Clinical trial NCT05077969
Conditions: 2019 Novel Coronavirus Disease 2019 Novel Coronavirus Infection 2019-nCoV Disease 2019-nCoV Infection COVID-19 COVID-19 Pandemic COVID-19 Virus Disease COVID-19 Virus Infection Covid19 Coronavirus Disease 2019 SARS-CoV2 Infection SARS-CoV-2 Acute Respiratory Disease
Keywords: COVID-19 COVID COVID19 SARS-CoV-2
Sponsor: Leidos Life Sciences
Start date: 2021-12-29; Completion date: 2022-07-08
Enrollment: 4 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This study is designed to test the efficacy and safety of combinations of two well-understood agents - famotidine and celecoxib. Each of these agents separately demonstrate clinical activity in mitigating COVID-19 disease symptoms or severity, and each of which appear to have separate and complementary mechanisms of action.

Detailed description:
Qualifying patients will have been confirmed positive for COVID-19 and have symptoms of World Health Organization (WHO) Ordinal Scale for Clinical Improvement with scores of ≤3 on the 11-point scale and will be randomly assigned, in a 1:1 ratio, to one of two regimens, with 659 participants per group, as follows:

Group 1 (study product) participants will receive 80 mg famotidine by mouth (PO) 4 times per day (QID) + 400 mg celecoxib as a first dose, followed by 200 mg celecoxib (PO) 2 times per day (BID), for 5 days. Following this 5-day period, participants will continue their famotidine treatment for an additional 9 days.

Group 2 (reference therapy) participants will receive matching placebos QID and BID, for 5 days. Following this 5-day period, participants will continue to receive matching famotidine placebo, QID, for an additional 9 days.

Safety and efficacy of famotidine and celecoxib will be evaluated.

This is a completely virtual trial and you can participate from your own home. Please call 1-888-370-9330 to speak to someone regarding study participation in your area.

Arms: arm 1: Participants will receive 80 mg famotidine (PO) QID and 400 mg celecoxib as a first dose, followed by 200 mg (PO) BID celecoxib, for 5 days. Following this 5-day period, participants will continue their famotidine treatment for an additional 9 days. arm 2: Participants will receive matching placebos QID and BID, for 5 days. Following this 5-day period, participants will continue to receive matching famotidine placebo, QID, for an additional 9 days.
Interventions: intervention 1: Famotidine intervention 2: Celecoxib intervention 3: Placebo
Intervention descriptions: intervention 1: 80 mg tablet, QID for 14 days intervention 2: 400 mg (initial dose), then 200 mg capsule, BID for 5 days intervention 3: tablet, QID for 14 days; capsule, BID for 5 days

Protocol documents:
ICF_001.pdf: 
LEAP-CT for evaluation of post-exposure prophylaxis for newly-infected COVID-19 patients 
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RESEARCH PARTICIPATION INFORMATION 
AND 
CONSENT FORM 
For Protocol Addendum #2 
 
 
TITLE: 
A virtual Phase 2 randomized, placebo-controlled, double 
blind study to evaluate the safety and efficacy of the 
combination of famotidine and celecoxib as a post-exposure 
prophylaxis (PEP) for newly infected COVID-19 patients 
 
SUB-STUDY TITLE:  
A virtual Phase 2 randomized, placebo-controlled, double-
blind study to evaluate the safety and efficacy of the 
combination of famotidine and celecoxib with and without 
ivermectin as a post-exposure prophylaxis (PEP) for newly-
infected COVID-19 patients 
 
SHORT TITLE: 
LEAP-CT for evaluation of post-exposure prophylaxis for 
newly-infected COVID-19 patients 
 
PROTOCOL NO.: 
LDOS-21-001-02 
 
IND 153669 
 
WCG IRB Protocol #20211500 
 
SPONSOR: 
Leidos, Inc. 
 
FUNDING  
ORGANIZATION: 
United States Department of Defense (DoD) 
 
Defense Threat Reduction Agency (DTRA) 
<<CF-Main Header Block - Investigator>> 
INVESTIGATOR: 
Name 
 
Address 
 
City, State  Zip 
 
Country 
 
STUDY-RELATED 
PHONE NUMBER(S): 
<<CF-Main User Defined #1>> 
 
Phone Number 
 
Phone Number (24 hours) 
 
[24-hour number is required] 
 


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INFORMED CONSENT SUMMARY 
 
You are being asked for your consent to take part in a research study. This document 
provides a concise summary of this research. It describes the key information that we 
believe most people need to decide whether to take part in this research. Later sections 
of this document will provide all relevant details. 
 
What should I know about this research? 
 
• Someone will explain this research to you. 
• Taking part in this research is voluntary. Whether you take part is up to you. 
• If you don’t take part, it won’t be held against you. 
• You can take part now and later drop out, and it won’t be held against you. 
• If you don’t understand, ask questions. 
• Ask all the questions you want before you decide. 
 
How long will I be in this research? 
 
We expect that your taking part in this research will last 90 days. 
 
Why is this research being done? 
 
The purpose of this research is to study whether an investigational combination of 
famotidine (commonly used to treat heartburn) and celecoxib (commonly used to treat 
arthritis) can improve symptoms in people who are newly diagnosed with COVID-19, 
showing mild symptoms. 
 
What happens to me if I agree to take part in this research? 
 
If you decide to take part in this research study, the general procedures include taking 
the study drugs or placebos, measuring your heart function with a mobile 
electrocardiogram (ECG), getting your blood drawn, and answering questionnaires. 
 
Could being in this research hurt me? 
 
The most important risks or discomforts that you may expect from taking part in this 
research include risks from famotidine (headache, dizziness, constipation, diarrhea, 
kidney injury) and celecoxib (abdominal pain, diarrhea, upset stomach, swelling, 
dizziness, sore throat, rash, kidney injury, and liver injury). 
 


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Will being in this research benefit me? 
 
The most important benefit that you may expect from taking part in this research include 
improvement of your symptoms from COVID-19. However, this cannot be promised.  
Possible benefits to others include learning about another treatment for COVID-19. 
 
What other choices do I have besides taking part in this research? 
 
Instead of being in this research, your choices may include other medications used to 
treat COVID-19, like remdesivir, baricitinib and dexamethasone if you are in the 
hospital; monoclonal antibodies and/or antiviral treatments that have been granted 
Emergency Use Authorization (EUA) from the US Food and Drug Administration (FDA), 
for those who qualify; supportive care; and joining another research study. 
 
INFORMED CONSENT FORM 
 
You are being asked to participate in an on-line (virtual) clinical research study that 
seeks to find a possible treatment for COVID-19. Please take your time to read this 
consent form so that you understand the purpose, risks, and benefits. Taking part in this 
study is voluntary.   
 
We urge you to ask any questions you might have of the study team, and to make your 
decision thoughtfully.  If you decide to participate, you must sign this form to show that 
you want to take part. 
 
Why is this research study being done? 
 
Coronavirus disease 2019 (COVID-19) is a highly infectious virus (called coronavirus, or 
SARS-CoV-2) that was newly discovered in 2019.  It has spread rapidly around the 
world causing a global pandemic, and millions of people have become very sick. You 
are being asked to take part in this study because you have either recently tested 
positive for COVID-19, or you suspect that you have the illness and are waiting for the 
results of a laboratory test. You are likely experiencing mild symptoms, but can still 
perform daily tasks.  People who have COVID-19 may have flu-like symptoms such as 
cough, shortness of breath, nausea, and feeling tired, fever, chills, muscle stiffness, 
headache, sore throat, and/or loss of smell.   
 
Right now, there are two FDA approved treatment for COVID-19 in hospitalized patients 
– Remdesivir (Veklury®), Olumiant® (baricitinib). Some monoclonal antibody and/or 
antiviral therapies have been granted an EUA for the treatment of mild to moderate 
COVID-19 symptoms may be available to people 12 years of age or older with positive 
results of direct SARS-CoV-2 viral testing, and who are at high risk for progressing to 
severe COVID-19, including hospitalization and death. 






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Once the doctor confirms you are eligible to participate you will be enrolled in the study. 
You will: 
 
• Receive a package containing your assigned study medications. The package 
will not tell you which drugs you are being given. You will be asked to confirm 
with the study doctor that you received the package.  
• Be asked to take your medicines each day, as directed; 
• Provide 2 additional blood samples (on Day 7 and Day 14) of 10 mL – 15 mL 
(about 2-3 teaspoons); 
• Be asked about any new symptoms you’re experiencing and how bad they are 
making you feel (daily, for 90 days); 
• Take your temperature and measure your oxygen levels every day for 90 days 
(You will be provided with the equipment to measure these at no cost to you); 
• Utilize a heart function monitor to record a mobile ECG on Day 7 and Day 14; 
• Follow-up with your doctor for any health concerns or issues; 
• Be evaluated by remote interview with the study doctor (2 months after the first 
day you take the study drugs and again at 3 months after the first day you started 
taking the study drugs). 
 
This study will be virtual. This means that you will not physically visit the study doctor in 
person, and the study drugs will be delivered to your home or designated address. In 
order to collect the necessary blood samples, a phlebotomist will come to your home 3 
separate times, and draw your blood (at screening, Day 7, and Day 14). The 
phlebotomist will be scheduled through the electronic platform. You will be asked to take 
the study drugs, and report that you did so at the appropriate times in an online form 
through a study website (with a secure link designed to protect your privacy). You will 
be able to access the website on your personal electronic device, such as a cell phone, 
tablet or laptop. You will also visit this website daily to answer questions about your 
COVID-19 symptoms, and your general health and well-being. The online questionnaire 
will take about 5 to 10 minutes to complete every day.  
 
You will be provided with three electronic devices that you will use to collect the 
necessary data about your body temperature, oxygen levels, and heart function during 
the study.  Your doctor will receive your test results through the website and look at the 
data. Help is available through the website at all times if you have any issues or 
questions. 
 
Your participation in this study will last approximately 3 months (90 days). 
 


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You can decide to stop taking part in the study at any time. If you decide to stop, let 
your study doctor know as soon as possible. This is so your study doctor can perform 
an assessment and talk to you about any follow-up care and testing that could be 
helpful for you. 
  
What side effects can I expect from taking part in the study? 
 
You may have side effects while taking the study drugs.  Some, but not all, of the 
common side effects are listed below.  Both of the FDA-approved study drugs have a 
good safety profile and are established as safe for human use when used at the FDA-
approved dose for their given indications; however, the dose you may be receiving is 
more than the FDA-approved dose, and these drugs have never been used together to 
treat COVID-19. 
 
It is possible that you may experience one or more of the known side effects, or you 
may experience a side effect that is unknown, or you may experience no side effects at 
all.  Many of these side effects resolve when you stop taking the drugs, but in some 
cases, the side effects may be serious and/or lasting. Other side effects may be rare, 
but very serious, and even result in death.  The study doctors will not know who will or 
will not have side effects.  You, as the participant, are the only person allowed to take 
the study drugs as directed. You must keep the study drugs out of the reach of children 
and persons who might not be able to read or understand that they should not take the 
study drugs.   
 
Famotidine Side Effects:  
 
• Less likely: Fever, nausea, dry mouth, fatigue (or tiredness), dizziness, diarrhea, 
and/or constipation.   
• Rare: Fast/slow/irregular heartbeat, fainting, seizures, rash, bruising/bleeding, 
and mental/mood changes. 
 
Celecoxib Side Effects:   
 
• Less likely:  Sore throat, dizziness, gas, diarrhea, and abdominal pain.   
• Rare:  Rash, severe headache, pain or swelling in the groin or calf, difficulty 
swallowing, upper respiratory tract infection, kidney injury, liver injury, and 
serious cardiovascular thrombotic events like myocardial infarction and stroke. 
 


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Celecoxib + Famotidine Side Effects:   
 
• There may be unknown side effects from the combination of these two drugs. 
 
Other Possible Risks Associated with Participating in this Study 
 
Blood draw risks: We will be collecting many blood samples from you for evaluation.  
The risks of drawing blood (venipuncture) include temporary discomfort from the needle 
stick, bruising, bleeding, and rarely, infection.  Blood drawn by trained professionals will 
help minimize this risk. 
 
ECG risks: You will use a mobile device to obtain an ECG at 3 time points during the 
study and there is very little risk using this FDA-approved device.  
 
