoint is defined in Section 9.1, Primary Endpoint, and this current section provides 
further details on the exact derivation of this endpoint. 
The eight symptoms included in the definition of the primary endpoint are cough, sore throat, nasal 
congestion, headache, chills and/or sweats, myalgia, fatigue, and nausea (with or without 
vomiting). The single sign included in the definition of the primary endpoint is temperature. 
Together these nine signs and symptoms are used to define resolution. 
The first step in derivation of the primary endpoint is at each of the twice-daily assessments at 
which the subject records signs and symptoms in the e-diary to classify subjects on the basis of 
which of the following applies: 
(i) 
Success (S), which corresponds to resolution, if all of the above eight symptoms are graded 
with a severity score of 0 (absent) or 1 (mild), and temperature < 100.5° F; 
(ii) 
Failure (Fn) if n (≥1) of the nine signs and symptoms do not meet the condition described in 
(i) above; 
(iii) 
Disease progression (D) if the subject has RR ≥ 20/min and SpO2 < 96% (both based on the 
average of three replicate assessments over 10 minutes) and 
(iv)  Missing (M) if the subject did not record all signs and symptoms entries in their e-diary at 
this timepoint. 
Note: For subjects that at a particular timepoint are missing data for a subset of their nine signs and 
symptoms the data handling rules will be described in the SAP. 
To achieve "sustained resolution" a subject must first record five consecutive timepoints 
(corresponding to an approximately 48-hour period) at which the signs and symptoms have 
resolved (i.e., assessment results SSSSS).  
Time to sustained resolution of COVID-19 signs and symptoms is the time (in hours) of the first 
"S" in a sequence "SSSSS" for which there is no subsequent symptom recurrence and no subsequent 
disease progression during the subjects' remaining time on study. 
After recording "SSSSS" a subject is defined to have had symptom recurrence if there are three 
(corresponding to an approximately 24-hour period) or more consecutive values of Fn with n ≥ 2 in 

 
 
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each case, i.e., three or more consecutive assessments where two or more of the nine signs and 
symptoms do not meet the condition described in (i) above. 
A subject is defined to have had subsequent disease progression if, after recording "SSSSS", they 
have "D" (disease progression) at even a single timepoint, or if pulmonary imaging demonstrates 
COVID-19 pneumonia 
Note: A subject that has symptom recurrence and/or disease progression is still eligible to later 
have the event for the primary endpoint, if they subsequently have five consecutive 
assessments at which the signs and symptoms have resolved ("SSSSS"), but with no further 
subsequent rebound or subsequent disease progression during the subjects’ remaining time 
on study. 
Analyses of the Primary Endpoint 
The method of primary analysis for the primary endpoint is nonparametric randomization-based 
covariate adjustment for time-to-event outcomes using Efron's method for handling ties, with 
stratification by the design's stratifications factors (age category [40-49, ≥50] and baseline disease 
severity score [<1.25, ≥1.25]), and with between one to four pre-specified (in the SAP) prognostic 
baseline covariates to improve precision of the estimate of the hazard ratio. This analysis will be 
based on the methods of Saville and Koch [20] as extended to stratified analyses by Hussey et al 
[21].  Testing for treatment will be carried out at the 5% two-sided significance level, and 95% 
two-sided confidence interval (CI) for the hazard ratio will also be derived. This primary analysis 
will be based on the FAS. 
The non-parametric Kaplan-Meier method will also be used for the FAS to estimate the survival 
curves, within the plot of which the number of subjects at risk will also be displayed. The median 
survival time will be estimated for each treatment group, together with its 95% CI using the 
Brookmeyer & Crowley method [19]. Estimates of the 25th and 75th percentiles will also be derived 
together with their corresponding 95% CIs. 
A secondary analysis will be carried out on the FAS for the primary endpoint based on a Cox 
Proportional Hazards model, using Efron's method for handling ties, including the same 
stratification factors and covariates as included in the primary analysis. In the analyses described 
above the following rules for event times and censoring will be implemented: 
(i) 
Subjects that are hospitalized will be censored at 360 hours (which corresponds to the end 
of the time window for the Day 14 visit) and this rule takes precedence over all other rules; 
(ii) 
A subject that records "SSSSS" i.e., five consecutive timepoints (corresponding to an 
approximately 48-hour period) at which the signs and symptoms have resolved who does 
not have any subsequent symptom recurrence or subsequent disease progression during the 
subject's remaining time on study, will have the event at the time of the first "S" in this 
sequence; 

