Respiratory Application of a Novel Ultraviolet Light Delivery Device for Patients Infected With COVID-19: A Pilot Study
Phase: NA
Conditions: Coronavirus
Sponsor: Cedars-Sinai Medical Center

Protocol: UVL-0001 
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Respiratory application of a novel ultraviolet light delivery device 
for patients infected with COVID-19: A Pilot Study 
 
 
NCT04572399 
September 30, 2020 
 
PRINCIPAL INVESTIGATOR: 
George Chaux, MD 
 
CO-INVESTIGATORS:  
Peter Chen, MD 
Michael Lewis, MD 
Ruchi Mathur, MD 
Gil Melmed, MD 
Rekha Murthy, MD 
Isabelle Pedraza, MD 
Mark Pimentel, MD 
Ali Rezaie, MD 
Will Takakura, MD 
 
 
 
 
STUDY COORDINATOR: 
Gillian Barlow, PhD 
Shane White 
 
 
 
 
 
 
SPONSOR: 
 
 
 
 
Aytu BioScience 
 
 
 
 
 
 
373 Inverness Parkway 
 
 
 
 
 
 
Suite 206 
 
 
 
 
 
 
Englewood, CO 80112 
 
 
 
 

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Table of Contents 
1. 
BACKGROUND ................................................................................................................................ 6 
1.1 Study Disease .............................................................................................................................................. 6 
1.2 Study Interventions .................................................................................................................................. 6 
1.3 Study Rationale .......................................................................................................................................... 7 
2. 
STUDY OBJECTIVE ........................................................................................................................ 7 
3. 
STUDY DESIGN ............................................................................................................................... 8 
3.1 Accrual goal ................................................................................................................................................. 8 
3.2 Duration of Study Participation ........................................................................................................... 8 
4. 
STUDY ENTRY, ENROLLMENT AND WITHDRAWAL .......................................................... 8 
4.1 Study Entry ................................................................................................................................................... 8 
4.2 Enrollment Procedure .......................................................................................................................... 11 
4.3 Cancellation Guidelines ........................................................................................................................ 11 
5. 
PATIENT SELECTION / ELIGIBILITY CRITERIA ................................................................ 11 
5.1 Inclusion (Eligibility) Criteria ............................................................................................................ 11 
5.2 Exclusion (Eligibility) Criteria ........................................................................................................... 12 
5.3 Study Population ..................................................................................................................................... 12 
5.4 Setting ......................................................................................................................................................... 12 
6. 
STUDY DESIGN, CLINICAL, AND LABORATORY EVALUATIONS ................................... 12 
6.1 Study Design ............................................................................................................................................. 12 
6.1.1 Study Calendar .................................................................................................................................................. 13 
6.2 Specimen Collection............................................................................................................................... 13 
6.3 Ultraviolet (UV) Respiratory Tract Light Therapy Procedure ............................................... 13 
6.3.1 Securement for Endotracheal Use............................................................................................................. 15 
6.3.2 Treatment Procedure ..................................................................................................................................... 15 
6.3.3 Monitoring patient during the UV treatment and termination criteria .................................... 15 
Subjects will be monitored closely by the study investigator during the treatment. This 
includes close monitoring of O2 saturation, minute ventilation,PEEP,peek inspirator pressure, 
pulse rate, blood pressure every 5 minutes. A procedure report will be prepared. Procedure 
will be terminated if oxygen saturation drops below 88% or clinical instability as per 
investigators discretion. ........................................................................................................................................... 15 
6.3.4 Disinfecting the UV Respiratory Tract Light Therapy Device Control Unit and Umbilical 15 
6.4 Treatment Schedule............................................................................................................................... 16 
6.5 Results Documentation ........................................................................................................................ 16 
7. 
ADVERSE EVENTS ....................................................................................................................... 17 
7.1 Possible Risk Associated with the Device (i.e. Treatment Emergent Adverse Eevent) . 17 
7.2 Expected Adverse Events ..................................................................................................................... 17 
7.3 Serious Adverse Events ........................................................................................................................ 17 
8. 
DATA AND SAFETY MONITORING PLAN ............................................................................. 17 
9. 
STATISTICAL CONSIDERATIONS ........................................................................................... 18 
9.1 Primary Study Endpoints ..................................................................................................................... 18 
Primary endpoint: ......................................................................................................................................... 18 
9.2 Secondary Study Endpoints ................................................................................................................ 18 
9.4 Sample size, accrual and study duration ........................................................................................ 19 
9.5 Statistical Analysis ................................................................................................................................. 19 

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10. 
INVESTIGATORS RESPONSIBILITIES ............................................................................... 20 
10.1 Investigator Responsibility/Performance .................................................................................. 20 
10.2 Confidentiality ....................................................................................................................................... 20 
10.3 Informed Consent and Permission to Use Protected Health Information ....................... 20 
10.4 Source Documentation and Investigator Files .......................................................................... 21 
10.5 Recording and Processing of Data ................................................................................................. 21 
10.6 Non-Protocol Research ...................................................................................................................... 21 
10.7 Ethics ........................................................................................................................................................ 22 
10.8 Essential Documents for the conduct of clinical trial ............................................................. 22 
11. 
REFERENCES............................................................................................................................. 22 
 