Reproductive risks: There may be other unknown risks or side effects or discomforts 
that we cannot predict, especially to an unborn child. Because the drugs in this study 
may affect an unborn baby, you should not become pregnant or father a baby while on 
this study.  You must use acceptable methods of birth control such as oral 
contraceptives (the pill), an intrauterine device (IUD), and/or condoms. Your doctor will 
discuss this with you.  You also should not breastfeed a baby while on this study.   
 
Risk of randomization: You will be assigned to a treatment group by chance.  There is 
a risk that the treatment you are assigned to may not work as well, or may have more 
side effects, than the other group. Your condition and/or symptoms may not improve, or 
may worsen while participating in this study. 
 
Risks of drug interactions: The study drug(s) could interact with the other study drugs.  
These drug interactions could lead to increased side effects.  Your study doctor will 
review all of the drugs and supplements you are currently taking before you start this 
investigational treatment. 
 
There are some drugs that you cannot keep taking while on the study, and the study 
doctor will talk to you about. In some cases, you cannot participate in the study if you 
decide to stay on certain medications. 
 
Risk of collecting a sample of mucus from your nose for a PCR test (a sample will 
only be collected if you tested positive using an at-home test):  The swab used to 
collect a sample of mucus from your nose is a long flexible stick with a soft tip.  You 
may experience some discomfort including coughing, mild bleeding, or watery eyes. 
 


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What are the benefits of this study if I decide to participate? 
 
You might not receive any direct benefit by participating in this study. If you are 
randomized into the group that gets the investigational combination of FDA-approved 
study drugs, there is a chance that your condition and symptoms will improve, but there 
is no guarantee. The combination of the study drugs was selected because researchers 
hope that these drugs will help reduce how badly you feel. You will be providing 
valuable information that may help others who become sick with COVID-19 in the 
future.  We hope the valuable information learned from this study will directly benefit 
other people by providing a safe and effective treatment for those infected with COVID-
19.   
 
A Data Safety and Monitoring Board (DSMB), an independent group of experts, will be 
reviewing data from this research throughout the study.  One of the most important 
answers we seek to obtain is whether this combination of drugs is not only safe to give, 
but also whether the doses of the drugs are effective to treat COVID-19.  Because we 
are evaluating the safety and effectiveness of this drug combination, the DSMB will 
review the data at certain time points, and can be called to meet in case of an 
emergency.  We will tell you in a timely matter about any new information given to us 
from the DSMB that may affect your health, welfare, or willingness to stay in this study. 
 
If I choose to participate in the study, can I change my mind later? 
 
Your participation is voluntary, so you can decline to take party in this study. You also 
may withdraw from the study at any time. Your decisions will not result in penalty or loss 
of benefits to which you are otherwise entitled. If you decide to withdraw your 
permission to participate: 
 
• We will no longer use or share medical information about you, or your samples 
and data, for this research study, except where the law allows us to do so; 
• We are unable to delete any information we have already shared with your 
permission; 
• We may continue using and sharing information that was gathered before your 
withdrawal if it is necessary for the soundness of the overall research; 
• We will keep our records of the care we provided to you for as long as required 
by law.  
 
Your decision not to participate, or to withdraw, will not affect your medical care.  Your 
study doctor will continue to answer any questions you may have, and you will also be 
advised to see your primary care provider.  Alternatively, the study doctor may decide to 
take you out of the study if new information about the study medication becomes 


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available that would jeopardize your health and well-being, or if he/she feels it is in your 
best interest. The study doctor also has the ability to remove you from the study without 
your consent.  
 
Will it cost me to participate? 
 
All clinical and professional fees that are associated with this study will be provided at 
no cost to you. The study medications will also be provided and shipped to your home 
at no cost.  The mobile ECG device, thermometer, and pulse oximeter that are provided 
will be at no cost to you, and they are yours to keep. 
 
Will I be paid to participate? 
 
<<CF-Main Payment for Part. Paragraph>>For your time, you will be given $50.00 for 
each completed study visit, up to a maximum of $300.00, at the end of the trial (Study 
Day 90).  The study visit payments are as follows: 
 
Study Visit Number 
Study Day 
Payment 
Screening, Visit 1 
Day -7 to Day -1 
Includes a blood draw 
$50 
Study Visit 2 
Day 1 Baseline/Start of 
Treatment 
No payment 
Study Visit 3 
Day 7 (±1 day) 
Includes a blood draw 
$50 
Study Visit 4 
Day 14 (±1 day) 
Includes a blood draw 
$50 
Study Visit 5 
Day 30 (±1 day) End of 
Treatment 
$50 
Study Visit 6 
Day 60 Observation period 
$50 
Study Visit 7 
(Conclusion of study 
participation) 
Day 90 Observation period 
$50 
 
When you have completed all study visits, a payment will be made to you in the form of 
a gift card to the e-mail address you used to register for this study.  The total 
compensation for this study, if you complete all study visits, is up to $300.  If you 
withdraw or terminate from the study before the end of the study, you will be paid for 
each visit you completed. 
 


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You and/or your insurance plan will need to pay for the standard costs of medical care 
for treating your condition if needed while participating in the study, just as you would if 
you were seeking medical care for COVID-19 from your primary care provider.  
 
What happens if I am injured in this study? 
 
This study is funded by the U.S. Department of Defense (DoD), with Leidos, Inc. acting 
as the Sponsor for the study on behalf of the DoD. The funder and clinical sites have no 
plans to pay for any research-related injury, or associated costs that are not covered as 
part of the study plan. If you are injured in this study, treatment will be provided. If you 
suffer a study-related injury while participating, Leidos, Inc. will provide reimbursement 
for the costs of medical treatment. 
<<CF-Main Financial Disclosure>> 
Will my personal information be kept private? 
 
Information gathered in this research study may be published or presented in public 
forums, but your name and other identifying information will not be used or revealed.  
Medical records that contain your identity will be treated as confidential.  All records will 
be kept in a locked and secure area and only those persons assigned to this study will 
have access to those records.  All study documents related to you and your participation 
will show only your assigned patient number (or code).  If any of your research records 
need to be copied, your name and all identifying information will be removed. 
 
Your personal information may also be disclosed if required by law.  Despite these 
efforts to keep your personal information confidential, we cannot guarantee absolute 
confidentiality.  However, your privacy is very important to us, so every reasonable effort 
will be made to keep your personal information in your research record private and 
confidential.   
 
Other regulatory groups may become aware of your participation in this study and may 
require access to your study records in the event of an audit. These groups may 
include: 
 
• The FDA and the groups it works with to review studies; 
• Government agencies, such as the Human Research Protection Office (HRPO) 
for the US Army Medical Research and Development Command (USAMRDC), 
involved in keeping research safe for people; 
• WCG Institutional Review Board -, a group of people who review the research 
with the goal of protecting people who take part in the study; <<CF-Main SMO 
Company 1>><<CF-Main Affiliated IN Language 1>> 


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• The funders, the DoD & The Defense Threat Reduction Agency (DTRA), and 
Leidos, Inc., the sponsor of this clinical study;  
• Monitoring entities contracted to the sponsor to ensure the trial is done in 
accordance with FDA regulations, and the data provided from this trial are 
accurate, and valid.   
 
The Use of Private Health Information 
 
Health information about you will be collected if you choose to be part of this research 
study.  Health information is protected by law, as explained in the <<CF-Main User 
Defined #2>>[Site] Privacy Notice.  If you have not received this notice, please request 
a copy from the study staff.  At <<CF-Main User Defined #2>>[Site] your information will 
only be used or shared as explained and authorized in this consent form, or when 
required by law.  It is possible that some of the other people or groups who receive your 
health information may not be required by Federal privacy laws to protect your 
information and may share it without your permission.   
 
To participate in this research you must allow the study team to use your protected 
health information (PHI).  PHI is any information in the medical record or patient file that 
can be used to identify you, like your name, age, ethnicity, home address, and health 
status.  Federal regulations allow researchers to access and use PHI when necessary 
to conduct clinical studies.  If you do not want us to use your PHI, you may not 
participate in this study.  The research-related therapy is investigational; therefore, it is 
not available to you unless you allow the use of your PHI.   
 
People usually have a right to access their medical records.  However, this research 
study is blinded.  This means that you will not know which treatment group you are in. 
until after the study has ended.  You may receive the drug combination, or you may 
receive placebo.  While this research study is in progress, you may not be allowed to 
see or copy certain information that is related to this research study.  This is only for the 
period of the research.  You will be allowed to see that information when the entire 
research project is complete.   
 
If I have questions or concerns during the study, who do I contact? 
 
You have the right to ask any questions you may have about this research.  If you have 
questions, complaints, concerns, or believe you have developed an injury related to this 
research, contact <<CF-Main User Defined #3>>[Name] at [Number(s)], or the study 
doctor on 24 hour call at <<CF-Main User Defined #4>>[Number].  The study doctor will 
notify the sponsor.  You are not waiving any of your legal rights by signing this consent 
form, nor releasing the sponsor from their legal and professional responsibilities.  We 
will make every effort to prevent injuries or illness from occurring while you are in the 
study. 


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If you have questions regarding your rights as a research participant, or you have 
general questions, complaints or concerns about the research or your privacy and the 
use of your PHI, contact the research subjects’ protection advocate in the <<CF-Main 
User Defined #2>>[Site] Subjects Protection Office at<<CF-Main User Defined 
#4>>[Number].  You may also call this number if you cannot reach the research team or 
wish to talk to someone else.   
 
This research is being overseen by WCG Institutional Review Board (IRB). An IRB is a 
group of people who perform an independent review of research studies. You may talk 
to them at 
 or via email at 
 if:  
 
o You have questions, concerns, or complaints that are not being answered by the 
research team. 
o You are not getting answers from the research team. 
o You cannot reach the research team. 
o You want to talk to someone about the research. 
o You have questions about your rights as a research subject. 
 
For more information about participation in a research study, and about the IRB, a 
group of people who review the research to protect your rights, please visit the WCG 
IRB’s web site at (www.wcgirb.com).  Included on this web site, under the heading 
“Participant Information”, you can access Federal regulations and information about the 
protection of human research participants.  If you do not have immediate access to the 
internet, copies of these Federal regulations are available by calling the <<CF-Main 
User Defined #2>>[Site] at the <<CF-Main User Defined #4>>[Number].  
 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as 
required by U.S. Law.  This Web site will not include information that can identify you.  
At most, the Web site will include a summary of the results.  You can search this Web 
site at any time. 
 


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SIGNATURE AND CONSENT 
 
Before making the decision regarding enrollment in this research, you should have: 
 
• Discussed this study with the study doctor or his/her designee; 
• Reviewed the information in this form; 
• Had the opportunity to ask any questions you may have. 
 
Your signature below means that you have received this information, have asked the 
questions you currently have about the research, and have received the answers to 
those questions.  You can print a copy of your signed and dated form from the 
 
portal to keep for future reference. 
 
Participant:  By signing this consent form, you indicate that you are voluntarily 
choosing to take part in this research. 
 
 
________________________     _______      _______     _______________________ 
           Signature of Participant                    Date               Time                        Printed Name 
 
 
Person Explaining the Research (Principal Investigator or Designee):  Your 
signature below means that you have explained the research to the participant and 
have answered any questions about the research. 
 
 
________________________     _______      _______     _______________________ 
           Principal Investigator                        Date                Time                         Printed Name 
                 or Designee 
 
 


LEAP-CT for evaluation of post-exposure prophylaxis for newly-infected COVID-19 patients 
18 February 2022 
IRB Approved Template 
MUST BE APPROVED 
FOR SITES BEFORE USE 
AS MODIFIED 
Jul 07, 2022 
 
Page 15 of 15 
Leidos, Inc.  
Study Number LDOS-21-001-02  
US Main ICF Version 2.0_18 February 2022 
 Participant Initials: ___ 
PARTICIPATION IN A FOLLOW-ON RESEARCH STUDY 
 
We may contact you in the near future to see if you would like to participate in a 
potential long-term observational study that will be using the data and information 
already provided by you. During this year-long study, we would ask you to provide daily 
or weekly updates on your health post-COVID. Please indicate below if you would like 
to be contacted in the future to be a part of this study.   
 
 
Yes, you may contact me about participating in this related research study. 
 
 
No, I do not want to be contacted about this related research study. 
 