 
 
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(iii) 
A subject not satisfying case (i) or (ii), who takes nirmatrelvir/ritonavir or molnupiravir 
after initiating study treatment will be censored at the time that they first took this antiviral 
medication; and 
(iv) 
Subjects not satisfying case (i), (ii), or (iii) will be censored at the last time that they have 
e-diary data recorded.  
Note: Subjects taking nirmatrelvir/ritonavir or molnupiravir after initiating study treatment must 
have recorded "SSSSS" (or equivalent) prior to starting this antiviral medication to be 
counted under case (ii), and if not then they will be counted under case (iii).  
Further details on data handling rules will be provided in the SAP. 
Supportive analyses for each of the methods described in this section will also be carried out for 
the PP population. Further sensitivity analyses for the primary endpoint will be described in the 
SAP. 
Analyses of the Key Secondary Endpoint 
At each of the twice-daily assessment times at which the subject is scheduled to take the SARS-CoV-2 
antigen test the results will be either Negative (N), Positive (P), Inconclusive (I) or Missing (M). 
The first step in defining the key secondary endpoint is to identify cases that will be counted as having 
“two consecutive negative SARS-CoV-2 antigen tests”.  The following sequences will be counted as 
satisfying this condition: (a) “NN” and the two tests are at least six hours apart; (b) multiple consecutive 
“N” values where the first and last must be at least six hours apart; or (c) “N” followed by up to three 
“M” or “I” values followed by "N" where the two "N" values must be at least six hours apart. In the 
remainder of Section 9.4.1.3 the use of "NN" will be refer to any of cases (a)-(c). 
The second step is to identify cases that are counted as subsequent virological rebound which is defined 
as "having two or more positive tests out of three consecutive assessments". This would include "PPP", 
"PPN", "PNP", "NPP", or "PP". In addition, if a "P" is followed by an "M" or “I” then the "P" will be 
carried forward so that this will also be counted as a rebound. 
The key secondary endpoint is then calculated as time to first of two consecutive negative SARS-CoV-
2 antigen tests (with a minimum time between tests of 6 hours) without subsequent virological rebound, 
during the subjects' remaining time on study. Subsequent virological rebound is defined as having two 
or more positive tests out of three consecutive assessments. 
The following rules for event times and censoring of the key secondary endpoint will be implemented: 
(i)  
Subjects that are hospitalized, who progress to more severe forms of COVID-19, or who require 
therapy with an FDA-authorized COVID-19 treatment will be censored at 360 hours (which 
corresponds to the end of the time window for the Day 14 visit) and this rule takes precedence over all 
other rules; 
(ii) 
A subject that records "NN" based on two tests at least six hours apart without subsequent 
rebound during the subject's remaining time on study will have the event at the time of the first "N" in 

 
 
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this sequence, and 
(iii)  Subjects not satisfying case (i) or (ii) will be censored at the time of their last self-assessment 
/diagnostic test.  
 
 
The primary analysis of this key secondary endpoint will be nonparametric randomization-based 
covariate adjustment for time-to-event outcomes using Efron's method for handling ties, with 
stratification by the design's stratifications factors, and with the same 1-4 pre-specified prognostic 
baseline covariates as included in the primary analysis of the primary endpoint.  The 95 % two-
sided CI for the hazard ratio will also be derived. The primary analysis will be based on the FAS. 
In addition, the same Kaplan-Meier-based analyses as described for the primary endpoint will also 
be provided for this key secondary endpoint. 
A secondary analysis of this key secondary endpoint will be carried out on the FAS based on a Cox 
Proportional Hazards model, using Efron's method for handling ties, including the same 
stratification factors and covariates as included in the primary analysis of this endpoint. 
Multiplicity Adjustment 
The key secondary endpoint will only be formally tested if statistical significance has been obtained 
for the primary endpoint. This step-down procedure ensures that there will be strong control of the 
experiment-wise type 1 error across the primary endpoint and the key secondary endpoint. 
9.4.2 Safety Analyses 
Summaries for all safety data will be presented by treatment group based on the Safety population. 
The number of hospitalizations will be tabulated and full details will be provided in listing form for 
any such hospitalizations. See section on Reporting Requirements for regulatory reporting of 
presumed device-related SAEs and patterns of device-related AEs. 
A TEAE is defined to be an adverse event (AE) which starts after initiation of treatment, or an AE 
which was present prior to initiating treatment but which increases in severity after starting 
treatment, excluding signs and symptoms of COVID-19. Incidence tables by system organ class 
and preferred term will be produced for AEs, SAEs, TEAEs, device related TEAEs (including 
separately those that are anticipated and unanticipated, as designated by severity level, and resulting 
clinical outcomes such as treatment discontinuation/withdrawal), TEAEs that led to discontinuation 
of treatment, and TEAEs by severity. The details of SAEs and any deaths will also be summarized.  
Protocol deviations will be summarized in tabular and listing form. 
 