 
 

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INVESTIGATOR'S AGREEMENT 
 
This clinical trial shall be conducted in compliance with the protocol, as referenced herein, and all 
applicable local, national, and international regulatory requirements to include, but not be limited 
to: 
 
• International Conference on Harmonization (ICH) Guidelines on Good Clinical Practice 
(GCP) 
• Ethical principles that have their origins in the Declaration of Helsinki  
• Food and Drug Administration (FDA) Code of Federal Regulation (CFR): 
o 
Title 21CFR Part 50 and 45 CFR Part 46, Protection of Human Patients 
o 
Title 21CFR Part 54, Financial Disclosure by Clinical Investigators 
o 
Title 21CFR Part 56, Institutional Review Boards 
o 
Title 45 CFR Parts 160, 162, and 164, Health Insurance Portability and 
Accountability Act (HIPAA) 
 
As the Principal Investigator, I understand that my signature on the protocol constitutes my 
agreement and understanding of PI responsibilities to conduct the clinical trial in accordance to 
the protocol and applicable regulations.  Furthermore, it constitutes my understanding and 
agreement that any changes initiated by myself, without prior agreement in writing from the 
Sponsor, shall be defined as a deviation from the protocol, and shall be formally documented as 
such. 
 
 
I understand that my signature constitutes agreement and understanding of acceptance of the 
defined responsibilities of a Sponsor-Investigator as defined by the protocol, applicable FDA 
Regulations, and/or business contracts, but does not in any capacity relieve me of my 
responsibilities as the Sponsor-Investigator.  Additionally, my signature constitutes my 
understanding and agreement that any changes to the protocol shall be implemented timely with 
my review and approval prior to implementation. 
 
 
 
 
 
 
 
 
 
 
 
 
 

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INVESTIGATOR'S AGREEMENT 
 
 
I confirm that I have read this protocol, I understand it, and I will work according to this protocol 
and to the ethical principles stated in the latest version of the Declaration of Helsinki, the applicable 
ICH guidelines for good clinical practices, and the applicable federal, state, and local laws, rules, 
and regulations relating to the conduct of the protocol.   
I have read and understand the information in the Instructions for Use (and/or other such pertinent 
safety information) regarding the risks and potential benefits.   
I agree to inform all those who assist/collaborate with me in the conduct of this study of their 
responsibilities and obligations.  
Once the protocol has been reviewed and approved by the Institutional Review Board (IRB) I 
understand that any change(s) made during the course of the study must also (first) be approved 
by the IRB prior to implementation, except when such modification is made to remove any 
immediate hazard(s) to the subject(s).   
I certify that I and the study staff responsible, have received the requisite training to conduct this 
research protocol.   
I agree to maintain the confidentiality of all information received and/or developed in connection 
with this protocol. 
 
 
 
 
Print Name of Physician 
 
 
 
 
 
Physician’s Signature 
Date 
 
 
 
 
 

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1. BACKGROUND 
 
1.1 Study Disease 
 
Coronaviruses (CoV) are a large family of viruses that cause illness ranging from the common 
cold to more severe diseases such as Middle East Respiratory Syndrome (MERS-CoV) and Severe 
Acute Respiratory Syndrome (SARS-CoV). 
 
Coronavirus disease (COVID-19) is a new strain that was discovered in 2019 and has not been 
previously identified in humans.  COVID-19 is caused by infection from the severe acute 
respiratory syndrome coronavirus 2 (SARS-CoV-2 virus). 
 
Common signs of infection include respiratory symptoms, fever, cough, shortness of breath and 
breathing difficulties. In more severe cases, infection can cause pneumonia, severe acute 
respiratory syndrome, kidney failure and even death. On March 11, the COVID-19 outbreak was 
characterized as a pandemic by the World Health Organization (WHO).1 
 
1.2 Study Interventions 
 
The Cedars Sinai UV Respiratory Tract Light Therapy Device consists of a light-emitting diode 
(LED) catheter intended to provide adjunctive therapy to hospitalized patients with COVID-19, 
including both ambulatory and intubated patients. The device consists of an array of twelve (12) 
Ultraviolet Light A (UVA) diodes in the 343 nm (±5 nm) spectrum that is intended to be inserted 
in standard endotracheal tubes of mechanically ventilated patients for 20 minutes every 24 hours 
for the reduction in bacterial and viral burden. 
 
The UV Respiratory Tract Light Therapy Device consists of a UVA Light Catheter, Umbilical, 
and Control Unit. The System has been designed to be used in routine commercially available 
endotracheal and nasopharyngeal tubes. For endotracheal applications, the UVA Light Catheter 
will be attached to the Avanos(R) multiaccess port and maintained inside a sealed sheath when not 
in use.  
 