 
________________________     _______      _______     _______________________ 
           Signature of Participant                    Date               Time                        Printed Name 

Prot_000.pdf: 
LEAP-CT as a Post-exposure Prophylaxis for Newly-infected  
            Protocol  LDOS-21-001-02 
COVID-19 Patients 
1 
Version 2.0; 11 April 2022 
ADDENDUM 2 TO PROTOCOL LDOS-21-001 
Protocol Title: A virtual Phase 2 randomized, placebo-controlled, double-blind study to evaluate 
the safety and efficacy of the combination of famotidine and celecoxib as a post-exposure 
prophylaxis (PEP) for newly-infected COVID-19 patients 
Protocol Number: LDOS-21-001-02 
Study Phase:  2  
Short Title: LEAP-CT for evaluation of post-exposure prophylaxis for newly-infected COVID-
19 patients 
Sponsor Name: Leidos, Inc. 
Legal Registered Address:  
1750 Presidents Street 
Reston, VA 20190 
USA 
Regulatory Agency Identifier Number(s): IND 153669 
Approval Date: xx April 2022 
Date:  11 April 2022 
Version: 2.0  


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SIGNATURE PAGE 
Sponsor’s Approval 
The protocol has been approved by Leidos, Inc. 
Responsible Medical Officer: 
 
 
 
 
 
Date 
Sponsor’s Authorized Officer: 
  
  
  
  
 
 
Date 
Medical Monitor Name and Contact Information: 
 
 
 
 
 
 


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INVESTIGATOR’S AGREEMENT 
 
I have read the Leidos LDOS-21-001 and LDOS-21-001-01 study protocols and agree to 
conduct the study in accordance with these protocols, all applicable government regulations and 
the principles of the ICH E6 Guidelines for Good Clinical Practice. I also agree to maintain the 
confidentiality of all information received or developed in connection with this protocol. 
 
 
 
Printed Name of Investigator 
 
 
 Signature of Investigator 
Date 
  


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PROCEDURES IN CASE OF EMERGENCY 
In case of emergency, Table 1 provides contact information as reference. 
Table 1: 
Emergency Contact Information 
Role in Study 
Name 
Address/ Telephone Number 
Clinical Study Leader 
 
 
Responsible Physician 
 
 
Drug Safety Physician  
 
 
24-Hour emergency contact 
 
 


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PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE 
 
DOCUMENT HISTORY 
Document 
Date 
V1.0 Initial Version 
12 August 2021 
V1.1, Amendment 1 
07 December 2021 
V2.0, Amendment 2 
07 March 2022 
 
 
 
Amendment 2 
Overall Rationale for the Amendment: 
Section # and Name 
Description of Change 
Brief Rationale 
3. Study Population 
Added language on recruitment 
process and compensation of 
participants 
Recruitment numbers have been 
low and most potential leads have 
inquired about monetary 
compensation. Included recruitment 
process to clarify question 
1.1 and 3.2 Inclusion Criteria, 
2 
Added FDA-authorized at-
home antigen positive test 
results to inclusion criterion, 
with need for confirmatory 
PCR testing while participant 
goes through screening 
Recruitment numbers have been 
low and potential leads have been 
using the U.S. Government-
provided at-home antigen tests 
instead of seeking a PCR test. 
Table 5 Schedule of 
Activities 
Added row for collecting a 
nasal swab for confirmatory 
PCR testing. 
Deleted Day -7 to Day -1 from 
header row. 
FDA requested any prescreened 
participant that was positive by at-
home antigen testing be confirmed 
positive by PCR. 
Deleted the timeframe as it was 
causing confusion with site 
personnel. 
5.1 Screening 
Added language to the 
phlebotomy visit regarding 
collecting a nasal swab for 
confirmatory PCR testing for 
those positive by at-home 
antigen test at prescreening 
The FDA requires a confirmatory 
PCR positive test result for those 
participants that were consented 
using a positive test result from an 
at-home antigen test. 
 
 


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TABLE OF CONTENTS 
ADDENDUM 2 TO PROTOCOL LDOS-21-001 ...........................................................................1 
SIGNATURE PAGE .......................................................................................................................2 
INVESTIGATOR’S AGREEMENT ...............................................................................................3 
PROCEDURES IN CASE OF EMERGENCY ...............................................................................4 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ............................................5 
1. 
PROTOCOL SUMMARY ............................................................................................9 
1.1. 
Synopsis ........................................................................................................................9 
1.2. 
Background .................................................................................................................18 
1.3. 
Benefit/Risk Assessment ............................................................................................18 
1.4. 
Objectives and Endpoints ...........................................................................................19 
1.4.1. 
Objectives ...................................................................................................................20 
1.4.2. 
Endpoints ....................................................................................................................20 
2. 
STUDY DESIGN .......................................................................................................21 
2.1. 
Overall Design ............................................................................................................21 
2.2. 
Scientific Rationale for Study Design ........................................................................21 
2.3. 
Justification for Dose ..................................................................................................21 
2.4. 
End of Study Definition ..............................................................................................21 
3. 
STUDY POPULATION .............................................................................................22 
3.1. 
Screen Failures ............................................................................................................22 
3.2. 
Inclusion Criteria ........................................................................................................22 
3.3. 
Exclusion Criteria .......................................................................................................23 
3.4. 
Study Intervention(s) Administered ...........................................................................24 
3.5. 
Preparation/Handling/Storage/Accountability ............................................................24 
3.6. 
Measures to Minimize Bias: Randomization and Blinding ........................................25 
3.7. 
Study Intervention Compliance ..................................................................................25 
3.8. 
Concomitant Therapy .................................................................................................25 
3.8.1. 
Prohibited Concomitant Medication ...........................................................................25 
3.8.2. 
Rescue Medicine .........................................................................................................26 
3.9. 
Dose Modification ......................................................................................................26 
3.10. 
Intervention after the End of the Study .......................................................................27 
4. 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL .......................................28 


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4.1. 
Discontinuation of Study Intervention........................................................................28 
4.2. 
Participant Discontinuation/Withdrawal from the Study ...........................................28 
4.3. 
Lost to Follow-up .......................................................................................................28 
5. 
STUDY ASSESSMENTS AND PROCEDURES ......................................................29 
5.1. 
Screening ....................................................................................................................29 
5.2. 
Baseline and Enrollment .............................................................................................30 
5.3. 
Treatment Period ........................................................................................................30 
5.4. 
Follow-up ....................................................................................................................30 
5.5. 
Efficacy Assessments .................................................................................................30 
5.6. 
Safety Assessments .....................................................................................................30 
5.6.1. 
Demographic/Medical History ...................................................................................31 
5.6.2. 
Physical Examinations ................................................................................................31 
5.6.3. 
Clinical Safety Laboratory Assessments ....................................................................31 
5.6.4. 
Suicidal Ideation and Behavior Risk Monitoring .......................................................31 
5.7. 
Adverse Events and Serious Adverse Events .............................................................31 
5.7.6. 
Disease-Related Events and/or Disease-Related Outcomes Not Qualifying as 
AEs or SAEs ...............................................................................................................32 
5.8. 
Treatment of Overdose ...............................................................................................33 
5.9. 
Pharmacokinetics/Pharmacodynamics .......................................................................33 
6. 
EXPLORATORY ENDPOINTS ................................................................................34 
6.1. 
Exploratory Endpoints: Tracking participants’ self-assessments on multiple 
dimensions. .................................................................................................................34 
6.2. 
Participant Protocol Debrief: Participants will respond to a trio of probes. ...............35 
7. 
STATISTICAL CONSIDERATIONS .......................................................................36 
7.1. 
Statistical Hypotheses .................................................................................................36 
7.2. 
Sample Size Determination ........................................................................................36 
7.3. 
Populations for Analyses ............................................................................................36 
7.4. 
Statistical Analyses .....................................................................................................37 
7.4.1. 
Demographics and Baseline Characteristics ...............................................................37 
7.4.2. 
Efficacy Analyses .......................................................................................................37 
7.4.3. 
Interim Analyses .........................................................................................................38 
7.4.4. 
Independent Data Safety Monitoring Board (DSMB) ................................................38 


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8. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ..................................................................................................39 
8.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight Considerations ....................39 
8.1.1. 
Regulatory and Ethical Considerations ......................................................................39 
8.1.2. 
Financial Disclosure ...................................................................................................39 
8.1.3. 
Informed Consent Process ..........................................................................................39 
8.2. 
Appendix 2: Data Management ..................................................................................40 
8.2.1. 
Data Protection ...........................................................................................................40 
8.2.2. 
Dissemination of Clinical Study Data ........................................................................40 
8.2.3. 
Data Quality Assurance ..............................................................................................40 
8.2.4. 
Source Documents ......................................................................................................40 
8.2.5. 
Study and Site Closure................................................................................................40 
8.2.6. 
Publication Policy .......................................................................................................40 
8.3. 
Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting ........................................................................41 
8.4. 
Appendix 4: Self-Rating of Symptoms and Symptom Scoring ..................................42 
8.5. 
Appendix 5: Contraceptive Guidance and Collection of Pregnancy 
Information .................................................................................................................43 
9. 
REFERENCES ...........................................................................................................44 
LIST OF TABLES 
Table 1: 
Emergency Contact Information ...................................................................................4 
Table 2: 
WHO 11–point Clinical Progression Scale ..................................................................9 
Table 3: 
Objectives and Endpoints ...........................................................................................10 
Table 4: 
Study Interventions .....................................................................................................13 
Table 5: 
Schedule of Assessments ............................................................................................16 
Table 6: 
Benefits, Risks, and Mitigations .................................................................................18 
Table 7: 
Study Interventions .....................................................................................................24 
Table 8: 
Analysis Populations ..................................................................................................36 
 
LIST OF FIGURES 
Figure 1: 
Study Design ...............................................................................................................15 
 
 


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1. 
PROTOCOL SUMMARY 
1.1. 
Synopsis 
Please refer to the Master Protocol LDOS-21-001 for a comprehensive background and rationale 
for this study of a combination of famotidine and celecoxib as a post-exposure prophylaxis (PEP) 
for newly-infected COVID-19 patients. 
This study (LDOS-21-001-02) is designed to test the efficacy and safety of combinations of two 
well-understood agents—famotidine and celecoxib. Each of these agents separately demonstrate 
clinical activity in mitigating COVID-19 disease symptoms or severity, and each of which 
appear to have separate and complementary mechanisms of action. 
Study Description: This is a virtual Phase 2 randomized, placebo-controlled, double-blind study 
to evaluate the safety and efficacy of the combination of famotidine and celecoxib as a post-
exposure prophylaxis (PEP) for newly-infected COVID-19 patients. Qualifying patients will 
have been confirmed positive for COVID-19 and have symptoms of WHO Ordinal Scale for 
Clinical Improvement with scores of ≤3 on the 11–point scale (Table 2), and will be randomly 
assigned, in a 1: ratio, to one of two regimens, with 659 participants per group, as follows: 
• Group 1 (Study Product): 80 mg famotidine (PO) QID + celecoxib 400 mg first dose, 
followed by 200 mg (PO) BID for 5 days. Following this 5-day period, participants will 
continue their 80 mg famotidine QID treatment for an additional nine days. 
Group 2 (Reference Comparator): Matching placebo for famotidine and celecoxib 
respectively, QID + BID for five days. Following this 5-day period, participants will 
continue to receive matching famotidine placebo, QID, for an additional 9 days. 
There will be a subsequent follow-up period of 90 days from Baseline (Day 1 of treatment). 
Table 2: 
WHO 11–point Clinical Progression Scale 
Score  Descriptor  
Patient State  
0  
Uninfected; no viral RNA detected  
Uninfected  
1  
Asymptomatic; viral RNA detected  
Ambulatory Mild  
2  
Symptomatic; independent  
Ambulatory Mild  
3  
Symptomatic; assistance needed  
Ambulatory Mild  
4  
Hospitalized; no oxygen therapy 
Hospitalized Moderate  
5  
Hospitalized; oxygen by mask or nasal prongs  
Hospitalized Moderate  
6  
Hospitalized; oxygen by NIV or high flow  
Hospitalized Severe  
7  
Intubation and mechanical ventilation, pO2/FiO2 ≥150 
or SpO2/FiO2 ≥200  
Hospitalized Severe  
8  
Mechanical ventilation pO2/FiO2 <150 (SpO2/FiO2  
<200) or vasopressors  
Hospitalized Severe  
9  
Mechanical ventilation, pO2/FiO2 <150 and 
vasopressors, dialysis, or ECMO  
Hospitalized Severe  