 

 
 
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9.4.3 Interim Analysis 
A blinded sample size review will be carried out by an independent statistician based on the first 
164 randomized subjects after the last of these subjects has reached the Day 14/ET visit. The 
pooled proportion (pOBS) of subjects with an event will be determined and if this is less than 0.70 
then in order to obtain approximately 228 events at the end of the study the total number of 
randomized subjects will be increased to 326 * 0.70/pOBS (rounded up to the nearest multiple of 2, 
due to the 1:1 active:sham randomization) subject to a cap of 380. The number of randomized 
subjects will not be decreased, and no unblinded assessment of efficacy will be carried out at this 
time. 
 
10.0 OPERATIONAL CONSIDERATIONS AND SUPPORTING DOCUMENTS 
 10.1 Ethical Considerations 
This study will be conducted in conformity with the principles set forth in The Belmont Report: 
Ethical Principles and Guidelines for the Protection of Human Subjects of Research (US National 
Commission for the Protection of Human Subjects of Biomedical and Behavioral Research; April 
18, 1979), and the federal policy for the Protection of Human Subjects codified in 45 CFR Part 
46, 21 CFR Part 50 (Protection of Human Subjects), and the ICH E6(R2). 
An OHRP-registered IRB will review and approve this protocol, associated informed consent 
documents, recruitment material, and handouts or surveys intended for the subjects, prior to the 
recruitment, screening, and enrollment of subjects. The IRB review shall be in accordance with 
45 CFR 46 and 21 CFR 50, 21 CFR 56 (IRBs), 21 CFR 812 and other federal, state, and local 
regulations and policies, as applicable. 
Any amendments to the protocol or informed consent documents will be approved by the IRB 
before they are implemented. The participating clinical site PI will notify the Sponsor of 
deviations from the protocol and reportable SAEs, and, as applicable, to the IRB per the Reporting 
Requirements. 
EmitBio Inc must receive the documentation that verifies IRB approval for this protocol, informed 
consent documents, and associated documents prior to the recruitment, screening, and enrollment 
of subjects and the provision of adequate numbers of RD-X19 devices to conduct the protocol. 
 10.1.1 Informed Consent Process 
Informed consent is a process that is initiated prior to an individual agreeing to participate in a 
trial and continuing throughout the individual’s trial participation. Investigators or designated 
research staff will obtain a subject’s informed consent in accordance with the requirements of 45 
CFR 46, 21 CFR 50 and 21 CFR 56, state and local regulations and policy, and ICH E6 GCP 
before any study procedures or data collection are performed. The participating clinical site PI or 
other study staff may obtain oral or written information for the purpose of screening, recruiting, 

 
 