The UVA Light Catheter sterilized by ethylene oxide [STERILE|EO] sterilization and intended 
for a single patient for the duration of treatment, and then should be disposed of per hospital 
policies. The UVA Light Catheter is a medical-grade fluorinated ethylene propylene (FEP) 
catheter tube that has the light UVA light array fixture mounted inside, which is inserted entirely 
inside the airway to deliver the light therapy. The UVA Light Catheter is marked with 1 cm 
markings to ensure that the device is inserted to the correct distance before the UV light is turned 
on. The UVA Light Catheter is connected to the Umbilical, which is a flexible power and air 
connector between the Light Catheter and Controller. The Umbilical may be cleaned, disinfected, 
and reused, with a useful life of up to twenty treatments. The Controller houses the user interface 
controls, and air compressor, and associated firmware. The Controller may be cleaned, disinfected, 
and reused, with a useful life of up to five years.  
 

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As the virus infects the cells on the surface of the airway, acute respiratory viral infection (mainly 
from SARS-CoV-2, the virus responsible for COVID-19) thought to enter via the nasal passages 
and pharynx makes its way down the trachea and upper airways. Eventually, the infection results 
in a cytokine storm affecting the lungs, and subsequent damage to alveoli and lung tissue results 
in the lethality seen in more severe flu viral infections, especially those fatalities among healthy 
young adults. In addition, bacteria and fungi can cause a secondary infection in mechanically 
ventilated patients. 
 
 
1.3 Study Rationale 
 
The Cedars Sinai UV Respiratory Tract Light Therapy Device is intended to eliminate 
microorganisms using UV-A light, thereby reducing the viral burden of SARS-CoV-2, and in 
intubated patients may also reduce the additional risk of ventilator-associated infections, 
including tracheobronchitis, pneumonia, sepsis, and death.  
 
The Cedars Sinai UV Respiratory Tract Light Therapy Device is intended for salvage of 
ventilated patients in the ICU with COVID-19 to reduce viral load, reduce ventilator-associated 
pneumonia, and may reduce ventilator times, and reduce mortality. This is applied in addition to 
the best practice standard of care treatment for these patients who in some series may have a 
mortality rate in excess of 70%.  
 
2. STUDY OBJECTIVE 
 
To demonstrate basic safety and proof of principle for Endotracheal UV Light Device. 
 
Primary Endpoint: 
Reduction of viral load in upper airway in patients admitted to hospital positive for COVID-19. 
 
Secondary Endpoints: 
 
Overall reduction or change for the following endpoints: 
• Bacterial load in upper airway 
• Development of ventilated associated pneumonia (VAP) 
• Days to extubation 
• Days to Discharge 
• Inflammatory marker changes 
• Clinical Outcomes: death, hospitalized on ventilator or ECMO, hospitalized on non-
invasive ventilation, hospitalized on supplemental O2, hospitalized not on O2, not 
hospitalized but with limitations, not hospitalized and no limitations. 
• Sampling and microbiologic assessment of endotracheal tube tip from extubated patients 
 

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3. STUDY DESIGN 
 
3.1 Accrual goal 
 
Patients newly intubated (within 24 hours) on mechanical ventilation with COVID-19 who meet 
all other study inclusion criteria and none of the study exclusion criteria. 
 
Target Total: 5 subjects 
 
 
3.2 Duration of Study Participation 
 
Subjects will be treated for up to 5 days and will be followed until day 30, discharge from 
hospital or death(whichever comes earlier);; adverse events will be captured throughout study. 
 
 
Day 0: Enrollment, informed consent, baseline assessment, pre-insertion endotracheal sampling 
(within 24 hrs of enrollment), device deployment (within 24 hours of enrollment).  
 
Day 1: endotracheal sampling (24h after initial device deployment); ongoing daily UV light 
treatment while mechanical ventilation is continued. 
 
Days 2 – 4: endotracheal microbiologic assessment, daily UV light treatment while mechanical 
ventilation is continued (for total of up to 5 doses, day 0 through day 4) 
 
Day 5 – endotracheal and catheter tip sampling 
 
Days 5-30: Assessment of clinical status 
 
4. STUDY ENTRY, ENROLLMENT AND WITHDRAWAL  
 
4.1 Study Entry 
 
For subjects prospectively enrolled, study entry, as used in this protocol, will be defined as a 
subject (or surrogate) signing informed consent.  Study enrollment, as used in this protocol, will 
be defined as the investigator’s confirmation of the subject’s eligibility by signing an eligibility 
checklist. Each study participant, including participants who have screened failed, who sign an 
informed consent form, should be entered into the study database.  
 
Hospital leadership is closely monitoring the COVID-19 cases and are in communication with 
investigators running COVID-19 trials. Treating physicians of COVID-19 patients will be made 
aware of the research offering.  
 

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If they have capacity to consent for themselves, treating physicians will ask patients if they are 
willing to be approached about research options. Researchers may approach potential subjects 
who indicate they are interested.  
 
If patients do not have capacity to consent for themselves, treating physicians will work with 
researchers to identify an appropriate surrogate and connect researchers with surrogate decision 
makers to determine if a research option is appropriate for the patient. 
 
Note: patients may be in isolation units. Therefore, this contact may be made over the phone into 
the patient’s room with visualization from the treating physician and research from the window 
outside the room to minimize contact. 
 
Research teams may also request to receive a daily list of COVID-19 patients in the hospital or 
may use Deep6 or reports requested by EIS to identify potentially eligible patients.  The research 
staff can pre-screen the patients by reviewing the EHR and then approach the treating physician 
if the patient may be an appropriate study candidate. 
 
