Clinical trial NCT04583956
Conditions: COVID-19
Keywords: Adults COVID-19 Multicenter Platform Putative Therapeutics
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Start date: 2020-10-23; Completion date: 2021-09-13
Enrollment: 214 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a platform trial to conduct a series of randomized, double-blind, placebo-controlled trials using common assessments and endpoints in hospitalized adults diagnosed with Coronavirus Disease 2019 (COVID-19). Big Effect Trial (BET) is a proof-of-concept study with the intent of identifying promising treatments to enter a more definitive study. The study will be conducted in up to 70 domestic sites and 5 international sites. The study will compare different investigational therapeutic agents to a common control arm and determine which have relatively large effects. In order to maintain the double blind, each intervention will have a matched placebo. However, the control arm will be shared between interventions and may include participants receiving the matched placebo for a different intervention.

The goal is not to determine clear statistical significance for an intervention, but rather to determine which products have clinical data suggestive of efficacy and should be moved quickly into larger studies. Estimates produced from BET will provide an improved basis for designing the larger trial, in terms of sample size and endpoint selection. Products with little indication of efficacy will be dropped on the basis of interim evaluations. In addition, some interventions may be discontinued on the basis of interim futility or efficacy analyses.

One or more interventions may be started at any time. The number of interventions enrolling are programmatic decisions and will be based on the number of sites and the pace of enrollment. At the time of enrollment, subjects will be randomized to receive any one of the active arms they are eligible for or placebo. Approximately 200 (100 treatment and 100 shared placebo) subjects will be assigned to each arm entering the platform and a given site will generally have no more than 3 interventions at once.

The BET-A stage will evaluate the combination of remdesivir with risankizumab vs remdesivir with a risankizumab placebo. The primary objective is to evaluate the clinical efficacy of different investigational therapeutics relative to the control arm in adults hospitalized with COVID-19 according to clinical status (8-point ordinal scale) at Day 8.

Detailed description:
This is a platform trial to conduct a series of randomized, double-blind, placebo-controlled trials using common assessments and endpoints in hospitalized adults diagnosed with Coronavirus Disease 2019 (COVID-19). Big Effect Trial (BET) is a proof-of-concept study with the intent of identifying promising treatments to enter a more definitive study. The study will be conducted in up to 70 domestic sites and 5 international sites. The study will compare different investigational therapeutic agents to a common control arm and determine which have relatively large effects. In order to maintain the double blind, each intervention will have a matched placebo. However, the control arm will be shared between interventions and may include participants receiving the matched placebo for a different intervention.

The goal is not to determine clear statistical significance for an intervention, but rather to determine which products have clinical data suggestive of efficacy and should be moved quickly into larger studies. Estimates produced from BET will provide an improved basis for designing the larger trial, in terms of sample size and endpoint selection. Products with little indication of efficacy will be dropped on the basis of interim evaluations. In addition, some interventions may be discontinued on the basis of interim futility or efficacy analyses.

One or more interventions may be started at any time. The number of interventions enrolling are programmatic decisions and will be based on the number of sites and the pace of enrollment. At the time of enrollment, subjects will be randomized to receive any one of the active arms they are eligible for or placebo. Approximately 200 (100 treatment and 100 shared placebo) subjects will be assigned to each arm entering the platform and a given site will generally have no more than 3 interventions at once.

The BET-A stage will evaluate the combination of remdesivir with risankizumab vs remdesivir with a risankizumab placebo. Subjects will be assessed daily while hospitalized. Once subjects are discharged from the hospital, they will have a study visit at Days 8, 15, 22, 29, and 60 as an outpatient. The Day 8, Day 22 and Day 60 visits do not have laboratory tests or collection of samples and may be conducted by phone. All subjects will undergo a series of efficacy and safety laboratory assessments. Safety laboratory tests and blood (serum and plasma) research samples and oropharyngeal (OP) swabs will be obtained on Day 1 (prior to study product administration) and Days 3, 5, 8, and 11 while hospitalized. OP swabs (oropharyngeal swabs are preferred, but if these are not obtainable, saliva or nasopharyngeal or nasal swabs may be substituted) and blood research samples plus safety laboratory tests will be collected on Day 15 and 29 if the subject attends an in-person visit or is still hospitalized. However, if infection control considerations or other restrictions prevent the subject from returning to the clinic, Day 15 and 29 visits may be conducted by phone and only clinical data will be obtained.

The primary objective is to evaluate the clinical efficacy of different investigational therapeutics relative to the control arm in adults hospitalized with COVID-19 according to clinical status (8-point ordinal scale) at Day 8. The key secondary objectives are 1) to evaluate the clinical efficacy of different investigational therapeutics as assessed by time to recovery compared to the control arm, and 2) to evaluate the proportion of subjects alive and without respiratory failure through Day 29.

Contacts:

20-0013 Central Contact

Telephone: 1 (301) 7617948

Email: DMIDClinicalTrials@niaid.nih.gov

Arms: arm 1: 200-mg intravenous (IV) remdesivir loading dose on Day 1, followed by a 100-mg once-daily IV maintenance dose up to a 10-day total course while hospitalized and 1200-mg IV risankizumab placebo infusion (300-mg x 4 vials) once on Day 1. N=100. arm 2: 200-mg intravenous (IV) remdesivir loading dose on Day 1, followed by a 100-mg once-daily IV maintenance dose up to a 10-day total course while hospitalized and 1200-mg IV risankizumab infusion (300-mg x 4 vials) once on Day 1. N=100.
Interventions: intervention 1: Placebo intervention 2: Remdesivir intervention 3: Risankizumab
Intervention descriptions: intervention 1: Risankizumab placebo will be given at an equal volume at the same schedule. intervention 2: Remdesivir is a single diastereomer monophosphoramidate prodrug for the intracellular delivery of a modified adenine nucleoside analog GS-441524. intervention 3: Risankizumab is a humanized immunoglobulin (Ig) G1 antagonistic monoclonal antibody (mAb) directed against the p19 subunit of the human cytokine interleukin-23. Risankizumab is formulated in a buffer of 4.4 mM disodium succinate hexahydrate/succinic acid, 225 mM sorbitol, 0.2 mg/mL polysorbate 20, and WFI in a 6R vial.

Protocol documents:
ICF_001.pdf: 
Division of Microbiology and Infectious Diseases (DMID), National Institute of Allergy and Infectious 
Diseases (NIAID), National Institutes of Health (NIH) / Protocol Number 20-0013 
Page 1 of 19   
 
 
Lindsey Baden, MD 
Advarra IRB Approved Version 18 Jan 2021 
Revised 11 Feb 2021 
 
RESEARCH PARTICIPANT INFORMED CONSENT FORM 
FOR STUDY A 
 
Sponsor / Study Title: 
  
Division of Microbiology and Infectious Diseases (DMID), 
National Institute of Allergy and Infectious Diseases 
(NIAID), National Institutes of Health (NIH) / “A 
Multicenter Platform Trial of Putative Therapeutics for the 
Treatment of COVID-19 in Hospitalized 
Adults”ACTIV5/BET 
 
Protocol Number: 
 
20-0013 
 
Principal Investigator: 
(Study Doctor) 
 
Lindsey Baden, MD 
 
Telephone: 
 
617-732-5700 
617-732-5700 pager #31269 (24 Hours) 
 
Address: 
Brigham and Women's Hospital 
75 Francis Street 
Boston, MA    02115 
 
 
 
This form is for use in a research study that may involve participants who may or may not have 
the capacity to consent to take part in the study.  When the participant cannot legally consent to 
take part, pronouns “you” and “your” should be read as referring to the participant rather than the 
person (legally authorized representative) who is signing and dating this form for the participant. 
In cases where the participant’s representative gives consent, the participant should be informed 
about the study to the extent possible given his/her understanding. During the course of the 
study, if the participant regains the capacity to consent, informed consent will be obtained from 
the participant and the participant offered the ability to leave the study if desired. 
 
KEY INFORMATION 
This consent form describes a clinical research study and is designed to help you decide if you 
would like to be a part of the study. A clinical research study helps doctors test new ways to treat 
a disease. One way to do this is by studying new drugs, to see if they could be used as medicines. 
In a study, the drugs are “experimental,” which means they have not been proven to work. That 
is why studies are needed to find out if new drugs are safe and work in people. 
 
This section provides the information we believe is most helpful and important to you in making 
your decision about participating in this study. More information that may help you decide can 
be found in other sections of the document. 
 
 


Division of Microbiology and Infectious Diseases (DMID), National Institute of Allergy and Infectious 
Diseases (NIAID), National Institutes of Health (NIH) / Protocol Number 20-0013 
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Lindsey Baden, MD 
Advarra IRB Approved Version 18 Jan 2021 
Revised 11 Feb 2021 
 
What you should know about this study:   
• You are being asked to join this clinical research study because you are currently 
hospitalized with an illness known as COVID-19 caused by the new coronavirus, SARS 
CoV-2.  
• This study is taking place at more than one site. 
• This is a study that will test a series of different drugs, so drugs will be added or removed 
over time. However, the drugs that are currently being studied at this site are described in 
this consent. 
• Read this consent form carefully or have someone you trust read it to you. Take as much 
time as you need to understand the study. 
• Ask the study team to explain any words or information that you do not understand. 
• You are a volunteer and you do not have to join this study. Your other option is to 
continue receiving any other care you have already been receiving. If you join the study, 
you can change your mind later. You can decide not to take part, or you can quit at any 
time. There will be no penalty or loss of benefits if you decide not to join or to quit the 
study. However, please note that the United States Food and Drug Administration (FDA) 
requires that any information collected up to the point of your withdrawal cannot be 
removed from the study. 
• The study doctor or the sponsor can stop your participation at any time without your 
consent for the following reasons: 
o If it appears to be medically harmful to you; 
o If you fail to follow directions for participating in the study; 
o If it is discovered that you do not meet study requirements; 
o If the study is cancelled; or 
o For administrative reasons. 
• During the study, we will tell you if we learn any new information that might affect 
whether you wish to continue to be in the study. 
• As a part of this research, we will take blood from you to do genetic testing, which 
identifies your DNA. DNA is inherited material in your cells that tells us how your body 
works. We will do these tests to learn how your body responds to COVID-19.  
 
What is this study about? 
There are few approved medicines to treat COVID-19 illness. Some people who become sick 
with COVID-19 have serious disease and must be hospitalized, and a small number of people 
die. Research studies suggest that a recently approved drug called remdesivir (VEKLURY®) 
helps hospitalized people with COVID-19 recover faster than people who do not get remdesivir. 
We want to find out if other drugs given with remdesivir can improve recovery and are safe.  
 
Over time, we will test a series of different drugs, so drugs will be added or removed over time. 
However, the drugs that are currently being studied at this site are described in this consent. 
 
What drugs are being studied? 
This study is designed to test remdesivir in combination with either 1 other study drug or 
placebo. A placebo is an inactive agent that looks exactly like the study drug but does not have 
any active drug in it. Using a placebo is common in research studies. It will help us know 
whether the results of the study are actually caused by the study drug(s). 


Division of Microbiology and Infectious Diseases (DMID), National Institute of Allergy and Infectious 
Diseases (NIAID), National Institutes of Health (NIH) / Protocol Number 20-0013 
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Lindsey Baden, MD 
Advarra IRB Approved Version 18 Jan 2021 
Revised 11 Feb 2021 
 
 
There may be more than 1 study drug that is available to be combined with remdesivir at a given 
time. The study drugs currently available to be combined with remdesivir at this site are 
described below (see Section 3). 
 
What study drugs will you get? 
Remdesivir is given to all people who enroll in this study. In addition to remdesivir, you will get 
1 other study drug (see Section 3) or placebo. What you are assigned to receive in combination 
with remdesivir is decided by chance, like rolling dice. We will first check your health to see 
how many of the study drugs would be safe for you to use. Then, you will be assigned to receive 
one of the study drugs that you are eligible for or placebo. If 1 study drug is being tested at this 
site, you will have an equal chance of being assigned to the study drug or placebo.  If more than 
1 study drug is being tested at this site, you will have a higher chance of receiving a study drug 
than placebo. You can ask someone on the study team if you have any questions about what 
study drug or placebo you may get. 
 