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Score  Descriptor  
Patient State  
10  
Dead  
Dead  
Study Objectives and Endpoints: The objectives of the study are to evaluate the safety and 
efficacy of famotidine and celecoxib when used as a treatment for COVID-19. The study specific 
objectives and endpoints are described Table 3 and within Section 1.4. 
Table 3: 
Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
 
Efficacy 
 
The percentage of patients with at least one COVID-19–related 
medically attended contact, due to increased symptom severity, through 
Day 30 in both the placebo and the overall trial population, or incidence 
of death (all-cause mortality). Medically attended visits could include 
telemedicine visits, in-person physician visits, urgent care or emergency 
department visits, hospitalization. 
Secondary 
 
Safety 
 
 
 
 
Efficacy 
Incidence of Related Serious Adverse Events (SAE) 
Incidence of discontinuation due to related SAE 
Oxygenation Status (oxygen saturation ≤ 94%, necessitating 
supplemental oxygen, as measured by daily pulse oximeter ratings) 
 
The percentage of participants with at least three COVID-19–related 
medically attended contacts due to increased symptom severity, through 
Day 30. 
Exploratory 
 
Efficacy 
Rate of hospitalization, as well as all-cause mortality rate.  
Additionally, multiple Patient-Reported Outcome (PRO) endpoints will 
be used to establish how participants feel and function in relation to 
disease and treatment.  These endpoints will include daily ratings of 
symptom type and severity. Symptoms will be captured using a 0-10, 
11-point numerical rating scale ranging from “None” to “Extreme.”  
Daily ratings of perceived incapacity will also be obtained using a 0-10, 
11-point numerical rating scale ranging from “No Limitation” to 
“Extreme Limitation."   
At the conclusion of their participation, participants will also report on 
their global impression of therapeutic change using an established 7-pt 
Patient’s Global Impression of Change Scale (PGIC), their belief 
regarding active vs. placebo group assignment, and their qualitative 
impressions of their illness experience elicited through narrative probes.    
In addition to the above subjective measures, daily body temperature 
ratings will be captured and recorded.   
 


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Inclusion criteria:  
1. Participant must be at least 18 years of age, inclusive, at the time of signing the Informed 
Consent. 
2. Confirmed SARS-CoV-2 PCR positive or positive by FDA-authorized at-home antigen 
test within 5 days of enrollment (i.e., signing the ICF), as shown by medical history and 
reported PCR or antigen test result; confirmatory PCR testing is required for participants 
with an antigen-positive test result before starting study medication. 
3. Reports having one or more symptoms consistent with SARS-CoV-2 (as defined in 
Appendix 3, Table 4 of the Master Protocol, LDOS-21-001). 
4. COVID-19 Diagnosis must be WHO Grade <3, as referenced in Section 1.1, Table 2 
5. Contraceptive use by men or women should be consistent with Appendix 4 of the Master 
Protocol (LDOS-21-001). 
6. Reliable access to the Internet via a browser installed on personal device or computer.  
7. Capable of understanding and providing of signed informed consent. 
Exclusion criteria: 
Participants are excluded from the study if any of the following criteria apply: 
1. Pregnancy or breastfeeding 
2. Ongoing antiviral or antiretroviral treatment 
3. Known history of HIV 
4. Ongoing anti-inflammatory treatment that cannot be temporarily discontinued during the 
study. This includes nonsteroidal anti-inflammatory drugs (NSAIDs), and corticosteroids 
– including Dexamethasone (dexamethasone administration restricted to recommended 
standard of care use per NIH COVID-19 Guidelines) 
a. drugs dependent on gastric pH for absorption, e.g., dasatinib, delavirdine, 
mesylate, cefditoren, and fosamprenavir 
b. tizanidine (CYP1A2) substrate,  
c. drugs that interfere with hemostasis (e.g., warfarin, aspirin, selective serotonin 
reuptake inhibitors [SSRIs]/serotonin norepinephrine reuptake inhibitors 
[SNRIs]), 
d. angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers 
(ARB), or beta-blockers, 
e. diuretics, 
f. digoxin. 
5. Ongoing treatment that cannot be temporarily discontinued during the study, with: 
antimalarials, antiarrhythmics, tricyclic antidepressants, natalizumab, quinolones, 
macrolides, agalsidase alfa and beta 
6. Ongoing famotidine, celecoxib or other COVID-19 clinical investigational treatment(s) 
within the past 30 days, or current participation in another investigational clinical trial. 


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7. History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other 
NSAIDs 
8. History of immunosuppression 
9. Rejection of participation by Principal Investigator or Sponsor 
10. Any contraindication for famotidine or celecoxib treatment: 
a. Famotidine or celecoxib hypersensitivity  
b. Retinopathy, visual field or visual acuity disturbances 
c. History of cardiovascular disease, such as congestive heart failure, QT prolongation, 
myocardial infarct, bradycardia (< 50 bpm), ventricular tachycardia, other 
arrhythmias 
d. Myasthenia gravis 
e. Psoriasis or porphyria 
f. History of renal failure/dialysis or a glomerular clearance <60 mL/min 
g. History of severe hypoglycemia 
h. Moderate or severe hepatic impairment, e.g., Child-Pugh Class B or C 
i. Known or suspected to be poor CYP2C9 metabolizers based on genotype or previous 
history or experience with other CYP2C9 substrates, such as warfarin and phenytoin. 
Data Collection: Throughout the study, participants will enter data using their personal web-
enabled devices via a secure internet URL, into an adaptive self-reporting platform (
, 
and transmitted to the ClinTrial database. This will allow for tracking increases and decreases in 
symptom severity and capability to perform tasks throughout the treatment phase of the study 
and, subsequently, through the follow-up phase. Participants will be able to report their 
symptoms, potential adverse events (AEs), and all other required data, once daily each day.  
Tracking symptoms during follow-up will help establish and identify the emergence of new 
symptoms or return of previously noted symptoms following treatment. 
Data Safety Monitoring Board: An independent Data Safety Monitoring Board (DSMB) will 
be established to monitor safety data at regular intervals to ensure the continuing safety of 
participants enrolled in the study. Summary data tables and listings, as well as any individual 
participant data will be provided to the DSMB by unblinded personnel (e.g., independent 
unblinded biostatistician), who will not be the same staff responsible for the analysis and 
operational aspects of the study. Summary data may be initially provided in semi-unblinded 
fashion (e.g., participants sorted by study treatment regimen, without disclosure of the actual 
treatment administered). Should the DSMB require fully-unblinded data, these tables and listings 
will then be provided. 
Statistical Methods: The study will aim to enroll up to 1465 participants, which assumes a 10% 
screen failure rate, with a final allocation of 659 participants in the treatment arm and 659 in the 
control arm. 
This sample size of ensures a power of 90% at a 2-sided α of 5%, assuming a 1:1 randomization, 
a placebo rate of 6% (of participants with at least one COVID-19–related medically attended 
contact, due to increased symptom severity, or incidence of death due to COVID-19 through Day 
30) and an assumed relative risk reduction of 65% to 2.4% in the active treatment arms. The 
statistical test of the null hypothesis of no between-group difference in proportions, as specified 


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in the primary endpoint, will be tested using a χ2 test at a two-sided 5% significance level. An 
interim analysis for futility will be performed after 50% of participants have completed the 
primary endpoint assessment at day 30. Safety analyses will be performed on the Safety 
Population, consisting of all participants who are randomized and received study drug, analyzed 
by actual treatment arm. A more detailed description of the statistical methods can be found in 
Section 7. 
Protocol Title: A virtual Phase 2 randomized, placebo-controlled, double-blind study to evaluate 
the safety and efficacy of the combination of famotidine and celecoxib as a post-exposure 
prophylaxis (PEP) for newly-infected COVID-19 patients. 
Short Title: LEAP-CT as a post-exposure prophylaxis for newly-infected COVID-19 patients. 
Rationale: Please refer to the Master Protocol LDOS-21-001 for a comprehensive background 
and rationale for this study of a combination of famotidine and celecoxib as post-exposure 
prophylaxis (PEP) for newly-infected COVID-19 patients. 
Overall Design: This is a Phase 2, randomized double-blind placebo-controlled decentralized 
virtual study in which outpatient participants, newly diagnosed for COVID-19, will be 
randomized in a 1:1 ratio to one of two study groups (1 treatment group and 1 control group). 
The study is designed as a virtual trial in that it will be conducted, in situ, with home-based 
participants entering self-assessments via a web-enabled adaptive platform – 
The 
participants will be under the oversight of regionally based investigators who will be responsible 
for study conduct and the review of blinded data on a periodic basis. 
Intervention Groups and Duration: The treatment regimen for this study is shown in Table 4. 
Table 4: 
Study Interventions 
Regimen 
Dose 
# of Participants 
Group 1 
80 mg famotidine (PO) QID + celecoxib 400 mg first dose, 
followed by 200 mg (PO) BID for 5 days. Following this 5-day 
period, participants will continue their 80 mg famotidine QID 
treatment for an additional nine days. 
659 
Group 2 
Matching Placebo for famotidine and celecoxib respectively – QID 
+ BID for five days. Following this 5-day period, participants will 
continue to receive matching famotidine Placebo, QID, for an 
additional 9 days. 
659 
Disclosure Statement: This is a Phase 2 randomized, double-blind, placebo-controlled study to 
evaluate the safety and efficacy of the combination of famotidine and celecoxib as a post-
exposure prophylaxis (PEP) for newly-infected for COVID-19 patients. These participants will 
not be hospitalized at enrollment, and all study activities will be performed at the participant’s 
home. Investigational product and matching Placebo will be shipped directly to the participant 
from the Sponsor’s supplier. There will be no other physical location where participants are seen. 
Virtual research teams will be organized by U.S. geographical region under the oversight of a 
Principal Investigator licensed to practice in the state(s) in which participants reside. Each site or 
group of affiliated sites will be required to designate at least one physical location to serve as a 
research facility for storage of any paper documents generated, mail correspondence or location 


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for inspection activity. This designated location will be listed as a research facility under Section 
#3 of Form FDA 1572. 
Number of Participants: Approximately 1800 participants will be screened to achieve 1465 
randomly assigned to study intervention and at least 1318 evaluable participants for an estimated 
total of 659 evaluable participants per group. 
Study Design: The study design is shown schematically in Figure 1. 
Schedule of Assessments: The participants will have responsibility for entering self-assessment 
of symptom severity, body temperature, blood oxygen concentration (spO2) using Sponsor-
supplied devices, using the web-based 
platform. The study Schedule of Assessments is 
shown in Table 5. 