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or determining the eligibility of prospective subjects without the informed consent of the 
prospective subject if the process is approved by the IRB. 
At the screening or first study visit, informed consent will be obtained and documented before 
any study procedures are performed. Subjects will receive a concise and focused presentation of 
key information about the clinical trial, verbally and with a written consent form. The key 
information about the purpose of the study, the procedures and experimental aspects of the study, 
study device, potential risks, benefits and discomforts, the expected duration of the subject’s 
participation in the trial, and alternative treatments and procedures that may be available to the 
subject. The explanation will be organized and presented in lay terminology and language that 
facilitates understanding why one might or might not want to participate. 
Subjects will receive an explanation that they will be compensated for their participation on a per 
visit basis, and medical treatments are available if device-related injury occurs, and, if so, what 
that treatment is, or where further information may be obtained. Subjects will be informed of the 
anticipated financial expenses, if any, to the subject for participating in the trial, as well as any 
anticipated prorated payments, if any, to the subject for participating in the trial. They will be 
informed of whom to contact (e.g., the participating clinical site PI and the Sponsor) for answers 
to any questions relating to the research project. Information will also include the foreseeable 
circumstances and/or reasons under which the subject’s participation in the trial may be 
terminated. The subjects will be informed that participation is voluntary and that they are free to 
withdraw from the study for any reason at any time without penalty or loss of benefits to which 
the subject is otherwise entitled.  
Subjects will be informed that records identifying the subject will be kept confidential, and, to the 
extent permitted by the applicable laws and/or regulations, will not be made publicly available. If 
the results of the trial are published, the subject’s identity will remain confidential. Subjects will 
be informed, even if identifiers are removed, that information collected from this research and/or 
specimens may be used for secondary research, including the sharing of deidentified data.  
Subjects will be informed that the monitor(s), auditors(s), IRB, and Sponsor will be granted direct 
access to the subject’s original medical records for verification of clinical trial procedures and/or 
data without violating the confidentiality of the subject, to the extent permitted by the applicable 
laws and regulations, and that, by signing a written ICF, the subject is authorizing such access. 
ICFs will be IRB-approved, and subjects will be asked to read and review the consent form. 
Subjects must sign the ICF prior to starting any study procedures being done specifically for this 
trial. Once signed, a copy of the ICF will be given to the subject for their records. 
New information will be communicated by the participating clinical site PI to subjects who 
consent to participate in this trial in accordance with IRB requirements. The informed consent 
document will be updated, and subjects will be re-consented per IRB requirements, if necessary. 

 
 
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 10.1.2 Confidentiality and Privacy 
Subject confidentiality is strictly held in trust by the participating investigators, their staff, and the 
sponsor(s) and their agents. This confidentiality is extended to cover clinical information relating 
to subjects, test results of biological specimens and all other information generated during 
participation in the study. No identifiable information concerning subjects in the study will be 
released to any unauthorized third party. Subject confidentiality will be maintained when study 
results are published or discussed in conferences. 
The study monitor, other authorized representatives of the sponsor and representatives of the IRB 
may inspect all documents and records required to be maintained by the participating clinical site 
PI, including, but not limited to, screening, medical and laboratory results for the subjects in this 
study. The participating clinical site will permit access to such records. 
All source records, including electronic data, will be stored in secured systems in accordance with 
institutional policies and federal regulations. 
All study data and research specimens that leave the site (including any electronic transmission 
of data) will be identified only by a coded number that is linked to a subject through a code key 
maintained at the clinical site. Names or readily identifying information will not be released unless 
strictly required by law. 
 10.2 Clinical Monitoring 
Monitoring will be conducted during the conduct of the trial, and will include, but is not limited 
to, source document verification, review of regulatory files, device accountability records, e-
CRFs, ICFs, medical and laboratory reports, training records, and protocol and GCP compliance. 
The monitors will have access to all study related documents and will meet with appropriate 
clinical site staff to discuss any problems and outstanding issues. Visit findings and discussions 
will be documented.  Some monitoring visits may be conducted remotely. 
 10.3 Quality System 
To ensure the reliability of study data, the clinical sites must maintain an appropriate quality 
system for the purposes of measuring, documenting and reporting study conduct, protocol 
adherence, human subjects’ protections, and reliability of the protocol-driven data collected 
independent of sponsor site monitoring. 
 10.4 Data Collection and Management Responsibilities 
Data collection is the responsibility of the study staff at the participating clinical trial site under 
the supervision of the participating clinical site PI and the overall study PI. The participating 
clinical trial site PI must maintain complete and accurate source documentation. Clinical research 
data from source documentation, including, but not limited to, diary cards, AEs/SAEs, 
concomitant medications, medical history, physical assessments, and clinical laboratory data, will 
be entered by the participating clinical site into eCRFs via a 21 CFR Part 11-compliant internet 

 
 