If you join this study, you will be randomly assigned to a study drug group. We will tell you 
which study drug group you have been assigned to, however, we cannot tell you if you will 
receive the actual study drug or placebo. The study doctors will not know this either, but they 
can find out in case of emergency. This is called a double-blind study, since neither you nor the 
study doctors know if you got the study drug or placebo. 
 
What will happen during this study? 
If you agree to join this study, we will first check your health to make sure it is safe for you to 
join. If you qualify for this study and decide to join, you will get remdesivir once daily for up to 
10 days. It is given as an infusion into your bloodstream through an intravenous tube placed in a 
vein in your arm using a needle (IV line). You will also receive 1 other study drug or placebo, 
depending on your study drug assignment. More information about the study drugs and how they 
are given is provided below. 
 
While you are in the hospital, we will collect information from your hospital records. We will 
take one or more blood sample(s) and one swab (throughout this form swab collections can mean 
swabs can be collected from deep inside your nose, the middle of your nose, or your throat) from 
you about 5 times, depending on how long you remain in the hospital. 
 
You will have up to 5 follow-up study visits after you leave the hospital. The exact number will 
depend on when you are discharged. At least 3 follow-up visits will be conducted over the 
phone. The others may be in-person visits at the study site or may be conducted over the phone. 
During follow-up visits, we will collect information about your health since your last visit. For 
in-person visits, we will also take one or more blood sample(s) and one swab. 
 
We will use the blood and swab samples collected on this study for research and safety tests. 
Swab samples will be tested for SARS-CoV-2. 
 
Your total amount of time on this study will be about 2 months.  
 


Division of Microbiology and Infectious Diseases (DMID), National Institute of Allergy and Infectious 
Diseases (NIAID), National Institutes of Health (NIH) / Protocol Number 20-0013 
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Lindsey Baden, MD 
Advarra IRB Approved Version 18 Jan 2021 
Revised 11 Feb 2021 
 
What are the main study risks? 
The main risks of being in this study are related to the study drugs. The study drug remdesivir 
has been studied in healthy (not sick) people and in people with COVID-19 or other viral 
infections. Some of these people had side effects which were temporary and went away after a 
few days. Some people did not have side effects. The most common side effects included 
abnormal liver function test results, abnormal blood clotting test results, constipation, nausea, 
vomiting, decreased appetite, headache, and pain or infection around the IV line. The abnormal 
liver function tests lasted longer than a few days but came back to normal levels during the 
studies. 
 
Risks of the other study drugs currently being tested at this site are given below (See Section 3). 
 
Some people may have some side effects from the study drugs. Other people may have no side 
effects. Allergic reactions to these drugs, including hives, trouble breathing, or other allergic 
responses are very rare but are a possible effect of any drug. Allergic reactions may be severe or 
life-threatening. There may also be side effects and risks that we do not know about yet, even 
serious or life-threatening ones. We will watch you carefully for side effects during this study. 
We will provide short-term medical care if there are side effects from the study drugs that can be 
treated. 
 
If you are pregnant or nursing a child during the study, there may be risks to you, the embryo, 
fetus, or nursing child from the study drugs. Therefore, you cannot join this study if you are 
pregnant or breastfeeding. If you are nursing a child, you must agree to discontinue breastfeeding 
while on this study. If you can become pregnant, you must agree to remain abstinent (not having 
sexual relations) or use contraception. If a hormonal method of contraception is used (for 
example, an implant, a hormone-releasing intrauterine device [IUD], injections, pills, a vaginal 
ring, or a skin patch) a barrier method must also be used at the same time (for example, male 
condom, diaphragm, cervical cap) while taking part in this study and for 5 months after your last 
dose of the study drug or placebo. Please speak to the study doctor or study staff about 
acceptable methods of birth control.  
 
Are there benefits to being in the study? 
You may or may not benefit from being in this study. Results from studies suggest that your time 
in the hospital may be shorter by taking remdesivir. Everyone in this study receives remdesivir. 
 
What are your other options? 
You do not have to join this study if you do not want to. You can keep getting treated with 
standard care for COVID-19, which may include treatment with remdesivir.  
 
There might be other clinical trials that you can join for experimental treatments for COVID-19. 
However, you cannot participate in this study and other clinical trials for experimental treatments 
for COVID-19 at the same time.  
 
 


Division of Microbiology and Infectious Diseases (DMID), National Institute of Allergy and Infectious 
Diseases (NIAID), National Institutes of Health (NIH) / Protocol Number 20-0013 
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Lindsey Baden, MD 
Advarra IRB Approved Version 18 Jan 2021 
Revised 11 Feb 2021 
 
The rest of this document will describe more about the research study. This information should 
be considered before you make your choice. Members of the study team will talk with you about 
the information described in this document. 
 
1. 
What will happen if you want to join this study? 
 
If you think you may want to join this study, we will describe the study and answer any 
questions you may have. You can also talk to your friends and family about the study.  
 
If you agree to be in the study, we will ask you or your Legally Authorized Representative 
(LAR) to sign and date this consent form. When you sign your name or put your mark on the 
consent form and date it, it means that you agree to be in the study. You can change your mind at 
any time and leave the study. If you decide not to join the study or to leave the study later, you 
will not lose any regular health care services you already are getting. Approximately 200 
hospitalized adults with COVID-19 will be asked to participate in each stage of this study. 
 
To determine if you qualify for this study, we will ask you some questions about your health, 
including any chronic medical conditions and medications you take for them, allergies to 
medications, any COVID-19 symptoms you have had, and which medications you received from 
your regular doctor during this COVID-19 illness. We will perform a physical exam and measure 
your height and weight. We will review your hospital records for the result(s) of your SARS-
CoV-2 test and any X-rays or CT scans you have had during this COVID-19 illness, and may 
also collect some of the other information listed above, such as COVID-19 symptoms, 
medications, etc. If you have had blood tests done within the past 48 hours to check how well 
your liver and kidneys are working, we will review the results of these tests in your hospital 
records; otherwise, we will collect a blood sample to do these tests. If you are a woman who is 
capable of getting pregnant, we will do a pregnancy (urine or blood) test. A member of the study 
team will explain these tests further. When we have the results, we will explain them to you. 
 
2. 
What does the study involve? 
 
If you qualify for the study and decide to join, you will get up to 10 days of remdesivir while you 
are in the hospital. You will also receive another study drug or placebo, depending on which one 
you were assigned to, also only while you are in the hospital. More information about the study 
drugs, how they are given, and their risks is provided below in Section 3. After you are 
discharged from the hospital, you will not receive any more study drugs. If you are readmitted to 
the hospital before Day 11, you may receive the rest of your remdesivir infusions, up to Day 10. 
 
Each day you are in the hospital, we will obtain some information about you from your inpatient 
hospital records, such as whether you are receiving oxygen or need additional help breathing and 
what types of other medicines you are being given as part of your clinical care. This information 
will help us determine how sick you are and whether you are improving. We will take one or 
more blood sample(s) and one swab from you on Days 1, 3, 5, 8, and 11 as long as you remain in 
the hospital.  
 


Division of Microbiology and Infectious Diseases (DMID), National Institute of Allergy and Infectious 
Diseases (NIAID), National Institutes of Health (NIH) / Protocol Number 20-0013 
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Lindsey Baden, MD 
Advarra IRB Approved Version 18 Jan 2021 
Revised 11 Feb 2021 
 
You will have follow-up visits on Days 8 (if you have already been discharged from the 
hospital), 15, 22, 29 and 60. The Day 15 and Day 29 visits will be in-person visits, if possible. If 
you have already been discharged from the hospital at these timepoints, we may ask you to come 
back to the site for these visits. However, if this is not possible due to quarantine restrictions or 
similar reasons, we will call you to collect information over the phone. All Day 8, Day 22, and 
Day 60 visits will be conducted over the phone (if you have already been discharged). For all 
follow-up visits (both in-person and by telephone), we will ask how you are feeling and if you 
have been sick. If you were already discharged, we will ask if you had any additional hospital 
stays or clinic visits or needed additional treatments or medicines since your discharge. If you 
have in-person visits on Days 15 and 29, we will also take one or more blood sample(s) and one 
swab.  
 
The total amount of blood that we will collect from you for this study is up to about 31 
tablespoons. We will use the blood samples and swabs collected on this study for research and 
safety tests. Swabs will be tested for SARS-CoV-2. Swabs will be collected from deep in your 
nose. If this is not possible, the swab will be taken from the middle or front of your nose or 
throat. 
 
As part of this study, we will collect some extra blood samples from you (included in the total 
amount given above) that we do not need for our current study goals. We will use your coded 
information, leftover samples, and extra blood samples collected during your participation on 
this study for secondary research. Secondary research is research that is not part of this study, 
and the research is not planned yet. This research will occur in the future and it will help us to 
understand how the study drugs work and to develop new treatments and lab tests. This 
secondary research will not include genetic testing. More information about secondary research 
is provided below.  
 
The last visit for this study is at Day 60. Your study participation will be complete after this visit. 
Your total amount of time on this study will be about 60 days. 
 
3. 
What are the study drugs and their risks? 
 
Remdesivir 
Description: Remdesivir is an antiviral drug that blocks viruses like SARS-CoV-2 from 
replicating, or reproducing. The United States Food and Drug Administration (FDA) recently 
approved remdesivir as a treatment for COVID-19, which means it can be given to COVID-19 
patients as standard treatment. 
 
Remdesivir is given as an infusion into your bloodstream through an intravenous tube placed in a 
vein in your arm using a needle (IV line). It is given once daily for up to 10 days. Each dose 
takes about 30 minutes to give, but could take up to 2 hours.  
 
Risks: The most common side effects seen in people who received remdesivir in research studies 
included: 
• Abnormal liver function test results 
• Abnormal blood clotting test results 


Division of Microbiology and Infectious Diseases (DMID), National Institute of Allergy and Infectious 
Diseases (NIAID), National Institutes of Health (NIH) / Protocol Number 20-0013 
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Lindsey Baden, MD 
Advarra IRB Approved Version 18 Jan 2021 
Revised 11 Feb 2021 
 
• Constipation 
• Nausea 
• Vomiting 
• Headache 
• Dizziness 
• Pain or infection around the IV line 
 
The abnormal liver function tests lasted longer than a few days but came back to normal levels 
during the studies. We have not seen any long-lasting kidney problems in humans who have 
taken remdesivir. We will be following your liver and kidney function during the study. If you 
have any abnormal test results that may require medical care, we will share these results with 
you. 
 
In previous study with participants hospitalized with COVID-19, the most common adverse 
events included:  
• Decreased renal function 
• Decreased hemoglobin (anemia) 
• Decreased lymphocyte count 
• Respiratory failure 
• Fever 
• Increased blood glucose 
The occurrence of these adverse events were similar in the remdesivir and placebo groups. 
 
None of the side effects in studies of remdesivir have been serious. Some people may have some 
side effects after the infusion. Other people may have no side effects. These side effects are 
temporary and should not last more than a few days. 
 
We will monitor you closely for side effects while you are getting remdesivir. We will have 
medicine and equipment available to treat any side effects, including severe effects, if needed. If 
you have severe side effects that do not get better, we will not give you any more doses of 
remdesivir. 
 
Risankizumab 
Description: Risankizumab is a drug that is approved by the FDA to treat a condition called 
plaque psoriasis. It is a type of drug called a monoclonal antibody, and it works by attaching to 
natural proteins in the body that can cause inflammation. It ultimately reduces inflammation 
inside the body. Because inflammation seems to be one of the most serious problems during 
COVID-19 illness, we think that this drug may helpful. Risankizumab is not approved by the 
FDA to treat COVID-19, but they have given us permission to test it in this study. 
 
Risankizumab is given as an infusion into your bloodstream through an intravenous tube placed 
in a vein in your arm using a needle (IV line). It is given once and the infusion takes about 1 to 2 
hours. 
 