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Table 5: 
Schedule of Assessments 
Study Activities and Assessments 
Screening & 
Randomization 1 
 
Treatment Period 
Observation Period 2 
Visit Number 3 
1 
2 
3 
4 
5 
6 
7 
Study Day 
 
Day 1 
Baseline/ 
Start of 
Treatment4 
Day 7(±1)   
Day 14 (±1) 
Day 30(±1)   
End of 
Treatment  
Day 60  
Day 90  
Informed consent5 
X 
 
 
 
 
 
 
Inclusion and Exclusion criteria 
X 
X 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
Medical History, including weight reporting6 
X 
 
 
 
 
 
 
Concomitant medication review 
X 
X 
X 
X 
X 
 
 
Blood draw for comprehensive metabolic panel 
(mobile phlebotomy & laboratory service) 
X 
 
X 
X 
 
 
 
Nasal swab for confirmatory PCR test for at-home 
antigen positive test prescreened participants 
(mobile phlebotomy & laboratory service) 
X 
 
 
 
 
 
 
Randomization and initiation of drug shipment7 
X 
 
 
 
 
 
 
Review of reported baseline symptoms  
 
X 
 
X 
 
 
 
Confirmation of Study Drug Receipt & Initial Dose 
 
X 
 
 
 
 
 
Confirmation of Study Drug Return Shipment8 
 
 
 
 
X 
 
 
Review of eDiary for study drug compliance9 
 
 
X 
X 
X 
 
 
Adverse Events Review 
 
X 
X 
X 
X 
 
 
Participant Intake of study drug 
 
Daily on Days 1–14 
 
 
 


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Study Activities and Assessments 
Screening & 
Randomization 1 
 
Treatment Period 
Observation Period 2 
Visit Number 3 
1 
2 
3 
4 
5 
6 
7 
Study Day 
 
Day 1 
Baseline/ 
Start of 
Treatment4 
Day 7(±1)   
Day 14 (±1) 
Day 30(±1)   
End of 
Treatment  
Day 60  
Day 90  
Symptom questionnaires, spO2, and temperature 
 
Daily for the entire treatment and observation period (Days 1–90) 
Mobile ECG 
 
X 
X 
X 
 
 
 
1 Participant will complete demography, medical history, concomitant medications, and questions regarding inclusion and exclusion criteria [including results of 
SARS-CoV-2 PCR test and self-administered urine pregnancy test] via 
 Site will review participant responses and confirm information with 
participant by Visit 2. 
2 During the observational period, while participant is not taking any IP, participant will record long term symptoms for Covid-19, but will be directed to consult 
with his/her primary care physician (PCP) for follow up of any health changes. Planned contacts with participants on Days 60 and 90 will be performed by 
study support staff only to confirm continued participation in the study. 
3All participant visit activities will be performed remotely. 
4 Visit 1/participant informed consent must be performed within 5 days of a positive PCR or at-home antigen test, as per inclusion criteria. As IP will be shipped 
to the participant upon randomization, treatment start date (Visit 2/Day 1) may not occur until a few days after initiation of IP shipment. Participant will start 
treatment after IP receipt and review of inclusion/exclusion criteria with site. Date of first IP intake will always be considered Day 1, even if IP shipment is 
delayed outside of expected timeframe. If IP intake is delayed due to shipment, this will not be considered a protocol deviation. 
5 Participant will complete Informed Consent Process via 
 
6 Medical history should include relevant history from within the past 3 years, with inclusion of relevant medical events within the past 5 years. 
7 IP will be shipped directly from drug depot to participants after randomization occurs within 
Site investigator will confirm participant eligibility Visit 
2. 
8 Participant will be provided return envelope for return of IP directly from participant to drug depot. At Visit 4, site will confirm with participant that he/she has 
shipped the IP back to the depot. Depot will be responsible for performing IP accountability. 
9 Participant eDiary review will be performed by the clinical site staff.


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1.2. 
Background 
Refer to the Master Protocol (LDOS-21-001) for a comprehensive background discussion. For 
this study, a secure, adaptive, interactive source data collection platform, 
will be used. 
Because the platform is web-enabled, it provides a means for real-time data collection by the 
participant or study staff through any device that can access the internet. 
1.3. 
Benefit/Risk Assessment 
More detailed information about the known and expected benefits and risks and reasonably 
expected adverse events of each of the investigational products may be found in the Package 
Insert for famotidine and celecoxib respectively, and are provided in the Investigator’s Brochure. 
Refer to the Master Protocol (LDOS-21-001) for overall discussion of Benefit/Risk. The factors 
discussed here are specific to this study in home-based patients. Table 6 details the potential 
benefits, risks, and mitigations associated with study participation. 
Table 6: 
Benefits, Risks, and Mitigations 
Factors 
Discussion 
Evidence and uncertainties 
Analysis of 
condition 
COVID-19 
Progression 
Patients with COVID-19 disease can present with a 
range of mild-to-severe non-specific clinical signs and 
symptoms, which develop two-to-fourteen days after 
exposure to SARS-CoV-2. These symptoms include 
cough or shortness of breath, and at least two of the 
following: fever, chills, repeated rigor, myalgia, 
headache, oropharyngitis, anosmia, and ageusia. More 
severe symptoms warranting hospital admission include 
difficulty breathing, a persistent sense of chest pain or 
pressure, confusion or difficulty to arouse, as well as 
central cyanosis. Of hospitalized patients, 33% develop 
Acute Respiratory Distress Syndrome (ARDS), the most 
common cause for admission to the ICU; approximately 
28% of patients admitted to the ICU will die 
Current Treatment 
Options 
Only one 
pharmacological agent 
(remdesivir) has been 
FDA-approved for the 
treatment of 
hospitalized COVID-
19 patients. 
Currently, there is no FDA-approved therapy for treating 
the early symptoms of COVID-19 and mitigating 
disease progression. Clinical management consists of 
supportive care, including ventilation in case of 
respiratory failure. 
Remdesivir and dexamethasone are not applicable 
treatment options for this outpatient study. 
Benefit 
Famotidine and 
Celecoxib have shown 
efficacy alone, and in 
(limited) combination, 
against viral 
mechanisms. 
As noted in the Master Protocol, each of the two drugs 
in the combination therapy have been approved by FDA 
and are available either OTC or by prescription. 
Published reports indicate that each may independently 
act to reduce the morbidity and mortality associated with 
host responses to SARS-CoV-2 infection in those 
patients that develop COVID-19. 


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Factors 
Discussion 
Evidence and uncertainties 
Risk 
Study treatments (IP) 
in combination and at 
proposed dosages and 
regimens. 
The two investigational products have a long history of 
use as both prescription and over-the-counter products. 
They have demonstrated acceptable safety profiles in 
their labelled indications and usage. 
There are limited data available, to-date, of the proposed 
investigational products in combination, and at the 
proposed dosages and regimens for the proposed 
indication. However, there are studies of famotidine 
(400 mg PO) and celecoxib (200 mg PO, BID) in 
combination against COVID-19 in 61 patients (Personal 
communication from 
 15 March 
2021). These have shown only small incidences of 
adverse events (one patient hospitalized and one 
incidence of allergic reaction in the former study). 
Risk Management 
Study Treatment 
If intolerable side effects occur during the study, 
participants will be withdrawn from the trial in the 
participant’s best interest. Patients with a history of 
allergic reactions or other significant uncontrolled 
medical conditions will be excluded from the study. In 
the event of adverse events or reactions, trained health 
professionals at the study site will take the appropriate 
measures for treatment, advice, or withdrawal from 
study. 
Study procedures 
Patients will be carefully screened for any exclusion 
criteria to any of the planned study procedures, and will 
be excluded if the procedure is deemed to pose 
unacceptable safety risks to the patient. 
Safety Oversight 
An independent DSMB will monitor the study progress 
for trends indicating unfavorable risk or safety profile. 
1.4. 
Objectives and Endpoints 
Study Description: This study (LDOS-21-001-02) is a virtual Phase 2 randomized, placebo-
controlled, double-blind study to evaluate the safety and efficacy of the combination of 
famotidine and celecoxib as a PEP for newly-infected COVID-19 patients. This study is 
designed to test the efficacy and safety of combinations of two well-understood agents: 
famotidine and celecoxib. Each of these agents separately demonstrate clinical activity in 
mitigating COVID-19 disease symptoms or severity, and each of which appear to have separate 
and complementary mechanisms of action. Qualifying patients will have been confirmed 
COVID-19 – positive, and have symptoms of WHO Ordinal Scale levels ≤3, and will be 
randomly assigned, in a 1:1 ratio, to one of two regimens, with 659 participants per group, as 
follows:  
• Group 1 (Study Product): 80 mg famotidine (PO) QID + celecoxib 400 mg first dose, 
followed by 200 mg (PO) BID for 5 days. Following this 5-day period, participants will 
continue their 80 mg famotidine QID treatment for an additional nine days. 


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• Group 2 (Reference Comparator): Matching Placebo for famotidine and celecoxib 
respectively, QID + BID for five days. Following this 5-day period, participants will 
continue to receive matching famotidine Placebo, QID, for an additional 9 days. 
There will be a subsequent follow-up period of 90 days from Baseline. 
1.4.1. 
Objectives 
The objectives of the study are to evaluate the safety and efficacy of famotidine and celecoxib 
when used as a treatment for COVID-19. 
1.4.2. 
Endpoints 
Primary efficacy endpoint will include the percentage of participants with at least one COVID-
19–related medically attended contact, due to increased symptom severity, through Day 30 in 
both the placebo and the investigational treatment population, or incidence of death (all-cause 
mortality). Medically-attended visits could include telemedicine visits, in-person physician visits, 
urgent care or emergency department visits, hospitalization. 
Secondary endpoints will include the incidence of related serious adverse events (SAEs) and 
the incidence of discontinuation due to related SAEs, as well as oxygenation status (oxygen 
saturation ≤ 94%, necessitating supplemental oxygen as measured by daily pulse oximeter 
ratings). 
Exploratory endpoints will be evaluated for all study participants. The rate of hospitalization 
and all-cause mortality rate will be assessed for all participants. Additionally, multiple PRO 
endpoints will be used to establish how participants feel and function in relation to disease and 
treatment. These endpoints will include daily ratings of symptom type and severity from which 
estimates of symptom onset and duration can be derived, along with the tracking of dynamic 
trends over time. Symptoms will be captured using an 11–point numerical rating scale (NRS) 
ranging from “None” to “Extreme”, which corresponds to 0–10. The default symptom list 
provided to participants will include labels for 20 symptoms that have been commonly associated 
with COVID-19 (see Appendix 3 in the Master Protocol, LDOS-21-001) with the capability of 
adding individualized symptoms not appearing in the common list. Daily ratings of perceived 
incapacity will also be obtained to assess the overall impact of symptoms on participant’s day-to-
day functionality, using the 11–point NRS with a range from “No Limitation” to “Extreme 
Limitation." At the conclusion of their participation, participants will also report on their global 
impression of therapeutic change using an established 7–point scale (PGIC), their belief 
regarding active v. placebo group assignment, and their qualitative impressions of their illness 
experience elicited through narrative probes. Participants will be oriented to and trained on the 
use of these PRO instruments to ensure comprehensibility and usability, in accordance with 
recent FDA guidance for assessing COVID-19 in outpatient clinical trials. In addition to the 
above subjective measures, daily spO2 and body temperature ratings will be captured using 
Sponsor-provided pulse oximeter and thermometer, and recorded by participants.  


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2. 
STUDY DESIGN 
2.1. 
Overall Design 
This is a randomized double-blind placebo-controlled study in which patients newly-diagnosed 
with COVID-19, with symptoms of WHO Ordinal Scale levels ≤3, will be randomized in a 1:1 
ratio to receive oral tablets/capsules of the study products, or placebo, in addition to the standard 
of care (SOC), for 5 days. Following this 5-day period, participants assigned to Group 1 will 
continue their famotidine QID treatment for an additional nine days. Those participants assigned 
to Group 22 will continue their famotidine-matching placebo QID administration for an 
additional nine days. The study will maintain equal distribution of male and female participants. 
There will be a subsequent follow-up period of 90 days from Baseline. 
2.2. 
Scientific Rationale for Study Design 
Rather than focusing on direct-acting antiviral drugs (a historically ineffective strategy for acute 
viral pneumonias (Ruuskanen O, 2011), we seek to identify and develop combinations of 
pharmaceutical agents with complementary mechanisms-of-action (MOA) that will mitigate the 
hyperinflammatory cascade triggered by SARS-CoV-2 infection.  We propose that selection of 
pharmaceuticals, which target more specific mechanistic pathways involved in COVID-19 
inflammation, will reduce off-target non-specific effects, which may complicate clinical 
management, reduce efficacy and increase treatment-emergent adverse events.  The decades of 
experience in developing therapeutic drug cocktails for AIDS guides our strategy; optimal 
solutions typically require multiple drugs with complementary MOA.   
This study is designed to test the efficacy and safety of combinations of two well-understood 
agents; famotidine and celecoxib. Each of these agents separately demonstrate clinical activity in 
mitigating COVID-19 disease symptoms or severity, and each of which appear to have separate 
and complementary mechanisms of action (MOA). The combination therapy will be assessed in 
patients hospitalized for moderate-to-severe COVID-19 (LDOS-21-001-01), and compared to 
matched placebo interventions to best elucidate the therapeutic value and safety of the two-
component intervention. Data collection and entry will be optimized through an adaptive clinical 
data platform—
 
2.3. 
Justification for Dose 
A comprehensive review of dose justification is provided in Section 2.2 of the Master Protocol 
(LDOS-21-001). 
2.4. 
End of Study Definition 
A participant is considered to have completed the study if he/she has completed all phases of the 
study, including the follow-up. 
The end of the study is defined as the date of the last visit of the last participant in the study, or 
the last scheduled procedure shown in the Schedule of Activities (SoA) for the last participant in 
the trial (Day 90). Thus, the last participant to complete their Day 90 Follow-up Visit will be 
considered Last Patient Last Visit (LPLV). 