Process of Informed Consent Considerations: 
 
Given limited supplies of personal protective equipment and isolation requirements, consent may 
be provided over the phone and, when feasible, with direct visualization through the patient room 
window or using a video platform to minimize entry into the room.  A picture of the consent 
form with patient signature may be utilized as documentation of informed consent. The signed 
consent in these circumstances will be photographed and saved electronically. The consenting 
physician and witness (when the patient is a non-English speaker) will sign a second full copy of 
the consent and print/attach the photographed patient’s signature page. 
 
Given isolation precaution for this population, potential subjects who have capacity to consent 
and who have access to a smartphone, tablet, or computer with them in their room may be 
provided a link to a digital version of the consent form using REDCap or DocuSign to avoid the 
use of paper, which cannot be removed from the containment unit. If the potential subject does 
not have access to a smartphone/online consent form, then a paper copy will be used.  An 
electronic consent may also be sent by email to a surrogate off site. 
 
While patients may be approached soon after their visit and/or admission begins, they can take 
time to consider and discuss participation with others before deciding. All questions will be 
answered by an investigator prior to signing the consent form.  
 
For the enrollment of non-English speaking subjects, certified medical interpreters will be used 
with the short form consent. A certified medical interpreter will be present (over the phone) to 
translate the document and interpret the consent discussion following IRB policy. A witness to 
the consent process must sign the consent form and short form, but the witness does not need to 
be fluent in both languages.  If the interpreter is unable to sign as witness, a chart note should 
document the identity and involvement of the interpreter. 
 
As a last resort, if the potential subject has capacity to consent, but:  

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1. a potential subjects’ room does not have a window for consent form visualization; thus a 
paper consent form cannot be used to document consent, AND  
2. the potential subject could not use their own device (e.g., are not comfortable enough 
with the technology to use it for this purpose) and/or there was no other device available, 
thus an electronic signature or photograph of a hard copy signature cannot be obtained, 
then the consent process can follow that of subjects who have capacity to obtain consent 
but cannot physically sign the consent. This consent process is as follows: the consent 
discussion is over the phone with the consenting investigator, study team member if 
applicable, translator if applicable, and an independent witness (e.g., the clinical nurse). 
The witness will sign the consent form for two purposes: 1) to document translation was 
provided, if short forms were used to enroll a non-English speaker, and 2) to document 
the patient agreed to participate but could not physically sign the form.  There should also 
be a chart note to describe the process and explain why the subject was physically unable 
to sign the consent form. 
 
 
Considerations for the Enrollment of Individuals who Lack 
Capacity to Consent: 
 
Related to the enrollment of cognitively impaired subjects through a surrogate informed consent 
process (CA law): 
The research relates to life-threatening diseases and conditions of the participants and holds out 
the prospect of direct benefit. The consenting co-investigators (MDs) will determine the patient’s 
capacity to provide consent. Subjects who lack capacity will be given the opportunity to dissent 
where appropriate. An individual who has Power of Attorney or who is otherwise authorized to 
make health care decisions for a potential research subject may not provide consent on behalf of 
the potential subject if the potential subject has the cognitive capacity to provide consent for 
themselves. The research will not enroll persons under psychiatric conservatorship or persons on 
a voluntary or involuntary psychiatric hold. The surrogates will not be paid for providing 
informed consent. If a subject should regain capacity during their participation, they will be 
informed of the nature of their participation and given the opportunity to consent to continue to 
participate in the research or refuse to continue to take part in the study. The study team will 
document the surrogate decision makers who are involved and available to provide informed 
consent for the subject, their relationship to the subject, and their respective decisions. 
 
Surrogate Consent obtained remotely: REDCap or DocuSign may be used for remote consent of 
surrogate decision makers, as there are restrictions in place that preclude in-person visitors. The 
remote consent process may take place over the phone or via a video visit to allow the consent 
conversation and process, and signature may be obtained either through REDCap or DocuSign, 
or the surrogate may scan/email their signed copy for the investigator to either print and sign, or 
add an Adobe digital signature. If need be, the surrogate could fax their signature page instead of 
scanning/emailing.  
 
Review the surrogate consent section in the consent process policy (starting on page 18 of the 
policy), including the decision tree for who can serve as surrogate decision maker per California 

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law in non-emergency and emergency settings (starting on page 20 of the policy). If a surrogate 
decision maker is not able to sign (e.g. spouse), then the study team can continue down the 
priority list of surrogate decision makers.  
 
Note: In some instances a surrogate decision maker is able to provide verbal consent, but unable 
to use REDCap or other technology needed for the documented consent process to take place. 
Given the limitations to visitors and widespread nature of the risks of COVID-19, in these 
instances, obtain the surrogate’s permission to contact another surrogate decision maker who will 
be able to provide the documented consent. Record a note in the research record of this consent 
conversation and the process used to subsequently obtain written/documented consent from a 
surrogate decision maker. 
 