Risks: The most common side effects seen in people receiving risankizumab include: 
• Upper respiratory infection 


Division of Microbiology and Infectious Diseases (DMID), National Institute of Allergy and Infectious 
Diseases (NIAID), National Institutes of Health (NIH) / Protocol Number 20-0013 
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Lindsey Baden, MD 
Advarra IRB Approved Version 18 Jan 2021 
Revised 11 Feb 2021 
 
• Fungal skin infection 
• Headache 
• Tiredness 
 
Because of the way risankizumab works, it may increase the risk of serious infections, such as a 
bacterial skin infection (cellulitis), infection of a bone (osteomyelitis), herpes zoster infection, or 
others. However, the chance that this would happen with the single infusion of risankizumab that 
is being given in this study is very low. 
 
Risankizumab can cause an allergic reaction, which may include fever, chills, nausea, hives, 
itching, decreased blood pressure, swelling, decreased oxygen supply, wheezing, difficulty 
breathing, and an abnormal heartbeat. Severe allergic reactions (called anaphylaxis) can cause 
heart attacks and, if untreated, even death. We cannot always predict in advance who might 
develop this serious reaction. 
 
We will monitor you closely for side effects while you are getting the risankizumab and will 
have medicine and equipment available to treat side effects, including severe effects, if needed. 
If you have a severe side effect that does not improve with treatment, we will stop the infusion. 
 
Placebo 
Description: The placebo for this study is an inactive liquid that is similar to risankizumab, but 
does not have any active drug in it. It is given once as an IV infusion that takes about 1 to 2 
hours. 
 
Risks: The main risks of a placebo infusion are those associated with IV line placement described 
below (see Section 4). 
 
4. 
What are the other risks or discomforts of the study? 
 
General study drug risks 
Since these are new drugs that we are still studying, they may cause other changes that could hurt 
or bother you that we do not know about. People can have allergic reactions to drugs, including 
hives, trouble breathing, or other allergic responses. This is very rare but is also a possible effect 
of any drug. Allergic reactions may be severe or life-threatening. 
 
Short-term medical care will be provided if there are side effects from the study drugs that can be 
treated. It is important that you always tell the study staff if you have any problems and always 
keep in touch with them.  
 
Blood draws and IV line placement 
We will insert a new, clean needle into a vein in your arm to take blood samples and to insert the 
IV line. If you already have an IV line, the blood samples can be taken from that. You may feel a 
pinch when the needle goes through your skin. A bruise may appear where it was put in. You 
may also have swelling, and the area may be sore. These things are common and should go away 
in a couple of days. Drawing blood may cause brief discomfort and fainting. Fainting is usually 
for a short period and would be managed by having you lie down and elevate his/her legs. There 


Division of Microbiology and Infectious Diseases (DMID), National Institute of Allergy and Infectious 
Diseases (NIAID), National Institutes of Health (NIH) / Protocol Number 20-0013 
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Lindsey Baden, MD 
Advarra IRB Approved Version 18 Jan 2021 
Revised 11 Feb 2021 
 
is a very small chance of an infection where you have the tube in your arm. An infection could 
be treated with antibiotics. 
 
Swab collection 
Throat swab: This procedure may be uncomfortable, and it causes many people to gag. 
 
Middle nose swab: This procedure may tickle and be slightly uncomfortable. 
 
Deep nose swab: Most people feel pressure and discomfort during this procedure, and it can 
cause a nosebleed. 
 
Confidentiality risks 
We will be careful to keep your study information confidential, but there is a small risk that 
someone not involved in the study could get this information. 
 
Partners Alert System 
Partners has an electronic system that lets your study doctors know if you are admitted to a 
Partners hospital, or if you visit a Partners hospital Emergency Department.  Partners hospitals 
want to make sure the study doctors know about any possible problems or side effects you 
experience while you are taking part in the study. If you obtain emergency medical care at 
another hospital or clinic, please let your study doctor or study staff know as soon as possible. 
 
Study Information Included in Your Electronic Medical Record 
A notation that you are taking part in this research study may be made in your electronic medical 
record. Information from the research that relates to your general medical care may be included 
in the record (for example: list of allergies, results of standard blood tests done at the hospital 
labs). 
 
Genetic Testing: 
As stated above, we will perform genetic testing on your blood sample. This genetic testing will 
focus on COVID-19 and provide information about how your body responds to the disease. 
Following genetic testing, and with your consent, your genetic testing information may be 
shared. A summary of the genetic results from all participants in this study can be placed in a 
public, unrestricted open access database that anyone can freely use. No individual genetic 
testing information or results will be placed in an open access database. The risk of anyone 
identifying you with this information is very unlikely.   
 
Since your genetic data and health information may be stored and shared with other researchers, 
there may be a risk that information resulting from research genetic testing could be misused for 
discriminatory purposes.  
 
A federal law, called the Genetic Information Nondiscrimination Act (GINA), generally makes it 
illegal for health insurance companies, group health plans and most employers to discriminate 
against you based on your genetic information. 
 
This law generally will protect you in the following ways: 


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• Health insurance companies and group health plans may not request your genetic 
information that the sponsor will get from this research. 
• Health insurance companies and group health plans may not use your genetic information 
when making decisions regarding your eligibility or premiums. 
• Employers with 15 or more employees may not use your genetic information that the 
sponsor will get from this research when making a decision to hire, promote, or fire you 
or when setting the terms of your employment. The Sponsor will generally not provide 
this information to others without your consent. Your study site also has to follow 
privacy laws to protect your information. 
 
 
All health insurance companies and group health plans and all employers with 15 or more people 
must follow this law. 
 
Be aware that this Federal law does not protect you against genetic discrimination by companies 
that sell life insurance, disability insurance or long-term care insurance. 
 
If you have any questions, please ask your study doctor. Researchers who will have access to 
genetic information about you will take measures to maintain the confidentiality of your 
information. 
 
Please initial your decision for us to use your information and samples for genetic research 
for this research study: 
 
______ YES, you may use my information and samples for genetic research. 
 
______ NO, you may not use my information and samples for genetic research. 
 
Risks to pregnancy and nursing children 
If you are pregnant or nursing a child during the study, there may be risks to you, the embryo, 
fetus, or nursing child from the study drugs. If you are nursing a child, you must agree to 
discontinue breastfeeding while on this study. If you can get pregnant, you must agree to remain 
abstinent or use birth control while you are on this study and for 5 months after your last dose of 
the study drug or placebo. A member of the study team will talk with you about acceptable forms 
of birth control. You should not participate in this study if you can become pregnant and cannot 
use one of these birth control methods. Some methods of birth control will not work when you 
are taking certain drugs. Be aware that women can still become pregnant even if using an 
acceptable birth control method.  
 
If you think or know you have become pregnant during the study, please contact the research 
team member. You will not receive any more study drug. The team will ask your permission to 
follow-up with you about your health and the health of your baby until delivery. 
 
 


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5. 
Are there benefits to being in the study? 
 
You may or may not benefit from being in this study. Your participation in this study is 
important to learn more about the study drugs if they are safe and work in hospitalized 
participants with COVID-19.  
 
6. 
What instructions do you need to follow? 
 
You should not drink any alcohol for 14 days after you start receiving the study drug on Day 1. If 
you feel that you need other medicines or herbal products, you should talk to a member of the 
study team first. 
 
If you are nursing a child, you must agree to discontinue breastfeeding while on this study. If you 
can get pregnant, you must agree to remain abstinent or use birth control while you are on this 
study and for 5 months after your last dose of the study drug or placebo. 
 
You may not volunteer for another study that gives participants a new study drug for COVID-19 
for at least 29 days after you start receiving the study drug on Day 1. If you want to be in another 
study that follows people who have or have had COVID-19, you should talk to a member of the 
study team first, especially if the other study involves blood collection. 
 
7. 
What other choices do you have? 
 
Before you decide whether to be in this study, we will discuss other options that are available to 
you. Instead of being in this study, you could look for other studies of experimental drugs for 
COVID-19. You can also continue to receive regular supportive hospital care for patients with 
COVID-19 instead of joining a research study. This could include treatment with remdesivir. 
 
8. 
Will new findings be shared with you? 
 
If we find out any new information that may affect your choice to participate in this study, we 
will contact you to explain what we have learned. This may be information we have learned 
while doing this study or information we have learned from other scientists doing similar 
research in other places. 
 
We are doing genetic testing (sequencing) for research purposes and not to look for inherited 
disease or defects; therefore, we will not return results from sequencing. 
 
9. 
What will happen to your samples and personal information? 
 
We will store your samples and data (information) until we are able to test all samples for SARS-
CoV-2. Your stored samples and data will be marked with a code and not with your name. Only 
researchers linked to this study can get the codes. 
 


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Your study information will be placed in a secure electronic system. It will not include your 
name. This information cannot be traced back to you. Your samples will not be sold. You will 
not be paid for any products that result from this research.  
 
The only risk of allowing us to store your samples would be an accidental release of your 
identity. 
 
Some of the blood collected for this study may not be needed to do the research tests. We plan to 
store and use these leftover samples along with your information (identified only by ID codes) 
for secondary research. Secondary research is research that is not part of this study but will be 
performed in the future. You will not be told about the future research. Also, we will collect 
extra blood samples (about 3 teaspoons when other blood is drawn) to store and use for 
secondary research. Secondary research may help us understand how remdesivir and the other 
study drugs work, study other infections or diseases, or develop other treatments. The types of 
research may include development of new laboratory tests to better understand responses to 
infection or for studies to better understand virus infections, including SARS-CoV-2 infection.  
 
You may change your mind about secondary research and withdraw consent for the storage and 
use of your coded samples or information at any time. You will need to contact the study doctor 
using the contact information listed on page 1 of this form. We will do our best to follow your 
wishes but cannot promise that we will always be able to destroy your samples or data. For 
example, if your samples were already used, we would not be able to destroy them. 
 
Please initial your decision about permission for us to use your excess/leftover blood 
samples for future research: 
 
______ YES, you may collect and store my excess/leftover blood samples for an indefinite 
period of time and use them for future research. 
 
______ NO, you may not store my excess/leftover blood samples for an indefinite period of time 
and use them for future research. I understand that by saying NO, I can still take part in this 
study.    
 
10. 
What do you need to do for follow-up on this study? 
 
If you feel sick at any time during the study, it is important that you quickly tell the study team at 
the hospital (if you are still hospitalized) or call the study contact number you were given when 
you left the hospital (if you have been discharged). We may ask you to return to the study site for 
a medical exam and possible sampling.  
 
11. 
What will I have to pay for if I take part in this study? 
 
It will not cost you anything to be in this study. 
 
Study funds will pay for certain study-related items and services that are being done only for 
research. However, we may bill your health insurer for, among other things, routine items and 


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services you would have received even if you did not take part in the research. You will be 
responsible for payment of any deductibles and co-payments required by your insurer for this 
routine care or other billed care. 
 
If you have any questions about costs to you that may result from taking part in the research, 
please speak with the study doctors and study staff. If necessary, we will arrange for you to 
speak with someone in Patient Financial Services about these costs.  Before you agree to be in 
this study, you should contact your health insurer to see if your plan will cover the costs 
required as part of your participation. 
 
12. 
Will you be paid if you join this study? 
 
You will not receive any monetary compensation for your participation in this study.  
 
13. 
Who is watching over this study? 
 
A Data and Safety Monitoring Board (DSMB) will be looking at the study information very 
closely. The DSMB is made up of doctors and other people who are not directly involved in the 
study and who have a good understanding of severe coronavirus infections and research studies. 
The DSMB may recommend changing the study or stopping the study earlier than planned if 
they think it is not safe to continue. The National Institutes of Health (NIH), local ethics and 
health authorities, and the U.S. FDA will also be watching over this study and have the authority 
to stop the study at any time.   
 