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data entry system provided by the Sponsor’s delegated data coordinating and analysis clinical 
support organization. The data system includes password protection and internal quality checks, 
such as automatic range checks, to identify data that appear inconsistent, incomplete, or 
inaccurate. AEs and concomitant medications will be coded according to the most current versions 
of MedDRA and WhoDrug, respectively. The data coordinating and analysis CRO will be 
responsible for data management, quality review, analysis, and reporting of the study data for this 
study. The study sponsor is responsible for review of data collection tools and processes, and 
review of data and reports. 
AEs will be coded according to the MedDRA dictionary version 23.0 or higher. 
 10.5 DCT (Decentralized Team) Responsibilities 
• Perform remote televisits via StudyHub. Televisits may be performed via telephone if 
StudyHub not available. 
• Schedule remote televisits with subjects. At each televisit, schedule the next upcoming 
visit. If a subject does not show up for a televisit, complete the Visit Completion Report 
and document/mark as a missed visit. 
• Verify completion of the twice daily, SARS-CoV-2 rapid antigen tests. Preferably visual 
observation during televisit. 
• Observe SpO2 and temperature completion during televisit. 
• Direct observation and documentation of RD-X19 device administration during the 
televisit. 
• Verify completion of the eDiary for each televisit. 
• Subject re-training where necessary. 
• Completion of Visit Completion Report (source document). Upload report to StudyHub 
within 24 hours following televisit. Maintain originals of Visit Completion Reports until 
end of study and provide to Data Management. 
• Document any reported adverse events on the Visit Completion Report. Immediately 
following televisit, send an email to the applicable clinical site coordinator. (The  clinical 
site is responsible to follow up with the subject to evaluate and document any possible 
adverse events.) 
• Document any known study deviations on the Visit Completion Report. Immediately 
following televisit, send an email to the applicable clinical site coordinator. 
 10.6 Sponsor Responsibilities 
The sponsor is responsible for the following activities within the protocol. While many 
responsibilities and obligations may be formally transferred to third parties, the Sponsor is 
ultimately responsible: 
• Provision of investigational devices (RD-X19 and sham devices). 

 
 
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• System for stratified randomization. 
• Supplement investigator and site staff training. 
• Provision of all study supplies and materials required to conduct the protocol as written 
and approved. 
• Communication with regulatory bodies as defined in 21 CFR, ICH, and The Central IRB 
handbook. 
• Providing acetaminophen packets directly to the clinical sites for dispersement to study 
subjects. The sponsor files dispersement information to the CRO who maintains a study 
materials log to be included in the trial file. 
• The sponsor is responsible for review of deviations to verify whether a deviation is minor 
or major (violation). 
• The sponsor is responsible for reporting as specified in the Reporting Requirements. 
• Medical Monitoring – The Medical Monitor ensures the safety and integrity of study 
subjects throughout the trial, from the initial design of the study to the final close-out. A 
medical monitor acts as the point of reference for study team members and investigative 
sites. 
• Research and Data Compliance Monitoring 
 10.7 Source Documents 
Source documents contain all information in original records (and certified copies of original 
records) of clinical findings, observations, or other activities in a clinical trial necessary for the 
reconstruction and evaluation of the trial. Source data should be attributable, legible, 
contemporaneous, original, accurate, and complete. Each participating clinical site will maintain 
appropriate medical and research records for this trial, in compliance with ICH GCP, regulatory, 
and institutional requirements. Data recorded in the e-CRF derived from source documents should 
be consistent with the data recorded on the source documents. 
Interview of subjects is sufficient for obtaining medical history. Solicitation of medical records 
from the subject’s primary care provider is not required. 
At the end of the study, a copy of all datasets, including annotated CRFs and data dictionary, will 
be provided to EmitBio Inc. 
 10.8 Study Record Retention 
Study-related records, including the regulatory file, study device accountability records, consent 
forms, subject source documents and electronic records, should be maintained for a period of 2 
years following the date a marketing application is approved for the investigational device for the 
indication for which it is being investigated; or, if no application is filed or if the application is 
not approved for such indication, until 2 years after the investigation is discontinued and the 
Sponsor is notified. These documents should be retained for a longer period, however, if required 

 
 