 
4.2 Enrollment Procedure 
 
Completed and signed protocol-specific eligibility checklist;  
 
All pages of the original signed informed consent forms (ICFs), including HIPAA Form B;  
Relevant source documents or medical records such as:  subject medical history and physical 
exam, admission or discharge notes, diagnostic reports, pathologic confirmation of diagnosis, and 
relevant subject-specific written communication. 
 
Documentation from the Investigator that he/she has determined the subject meets eligibility 
criteria.  
 
  
 
4.3 Cancellation Guidelines 
 
The following are reasons for withdrawal of subjects from the study: 
 
▪ A subject does not meet the eligibility criteria; (the subject will be considered a screen 
failure).   
▪ A subject withdraws consent,  
 
Regardless of reason for withdrawal, an intention to treat analysis will be performed.  
 
5. PATIENT SELECTION / ELIGIBILITY CRITERIA 
 
5.1 Inclusion (Eligibility) Criteria 
 
1. Patients over 18 years of age  
2. Confirmed positive test result for SARS-CoV-2 
3. Mechanically ventilated  

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4. Endotracheal tube inner diameter at least 7.5 mm 
 
5.2 Exclusion (Eligibility) Criteria 
 
1. Unable to provide informed consent (or surrogate) 
2. Enrolled in a therapeutic clinical trial for same condition that does not allow recruitment 
in other trials. 
3. Pregnant women.  
 
While not an exclusion criterion, special care should be exercised in treating patients who 
are receiving concomitant therapy (either topically or systemically) with known 
photosensitizing agents such as anthralin, coal tar or coal tar derivatives, griseofulvin, 
phenothiazines, nalidixic acid, fluoroquinolone antibiotics, halogenated salicylanilides 
(bacteriostatic soaps), sulfonamides, tetracyclines, thiazides and certain organic staining 
dyes such as methylene blue, toluidine blue, rose bengal, and methyl orange. 
 
5.3 Study Population 
 
5 confirmed positive subjects with SARS-CoV-2, of whom have been newly (within last 24 
hours) intubated with an ETT size 7.5 or greater, on mechanical ventilation. 
 
Target enrollment: 5  
 
5.4 Setting 
 
Subjects will be identified from those individuals whom have presented themselves to 
hospital/department of health/doctor’s office as exhibiting signs and symptoms of COVID-19.  If 
they meet the inclusion criteria , the subjects (or their surrogate) will receive an explanation of 
the study. Subject (or surrogate) will be informed both verbally and in written form of the study 
and procedures involved. The PI, co-investigators and/or the study coordinator will obtain a 
signed/dated Informed Consent Document (ICD) before enrolling each subject. Study data will 
be safely stored in a physical central file database, and additionally digitized onto a HIPAA 
secure server.  
 
6. STUDY DESIGN, CLINICAL, AND LABORATORY EVALUATIONS 
 
6.1 Study Design 
 
The Ultraviolet (UV) Respiratory Tract Light Therapy Device is a novel delivery device for 
patients infected with COVID-19 whom have been mechanically intubated.  The purpose of this 

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study is to demonstrated basic safety and proof of principle for the Endotracheal UV light device 
in reducing SARS-CoV-2 viral load. 
 
6.1.1 Study Calendar 
 
Subjects will be treated for up to 5 days and will be followed for 30 days, or until extubation or 
death (whichever comes earlier); adverse events will be captured throughout study. 
 
 
 
Day 0: Enrollment, informed consent, baseline assessment, pre-insertion endotracheal sampling 
(within 24 hrs of enrollment), device deployment (within 24 hrs of enrollment) 
 
Day 1: endotracheal sampling (24h after initial device deployment, primary endpoint); ongoing 
daily UV light treatment while mechanical ventilation is continued. 
 
Days 2 – 4: endotracheal microbiologic assessment, daily UV light treatment while mechanical 
ventilation is continued 
 
Day 5 – endotracheal  and light catheter sampling 
 
Days 5-30: Assessment of clinical status 
 
 
 
 
6.2 Specimen Collection  
• Aspirate collection 
• Viral qPCR 
• Bacterial load 
 
6.3 Ultraviolet (UV) Respiratory Tract Light Therapy Procedure 
 
The UV Respiratory Tract Light Therapy Device should be used by physicians trained on the 
procedure for which the device is intended. The techniques and procedures described do not 
represent all medically acceptable protocols, nor are they intended as a substitute for the 
physician's experience and judgment in treating any specific patient. All available data, including 
the patient's signs and symptoms and other diagnostic test results, should be considered before 
determining a specific treatment plan. 
 
Mechanically Ventilated Patients 
 
1. Ensure bite block is inserted  
2. Ensure that patient has ETT size 7.5mm or greater, attached to the Avanos(R) 
mutliaccess port 
3. The device can be inserted with the patient in either the supine or the prone position 

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4. Ensure FIO2 is at 100% for at least 30 minutes prior to device deployment 
5. Perform routine respiratory suctioning of the endotracheal tube to ensure no mucous plug 
inside the tube. Please refer to sampling protocol for tracheal sample retrieval.  
6. The procedure needs to be performed in a manner that minimizes the likelihood of 
breaking the ventilatory circuit and exposing the circuit contents to ambient surroundings. 
The catheter will be enclosed in a plastic sleeve with a port that connects to the Y-port in 
the ventilatory circuit at or near the patient mouth. 
7. One of the study investigators must be present during the time period that the catheter is 
inserted in ETT. 
8. Inspect tubing and catheter device for damage. 
9. By holding the tubing, advance the catheter device approximately 13cm into the 
ventilatory circuit and the endotracheal tube, towards the carina, until the catheter 
marking aligns with the endotracheal tube entrance. 
 