14. 
How will your privacy be protected? 
 
We will keep your study information private. All files with information that could identify you 
will be kept in locked cabinets or secure password protected computers. People responsible for 
making sure that the research is done properly may look at your study records. This might 
include people involved in this study from this hospital and the U.S. government including the 
NIH and their designees and the U.S. Food and Drug Administration, the Institutional Review 
Board (Advarra IRB), and the drug companies that make the study drugs (remdesivir by Gilead 
Sciences, Inc., and risankizumab by AbbVie Inc.). All of these people will also keep your 
identity private. By signing and dating this consent form, you agree that results from this study, 
but not your identity, may be shared with local medical providers, makers of the study drugs, or 
government health organizations to help them better understand COVID-19. When results of an 
NIH research study are reported in medical journals or at scientific meetings, the participants 
who take part in the study are not named or identified.  
 
To help us protect your privacy, we have a Certificate of Confidentiality (Certificate) from the 
NIH. Study staff cannot provide to any person not connected with the research your name, or any 
materials that contain identifiable, sensitive information about you, unless permitted or required 
by a legal exception, such as state laws that require reporting of some contagious diseases. The 
most important protection provided by the Certificate is that the study staff cannot be forced to 
provide any of your identifiable, sensitive information, in any Federal, State, or local civil, 
criminal, administrative, legislative, or other proceeding, such as if there is a court subpoena, 


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without your permission. The study team will use the Certificate to resist any demands for 
information that would identify you. 
 
Your information protected by the Certificate may still be disclosed or used when the 
information: 
1. Is disclosed to people connected with the research, for example, information may be used 
for program evaluation internally by the NIH; or  
2. Is required to be disclosed by Federal, State, or local laws, for example, when 
information must be disclosed to meet the legal requirements of the federal U.S. FDA);  
3. Is necessary for your medical treatment and you have consented to this disclosure;  
4. Is for other research; 
5. Is disclosed with your consent (for example, an insurer or medical care provider gets your 
written consent for us to disclose the research information). 
 
The Certificate will not be used to prevent disclosure to state or local authorities of harm to self 
or others including, for example, child abuse and neglect, and by signing and dating below you 
consent to those disclosures. 
 
15. 
Will the study require any of your other health care providers to share 
your health information with the researchers of this study? 
 
As a part of this study, the researchers may ask to see your health care records from your other 
health care providers. You will be asked to give us a list of other health care providers that you 
use. 
 
To do this research, we will need to collect, use, and share your private health information. Your 
private information may include things learned from the procedures described in this consent 
form, as well as information from your medical record.  
 
If I take part in this research study, how will you protect my privacy? 
During this research, identifiable information about your health will be collected. In the rest of 
this section, we (Partners Hospitals) refer to this information simply as “health information”. 
Under federal law, health information is private. However, there are exceptions to this rule, and 
you should know who may be able to see, use, and share your health information for research 
and why they may need to do so. 
 
In this study, we may collect health information about you from: 
• Past, present, and future medical records 
• Research procedures, including research office visits, tests, interviews, and 
questionnaires 
 
Who may see, use, and share your identifiable health information and why they may need 
to do so: 
• Partners research staff involved in this study in order to conduct the research 
• The sponsor(s) of this study, and the people or groups it hires to help perform this 
research or audit the research 


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• Other researchers and medical centers that are part of this study and their ethics boards 
• A group that oversees the data (study information) and safety of this research 
• Non-research staff within Partners who need this information to do their jobs (such as for 
treatment, payment (billing), or health care operations) 
• Advarra IRB Review a group of people who review research studies to protect the rights 
and safety of research participants 
• People from organizations that provide independent accreditation and oversight of 
hospitals and research 
• People or groups that we hire to do work for us, such as data storage companies, insurers, 
and lawyers 
• Federal and state agencies (such as the Food and Drug Administration (FDA), the 
Department of Health and Human Services, the National Institutes of Health, and other 
US or foreign government bodies that oversee or review research) 
• Public health and safety authorities (for example, if we learn information that could mean 
harm to you or others, we may need to report this, as required by law) 
 
Some people or groups who get your health information might not have to follow the same 
privacy rules that we follow and might use or share your health information without your 
permission in ways that are not described in this form. For example, we understand that the 
sponsor of this study may use your health information to perform additional research on various 
products or conditions, to obtain regulatory approval of its products, to propose new products, 
and to oversee and improve its products’ performance. We share your health information only 
when we must, and we ask anyone who receives it from us to take measures to protect your 
privacy. The sponsor has agreed that it will not contact you without your permission and will not 
use or share your information for any mailing or marketing list. However, once your information 
is shared outside Partners, we cannot control all the ways that others use or share it and cannot 
promise that it will remain private. 
 
Because research is an ongoing process, we cannot give you an exact date when we will either 
destroy or stop using or sharing your health information.  Your permission to use and share your 
identifiable information does not expire.  
 
The results of this research study may be published in a medical book or journal, or used to teach 
others. However, your name or other identifying information will not be used for these purposes 
without your specific permission. 
 
Your Privacy Rights 
You have the right not to sign and date this form that allows us to use and share your health 
information for research; however, if you don’t sign and date it, you can’t take part in this 
research study. 
 
You have the right to withdraw your permission for us to use or share your health information 
for this research study. If you want to withdraw your permission, you must notify the person in 
charge of this research study in writing at the address listed on the first page of this form. Once 
permission is withdrawn, you cannot continue to take part in the study. 
 


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If you withdraw your permission, we will not be able to take back information that has already 
been used or shared with others. 
 
You have the right to see and get a copy of your health information that is used or shared for 
treatment or for payment. To ask for this information, please contact the person in charge of this 
research study, listed on page 1 of this form. You may only get such information after the 
research is finished. 
 
16. 
What other things should you know about this research study? 
 
A. ClinicalTrials.gov 
 
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. 
 
B. Conflict of Interest 
 
The policy of the NIH is to evaluate investigators at least yearly for any conflicts of interest. 
This process is detailed in a Conflict of Interest (COI) Guide. You may ask your study team 
for a copy of the COI Guide or for more information. This study has investigators that are 
NIH employees and some that are not. All non-NIH investigators are required to follow the 
principles outlined in the COI Guide but they are not required to report their specific 
financial holdings to the NIH. 
 
Gilead Sciences, Inc., the company that makes remdesivir, is providing remdesivir for this 
study to NIH without charge. AbbVie Inc., the company that makes risankizumab, is 
providing risankizumab for this study to NIH without charge. No NIH investigator involved 
in this study receives payments or other benefits from any company whose drug, product or 
device is being tested. However, there are some research partners not associated with the 
NIH working on this study who may receive payments or benefits, limited by the rules of 
their workplace. 
 
C. Whom to Contact About This Study? 
 
During the study, if you experience any medical problems, suffer a research-related injury, or 
have questions, concerns or complaints about the study, please contact the study doctor at the 
telephone number listed on the first page of this consent document. If you seek emergency 
care, or hospitalization is required, alert the treating physician that you are participating in 
this research study.  
 
An IRB is an independent committee established to help protect the rights of research 
participants If you have any questions about your rights as a research participant, and/or 
concerns or complaints regarding this research study, contact: 
 


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• By mail: 
Study Subject Adviser 
Advarra IRB 
6940 Columbia Gateway Drive, Suite 110 
Columbia, MD 21046 
• or call toll free:    877-992-4724 
• or by email:          adviser@advarra.com 
 
Please reference the following number when contacting the Study Subject Adviser: 
Pro00046406. 
 
D. What happens if I am injured as a result of taking part in this research study? 
 
We (Partners hospitals) will offer you the care needed to treat any injury that results from 
taking part in this research study. We reserve the right to bill your insurance company or 
other third parties, if appropriate, for the care you get for the injury.  We will try to have 
these costs paid for, but you may still be responsible for some of them.  For example, if the 
care is billed to your insurer, you will be responsible for payment of any of deductibles and 
co-payments required by your insurer.  To ask questions about this, talk to the study doctor or 
study staff.  Be aware that your health care payer/insurer might not cover the costs of 
study-related injuries or illnesses. 
 
 Injuries sometimes happen even when no one is at fault. There are no plans to pay you or 
give you other compensation for an injury, should one occur.  However, you are not giving 
up any of your legal rights by signing and dating this form. If you think you have been 
injured or have experienced a medical problem as a result of taking part in this research 
study, tell the person in charge of this study as soon as possible.  The researcher's name and 
phone number are listed on the first page of this consent form. 
 
 
In general, no long-term medical care or financial compensation for research-related injuries 
will be provided by the NIH or the Federal Government.  
 
A Declaration under the Public Readiness and Emergency Preparedness (PREP) Act was 
issued by the Secretary of the United States Department of Health and Human Services on 
March 10, 2020.  This Declaration limits the legal rights of a subject participating in clinical 
studies utilizing COVID-19 countermeasures. Because this study is covered by the Prep Act 
Declaration, covered persons, such as the manufacturers, study sponsor, researchers, 
healthcare providers and others have liability immunity (that is, they cannot be sued by you 
or your family under the laws of the United States). 
 
If you believe that you may have been harmed as a result of this research study, certain 
claims for serious injury or death caused by the countermeasure may be eligible for 
compensation through the Countermeasures Injury Compensation Program. This is a 
program set up by the United States Government.  


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Information about this program can be found at https://www.hrsa.gov/cicp/about/index.html 
or by calling 1-855-266-2427. If you are eligible for this program, you must file a claim 
within one year of the administration or use of the covered countermeasure. 
 
 
Informed Consent and Authorization 
Statement of Person Giving Informed Consent and Authorization 
• I have read this consent form. 
• This research study has been explained to me, including risks and possible benefits (if 
any), other possible treatments or procedures, and other important things about the study. 
• I have had the opportunity to ask questions. 
• I understand the information given to me. 
• By signing and dating this form, I do not give up any of my legal rights. 
• I will get a signed and dated copy of this consent form. 
 
Signature of Subject: 
 
I give my consent to take part in this research study and agree to allow my health information to 
be used and shared as described above. 
 
 
 
Printed Name of Subject 
 
 
 
 
 
Signature of Subject 
 
Date/Time 
 
 
Statement of Study Doctor or Person Obtaining Consent: 
• I have explained the research to the study subject. 
• I have answered all questions about this research study to the best of my ability. 
 
 
 
Printed Name of Person Obtaining Consent 
 
 
 
 
 
Signature of Person Obtaining Consent 
 
Date/Time 
 
 


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Signature of Authorized Representative for Adult: 
I give my consent for the person I am authorized to represent to take part in this research study 
and agree to allow his/her health information to be used and shared as described above. 
 
 
 
 
 
Print Name (check applicable box below) 
 Court-appointed Guardian 
 Health Care Proxy 
 Durable Power of Attorney 
 Family Member/Next-of-Kin 
 
 
 
 
 
Signature 
 
Date/Time 
 
If Family Member or Next-of-Kin, Describe Relationship to Subject: _____________________ 
 
 
Adult Assent 
Signature of Assenting Adult: 
I agree to take part in this research study and agree to allow my health information to be used 
and shared as described above. 
 