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3. 
STUDY POPULATION 
This study will enroll males and females aged 18 years or older that have tested positive with 
COVID-19, with a WHO grade that is ≤3. There is no restriction on a prospective participant’s 
Body Mass Index (BMI) or previous COVID-19 vaccination status. Prospective approval of 
protocol deviations to recruitment and enrollment criteria, also known as protocol waivers or 
exemptions, is not permitted. 
Study subjects will be recruited by social media, television, and radio advertisements that direct 
them to the study website (www.treatmycovid.com). These adverstisements are run in the market 
areas and states in which there are active clinical trial sites. Subjects should be literate and able 
to speak English in order to communicate with the professional staff involved in monitoring 
safety during the study and to complete the subject forms in 
 Individuals responding to 
recruitment messages will be instructed to contact the website or study call center phone number 
to receive further information. 
Individuals will be informed that they will be compensated for blood draws ($50 for each blood 
draw) and for their continued follow-up visits at Days 30, 60, and 90 ($50 per visit). If subjects 
complete all required study visits, then their total compensation is $300; compensation is 
prorated by the number of visits successfully completed and will be paid at Day 90 whether or 
not the subject is still enrolled in the study at that time. Compensation will be provided to 
participants in the form of an electronic Visa or Mastercard giftcard, which will be sent to the 
participant’s registered email address. 
3.1. 
Screen Failures 
Screen failures are defined in Section 3.2 of the Master Protocol (LDOS-21-001). Individuals 
who do not meet the criteria for participation in this study (screen failure) may not be rescreened. 
3.2. 
Inclusion Criteria 
1. Participant must be at least 18 years of age, inclusive, at the time of signing the informed 
consent 
2. Confirmed SARS-CoV-2 PCR positive or positive by FDA-authorized at-home antigen 
test within 5 days of enrollment (i.e., signing the ICF), as shown by medical history and 
reported PCR or antigen test result; confirmatory PCR testing is required for participants 
with an antigen-positive test result before starting study medication 
3. Reports having one or more symptoms consistent with SARS-CoV-2 (as defined in 
Appendix 3, Table 4 of the Master Protocol, LDOS-21-001) 
4. COVID-19 Diagnosis must be WHO Grade ≤3,as referenced in Section 1.1, Table 2 
5. Contraceptive use by men or women should be consistent with Appendix 4 of the Master 
Protocol (LDOS-21-001). 
6. Reliable access to the Internet via a browser installed on personal device or computer.  
7. Capable of understanding and providing of signed informed consent 


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3.3. 
Exclusion Criteria  
Participants are excluded from the study if any of the following criteria apply: 
1. Pregnancy or breastfeeding 
2. Ongoing antiviral or antiretroviral treatment 
3. Known history of HIV 
4. Ongoing anti-inflammatory treatment that cannot be temporarily discontinued during the 
study. This includes nonsteroidal anti-inflammatory drugs (NSAIDs), and corticosteroids 
– including Dexamethasone (dexamethasone administration restricted to recommended 
standard of care use per NIH COVID-19 Guidelines) 
a. drugs dependent on gastric pH for absorption, e.g., dasatinib, delavirdine, 
mesylate, cefditoren, and fosamprenavir 
b. tizanidine (CYP1A2) substrate,  
c. drugs that interfere with hemostasis (e.g., warfarin, aspirin, selective serotonin 
reuptake inhibitors [SSRIs]/serotonin norepinephrine reuptake inhibitors 
[SNRIs]), 
d. angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers 
(ARB), or beta-blockers, 
e. diuretics, 
f. digoxin. 
5. Ongoing treatment that cannot be temporarily discontinued during the study, with: 
antimalarials, antiarrhythmics, tricyclic antidepressants, natalizumab, quinolones, 
macrolides, agalsidase alfa and beta. 
6. Ongoing famotidine or celecoxib or other COVID-19 clinical investigational treatment(s) 
within the past 30 days, or current participation in another investigational clinical trial. 
7. History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other 
NSAIDs 
8. History of immunosuppression 
9. Rejection of participation by Principal Investigator or Sponsor 
10. Any contraindication for famotidine or celecoxib treatment: 
a. Famotidine or celecoxib hypersensitivity  
b. Retinopathy, visual field or visual acuity disturbances 
c. History of cardiovascular disease, such as congestive heart failure, QT prolongation, 
myocardial infarct, bradycardia (< 50 bpm), ventricular tachycardia, other 
arrhythmias 
d. Myasthenia gravis 
e. Psoriasis or porphyria 
f. History of renal failure/dialysis or a glomerular clearance <60 mL/min 
g. History of severe hypoglycemia 
h. Moderate or severe hepatic impairment, e.g., Child-Pugh Class B or C 


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i. Known or suspected to be poor CYP2C9 metabolizers based on genotype or previous 
history or experience with other CYP2C9 substrates, such as warfarin and phenytoin. 
3.4. 
Study Intervention(s) Administered 
Study intervention is defined as any investigational intervention(s), marketed product(s), or 
placebo, intended to be administered to a study participant according to the study protocol. Study 
interventions are presented in Table 7, below. 
Table 7: 
Study Interventions 
ARM Name 
Group 1: Investigational + SOC 
Group 2: Placebo + SOC 
Intervention Name 
Famotidine   
Celecoxib  
Placebo 
Type  
Drug  
Drug 
Matching placebo 
Dose Formulation 
Tablet 
Capsule 
Matching tablets, or 
capsules, as applicable, to 
the investigational drug 
products. 
Unit Dose 
Strength(s) 
80 mg 
400 mg (initial 
dose), then 200 mg 
None 
Dosage Level(s) 
QID for 14 
days 
BID for 5 days 
Matching placebo for 
famotidine QID for 14 
days; matching placebo 
for celecoxib BID for 5 
days; QD for 5 days  
Route of 
Administration 
Oral 
Oral 
Oral 
Sourcing 
Each of the study interventions will be supplied by the Sponsor, 
obtained from commercial sources, and, upon PI confirmation of 
eligibility, shipped directly to the study participant in pre-
packaged dispensing units. 
Packaging and 
Labeling 
Study Intervention will be provided in pre-packaged dispensing 
units. These will be labeled for investigational use, per FDA 
guidance. 
Alternative Name 
Pepcid® 
Celebrex® 
N/A 
3.5. 
Preparation/Handling/Storage/Accountability 
1. Only participants enrolled in the study may receive and self-administer study 
medications. Prior to shipping to the study participant, all study medications must be 


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stored in a secure, environmentally controlled, and monitored (manual or automated) area 
in accordance with the labeled storage conditions with access limited to the authorized 
site staff. IP Prep/Handling /Storage and accountability will be the responsibility of the 
study medication shipper. The site investigator will be responsible for authorizing drug 
shipment to the participant, and will confirm their receipt of the shipment as well.  
2. When study medications are taken, the study participant will enter confirmation on a 
daily basis into 
. The study medication shipper will complete accountability with 
the study regime by reviewing and comparing against returned medications. These data 
will be entered into be reported via 
.   
3. Further guidance and information for the final disposition of unused study medications 
are provided in the Manual of Operations. 
3.6. 
Measures to Minimize Bias: Randomization and Blinding 
Descriptions of randomization and blinding techniques are provided in Section 4.2 in the Master 
Protocol (LDOS-21-001).  
3.7. 
Study Intervention Compliance 
The study medications taken by the participant are noted in 
 daily. The Investigator will 
periodically monitor study intervention use within 
, and council the participant if there is 
concern about compliance. Information pertaining to missed doses is provided in Section 4.6 of 
the Master Protocol (LDOS-21-001). 
3.8. 
Concomitant Therapy 
Any medication or vaccine (including over-the-counter or prescription medicines, vitamins, 
and/or herbal supplements) that the participant is receiving at the time of enrollment or receives 
during the study must be recorded along with: 
• Reason for use 
• Dates of administration including start and end dates 
• Dosage instruction/prescription, including dose and frequency 
The Medical Monitor should be contacted if there are any questions regarding concomitant or 
prior therapy. 
Participants must abstain from taking prescription or nonprescription drugs (including vitamins 
and dietary or herbal supplements) within 1–3 days before the start of study intervention until 
completion of the follow-up visit, unless, in the opinion of the Investigator and Sponsor, the 
medication will not interfere with the study. Other concomitant medication may be considered on 
a case-by-case basis by the Investigator, in consultation with the Medical Monitor. 
3.8.1. 
Prohibited Concomitant Medication 
The following concomitant medications will be prohibited during the course of the study: 
• Aspirin 


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• CYP2C9 inhibitors, e.g., fluconazole, or inducers, e.g.. rifampin 
• Dexamethasone – NOTE: Standard of care is permitted for all participants while they 
are participating in this outpatient study. Per the National Institutes of Health (NIH) 
COVID-19 Treatment Guidelines, the panel recommends against the use of 
dexamethasone or other systemic glucocorticoids in the absence of another indication. 
Per NIH, there is currently a lack of safety and efficacy data on the use of these 
agents in outpatients, and they could potentially cause harm. If a participant needs to 
be hospitalized due to worsen COVID-19 symptoms and/or requires supplemental 
oxygen, then study medications are required to be stopped prior to the use of 
dexamethasone. These participants are considered clinical failures and will continue 
to be followed for outcome assessment.  
3.8.2. 
Rescue Medicine 
It is not anticipated that there would be need for rescue medication for these studies, as these are 
marketed medications that have been shown to be well-tolerated. In the case of an emergency, 
the participant should be monitored and supportive therapy should be employed, based on the 
judgment of medically trained personnel and the individual product labels. All rescue 
medications, including dosage, time of administration, and outcome are to be recorded in the 
platform.   
3.9. 
Dose Modification 
Dose modification from the specified study regimens will be required if any of the following 
occur after the administration of study drugs:  
• a participant’s glomerular clearance (GFR) drops to <60 mL/min without developing 
QT prolongation or CNS AEs (i.e., delirium, hallucinations, disorientation, or 
seizures) after the results from their weekly laboratory results have been obtained by 
the investigator; or  
• a QT wave prolongation is registered on their mobile ECG monitor; or  
• a central nervous system (CNS) AE (i.e., delirium, hallucinations, disorientation, or 
seizures) is reported by the subject. 
If any of the above occur, then the investigator will instruct the participant to stop all scheduled 
study medications.  
For those participants with a drop in GFR and no QT prolongation or CNS AEs, they may 
resume study medications after testing demonstrates the GFR is >60 mL/min. Upon resolution, 
study drugs can be added back in stepwise fashion, e.g., BID, then TID, and finally QID. All 
missed or withheld doses will be noted in 
 
For participants that had a QT prolongation or CNS AE (i.e., delirium, hallucinations, 
disorientation, or seizures), study medication will be permanently stopped and they will be 
followed for safety for the remainder of their study participation (Day 90). 


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3.10. 
Intervention after the End of the Study 
After study completion, study participant will be instructed to contact their personal physician to 
address any health-related issues. 


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4. 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
4.1. 
Discontinuation of Study Intervention 
Discontinuation of study intervention and participant discontinuation/withdrawal are addressed 
in the Master Protocol (LDOS-21-001). 
4.2. 
Participant Discontinuation/Withdrawal from the Study 
A discussion of participant discontinuation or withdrawal from the study is provided in Section 5 
of the Master protocol (LDOS-21-001). 
4.3. 
Lost to Follow-up 
A participant will be considered lost to follow-up if he or she repeatedly fail to enter their daily 
impressions via 
 and are unable to be contacted by the Investigator or designee.   
The following actions will be taken if a participant fails to participate, as above:   
• The Investigator or designee must attempt to contact the participant and counsel the 
participant on the importance of complying with the study conditions, and ascertain 
whether or not the participant wishes to and/or should continue in the study. All 
contact attempts and outcomes must be documented. Information regarding specific 
processes regarding contact of unresponsive participants can be found in the Manual 
of Procedures. 
Information pertaining to study and site closure is addressed in Section 8.1.9 of the Master 
Protocol. 


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5. 
STUDY ASSESSMENTS AND PROCEDURES 
Study procedures and their timing are summarized in the SoA (Table 5). Protocol waivers or 
exemptions are not allowed. Immediate safety concerns should be discussed with the Sponsor 
immediately upon occurrence or awareness to determine if the participant should continue or 
discontinue study intervention. Adherence to the study design requirements, including those 
specified in the SoA, is essential and required for study conduct. 
 