 
10. Check the Controller for the green light to turn on, indicating that the Device catheter is 
sufficiently inserted into the airway. 
11. Turn on the compressor and the UV light using the Controller. The 20-minute timer will 
begin automatically. 
12. Upon completion of the 20-minute treatment, the timer will be at zero, and the light will 
automatically shut off. The catheter can be safely withdrawn from the endotracheal tube 
back into the plastic sleeve until reuse in 24 hrs. 
 

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6.3.1 Securement for Endotracheal Use 
 
Ensure the catheter device is withdrawn into the plastic sleeve and is no longer in continuity with 
the ventilator circuit. Secure the catheter device/plastic sleeve and disconnect the controller. 
 
6.3.2 Treatment Procedure 
 
1. Once the UVA Light Catheter has been placed, and the position has been confirmed, 
connect the umbilical to the LED Control Panel. 
2. Turn on the compressor. 
3. Turn ON the Power switch. The Green Power Indicator will be illuminated. The timer 
will indicate 20 minutes. 
4. Push the Blue START Button to light up the LED array and to start the treatment. 
5. After treatment, the LED light array will automatically shut off. 
6. Removal of the UVA Light Catheter 
7. When therapy is complete, unplug the connection to the Control Unit. 
8. Turn off compressor 
9. Carefully grasp catheter hub and remove slowly with a constant steady pull into the 
polypropylene sleeve. 
10. Inspect catheter to ensure complete removal. 
11. Place catheter near the patient for use in the next 24-hour treatment. 
 
6.3.3 Monitoring patient during the UV treatment and termination criteria 
 
Subjects will be monitored closely by the study investigator during the treatment. This includes 
close monitoring of O2 saturation, minute ventilation,PEEP,peek inspirator pressure, pulse rate, 
blood pressure every 5 minutes. A procedure report will be prepared. Procedure will be 
terminated if oxygen saturation drops below 88% or clinical instability as per investigators 
discretion. 
 
6.3.4 Disinfecting the UV Respiratory Tract Light Therapy Device Control Unit and Umbilical 
 
1. Use a clean wipe with an intermediate sanitizing solution (e.g., isopropyl alcohol or 
CaviWipes towelette) to disinfect the control unit and umblical surface, ensuring to wet 
the surface thoroughly. 
2. Repeated use of another towelette may be required to ensure that the surface remains 
visibly wet for three minutes at room temperature (69°F/20°C).  This will confirm 
viricidal activity and effectiveness against HIV-1, HBV and HCV applications, and 
effectiveness against Clostridium difficile (vegetative cells only), Methicillin-Resistant 
Staphylococcus aureus (MRSA), Vancomycin-Resistant Enterococcus faecalis (VRE) 

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and Staphylococcus aureus with reduced susceptibility to vancomycin, and tuberculocidal 
activity and effectiveness against Staphylococcus aureus, and Pseudomonas aeruginosa. 
3. Do not reuse towelette. Dispose of used towelette in accordance with Federal, State, and 
local regulations for infectious materials disposal. 
4. Cleaning materials used that may contain blood, or other body fluids should be 
autoclaved and disposed of in accordance with Federal, State, and local regulations for 
infectious materials disposal. 
5. Place a large equipment bag on the controller and the umbilical. 
 
6.4 Treatment Schedule 
 
Subjects will be treated for up to 5 days and will be followed for 30 days, or until discharge from 
hospital or death (whichever comes earlier); adverse events will be captured throughout study. 
 
 
 
Day 0: enrollment, informed consent, baseline assessment, pre-insertion endotracheal assessment 
(within 24 hrs of enrollment), device deployment (within 24 hrs of enrollment) 
 
Day 1: endotracheal microbiologic assessment (24h after initial device deployment, primary 
endpoint); ongoing daily UV light treatment while mechanical ventilation is continued. 
 
Days 2 – 4: endotracheal microbiologic assessment, daily UV light treatment while mechanical 
ventilation is continued 
 
Day 5: Endotracheal  and light catheter sampling 
 
Days 5-30: Assessment of clinical status 
 
6.5 Results Documentation 
 
• Viral qPCR Results 
• Bacterial assessment/load 
• Days until extubation 
•  Days to discharge  
• 
Inflammatory markers   
•  Clinical Outcomes: death, hospitalized on ventilator or ECMO, hospitalized on 
noninvasive ventilation, hospitalized on supplemental O2, hospitalized not on O2, not 
hospitalized but with limitations, not hospitalized and no limitations  
•  Microbiologic assessment of endotracheal tube tip from extubated patients  
 
 
 