 
 
 
 
 
 
 
 
 
Printed Name of Assenting Adult 
 
 
 
 
 
Signature of Assenting Adult  
 
 
 
 
Date/Time 
 
 
Statement of Witness: 
I represent that the consent form was presented orally to the subject in the subject’s own 
language, that the subject was given the opportunity to ask questions, and that the subject has 
indicated his/her consent and authorization for participation by (check one box as applicable): 
 Making his/her mark above 
 Other means ______________________________________________________________ 
(fill in above) 
 
 
 
Printed Name of Witness 
 
 
 
 
 
Signature of Witness  
 
 
 
 
 
Date/Time 
 

SAP_003.pdf: 
CLINICAL RESEARCH IN INFECTIOUS DISEASES 
 
 
 
STATISTICAL ANALYSIS PLAN 
for 
DMID Protocol: 20-0013 
Study Title: 
A Multicenter Platform Trial of Putative 
Therapeutics for the Treatment of COVID-19 in 
Hospitalized Adults  
 
NCT04583956, NCT04583969, NCT04988035 
 
Version 3.0 
 
DATE: 23-MAY-2022 
 
THIS COMMUNICATION IS PRIVILEGED AND CONFIDENTIAL  
 
 


Statistical Analysis Plan - DMID Protocol: 20-0013  
Version 3.0 
23 May 2022 
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PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
STUDY TITLE 
Protocol Number Code: 
DMID Protocol: 20-0013 
Development Phase: 
See stage-specific SAP  
Products: 
Refer to stage-specific protocol 
Form/Route: 
Refer to stage-specific protocol 
Indication Studied: 
COVID-19 
Sponsor: 
Division of Microbiology and Infectious Diseases 
National Institute of Allergy and Infectious Diseases 
National Institutes of Health 
Clinical Trial Initiation Date: 
14 October 2020 
Estimated Clinical Trial Completion 
Date: 
TBD 
Date of the Analysis Plan: 
23 May 2022 
Version Number: 
3.0 
This study was performed in compliance with Good Clinical Practice. 
Information contained in this publication is the property of Division of Microbiology and Infectious Diseases and is confidential. This information 
may not be disclosed to third parties without written authorization from Division of Microbiology and Infectious Diseases. This report may not be 
reproduced, stored in a retrieval system or transmitted in any form or by any means - electronic, mechanical, recording or otherwise - without the 
prior authorization from Division of Microbiology and Infectious Diseases. This document must be returned to Division of Microbiology and 
Infectious Diseases upon request. 
 


Statistical Analysis Plan - DMID Protocol: 20-0013  
Version 3.0 
23 May 2022 
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PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
TABLE OF CONTENTS 
STUDY TITLE ................................................................................................................................2 
TABLE OF CONTENTS .................................................................................................................3 
LIST OF ABBREVIATIONS ..........................................................................................................6 
1. 
PREFACE .....................................................................................................................9 
2. 
INTRODUCTION ......................................................................................................10 
2.1. 
Purpose of the Analyses ..............................................................................................10 
3. 
STUDY OBJECTIVES AND ENDPOINTS ..............................................................11 
3.1. 
Study Objectives .........................................................................................................11 
3.1.1. 
Primary Objective .......................................................................................................11 
3.1.2. 
Secondary Objectives .................................................................................................11 
3.1.2.1. 
Key Secondary Objectives ..........................................................................................11 
3.1.2.2. 
Other Secondary Objectives .......................................................................................11 
3.1.3. 
Exploratory Objectives ...............................................................................................12 
3.2. 
Endpoints ....................................................................................................................13 
3.3. 
Study Definitions and Derived Variables ...................................................................15 
3.3.1. 
Definition of Study Day ..............................................................................................15 
3.3.2. 
Analysis Visit Windows .............................................................................................16 
4. 
INVESTIGATIONAL PLAN .....................................................................................18 
4.1. 
Overall Study Design and Plan ...................................................................................18 
4.2. 
Discussion of Study Design, Including the Choice of Control Groups ......................18 
4.3. 
Selection of Study Population ....................................................................................19 
4.4. 
Treatments ..................................................................................................................20 
4.4.1. 
Treatments Administered ............................................................................................20 
4.4.2. 
Identity of Investigational Product(s) .........................................................................20 
4.4.3. 
Method of Assigning Subjects to Treatment Groups (Randomization) .....................20 
4.4.4. 
Selection of Doses in the Study ..................................................................................20 
4.4.5. 
Selection and Timing of Dose for Each Subject .........................................................21 
4.4.6. 
Blinding ......................................................................................................................21 
4.4.7. 
Prior and Concomitant Therapy ..................................................................................21 
4.4.8. 
Treatment Compliance ................................................................................................21 


Statistical Analysis Plan - DMID Protocol: 20-0013  
Version 3.0 
23 May 2022 
Table of Contents (continued) 
 
- 4 - 
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4.5. 
Efficacy and Safety Variables ....................................................................................21 
5. 
SAMPLE SIZE CONSIDERATIONS .......................................................................24 
6. 
GENERAL STATISTICAL CONSIDERATIONS ....................................................26 
6.1. 
General Principles .......................................................................................................26 
6.2. 
Timing of Analyses .....................................................................................................29 
6.2.1. 
Interim Analyses .........................................................................................................29 
6.2.2. 
Final Analyses ............................................................................................................29 
6.3. 
Analysis Populations ..................................................................................................29 
6.3.1. 
Intention-to-Treat Analysis (ITT) Population ............................................................30 
6.3.2. 
Modified Intention-to-Treat (mITT) Population ........................................................30 
6.3.3. 
Safety Population ........................................................................................................30 
6.4. 
Covariates and Subgroups ..........................................................................................30 
6.4.1. 
Covariates for the Primary Endpoint ..........................................................................30 
6.4.2. 
Covariates for Secondary Endpoints ..........................................................................30 
6.4.3. 
Subgroups ...................................................................................................................31 
6.5. 
Missing Data ...............................................................................................................38 
6.5.1. 
General Guidelines Regarding Handling of Missing Data .........................................38 
6.5.2. 
Multiple Imputation ....................................................................................................45 
6.6. 
Data Handling and Transformations ...........................................................................48 
6.7. 
Multicenter Studies .....................................................................................................50 
6.8. 
Multiple Comparisons/Multiplicity ............................................................................50 
7. 
STUDY SUBJECTS ...................................................................................................52 
7.1. 
Disposition of Subjects ...............................................................................................52 
7.2. 
Protocol Deviations ....................................................................................................52 
7.3. 
Investigational Product Exposure and Compliance ....................................................52 
8. 
EFFICACY EVALUATION ......................................................................................53 
8.1. 
Primary Efficacy Analysis ..........................................................................................53 
8.2. 
Secondary Efficacy Analyses .....................................................................................53 
8.2.1. 
Key Secondary Efficacy Analyses ..............................................................................53 
8.2.2. 
Other Secondary Efficacy Analyses ...........................................................................55 
8.3. 
Exploratory Efficacy Analyses ...................................................................................58 


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9. 
SAFETY EVALUATION ..........................................................................................59 
9.1. 
Demographic and Other Baseline Characteristics ......................................................59 
9.1.1. 
Prior and Concurrent Medical Conditions ..................................................................59 
9.1.2. 
Prior and Concomitant Medications ...........................................................................60 
9.2. 
Measurements of Treatment Compliance ...................................................................60 
9.3. 
Adverse Events ...........................................................................................................60 
9.4. 
Deaths, Serious Adverse Events and other Significant Adverse Events ....................62 
9.5. 
Pregnancies .................................................................................................................63 
9.6. 
Clinical Laboratory Evaluations .................................................................................63 
9.7. 
Vital Signs and Physical Evaluations .........................................................................63 
9.8. 
Concomitant Medications ...........................................................................................63 
9.9. 
Other Safety Measures ................................................................................................64 
10. 
PHARMACOKINETICS ...........................................................................................65 
11. 
IMMUNOGENICITY ................................................................................................66 
12. 
OTHER ANALYSES .................................................................................................67 
13. 
REPORTING CONVENTIONS ................................................................................68 
14. 
TECHNICAL DETAILS ............................................................................................69 
15. 
SUMMARY OF CHANGES IN THE CONDUCT OF THE STUDY OR 
PLANNED ANALYSES ............................................................................................70 
15.1. 
Changes from Planned analyses for BET-B ...............................................................70 
15.2. 
Changes from Version 1.0 to Version 2.0 of the Master SAP ....................................70 
15.3. 
Changes from Version 2.0 to Version 3.0 of the Master SAP ....................................71 
16. 
REFERENCES ...........................................................................................................72 
17. 
LISTING OF TABLES, FIGURES, AND LISTINGS ..............................................73 
APPENDICES ...............................................................................................................................74 
APPENDIX 1. TABLE MOCK-UPS..........................................................................................75 
APPENDIX 2. FIGURE MOCK-UPS ......................................................................................139 
APPENDIX 3. LISTINGS MOCK-UPS ...................................................................................153 
 


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LIST OF ABBREVIATIONS 
ACTIV 
Accelerating COVID-19 Therapeutic Interventions and Vaccines 
ACTT 
Adaptive COVID-19 Treatment Trial 
AE 
Adverse Event 
ALT 
Alanine Aminotransferase 
AST 
Aspartate Aminotransferase 
ATC 
Anatomical Therapeutic Chemical 
BET 
Big Effect Trial 
BLOQ 
Below the Limit of Quantitation 
CI 
Confidence Interval 
cm 
Centimeters 
CoV 
Coronavirus 
COVID-19 
Coronavirus Disease 2019 
CRF 
Case Report Form 
CRP 
C-Reactive Protein 
CSR 
Clinical Study Report 
HLT 
High-Level Term 
DAIDS 
Division of AIDS 
DMID 
Division of Microbiology and Infectious Diseases 
DSMB 
Data and Safety Monitoring Board 
ECMO 
Extracorporeal Membrane Oxygenation 
eCRF 
Electronic Case Report Form 
EDC 
Electronic Data Capture 
eGRF 
Estimated Glomerular Filtration Rate 
ERC 
Endpoint Review Committee 
Hgb 
Hemoglobin 
INR 
International Normalized Ratio 
ITT 
Intent-to-Treat 
JAK 
Janus kinase 
kg 
Kilograms 


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LDH 
Lactate Dehydrogenase 
LLOD 
Lower Limit of Detection 
LLOQ 
Lower Limit of Quantification 
LOCF 
Last Observation Carried Forward 
MedDRA 
Medical Dictionary for Regulatory Activities 
MI 
Multiple Imputation 
mL 
Milliliter 
N 
Number (typically refers to subjects) 
NAAT 
Nucleic Acid Amplification Test 
NEWS 
National Early Warning Score 
NIAID 
National Institute of Allergy and Infectious Diseases 
NIH 
National Institutes of Health 
OP 
Oropharyngeal  
OR 
Odds Ratio 
PBMC 
Peripheral Blood Mononuclear Cells 
PCR 
Polymerase Chain Reaction 
PK 
Pharmacokinetic 
PLT 
Platelet 
PT 
Preferred Term 
Q1 
First Quartile 
Q3 
Third Quartile 
RR 
Respiratory Rate 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SARS 
Severe Acute Respiratory Syndrome 
SARS-CoV-2 
Severe Acute Respiratory Syndrome Coronavirus 2 
SD 
Standard Deviation 
SOC 
System Organ Class 
SpO2 
Blood Oxygen Saturation 
TEAE 
Treatment-Emergent Adverse Events 


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TLF 
Tables, Listings, and Figures 
TNF 
Tumor Necrosis Factor 
ULOQ 
Upper Limit of Quantification 
US 
United States 
WBC 
White Blood Cell 
WHO 
World Health Organization 


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1. 
PREFACE 
A novel coronavirus designated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first 
identified in December 2019 in Wuhan, China, and has since spread globally, resulting in an ongoing 
pandemic of Coronavirus Disease 2019 (COVID-19). Currently, remdesivir is the only FDA approved 
antiviral for the treatment of patients hospitalized with COVID-19, but even with this antiviral the mortality 
of COVID-19 remains high. Multiple putative therapeutics involving repurposed agents (licensed or in late 
development) have been proposed for treating COVID-19, but there is no way to evaluate many of these 
agents due to lack of suitable animal models that replicate human disease. There is an urgent need for rapid 
development and testing of interventions to treat COVID-19 in hospitalized patients. An adaptive platform 
trial is one approach to allow for accelerated testing and selection of promising therapeutic agents in order to 
meet ongoing public health needs. Each new intervention represents a new stage. Default elements are 
described in this Master Statistical Analysis Plan (SAP) and align closely with BET-A study. Any stage-
specific elements will be detailed in the respective stage-specific appendix of the SAP, and these supersede 
the corresponding elements described in this Master SAP. 
 