Procedures conducted as part of the participant’s routine clinical management (e.g., blood count) 
and obtained before signing of the ICF may be utilized for Screening or Baseline purposes, 
provided the procedures met the protocol-specified criteria and were performed within the time 
frame defined in Table 5. 
Regulatory, Ethical and Study Oversight Considerations are provided in Appendix 1 of the 
Master Protocol. 
5.1. 
Screening 
All Screening evaluations must be completed and reviewed to confirm that potential participants 
meet all eligibility criteria. The Investigator will maintain a Screening log to record details of all 
participants screened, and to confirm eligibility or record reasons for screening failure, as 
applicable. All participants will be consented prior to any study-specific tasks or tests being 
asked of the participant. Once consented, and the Investigator reviews Screening information to 
verify that the patient is eligible, they will be randomized to study group in 
 
Procedures conducted as part of the participant’s routine clinical management (e.g., blood count) 
and obtained before signing of the ICF may be utilized for Screening or Baseline purposes, 
provided the procedures met the protocol-specified criteria and were performed within the time 
frame defined in Table 5. 
The following will be performed/collected during screening: 
• Informed consent 
• Inclusion and Exclusion criteria, including confirmation of positive COVID-19 
infection by PCR test & confirmation of negative pregnancy test for child-bearing 
females by self-administered pregnancy test provided to participant 
• Demographics 
• Medical History (within the last 3 years, including relevant events not to exceed 5 
years) and body weight reporting 
• Concomitant medication review 
• Comprehensive metabolic panel via a mobile phlebotomy and laboratory service 
provider (Sponsor-contracted) 
• Nasal swab for confirmatory PCR testing for those participants prescreened with only 
a positive at-home antigen test via a mobile phlebotomy and laboratory service 
provider (Sponsor-contracted) 
• Randomization and initiation of drug shipment 


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5.2. 
Baseline and Enrollment 
Adherence to the study design requirements, including those specified in the SoA, is essential, 
and required for study conduct. 
The following will be performed/collected at Baseline/Day 1: 
• Concomitant medication review 
• Review of reported baseline symptoms  
• Confirmation of Study Drug Receipt & Initial Dose 
• Adverse Event Review 
• Participant Symptom, SpO2, mobile ECG, & Temperature reporting 
Eligibility to continue with dosing of study drug will be confirmed by the Investigator, at 
Baseline. Should a participant be found to have become ineligible at this time, it will be noted in 
 and the participant discontinued from the study as a Screen failure. 
5.3. 
Treatment Period 
Participants will take their daily study treatment regimen from Day 1 through Day 14 and will 
log into 
 whether they took their study medication and time taken and record SpO2 
reading, temperature, and symptoms and severity. On Days 7 (± 1 day) and 14 (± 1 day), 
participants will conduct a mobile ECG and will have a comprehensive metabolic panel blood 
draw performed to ensure GFR is >60 mL/min and other safety values are within acceptable 
ranges as determined by the investigator. The blood draw is conducted via a mobile phlebotomy 
and laboratory service through the Sponsor; laboratory values will be available in 
for 
investigator review. 
5.4. 
Follow-up 
The follow-up period will consist of virtual participant self-reporting of current symptoms, 
SpO2, and temperature via the 
 platform, until they reach Day 90. 
5.5. 
Efficacy Assessments 
Determination of efficacy of the combination therapy, relative to placebo, will be determined as 
described in Section 1.4. 
5.6. 
Safety Assessments 
The study participants will provide daily self-assessments of symptom progression, using the 
 platform. Body temperature, SpO2, and pulse will be measured and recorded by the 
participant daily, using Sponsor-provided thermometers and pulse oximeters, respectively. The 
study participants will perform a mobile ECG on Days 7 (± 1 day) and 14 (± 1 day) with the 
reads performed by the investigators, who will follow up with the participant. 
Should the symptoms reported by the participant go outside of the normal ranges, severity, or 
expected condition, 
 will trigger an alert to the site for the investigator to review for 
AEs/follow-up. 


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5.6.1. 
Demographic/Medical History 
Participants will self-report demographic and medical history information through the 
 
platform. 
5.6.2. 
Physical Examinations 
No physical examinations will be conducted for this study. 
5.6.3. 
Clinical Safety Laboratory Assessments 
There will be mobile clinical laboratory samples taken and assessed for safety during this study. 
All subjects will have baseline and weekly comprehensive metabolic panels performed through 
Day 14 to assess eGFR and other hepatic and safety parameters. 
5.6.4. 
Suicidal Ideation and Behavior Risk Monitoring 
Based on the long history of the use of these medications, there is no expectation that there is an 
increased risk of suicidal ideation or behavior. 
5.7. 
Adverse Events and Serious Adverse Events 
The definitions of an AE or SAE can be found in Appendix 2 of the Master Protocol (LDOS-21-
001). CNS-related AEs including confusion, delirium, hallucinations, disorientation, agitation, 
seizures, and lethargy will be captured in the eCRF as an AE of special interest (AESI). 
5.7.1. 
Time Period and Frequency for Collecting AE and SAE Information 
All SAEs will be reported from the start of study interventions (Baseline) until the end of the 
follow-up period, at the time points specified in the SoA (Table 5). Medical occurrences that 
begin after obtaining informed consent, but before the start of study intervention will be recorded 
in the Medical History/Current Medical Conditions field in 
not in the AE section. 
All SAEs will be recorded and reported to the Sponsor or designee immediately, and under no 
circumstance should this exceed 24 hours, as indicated in Appendix 2 of the Master Protocol 
(LDOS-21-001). The investigator will submit any updated SAE data to the Sponsor within 
24 hours of it being available. 
Investigators are not obligated to actively seek AE or SAE after conclusion of the study 
participation. However, if the Investigator learns of any SAE, including a death, at any time after 
a participant has been discharged from the study, and he/she considers the event to be reasonably 
related to the study intervention or study participation, the investigator must promptly notify the 
Sponsor. It is expected that, after the completion of the Follow-up period, that the study 
participant will be instructed to contact their personal physician to report any adverse events they 
may experience. 
5.7.2. 
Recording, Evaluating, and Assessment of AEs/SAEs 
The method of recording, evaluating, and assessing causality and relationship to study drug of 
AE and SAE and the procedures for completing and transmitting SAE reports are provided in  
Appendix 2 of the Master Protocol (LDOS-21-001). Care will be taken not to introduce bias 


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when detecting AEs and/or SAEs. Open-ended and non-leading 
screen prompts is the 
preferred method to inquire about AE occurrences. 
5.7.3. 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the Investigator is required to proactively follow each 
participant at subsequent contacts. All Seawall be followed until resolution, stabilization, the 
event is otherwise explained, or the participant is lost to follow-up (as defined in Section 4.3). 
Further information on follow-up procedures is given in Appendix 2 of the Master Protocol 
(LDOS-21-001). 
5.7.4. 
Regulatory Reporting Requirements for SAEs 
• Prompt notification by the Investigator to the Sponsor of an SAE is essential so that 
legal obligations and ethical responsibilities towards the safety of participants and the 
safety of a study intervention under clinical investigation are met. 
• The Sponsor has a legal responsibility to notify the FDA authority about the safety of 
a study intervention under clinical investigation. The Sponsor will comply with 
specific regulatory requirements relating to safety reporting to the regulatory 
authority (for example, the filing of a Form 3500A and/or Annual Safety Report 
under the applicable IND), Institutional Review Boards (IRBs) and Investigators. 
• Investigator safety reports must be prepared for suspected unexpected serious adverse 
reactions (SUSARs) according to applicable regulatory requirements and Sponsor 
policy, and forwarded to Investigators, as necessary. 
• An Investigator who receives an investigator safety report describing a SAE or other 
specific safety information (e.g., summary or listing of SAEs) from the Sponsor will 
review and then file it along with the Investigator’s Brochure and will notify the IRB, 
if appropriate according to local requirements. 
5.7.5. 
Pregnancy 
• Details of all pregnancies in female participants and female partners of male 
participants will be collected after the start of study intervention and until the end of 
the follow-up period.  
• If a pregnancy is reported, the Investigator should inform the Sponsor within 24 hours 
of learning of the pregnancy and should follow the procedures outlined in Appendix 
4 of the Master Protocol (LDOS-21-001). 
• Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, and ectopic pregnancy) are considered SAEs. 
5.7.6. 
Disease-Related Events and/or Disease-Related Outcomes Not Qualifying as AEs 
or SAEs 
Disease-related events (DREs) are addressed Section 6.2.6 in the Master Protocol (LDOS-21-
001). 


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5.8. 
Treatment of Overdose 
Recommendations with regard to treatment of overdose are provided in Section 6.3 of the 
Master Protocol (LDOS-21-001) 
5.9. 
Pharmacokinetics/Pharmacodynamics 
Pharmacokinetic and pharmacodynamic parameters are not evaluated in this study. 


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6. 
EXPLORATORY ENDPOINTS 
6.1. 
Exploratory Endpoints: Tracking participants’ self-assessments on 
multiple dimensions. 
Patient Recorded Outcomes (PRO) for symptom severity: Participants will select personally 
relevant COVID-19 symptoms from a list and track the severity of each on a daily basis before 
and after start of treatment using an 11–point NRS ranging from “None” to “Extreme”. After 15 
days, participants will continue to complete brief daily and weekly diaries for a total of 3 months 
following first day of treatment. The list of symptoms will initially contain typical COVID-19 
symptoms but will enable participants to add other symptoms that emerge that they attribute to 
their illness. 
Endpoints: The presence, severity and duration of COVID-19 signs and symptoms. Specific 
metrics include assessing the slope, time course, and extent of change in the mean severity score 
of various subsets of endorsed symptoms from prior to onset of treatment to specified post-
treatment days (e.g., Days 3, 7, 11, 15) and to specified clinical milestones (e.g., sustained 
clinical recovery). 
Hypotheses: The patient population consists of recently PCR-tested individuals who have begun 
to show one or more cardinal symptoms of COVID-19. Based on published epidemiological 
surveys the symptoms experienced by outpatients will typically persist over about 4–8 days, with 
some participants showing an initial period of symptom escalation, and another subset 
experiencing deterioration of their clinical status around day 7–15, potentially requiring 
hospitalization.  Moreover, a significant minority of participants will report some degree of 
enduring symptoms over the course of the ensuing weeks to months. We hypothesize that the 
daily trend following treatment will differ between the treatment groups and the placebo group 
with a faster and steeper decline in symptom severity scores after treatment and with 
significantly greater proportional improvement across symptoms with treatment than with 
placebo. We hypothesize that any early trend towards increasing severity will invert sooner 
following treatment than with placebo. We hypothesize that the 7–day AUC of symptom severity 
scores post treatment for key symptoms pertaining to everyday performance (difficulty 
breathing, myalgia and fatigue) will differ significantly and by more than 50% between treatment 
and placebo groups. 
Purpose: To demonstrate the utility of participants’ self-assessed symptom severity ratings to 
measure the degree and time course of clinical improvement and differentiate between treatment 
and controls groups. 
PRO for impact of illness on performance: Participants will respond daily to three functional 
queries, on an 11–point NRS ranging from “No Limitations” to “Extreme Limitations”, tracked 
daily before and after start of treatment. The three discrete dimensions of impact of treatment on 
capability to perform are: impaired ability to perform my essential tasks and duties; impaired 
ability to care for myself without assistance, and impaired ability to assist others. 
Endpoints: The presence, extent and duration of COVID-19-related functional impairments.  
Specific metrics include assessing the slope, time course, and extent of change in the three 
impairment scores from prior to onset of treatment to specified post-treatment days (e.g., Days 3, 
7, 11, 15) and to specified clinical milestones (e.g., sustained clinical recovery). 