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7. ADVERSE EVENTS 
 
7.1 Possible Risk Associated with the Device (i.e. Treatment Emergent Adverse Eevent)  
 
• Heat/thermal injury to nasal passages/pharynx (nasopharyngeal insertion) or 
trachea/vocal cords (endotracheal insertion) 
o This risk is mitigated by cooling the LEDs within the device via the chilled and 
compressed air pumped through the device during deployment. In addition, a 
thermistor will automatically shut off the device if the temperature of the device 
exceeds 43 degrees C.  
• Decreased ventilation/oxygenation due to partial airway occlusion in mechanically 
ventilated patients 
o This risk is mitigated through experimental determination that airway pressures 
and tidal volumes are not affected when the device is deployed in an ETT size 
7.5mm or greater. Therefore, patients with ETT sizes smaller than 7.5mm are 
excluded.  
• Trauma to the carina (due to over-insertion in mechanically ventilated patients) 
o This risk is mitigated by alignment of external cm markings on the device, 
intended to be inserted until the cm markings of the device align with markings of 
the ETT.  
• Allergic reaction to device materials 
o With proper use of the device, there is no physical contact between the device and 
the patient as the device is inserted within the ETT and never makes contact with 
external or internal airways.  
 
 
7.2 Expected Adverse Events 
 
Expected Adverse Events with this test procedure are unknown. 
 
 
7.3 Serious Adverse Events 
 
Serious injury or death  
 
Any adverse event and eventual complication must be recorded at any time during the treatments 
and the follow up visits, and throughout the entire study duration. Patients will be instructed to 
alert the study investigator by telephone of any side effects occurring in the period after the 
treatment and until the study end.  
 
For Reporting of adverse events see section 8. 
 
 
8. DATA AND SAFETY MONITORING PLAN 
 

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The study will be monitored by an independent data safety monitoring board. This board will be 
comprised of a pulmonologist/intensivist, clinical trial specialist, and biostatistician. The members 
will not be faculty or staff at CSMC. The DSMB will meet to review the safety and outcomes of 
the 5 patients, and no further study of the device will be conducted until the DSMB has concluded 
its review. The DSMB will convey any safety concerns to the investigators and the sponsor.  
 
During the study, the investigators will conduct continuous reviews of the data and subject safety, 
keeping track of the number of subjects, significant toxicities in accordance with the protocol and 
observed responses. All grade 3-5 adverse events (CTCAE v4.0) will be entered into study 
database and reviewed at research committee meetings. In addition, all adverse reactions 
considered “serious” will be entered into research database and reviewed by the monitor on an 
ongoing basis.  All adverse events will also be reported to 1-855-AYTU-BIO (1-855-298-8246). 
Additionally, all serious events will also be reported to the supervising IRB in the same timely 
manner.  
 
9. STATISTICAL CONSIDERATIONS 
 
9.1 Primary Study Endpoints 
 
The primary objectives of the study are to evaluate the effectiveness and saftey of UV Light 
treatment on hospitalized patients with COVID-19. 
 
  
Primary endpoint: 
1- Change in viral load from the ETT aspirate on day 0 to the last day of treatment. 
 
9.2 Secondary Study Endpoints 
 
• Bacterial load in upper airway 
• Development of ventilated associated pneumonia (VAP) 
• Days to extubation 
• Days to Discharge 
• Inflammatory marker changes 
• Clinical Outcomes: death, hospitalized on ventilator or ECMO, hospitalized on non-
invasive ventilation, hospitalized on supplemental O2, hospitalized not on O2, not 
hospitalized but with limitations, not hospitalized and no limitations. 
• Sampling and microbiologic assessment of endotracheal tube tip from extubated patients 
 
9.3 Exploratory endpoints 
 
• Change in inflammatory  and COVID-prognosticating markers day 0-7 (for those drawn 
for clinical care) 
o Ferrtin 
o Interleukin-6 

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o CRP 
o White blood cells 
o Procalcitonin 
o Lymphocyte count 
o D-dimer 
o CPK 
o Troponin 
• Percentage of Covid-related complications after treatment 
o Deep vein thrombosis 
o Pulmonary embolus 
o Cardiac event 
o cerebrovascular event 
o Renal failure 
o Increased liver enzymes 
 
 
9.4 Sample size, accrual and study duration 
 
 
 
TOTAL SAMPLE SIZE:  5 
 
TOTAL ACCURAL: 5 
 
STUDY DURATION: 4 weeks 
We are conducting a first-in-human open-label pilot study of the safety and effectiveness of 
Endotracheal UV light in patients with COVID19. Given that this is a pilot study, it is not 
powered to any specific endpoint.   
 
 
9.5 Statistical Analysis  
 
Demographic and baseline characteristics will be summarized for all the subjects. Demographics 
and baseline characteristics include: age, gender, race, ethnicity, height, weight, and body mass 
index (BMI). 
• Height (in cm)=height (in inches)*2.54 
• Weight (in kg) = weight (in lbs)*0.4536 
• BMI = weight/height2 (Kg/m2) 
Both primary and secondary endpoints will be presented using descriptive statistics. For 
continuous variables, descriptive statistics will include the number of subjects with data to be 
summarized (n), mean, standard deviation (SD), median, minimum (min) and maximum (max). 
The same number of decimal places as in the raw data will be presented when reporting min and 
max, one more decimal place than in the raw data will be presented when reporting mean and 
median, and two more decimal places than in the raw data will be presented when reporting SD. 