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2. 
INTRODUCTION 
2.1. 
Purpose of the Analyses 
This Statistical Analysis Plan (SAP) encompasses all interim analyses and the final analysis of primary, 
secondary and some exploratory outcome measures. These analyses will assess the efficacy and safety of 
different investigational therapeutic agents relative to a common control arm and will be included in each 
investigational therapeutic Clinical Study Report (CSR). The protocol for ACTIV – 5 DMID BET 20-0013 – 
v6.0 calls for a planned interim efficacy analysis once approximately 50 subjects per treatment arm reach 
Study Day 8 or discontinue the trial early. If a stage is planned to have a total sample size greater than 200 
subjects, then an additional planned futility analysis may be conducted. The details of the additional futility 
analysis will be described in the stage-specific SAP, if applicable. 


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3. 
STUDY OBJECTIVES AND ENDPOINTS 
3.1. 
Study Objectives 
The overall objective of the study is to evaluate the clinical efficacy and safety of different investigational 
therapeutics relative to the control arm among hospitalized adults who have COVID-19. 
3.1.1. 
Primary Objective 
The default primary objective for the different stages in this platform trial is to evaluate the clinical efficacy 
and safety of different investigational therapeutics relative to the control arm in adults hospitalized with 
COVID-19 according to clinical status (8-point ordinal scale) at Study Day 8. In each stage-specific appendix, 
the primary endpoint most applicable to the intervention in that stage will be identified. 
3.1.2. 
Secondary Objectives 
3.1.2.1. 
Key Secondary Objectives 
1. To evaluate the clinical efficacy of different investigational therapeutics, as assessed by time to 
sustained recovery, compared to the control arm up to and including Study Day 60. 
2. To evaluate the clinical efficacy of different investigational therapeutics, as assessed by whether 
subjects are alive and without respiratory failure (ordinal score < 7), compared to the control arm up to 
and including Study Day 29, among those with an ordinal score of 5 or 6 at baseline. 
If the key secondary objective is different than what is covered in the master SAP, it will be highlighted for 
each individual investigational intervention in the corresponding stage-specific appendix. 
3.1.2.2. 
Other Secondary Objectives 
1. To evaluate the clinical efficacy of different investigational therapeutics as compared to the control 
arm as assessed by: 
• Clinical severity 
o 8-Point Clinical Status Ordinal scale: 
▪ Time to an improvement of 1 category and 2 categories from Study Day 1 (baseline) up to 
and including Study Day 60 using clinical status, 
▪ Clinical status using 8-point ordinal scale at Study Days 1, 3, 5, 8, 11, 15, 22, and 29, 
o Mean change in the ordinal score from Study Day 1 to Study Days 3, 5, 8, 11, 15, 22, and 29 
o Oxygenation: 
▪ Supplemental oxygen use up to and including Study Day 29. 
o Non-invasive ventilation/high-flow oxygen: 
▪ Non-invasive ventilation/high-flow oxygen use up to and including Study Day 29, 
▪ Incidence and duration of new non-invasive ventilation or high-flow oxygen use up to and 
including Study Day 29 (i.e., a subject with a baseline ordinal score of 5 who worsens to an 
ordinal score of 6, 7, or 8). 


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o Invasive Mechanical Ventilation/ extracorporeal membrane oxygenation (ECMO): 
▪ Ventilator/ECMO use up to and including Study Day 29, 
▪ Incidence and duration of new mechanical ventilation or ECMO use up to and including 
Study Day 29 (i.e., a subject with a baseline ordinal score of 5 or 6 who worsens to an 
ordinal score of 7). 
o Proportion of subjects alive and without respiratory failure at Day 29 
• Hospitalization: 
o Duration of hospitalization (days) up to and including Study Day 29.  
• Mortality: 
o 14-day mortality (up to an including Day 15), 
o 28-day mortality (up to and including Day 29), 
o 59-day mortality (up to and including Day 60), 
o Time to death up to and including Day 29. 
• Markers of inflammation and coagulation. 
2. To evaluate the safety of different investigational therapeutics as compared to the control arm as 
assessed by: 
• Cumulative incidence of serious adverse events (SAEs) up to and including Study Day 60, 
• Cumulative incidence of Grade 3 and 4 clinical and/or laboratory adverse events (AEs) up to and 
including Study Day 60, 
• Discontinuation or temporary suspension of study product administration (for any reason), 
• Changes in white blood cell (WBC) count with differentials, hemoglobin, platelets, creatinine, 
total bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), estimated 
glomerular filtration rate (eGFR) and international normalized ratio (INR) over time. 
If other secondary objectives are different than what is covered in the master SAP, it will be highlighted for 
each individual investigation intervention in the corresponding stage-specific appendix. 
3.1.3. 
Exploratory Objectives 
1. To evaluate the virologic efficacy of different investigational therapeutics as compared to the control 
arm as assessed by: 
• Percent of subjects with SARS-CoV-2 detectable in saliva (or best technology) sample at Study 
Days 3, 5, 8, 11, 15, and 29,  
• Quantitative SARS-CoV-2 virus in saliva (or best technology) sample at Study Days 3, 5, 8, 11, 
15, and 29, 
• Percent of subjects with SARS-CoV-2 detectable in blood sample at Study Days 3, 5, 8, and 11,  
• Quantitative SARS-CoV-2 virus in blood at Study Days 3, 5, 8, and 11. 
2. To evaluate the impact of study interventions on markers of inflammation and immune response. 


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3. To evaluate post-baseline usage of key concomitant COVID-19 treatments (e.g., steroids) in 
investigational therapeutic arms as compared to the control arm. 
If the exploratory objectives are different than what is covered in the master SAP, it will be highlighted for 
each individual investigational intervention in the corresponding stage appendix. If data is not available for 
some of the exploratory endpoints at the time of the CSR, those endpoints will be reported in a separate CSR 
addendum.  
3.2. 
Endpoints 
Primary Endpoint 
The default primary endpoint is clinical status (8-point ordinal scale) on Study Day 8:  
1. Not hospitalized, no new or increased limitations on activities; 
2. Not hospitalized, but new or increased limitation on activities and/or requiring new or increased home 
oxygen, CPAP, or BiPAP; 
3. Hospitalized, not requiring new or increased supplemental oxygen - no longer requires ongoing 
medical care; 
4. Hospitalized, not requiring new or increased supplemental oxygen - requiring ongoing medical care 
(COVID-19 related or otherwise); 
5. Hospitalized, requiring new or increased supplemental oxygen; 
6. Hospitalized, requiring new or increased non-invasive ventilation or high-flow oxygen devices; 
7. Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 
8. Death. 
Key Secondary Endpoints 
One of the key secondary endpoints is time to sustained recovery (up to and including Study Day 60) and is 
defined as the first day on which the subject satisfies 1 of the following 3 categories from the clinical status 
ordinal scale (and does not return to a score of ≥ 4 up to and including Study Day 60): 
1. Not hospitalized, no new or increased limitations on activities; 
2. Not hospitalized, but new or increased limitation on activities and/or requiring new or increased home 
oxygen, CPAP, or BiPAP; 
3. Hospitalized, not requiring new or increased supplemental oxygen - no longer requires ongoing 
medical care. 
The other key secondary endpoint is whether the subject did not satisfy one of the following two categories 
from the ordinal scale up to and including Study Day 29. This analysis will only be completed for those 
subjects with baseline ordinal score of 5 or 6: 
7. Hospitalized, on invasive mechanical ventilation or ECMO;  
8. Death.  
If the key secondary endpoints are different than what is covered in this master SAP, it will be highlighted for 
each individual investigational intervention in the corresponding stage-specific appendix. 


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Other Secondary Endpoints 
The other secondary endpoints are: 
Efficacy 
• Time (days) from Study Day 1 to the first day for which a subject is assessed to be at least 1 category 
lower (improvement) than the subject’s baseline ordinal score up to and including Study Day 60; 
• Time (days) from Study Day 1 to the first day for which a subject is assessed to be at least 2 categories 
lower (improvement) than the subject’s baseline ordinal score up to and including Study Day 60; 
• Clinical status assessed using ordinal scale on Study Days 1, 3, 5, 8, 11, 15, 22, and 29; 
• Change in clinical status using change in ordinal scale from Study Day 1 to Study Days 3, 5, 8, 11, 15, 
22, and 29; 
• Days of supplemental oxygen or worse (i.e., ordinal score of 5, 6, 7, 8) up to and including Study Day 
29; 
• Days of non-invasive ventilation/high-flow oxygen or worse (i.e., ordinal score of 6, 7, 8) up to and 
including Study Day 29; 
• Whether a subject who has a baseline ordinal score of 5 requires new non-invasive oxygen use or 
worse (i.e., ordinal score of 6, 7, 8) during the study up to and including Study Day 29 (incidence); 
• Days a subject who has a baseline ordinal score of 5 has an ordinal score of 6 or greater up to and 
including Study Day 29; 
• Days of invasive mechanical ventilation/ECMO or worse (i.e., an ordinal score of 7 or 8) up to and 
including Study Day 29; 
• Whether subject who has a baseline ordinal score of 5 or 6 requires new invasive ECMO use or worse 
(i.e., ordinal score of 7 or 8) during study up to and including Study Day 29 (incidence); 
• Days a subject who has a baseline ordinal score of 5 or 6 has an ordinal score > 6 up to and including 
Study Day 29; 
• Whether a subject is alive and without respiratory failure (ordinal score < 7) at Study Day 29; 
• Time (days) to ventilation or death from Study Day 1 up to and including first 29 days of being on 
study. 
• Days of hospitalization from date of admission up to and including Study Day 29. 
• Values of C-reactive protein (CRP), ferritin, D-dimer, lactate dehydrogenase (LDH), and fibrinogen 
on Study Days 1, 3, 5, 8, and 11 (while hospitalized); and Study Days 15 and 29 (if attends in-person 
visit or still hospitalized). 
Safety 
• Whether a subject died from Day 1 up to and including Study Day 15. 
• Whether a subject died from Day 1 up to and including Study Day 29. 
• Whether a subject died from Day 1 up to and including Study Day 60. 
• Time (days) to death from Study Day 1 up to and including Study Day 29. 


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• Whether a subject experienced at least one SAE up to and including Study Day 60. 
• Whether a subject experienced at least one Grade 3 or Grade 4 AE up to and including Study Day 60. 
• Episodes of early discontinuation or interruption of study product administration. 
• Values of WBC with differential, hemoglobin, platelets, creatinine, eGFR, total bilirubin, ALT, AST, 
and INR on Study Days 1, 3, 5, 8, and 11 (while hospitalized); and Study Days 15 and 29 (if attends 
in-person visit or still hospitalized). 
Exploratory Endpoints 
The exploratory endpoints are:  
• Whether a subject used concomitant COVID-19 treatments (e.g., steroids) post-baseline up to and 
including Study Day 29. 
Details for the exploratory endpoints listed below are not provided in this master SAP will be provided in a 
separate SAP addendum and reported in a separate CSR addendum. 
• Whether a subject has detectable SARS-CoV-2 according to polymerase chain reaction (PCR) in 
saliva from oropharyngeal (OP) swab (or best technology) on Study Day 1; Study Days 3, 5, 8, and 11 
(while hospitalized); and Study Days 15, and 29 (if subject attends in-person visits or is still 
hospitalized); 
• Quantitative polymerase chain reaction (PCR) for SARS-CoV-2 in saliva from OP swab on Study 
Days 1, 3, 5, 8, and 11 (while hospitalized); and Study Days 15 and 29 (if subject attends in-person 
visit or is still hospitalized); 
• Whether a subject has detectable SARS-CoV-2 in blood at Study Days 1, 3, 5, 8, and 11 (while 
hospitalized); 
• Quantitative PCR for SARS-CoV-2 in blood on Study Days 1, 3, 5, 8, and 11 (while hospitalized);  
• Proteomic analysis of plasma cytokines and markers of inflammation;  
• Transcription, epigenetic, and molecular profiles of mRNA in peripheral blood mononuclear cells 
(PBMC); 
• Phenotypic and responsiveness markers in PBMC. 
3.3. 
Study Definitions and Derived Variables  
3.3.1. 
Definition of Study Day 
Study day will be calculated from the first dosing date of study product and derived as follows: 
• For post-dose study days: Assessment Date – First Dosing Date + 1 
• For days prior to the first dose: Assessment Date – First Dosing Date  
Therefore, Study Day 1 is the day of first dose of study product administration. If subjects are not treated with 
study product, then their Study Day 1 will be their randomization date. 