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by local policies or regulations. No records will be destroyed without the written consent of 
EmitBio.  
10.9 Protocol Deviations and Violations 
A protocol deviation is any non-compliance with the clinical trial protocol, any process that is 
noted in the protocol and refers to details in the protocol or GCP requirements, or any critical 
study procedures with specific instructions in ancillary documents referenced in the protocol. A 
protocol violation is a deviation that has the potential to impact the primary and key outcome 
measures of the trial, including safety and efficacy. See Definitions for more information. 
The non-compliance may be either on the part of the subject, the participating clinical site PI, or 
the study site staff. Following a deviation(s), corrective actions should be developed by the site 
and implemented promptly. All protocol deviations will be addressed in either general study, site, 
or subject study records. 
It is the responsibility of the participating clinical site PI and study staff to use continuous 
vigilance to identify and report deviations per the Reporting Requirements. The participating 
clinical site PI and study staff are responsible for knowing and adhering to the IRB requirements. 
Protocol deviations/violations will be recorded on the case report form, as well as in the subject’s 
chart, if the deviation is subject specific. 
10.10 Publication and Data Sharing Policy 
All study data and reports of study data are the property of the study sponsor. The sponsor may 
grant the PI the right to publish the results of this research in a scientific journal, conditional upon 
the review and concurrence of the sponsor.  
10.11 Conflict of Interest Policy 
The independence of this study from any actual or perceived influence, such as by the 
pharmaceutical industry, is critical. Therefore, any actual conflict of interest of persons who have 
a role in the design, conduct, analysis, publication, or any aspect of this trial will be disclosed and 
managed. Furthermore, persons who have a perceived conflict of interest will be required to have 
such conflicts managed in a way that is appropriate to their participation in the design and conduct 
of this trial. EmitBio Inc requires that all study team members disclose any conflict of interest. 
Clinical Study sites are required to maintain a mechanism for the management of all reported 
dualities of interest.  
10.12 Research Related Injuries 
For any potential research related injury, the participating clinical site PI or designee will assess 
the subject. Study staff will try to reduce, control and treat any complications from this trial. 
Immediate medical treatment may be provided by the participating clinical site, such as giving 
emergency medications to stop immediate allergic reactions. As needed, referrals to appropriate 

 
 
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health care facilities will be provided to the subject. The participating clinical site PI should then 
determine if an injury occurred as a direct result of procedures or the device used in this trial. 
If it is determined by the participating clinical site PI that an injury occurred to a subject as a direct 
result of the procedures or device used in this trial, then referrals to appropriate health care 
facilities will be provided to the subject. No financial compensation will be provided to the subject 
by EmitBio Inc. or the participating clinical site for any injury suffered due to participation in 
clinical research. 
 
 

 
 
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Castelo, G. Caruso, S. Rapelius, F. Alvez, F. Etchenique, F. Dimase, D. Alvarez, S.S. Aranda, C. 
Sánchez Yanotti, J. de Luca, S. Jares Baglivo, S. Laudanno, F. Nowogrodzki, R. Larrea, M. Silveyra, 
G. Leberzstein, A. Debonis, J. Molinos, M. González, E. Perez, N. Kreplak, S. Pastor Argüello, L. 

 
 
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Gibbons, F. Althabe, E. Bergel, F.P. Polack, Early High-Titer Plasma Therapy to Prevent Severe 
Covid-19 in Older Adults, New England Journal of Medicine. 384 (2021) 610–618. 
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V. Stosor, I. Shawa, P. Kumar, A.C. Adams, J. van Naarden, K.L. Custer, M. Durante, G. Oakley, 
A.E. Schade, T.R. Holzer, P.J. Ebert, R.E. Higgs, N.L. Kallewaard, J. Sabo, D.R. Patel, P. Klekotka, 
L. Shen, D.M. Skovronsky, Effect of bamlanivimab as monotherapy or in combination with 
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[22]    ANSI/AAMI/ISO 14155:2020, “Clinical investigation of medical devices for human subjects—Good 
clinical practice” 

 
 
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12.0 DEFINITIONS 
• Medical Device - Adverse Event 
Untoward medical occurrence, unintended disease or injury, or untoward clinical signs (including abnormal 
laboratory findings) in subjects, users or other persons, whether or not related to the investigational medical 
device and whether anticipated or unanticipated. 
[ISO 14155] 
 
• Medical Device - Serious Adverse Event 
Adverse event that led to any of the following:  
A) death.  
B) serious deterioration in the health of the subject, users, or other persons as defined by one or more of the 
following:  
a) a life-threatening illness or injury, or  
b) a permanent impairment of a body structure or a body function including chronic diseases, or  
c) in-patient or prolonged hospitalization, or  
d) medical or surgical intervention to prevent life-threatening illness or injury, or permanent impairment to 
a body structure or a body function;  
e) fetal distress, fetal death, a congenital abnormality, or birth defect including physical or mental 
impairment.  
[ISO 14155] 
 