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Hypotheses: We hypothesize that the daily trend following treatment will differ between the 
treatment and placebo groups with a quicker and steeper decline in functional impairment scores 
with significantly greater proportional improvement with treatment v. placebo (the treatment 
group will improve faster than the control group). We hypothesize that any existing trend 
towards increasing functional impairment will invert earlier following treatment than with 
placebo. We hypothesize that the 7–day AUC of functional impairment scores post treatment 
will differ significantly and by more than 50% between treatment and placebo groups. 
Purpose: To demonstrate the utility of participants’ self-assessed impairment ratings in 
capturing the degree and time course of improved real-world performance and differentiate 
between treatment and control groups. 
6.2. 
Participant Protocol Debrief: Participants will respond to a trio of 
probes. 
1. Participants will generate retrospective assessments of their overall degree of 
improvement at Day 15 following onset of treatment and at termination of participation 
using the PGIC (Patient’s Global Impression of Change) scale, an established, widely-
used 7-point qualitative rating scale of perceived treatment efficacy ( “very much 
improved,” “much improved,” “minimally improved,” “no change,” “minimally worse,” 
“much worse,” or “very much worse.”). 
Endpoint: The perceived presence or absence of overall clinical improvement. 
Hypothesis: The treatment groups will score higher on the PGIC than the placebo 
group. 
2. Participants will respond to the following prompt at the conclusion of their participation: 
“I believe I received:  1) an investigational drug,  or 2) a placebo”. 
Endpoint: Effectiveness of blinding provisions. 
Hypothesis: At least 20% of participants will not correctly select treatment. 
Purpose:  to explore the degree of awareness/ perception of participants to the 
impact of treatment. 
3. Participants will be given the option of selecting a short narrative that best describes their 
own individual outcome from a pool of alternatives (“sum-ups”), as well as the option of 
composing an open-ended narrative account. 
Endpoints: Qualitative information/insights extracted from participant’s accounts 
describing the personal significance of their treatment experience. 
Hypothesis: Participant descriptions of disease and treatment will reveal the 
patient point of view on efficacy and aspects of the treatment that matter to them. 
Purpose: In accordance with FDA’s PFDD principles, to learn what aspects of 
disease and treatment matter most to patients. 


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7. 
STATISTICAL CONSIDERATIONS 
7.1. 
Statistical Hypotheses 
The following statistical hypotheses will be tested in a hierarchical manner: 
H01: pFCI - pP = 0 
H11: pFCI - pP < 0 
 
H02: pFC - pP = 0 
H12: pFC - pP < 0 
where pFCI represents the proportion of participants with at least one COVID-19–related 
medically attended contact, due to increased symptom severity, or death due to COVID-19 rate 
through Day 30 for the famotidine/celecoxib combination, pFC represents the relative frequency 
of the same parameter for the famotidine/celecoxib combination, and pP the relative frequency 
for placebo. 
7.2. 
Sample Size Determination 
The sample size was estimated assuming that an interim analysis with stopping criteria for 
futility will be performed after 50% of participants have a primary endpoint assessment at Day 
30. The O'Brien-Fleming beta-spending function is used to determine the non-binding futility 
boundary. 
A total of 1318 evaluable participants, defined as part of the Full Analysis population (659 per 
group) are required to detect a relative reduction in the primary efficacy parameter of 60% in the 
active treatment arms compared to placebo (from of 6% in the placebo group to 2.4% in the 
active groups) with 90.0% power and using a two-sided χ2-test with 0.5% significance level, 
assuming variances are pooled, and that continuity correction was not used. Assuming a 10% 
screen failure rate, 1465 enrolled participants will be required. 
7.3. 
Populations for Analyses 
For purposes of analysis, populations are defined in Table 8. 
Table 8: 
Analysis Populations 
Population 
Description 
Enrolled 
All participants that have signed the Informed Consent Form, met the 
eligibility criteria, were randomized to study intervention, discontinued 
before first intake (Screening failures) or received at least one of study 
medication (Intent-To-Treat (ITT), Safety) 
Full Analysis (FAS) 
All participants who were randomized and received at least one dose of 
study medication. Participants in the FAS/ITT will be analyzed as 
randomized. 


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Population 
Description 
Per Protocol (PP) 
All participants who were included in the ITT, completed at least the 
30-day assessments, and had no major protocol deviations that could 
have an influence on the primary efficacy endpoint. Participants in the 
PPS will be analyzed as treated. 
Safety 
All participants randomly assigned to study intervention and who take 
at least one dose of study intervention. Participants will be analyzed 
according to the intervention they actually received. 
Participants excluded from the analysis sets mentioned above will be determined during the 
Blinded Data Review (BDR) and reasons for exclusions will be documented in the BDR report. 
7.4. 
Statistical Analyses 
The Statistical Analysis Plan (SAP) will be developed and finalized before database lock of the 
interim analysis and will describe the participant populations to be included in the analyses, and 
procedures for accounting for missing, unused, and spurious data. This section is a summary of 
the planned statistical analyses of the primary and secondary endpoints considering all relevant 
aspects of the FDA Guidance for Industry (E9) Statistical Principles for Clinical Trials (FDA 
Guidance for Industry E9 Statistical Principles for Clinical Trials, 1998). 
7.4.1. 
Demographics and Baseline Characteristics 
Disposition, demographics, medical history, prior/concomitant medication, and compliance will 
be displayed in a descriptive manner. Further details will be provided in the SAP. 
7.4.2. 
Efficacy Analyses 
The primary efficacy endpoint, the percentage of patients with at least one COVID-19–related 
medically attended contact, due to increased symptom severity or death (all-cause mortality) 
through Day 30, will be analyzed using a two group χ² test with pooled variances and no 
continuity correction. Statistics and the associated 95% confidence interval will be provided. The 
primary efficacy analysis will be performed using the ITT and will be repeated for robustness 
purposes with the PP. 
In case of missing data of the primary endpoint at day 30 (Visit 4), the primary analysis will 
consider participants (with missing primary endpoint data until day 30) as having at least one 
medically attended visit. For sensitivity purposes, the primary efficacy analysis will be repeated 
by excluding participants with missing primary endpoint until day 30 (Complete Case Analysis). 
The secondary safety endpoints: Incidence of Related Serious Adverse Events (SAE), 
Incidence of discontinuation due to related SAE and Incidence of death will also be analyzed 
using a χ² test. Descriptive statistics including exploratory confidence intervals/p-values will be 
provided. 
All other efficacy endpoints will be analyzed in an exploratory manner by applying appropriate 
statistical methods (e.g. χ² test for incidences, log rank test and Kaplan Meier method for 
cumulative incidences, ANOVA for continuous variables) using the FAS set. Descriptive 
statistics including exploratory confidence intervals/p-values will be delivered. 


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All other safety related endpoints will be analyzed in a descriptive way by providing 
descriptive statistics and/or shift tables from baseline to the assessment visits. 
For more details of the statistical analysis, methods/models refer to the SAP. 
7.4.3. 
Interim Analyses  
An interim analysis with stopping criteria for futility and validation of sample size is planned 
after 50% of the participants have completed the primary endpoint assessment at Day 30 (Visit 
4). 
To prevent power loss due to this interim analysis, a beta-spending function was used to 
calculate stopping bound according to O’Brien and Fleming (Lan, 1983) (O’Brien, 1979). The 
futility bound for difference in proportions between active treatments and placebo is 0.0232 in 
the interim analysis. The nominal level of significance is not affected α=0.05 (two-sided) and 
90% power is kept for the final analysis. The interim analysis will be performed on the Full 
Analysis set. 
If the primary endpoint is missing at Day 30, the participant will be excluded from the interim 
analysis (Complete Case Analysis). The interim efficacy analysis will be performed using a two-
group chi-square test comparing the FCI combination with placebo followed by the FC–placebo 
comparison. 
If the study is not stopped due to futility after the interim look, the assumptions for the sample 
size determination will be checked and the sample size may be increased if a decrease in 
treatment difference by more than 10% (due to a lower placebo rate and/or due to a higher rate in 
the active arms) is observed. 
The SAP will describe the planned interim analyses in greater detail. 
7.4.4. 
Independent Data Safety Monitoring Board (DSMB) 
The DSMB activities are described in Section 7.1.1 of the Master Protocol (LDOS-21-001). The 
delivered information will contain un-blinded information and will therefore be prepared by an 
unblinded statistician team from the CRO (
 The same team will perform 
the interim analysis but will not be involved in the final analysis. The information provided via 
those listings must be limited to DSMB members and will not be shared with any other personnel 
involved in the conduct or analysis of the study. 


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8. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
8.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations 
8.1.1. 
Regulatory and Ethical Considerations 
This study will be conducted in accordance with the protocol and with appropriate principles of 
patient protection, as detailed in the Section 8.1.1of the Master Protocol (LDOS-21-001). 
8.1.2. 
Financial Disclosure 
Investigators and sub-investigators will provide the Sponsor with sufficient, accurate financial 
information, as requested, to allow the Sponsor to submit complete and accurate financial 
certification or disclosure statements to FDA. Investigators are responsible for providing 
information on financial interests during the course of the study and for 1 year after completion 
of the study. 
8.1.3. 
Informed Consent Process 
• The informed consent process for this study will be entirely virtual and done via 
phone call between the participant and site investigator. No in-person consenting will 
be performed. 
• Upon initiating contact with the study staff, the prospective participant will be 
contacted by the site Investigator via phone call. The participant will be advised by 
the Investigator \on the nature of the study, and answer all questions regarding the 
study. If the prospective participant is deemed potentially qualified, the Informed 
Consent will be administered. 
• Participants must be informed that their participation is voluntary. Participants will be 
required to sign a statement of informed consent that meets the requirements of 21 
CFR 50, local regulations, ICH guidelines, Health Insurance Portability and 
Accountability Act (HIPAA) requirements, where applicable, and the IRB or study 
center.  
• The participant will sign the informed consent using 
 an electronic method 
that will capture the electronic signature of the participant and the PI..The authorized 
person administering the informed consent must also sign the ICF. 
• The medical record must include a statement that written informed consent was 
obtained before the participant was enrolled in the study and the date the written 
consent was obtained. The authorized person obtaining the informed consent must 
also sign the ICF. 
• Participants must be re-consented to the most current version of the ICF(s) during 
their participation in the study.  
• A copy of the ICF(s) must be provided to the participant.  


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8.2. 
Appendix 2: Data Management 
For this study, a secure, adaptive, interactive data collection platform, 
 will be used. 
Because the platform is web-enabled, it provides a means for real-time data entry by the 
participantthrough any device that can access the internet. The participant is able to enter their 
ratings of symptom status and impact, and will be provide choices in drop-down menus, which 
evolve, based on prior responses. 
8.2.1. 
Data Protection 
Data protection considerations are provided in Section 8.1.4 of the Master Protocol (LDOS-21-
001).  
8.2.2. 
Dissemination of Clinical Study Data 
Clinical study data dissemination is addressed in Section 8.1.6 of the Master Protocol (LDOS-
21-001).  
8.2.3. 
Data Quality Assurance 
Data quality assurance is addressed in Section 8.1.7 of the Master Protocol (LDOS-21-001). 
8.2.4. 
Source Documents 
Information pertaining to source documents, including definition, is addressed in Section 8.1.8 
of the Master Protocol (LDOS-21-001). 
8.2.5. 
Study and Site Closure 
Study and site closure is addressed in Section 8.1.9 of the Master Protocol (LDOS-21-001). 
8.2.6. 
Publication Policy 
Guidelines pertaining to publication of study results are detailed in Section 8.1.10 of the Master 
Protocol (LDOS-21-001).  
 
 


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8.3. 
Appendix 3: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting 
A detailed overview of Adverse Event information is provided in Appendix 2 of the Master 
Protocol (LDOS-21-001). 
 
 


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8.4. 
Appendix 4: Self-Rating of Symptoms and Symptom Scoring 
A detailed overview of 
-based self-rating of symptoms and symptom scoring is provided 
in Appendix 3 of the Master Protocol (LDOS-21-001). 
 
 


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8.5. 
Appendix 5: Contraceptive Guidance and Collection of Pregnancy 
Information 
A detailed overview of Contraceptive Guidance and Collection of Pregnancy information is 
provided in Appendix 4 of the Master Protocol (LDOS-21-001). 
 
 
 


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9. 
REFERENCES 
FDA Guidance for Industry E9 Statistical Principles for Clinical Trials. (1998). FDA. 
Lan, K. a. (1983). Discrete sequential boundaries for clinical trials. Biometrika, 70, 659-663. 
O’Brien, P. a. (1979). A Multiple Testing Procedure for Clinical Trials. Biometrics, 35, 549–556. 
doi:10.2307/2530245 
Ruuskanen O, L. E. (2011). Viral pneumonia. Lancet, 377(9773), 1264-1275. 
1.  
2.  COVID-19 Treatment Guidelines Panel. Coronavirus Disease 2019 (COVID-19) 
Treatment Guidelines. National Institutes of Health. Available at 
https://www.covid19treatmentguidelines.nih.gov/.