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If the raw data have three decimals or more, three decimals will be presented for mean, median, 
min and max, and SD. 
 
All the categorical data will be presented by counts and percentages. The denominator for each 
percentage will be the number of subjects within the population treatment group unless otherwise 
specified. All percentage will be presented with one decimal point. 
 
All analyses and summary outputs will be generated using SAS version 9.3. 
  
 
10. INVESTIGATORS RESPONSIBILITIES 
 
10.1 Investigator Responsibility/Performance 
 
The investigator (or a person designated by the investigator) should inform the patient (or 
surrogate) of all pertinent aspects of the study, including the written information. 
 
The investigator should provide the patient ample time and opportunity to inquire about details of 
the study and to decide whether or not to participate in the study.  All questions about the study 
should be answered to the satisfaction of the patient (or surrogate). Neither the investigator, nor 
the study staff, should coerce or unduly influence a patient to participate or to continue to 
participate in a study. 
 
10.2 Confidentiality 
 
The identity of the patients in this study will be treated as confidential. Patients eligible to 
participate in the study following the pre-treatment visit will be assigned a unique patient code. 
The results of the study, including any other data, may be published for scientific purposes but will 
not give the patients' name or include any identifiable references to them. 
 
However, any records or data obtained as a result of the patient participation in this study may be 
inspected by the sponsor, by any relevant governmental agency, by the Hospital Ethics Committee, 
or by the persons conducting this study, provided that such inspectors are legally obligated to 
protect any identifiable information from public disclosure, except where disclosure is otherwise 
required by law or a court of competent jurisdiction. These records will be kept private in so far as 
permitted by law.  
 
10.3 Informed Consent and Permission to Use Protected Health Information 
 
It is the responsibility of the investigator to obtain written informed consent from each subject (or 
surrogate) participating in this study after adequate explanation, in lay language, of the methods, 
objectives, anticipated benefits, and potential hazards of the study.  The investigator must also 
explain that the subject is completely free to refuse to enter the study or to discontinue participation 
at any time (for any reason) and receive alternative conventional therapy as indicated.  Prior to 

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study participation, each subject (or surrogate) will sign an IRB approved informed consent form 
and receive a copy of same (and information leaflet, if appropriate).  
 
The investigator or designee must explain to the subject before enrollment into the study that for 
evaluation of study results, the subject’s protected health information obtained during the study 
may be shared with the study sponsor, regulatory agencies, and the IRB.  It is the investigator’s 
(or designee’s) responsibility to obtain permission to use protected health information per HIPAA 
from each subject, or if appropriate, the subjects’ parent or legal guardian. 
 
10.4 Source Documentation and Investigator Files 
 
The investigator will maintain adequate and accurate records to document the conduct of the study 
and to ensure that study data can be subsequently verified.  These documents will be classified into 
two separate categories: (1) investigator study file and (2) subject clinical source documents that 
corroborate data collected on the CRF’s.  Subject clinical source documents would include 
hospital/clinic patient records; physician's and nurse's notes; original laboratory, radiology, 
pathology, and special assessment reports; QOL forms, signed informed consent forms.  When the 
CRF or any form is used as the source document, this will be clearly stated in the investigator 
study file. 
 
At a minimum, the following be documented in source documents: 
 
• Medical history/physical condition and diagnosis of the subject before involvement 
in the study sufficient to verify protocol entry criteria. 
• Study number, assigned subject number, and verification that written informed 
consent was obtained (each recorded in dated and signed notes on the day of entry 
into the study) 
• Progress notes for each subject visit. 
• Laboratory test results. 
• Condition and response of subject upon completion of or early termination from 
the study. 
 
10.5 Recording and Processing of Data 
 
Physical CRFs will be utilized at first and will be stored in a secure location at each investigation 
site.  Additionally, physical CRFs will be digitized, and sent to the sponsor’s HIPAA compliant 
server for analysis and long-term storage.  A CRF is required for every patient who received any 
study intervention.  The investigator will ensure that the CRF’s are accurate, complete, legible and 
timely. Separate source records are required to support all CRF entries.  All corrections to study 
data will be made by drawing a single line through the information to be corrected without 
obscuring it.  All corrections will be initialed, dated and explained, if necessary. Do not use 
“white-out” or obscuring correction tape.   
 
10.6 Non-Protocol Research 
 

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No investigative procedures other than those described in this protocol will be undertaken on the 
enrolled subjects without the agreement of the IRB. 
 
10.7 Ethics 
 
The investigator agrees to conduct the study in compliance with the protocol, current good clinical 
practices, and all applicable (local, FDA) regulatory guidelines and standard of ethics. 
 
10.8 Essential Documents for the conduct of clinical trial 
 
Essential documents are those documents with individually and collectively permit evaluation of 
the conduct of a trial and the quality of the data produced. 
 
The following documents will be on file: 
 
• CV’s and license of all investigators. 
• IRB documentation/correspondence. 
• Documentation of IRB certification. 
 
 
11. REFERENCES 
 
1. CDC Website. https://www.cdc.gov/coronavirus/2019-ncov/index.html