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3.3.2. 
Analysis Visit Windows 
The nominal visit as recorded in the electronic data capture (EDC) or within the permitted visit window as 
specified by the Schedule of Assessments will be used when data are summarized by visit (see Table 1 and 
Table 2). Any data relating to unscheduled visits will not be assigned to a particular visit or time point. 
However, the following exceptions will be made: 
• An unscheduled visit prior to the first dose of study product may be included in the calculation of 
baseline value, if applicable.  
Table 1: 
Clinical Status Study Day Windows 
Analysis Visit Day 
Nominal Day 
Target day 
Visit Window 
Screening 
Screening 
-1 to 1 
<1 
Baseline 
Day 1 (Hospitalized) 
1 
1 
Day 3 
Day 3 (Hospitalized) 
3 
3 
Day 5  
Day 5 (Hospitalized) 
5 
5 
Day 8  
Day 8 (Hospitalized) 
8 
8 
Day 8  
Day 8 (Discharged) 
8 
6-10 
Day 11  
Day 11 (Hospitalized) 
11 
11 
Day 15  
Day 15 (Discharged) 
15 
13-17 
Day 22  
Day 22 (Discharged) 
22 
19-25 
Day 29  
Day 29 (Discharged) 
29 
26-32 
Day 60 
Day 60 (Discharged) 
60 
57-63 
Table 2: 
Lab Sample Collection Study Day Windows 
Analysis Visit Day 
Nominal Day 
Target day 
Visit Window 
Screening 
Screening 
-1 to 1 
<1 
Baseline 
Day 1 (Hospitalized) 
1 
1 
Day 3 
Day 3 (Hospitalized) 
3 
2-4* 
Day 5  
Day 5 (Hospitalized) 
5 
4-6* 
Day 8  
Day 8 (Hospitalized) 
8 
7-9 
Day 11  
Day 11 (Hospitalized) 
11 
10-12 
Day 15 
Day 15 (Hospitalized) 
15 
14-16 
Day 15 
Day 15 (Discharged) 
15 
13-17 
Day 29 
Day 29 (Hospitalized) 
29 
28-30 
Day 29 
Day 29 (Discharged) 
29 
26-32 
*For windows that overlap, the priority will be given to the earlier date. For example, a lab sample drawn on Study Day 4 will be 
used as a Study Day 3 lab sample draw if there isn’t a lab sample drawn for Study Days 2 or 3, regardless of whether a Study Day 
5 lab is drawn.  
In general, the Study Day 1 (baseline) value will be the last non-missing value prior to the administration of 
the first dose. If multiple measurements occur on the same day, the last non-missing value prior to first dose 
will be considered as the baseline value. If these multiple measurements are recorded on Day 1 but the time is 


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not available, the average of these measurements (for continuous data) will be considered the Study Day 1 
value. For categorical measurements, if there are multiple records with the same time or no time recorded on 
the same day prior to the first dose, the value with the lowest severity will be selected as baseline (i.e., normal 
will be selected over abnormal). 


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4. 
INVESTIGATIONAL PLAN 
4.1. 
Overall Study Design and Plan 
This is a platform trial to conduct a series of randomized, double-blind, placebo-controlled trials using 
common assessments and endpoints in hospitalized adults diagnosed with COVID-19. This is a proof-of-
concept study with the intent of identifying promising treatments to enter a more definitive study (such as 
Adaptive COVID-19 Treatment Trial [ACTT], Accelerating COVID-19 Therapeutic Interventions and 
Vaccines [ACTIV], industry sponsored trials etc.). The study will be conducted at up to 70 domestic sites and 
5 international sites. The study will compare different investigational therapeutic agents to a common control 
arm and determine which have relatively large treatment effects. In order to maintain the double blind, each 
intervention will have a matched placebo. However, the control arm will be shared between 
stages/interventions and may include participants receiving the matched placebo for a different 
stage/intervention. 
The general goal of the stages included in this platform trial is not to determine clear statistical significance 
for an intervention, but rather to determine which products yield clinical data suggestive of efficacy and 
should be moved quickly into larger studies. However, clinical or drug development priorities may arise that 
require a larger sample size and a plan for a more definitive study. Estimates produced from this trial will 
provide an improved basis for designing the larger trial, in terms of sample size and endpoint selection. 
Products with little indication of significant efficacy will be dropped on the basis of interim evaluations. In 
addition, some interventions may be discontinued on the basis of interim futility or efficacy analyses. 
The study will include one Master Protocol (DMID Protocol 20-0013: ACTIV-5/Big Effect Trial) and an 
additional “stage” for each investigational intervention included in the study. Stage-Specific Appendices will 
be provided, detailing the protocol interventions and any specific exceptions to the Master Protocol. One or 
more interventions/stages may be started at any time. The number of interventions/stages enrolling 
concurrently are programmatic decisions and will be based on the number of sites and the pace of enrollment. 
At the time of enrollment, subjects will be randomized to a stage, and then to either the active arm of that 
stage or the matching placebo. There will be approximately 100 subjects in each active arm of the platform 
trial (though this may be modified as specified in each stage-specific appendix to accommodate special 
circumstances).  A given site will generally have no more than 3 interventions/stages at once. 
See the schedule of assessments in each stage-specific appendix for assessment details. The schedule is 
similar to Adaptive COVID-19 Treatment Trial (ACTT) to allow evaluation of endpoints used in the larger 
study. Subjects will be assessed daily while hospitalized. Once subjects are discharged from the hospital, they 
will have a study visit on Study Days 8, 15, 22, 29 and 60 as an outpatient. The outpatient Study Days 8, 22 
and 60 visits do not have laboratory tests or collection of samples and may be conducted by phone. Days 15 
and 29 visits are preferred to be in person in order to collect safety laboratory testing, stored samples, and 
virologic assessments. However, if infection control considerations and other restrictions limit the ability to 
have visits at Study Days 15 and 29 in person, they may also be conducted by phone and only clinical data 
will be obtained. 
4.2. 
Discussion of Study Design, Including the Choice of Control Groups 
This study utilizes an adaptive platform design that increases efficiency to identify safe and efficacious 
therapeutic agents for subjects with COVID-19 during the current outbreak. The platform design allows rapid 
addition of new therapeutic agents as they are identified and ready for testing in clinical trials. As the study is 
a multicenter, randomized, controlled study, we will be able to acquire rigorous data about the safety and 
efficacy of investigational therapeutic agents for COVID-19 that will lead to generalizable evidence. The trial 


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is designed to stop quickly if the agents are unlikely to have a large effect (odds ratio around 1) and will 
identify those with a large effect (e.g., odds ratio 2 or above). This trial is not designed for definitive 
determination of efficacy, but rather to identify agents for testing in larger definitive studies.  
Subject assignment to study intervention will be randomized, which is essential for providing evidence for 
efficacy of these new therapeutic agents. Finally, collecting clinical and virologic data on enrolled subjects 
using a standardized timeline and collection instruments should provide valuable information about the 
clinical course of and morbidities associated with COVID-19 in a diverse group of hospitalized adults. 
4.3. 
Selection of Study Population 
This trial will study putative therapeutics in a hospitalized adult population (≥18 years old) with COVID-19. 
The platform trial will have common inclusion criteria with modifications appropriate for each stage. 
Additional stage-specific criteria are included in the stage-specific appendices. Exclusion criteria are 
described in each stage-specific appendix. 
Inclusion Criteria: 
1. Admitted to a hospital with symptoms suggestive of COVID-19 and requires ongoing medical care. 
2. Subject (or legally authorized representative) provides informed consent prior to initiation of any 
study procedures. 
3. Subject (or legally authorized representative) understands and agrees to comply with planned study 
procedures. 
4. Male or non-pregnant female adult ≥18 years of age at time of enrollment. 
5. Illness of any duration and has laboratory-confirmed SARS-CoV-2 infection as determined by PCR or 
other commercial or public health assay (e.g., Nucleic Acid Amplification Test [NAAT], antigen test) 
in any respiratory specimen or saliva <14 days prior to randomization. 
6. Illness of any duration, and requiring, just prior to randomization, supplemental oxygen (any flow), 
mechanical ventilation or ECMO (ordinal scale category 5, 6, or 7). 
7. Women of childbearing potential must agree to either abstinence or use at least one acceptable method 
of contraception (duration will be study product defined). 
*Acceptable methods included barrier contraceptives (condoms or diaphragm) with spermicide, intrauterine 
devices (IUDs), hormonal contraceptives, oral contraceptive pills, and surgical sterilization. When applicable, 
stage-specific contraception requirements are included in each stage-specific appendix.  
8. Agrees not to participate in another blinded clinical trial (both pharmacologic and other types of 
interventions) for the treatment of COVID-19 through Day 29. 
Exclusion Criteria: 
See specific exclusion criteria described in each stage-specific appendix.  
Specific Populations: 
The inclusion of vulnerable subjects and exclusion of specific populations need to be customized according to 
each stage or intervention and its corresponding controls with the current understanding of epidemiology and 
clinical disease. Inclusion and exclusion of specific populations will be described for each stage in the stage-
specific appendices. 


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4.4. 
Treatments 
4.4.1. 
Treatments Administered 
Each stage in this platform trial may have different study products. Information about the study product(s) for 
a given stage can be found in the study protocol stage-specific appendix. 
4.4.2. 
Identity of Investigational Product(s) 
See stage-specific protocol for details of study product formulation. 
4.4.3. 
Method of Assigning Subjects to Treatment Groups (Randomization) 
Randomization will be stratified by study site and severity measured by baseline ordinal score (baseline 
ordinal score of 5 versus a baseline ordinal score of 6 or 7). 
Subjects will first be randomized to 1 of the stages to which they are eligible with equal allocation. Then 
patients are randomized to the active intervention or placebo version of that stage with allocation k:1, where k 
is the number of interventions for which a subject is eligible. For example, if a subject is eligible for 3 active 
interventions or stages that the site is currently randomizing, the subject will be randomized to 1 stage with a 
1:1:1 allocation to the 3 stages, then randomized to the selected intervention’s or stage’s active or placebo arm 
with a 3:1 allocation of active versus placebo. This process results in equal allocation of the 3 active 
intervention arms and the pooled placebo arm.  
Differing entry criteria across interventions adds complexity to this process. Subjects who are eligible for all 3 
interventions will be randomized to A, B, or C in the first randomization step, and then have a 25% chance of 
randomization to placebo in the second step. However, the subject who is not eligible for C will first be 
randomized to stages with A or B with equal probability, and will have a 33% chance of randomization to 
placebo in the second step, leading to equal size A, B, and pooled placebo groups for this stratum of subjects. 
Ultimately, evaluation of A versus placebo would need to only include subjects that were eligible to be 
randomized to A. 
The previous paragraph refers to a scenario in which the interventions have largely overlapping study 
populations. However, at some point the trial might study agents for non-overlapping cohorts. For example, 
there might be one or multiple interventions that are only appropriate for subjects who have a baseline ordinal 
score of 5, and a completely different set of interventions that are only appropriate for subjects who have a 
baseline ordinal score of 6 or 7. Since these interventions would occur in non-overlapping cohorts, they can 
be viewed as two different studies. Thus, the randomization process described above would be implemented 
separately in the two cohorts (baseline ordinal score groups). If there were two interventions in the first 
cohort, randomization would follow as above with k=2, and if there was one intervention in the second cohort, 
randomization would follow in that cohort as above with k=1. Since the study populations and interventions 
would not overlap, all analyses would be conducted completely separately by cohort. 
4.4.4. 
Selection of Doses in the Study 
All subjects in this study will be receiving remdesivir in addition to the investigational drug or placebo. The 
dose of remdesivir used in this study will be the same dose shown to be efficacious in the ACTT-1 clinical 
trial and are the US FDA approved doses. The duration of dosing may be adjusted by the site according to 
clinical severity. The maximum number of doses to be given during hospitalization is ten doses. This includes 
the loading dose and all maintenance doses given during the study and pre-study if applicable. 
Refer to the stage-specific appendix for details of doses of study products administered in each stage. 