• Unanticipated Adverse Device Effect 
Any serious adverse effect on health or safety or any life-threatening  problem or death caused by, or 
associated with, a device, if that effect, problem, or death was not previously identified in nature, severity, 
or degree of incidence in the investigational plan or application (including a supplementary plan or 
application), or any other unanticipated serious problem associated with a device that relates to the rights, 
safety, or welfare of subjects. 
[21 CFR 812.3] 
 
• Treatment Emergent Adverse Event 
A TEAE is any untoward medical condition that either starts after initiating treatment, or which was present 
prior to initiating treatment but increases in severity after starting treatment (21 CFR 312.32 (a)). A TEAE 
can therefore be any unfavorable and unintended sign (including an abnormal clinical laboratory finding), 
symptom or disease temporally associated with the use of a medicinal (investigational) product. 
[21 CFR 312.32] 
 
• Serious Adverse Event 
An SAE is defined in 21 CFR 312.32 as follows: “An AE is considered serious if, in the view of either the 
participating clinical site PI or appropriate sub-investigator or the sponsor, it results in any of the following 
outcomes: 
A) Death, 
B) A life-threatening adverse event, 

 
 
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C) Inpatient hospitalization or prolongation of existing hospitalization, 
D) A persistent or significant incapacity or substantial disruption of the ability to conduct normal life 
functions, or 
E) A congenital anomaly or birth defect. 
 
Important medical events that may not result in death, be life-threatening, or require hospitalization may be 
considered serious when, based upon appropriate medical judgement, they may jeopardize the patient or 
subject and may require medical or surgical intervention to prevent one of the outcomes listed in this 
definition. Examples of such medical events include allergic bronchospasm requiring intensive treatment in 
an emergency room or at home, blood dyscrasias or convulsions that do not result in inpatient 
hospitalization, or the development of drug dependency or drug abuse. 
[21 CFR 312.32] 
 
• Treatment Emergent Serious Adverse Event 
An SAE is defined in 21 CFR 312.32 as follows: “An TEAE is considered serious if, in the view of either 
the participating clinical site PI or appropriate sub-investigator or the sponsor, it results in any of the 
following outcomes: 
A) Death, 
B) A life-threatening TEAE, 
C) Inpatient hospitalization or prolongation of existing hospitalization, 
D) A persistent or significant incapacity or substantial disruption of the ability to conduct normal life 
functions, or, 
E) A congenital anomaly or birth defect. 
[21 CFR 312.32] 
 
• Device Deficiency/Malfunction 
Failure of an investigational medical device to perform in accordance with its intended purpose when used 
in accordance with the instructions for use, clinical protocol, or investigator’s brochure. 
[ISO 14155] 
 
• Deviation 
Instance of failure to follow, intentionally or unintentionally, the requirements of the clinical protocol or 
investigation plan. 
[ISO 14155] 
 
• Deviation - Minor 
There are many unplanned or unintentional violations/deviations or changes in study status that do not 
cause harm, place subjects at increased risk of harm, or adversely affect data integrity. The IRB does not 
require that these minor violations/deviations be reported. Examples of minor violations/deviations that do 
not need to be reported may include the following:  
• Out of window visits  
• Study procedures conducted out of timeframe  
• Subject failure to initial each page of the ICF (as applicable)  
• Subject failure to return subject materials (e.g., diaries, journals, etc.).  
• Administrative hold on a study not related to safety issues  
[Advarra IRB Handbook, Version 5] 
 

 
 
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• Deviations – Major/Violation 
Examples of accidental or unintentional protocol violations/deviations that must be submitted to the IRB 
include:  
• Changes necessary to eliminate apparent immediate hazards to the subject  
• Failure to document informed consent  
• Informed consent obtained after initiation of study procedures  
• Enrollment of a subject who did not meet all inclusion/exclusion criteria  
• Performing study procedure not approved by the IRB  
• Failure to report serious adverse event to the IRB and/or sponsor  
• Failure to perform a required lab test that, in the opinion of the investigator, may affect subject safety or 
data integrity  
• Device/Drug/study medication dispensing or dosing error  
• Study visit conducted outside of required timeframe that, in the opinion of the investigator, may affect 
subject safety  
• Failure to follow safety monitoring plan  
• Missing or unreturned investigational product  
[Advarra IRB Handbook, Version 5] 
 

 
 
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13.0 APPENDICES 
 
Appendix 1  - RD-X19 Investigational Device Manual (Instructions for Use)