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4.4.5. 
Selection and Timing of Dose for Each Subject 
Each stage in this platform trial may have different timing of dose. Information about the timing of dose for 
each study product(s) for a given stage can be found in the stage-specific appendix. 
4.4.6. 
Blinding 
The interventions the study subjects are eligible for and the intervention each subject is randomized to in the 
first randomization step will be known and collected on CRF. The treatment arm each subject is randomized 
to in the second step of randomization will be blinded (see Section 4.4.3). The treatment will be prepared by 
the licensed pharmacist and administered by blinded study personnel or hospital staff. All follow-up safety 
and efficacy evaluations will be performed by blinded clinic staff. The unblinded pharmacist at each site will 
utilize the unblinded pharmacist role within the Premier Interactive Response Technology (IRT) system to 
perform the Treatment Arm Lookup task to determine the treatment for subjects. No other user roles have 
access to this information within the system. 
4.4.7. 
Prior and Concomitant Therapy  
Each stage in this platform trial may have different permitted therapies that need to be customized according 
to each intervention. Information about the study permitted therapies for a given stage can be found in its 
stage-specific appendix. 
4.4.8. 
Treatment Compliance 
Each dose of study product will be administered by a blinded member of the clinical research team who is 
qualified and licensed to administer the study product. Administration date and time, and whether any doses 
were slowed, halted or missed will be entered into the electronic case report form (eCRF). 
4.5. 
Efficacy and Safety Variables 
For each study day while the subject is hospitalized and follow-up visits, the clinical status will be recorded 
on an 8- point ordinal scale. The clinical status scale is defined as follows: 
1. Not hospitalized, no new or increased limitations on activities; 
2. Not hospitalized, but new or increased limitation on activities and/or requiring new or increased home 
oxygen, CPAP or BiPAP; 
3. Hospitalized, not requiring new or increased supplemental oxygen* - no longer requires ongoing 
medical care; 
4. Hospitalized, not requiring new or increased supplemental oxygen* - requiring ongoing medical care 
(COVID-19 related or otherwise); 
5. Hospitalized, requiring new or increased supplemental oxygen*; 
6. Hospitalized, requiring new or increased non-invasive ventilation or high flow oxygen devices; 
7. Hospitalized, on invasive mechanical ventilation or ECMO; 
8. Death. 
The National Early Warning Score (NEWS) has demonstrated an ability to discriminate subjects at risk of 
poor outcomes [1]. This score is based on 7 clinical parameters (see Table 3). The NEWS is collected at 
baseline as a measure of ordinal score. It can be performed concurrently with the Ordinal Scale.  


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The 7 parameters can be obtained from the hospital chart or electronic medical record (EMR) using the last 
measurement prior to the time of assessment and a numeric score given for each parameter (e.g., a RR of 9 is 
one point, oxygen saturation of 92 is two points). The NEWS is recorded for the day on which it is obtained. 
ECMO and mechanical ventilated subjects should be assigned a score of 3 for respiratory rate (RR<8) 
regardless of the ventilator setting. Subjects on ECMO should get a score of 3 for heart rate since they are on 
cardiopulmonary bypass. 
Table 3: 
National Early Warning Score (NEWS) 
 
  Level of consciousness = alert (A), and non-alert and arousable only to voice (V) or pain (P), and unresponsive (U).  
Oxygenation, non-invasive ventilation/high flow oxygen, invasive mechanical ventilation/extracorporeal 
membrane oxygenation (ECMO) will be assessed using results of the 8-point ordinal scale. Hospitalization 
duration will be assessed using admittance and discharge dates. Mortality will be assessed using results from 
the electronic case report form (eCRF) serious adverse events (SAEs) form. That is, the number of days from 
Study Day 1 to the date of death. 
Safety will be assessed by the following:  
• Cumulative incidence of SAEs up to and including Study Day 60.  
• Cumulative incidence of Grade 3 and 4 clinical and/or laboratory AEs up to and including Study Day 
60. 
• Discontinuation or temporary suspension of study product administration (for any reason).  
• Changes in WBC count with differential, hemoglobin, platelets, creatinine, total bilirubin, ALT, AST, 
eGFR, and INR over time (analysis of lab values in addition to AEs noted above). 
Clinical labs will be drawn on Study Days 1, 3, 5, 8, 11 while the subject is hospitalized and on Study Days 
15 and 29 if the subject is able to return to the clinic or is still hospitalized.  


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Exploratory endpoints for post-baseline usage of key concomitant COVID-19 treatments (e.g., steroids) 
summarized by investigational therapeutic and control arms. The details of analyses for all virology and PK 
exploratory endpoints will be included in a separate analysis plan(s). 
The schedule of study assessments is provided in each stage-specific appendix of the SAP. 


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5. 
SAMPLE SIZE CONSIDERATIONS 
We have chosen a sample size of 100 per arm for the proof of concept stages. The power can be computed for 
the Study Day 8 ordinal score on the basis of an odds ratio representing clinical improvement. The odds ratio 
represents the odds of improvement in the ordinal scale for treatment relative to placebo. The sample size to 
detect a given odds ratio for 1:1 randomization using a 2-tailed test at level 𝛼 is given by 
 
12(𝑧𝛼/2 + 𝑧𝛽)2
𝜆2(1 −∑
𝑝𝑖
3)
𝐾
𝑖=1
, 
 
where 𝜆 is the log odds ratio, 𝑝𝑖 is the overall probability (combined over both arms) of being in the ith 
category of the K ordinal outcomes, 𝑧𝛼/2and 𝑧𝛽 are the 1 −𝛼/2 and 1 −𝛽 quantiles, respectively, of the 
standard normal distribution.  
However, to fully understand all aspects of the testing procedure, we have simulated the probabilities of an 
intervention: a) being declared futile after 50 subjects per arm, b) being declared efficacious after 50 subjects 
per arm, and c) being declared promising by 100 subjects per arm. 
The interim analysis will find an intervention futile if its point estimate for the primary endpoint has an odds 
ratio <1. An intervention can be declared efficacious early after 50 subjects per arm if two-sided p<0.001 and 
OR>1. If the intervention continues to 100 subjects, it will be declared promising if the final p-value is <0.20 
and OR>1, and statistically significant if the final p-value is <0.05. More details are provided in Interim 
Analysis Section. 
Table 4 displays the outcome probabilities in the control arm for sample size determination; this uses 
preliminary unpublished data from the remdesivir arm in ACTT study. The categories of the 8-point ordinal 
scale are described in Section 3.2. 
Table 4: 
Expected distribution of ordinal outcomes for the control arm at Study Day 8 
Severity Outcome 
Outcome (%) 
1. Not hospitalized, no new or increased limitations on activities 
0.0 
2. Not hospitalized, but new or increased limitation on activities and/or requiring new or 
increased home oxygen, CPAP or BiPAP 
34.6 
3. Hospitalized, not requiring new or increased supplemental oxygen - no longer requires 
ongoing medical care 
1.2 
4. Hospitalized, not requiring new or increased supplemental oxygen - requiring ongoing 
medical care (COVID-19 related or otherwise) 
10.6 
5. Hospitalized, requiring new or increased supplemental oxygen 
17.1 
6. Hospitalized, requiring new or increased non-invasive ventilation or high flow oxygen 
devices 
8.8 
7. Hospitalized, on invasive mechanical ventilation or ECMO 
24.2 
8. Death 
3.5 
Table 5 provides the probability to detect futility or efficacy given various odds ratios at interim and final 
analysis based on simulations (with 10,000 replications). An intervention with no effect (an odds ratio of 1) 


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had 50% chance of stopping at the interim analysis and has only a 10% chance to show promise. An 
intervention with an odds ratio of 2 has high power to show promise; that is, there is 91% probability that the 
final p-value will be less than .20 and only a 3% chance it will be stopped at an interim futility test. The 
powers in Table 5 are slightly lower than what would be determined from the Whitehead formula, because 
there is some minimal trade-off associated with testing for futility, especially for the alpha=.20 significance 
threshold. If the primary endpoint is different for a stage, stage-specific power and sample size computations 
that are relevant to that stage will be included in the stage-specific SAP. 
Table 5: 
Simulated early stopping probabilities at the interim review (n=50/arm), and power 
calculations for the final study size (n=100/arm) for Study Day 8 Ordinal Score 
 
Probability of stopping for futility or efficacy at 
interim analysis for a given true odds ratio  
Power at full study enrollment (100 active, 100 
control) 
OR 
Futility 
Efficacy 
Efficacy w/ alpha=.05 
Efficacy w/ alpha=.20 
0.75 
0.793 
0.000 
0.001 
0.008 
1.00 
0.502 
0.000 
0.026 
0.096 
1.25 
0.260 
0.004 
0.136 
0.329 
1.50 
0.126 
0.014 
0.348 
0.604 
1.75 
0.060 
0.036 
0.581 
0.802 
2.00 
0.028 
0.070 
0.765 
0.913 
2.25 
0.013 
0.119 
0.879 
0.961 
2.50 
0.006 
0.179 
0.939 
0.984 
 


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6. 
GENERAL STATISTICAL CONSIDERATIONS 
6.1. 
General Principles 
This is a proof of concept double-blind placebo controlled randomized trial testing a superiority hypothesis 
where interventions with a two-sided p-value < .20 will be declared promising and will be considered 
statistically significant if the final two-sided p-value is < .05. These data will be summarized by treatment 
(intervention name versus placebo) and when appropriate by baseline ordinal score. Additionally, data will be 
described according to the appropriate summary statistics, e.g. 
• Percentages/proportions/odds ratios for categorical data. For tabular summaries of 
percentages/proportions, the denominator (e.g., number of subjects in the specified population) will be 
displayed. 
• Means, standard deviation, median, and/or range for continuous data, median and confidence intervals 
for time-to-event data. 
Confidence intervals will be generated; 95% and 80% confidence intervals will be generated for primary and 
key secondary outcomes. For hazard ratio and odds ratio estimates, Wald confidence intervals will be used. 
For confidence intervals of proportions for other efficacy and safety outcomes, Blaker confidence intervals 
will be used. 
In general, all tables will have corresponding listings of data presented unless noted otherwise. 
When calculating treatment effects (e.g., differences, hazard ratios, odds ratios) from regression modelling, 
placebo will be used as the reference group. Subjects on interventions will only be compared to control 
subjects who could potentially have been randomized to that intervention (i.e., they met eligibility criteria for 
the intervention and are at a site where the intervention was enrolling at the time of the subject’s 
randomization). Analyses of newly added arm(s) will be performed comparing concurrently enrolled control 
subjects. For any modeling that uses covariates defined in Section 6.4, the category listed last for each 
variable in that section will be used as the control group for the interaction analysis and covariate-adjusted 
analyses. 
For the time-to-event analyses, the following SAS pseudocode will be used to generate stratum-specific 
median time to event estimates and confidence intervals and stratum-specific Kaplan-Meier curves.   
proc lifetest data=dataset plots=(s); 
 
time timevariable * censorvariable(1);  
 
test treatmentvariable; 
run; 
In this approach, timevariable represents the time until the event in question (e.g., recovery), 
censorvariable represents the censoring variable (e.g., 0= event observed, 1= event did not occur at the 
time of withdrawal, discharge, lost-to-followup, etc), and treatmentvariable  represents the intervention 
(e.g., 0= remdesivir + placebo, 1= remdesivir + new treatment).  
To perform a Cox proportional hazards analysis and generate the treatment hazard ratio along with its Wald 
confidence interval and p-value from the score test after adjusting for other covariates, the following SAS 
pseudocode will be used.   
 proc phreg data=dataset; 
 
 class treatmentvariable(ref=placebolabel) othercovariates; 
 
 model timevariable * censorvariable(1) = treatmentvariable othercovariates / 
 
 ties=efron;  
 
 hazardratio treatmentvariable / diff=ref cl=wald; 


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 ods output hazardratios = hrest globaltest=pvalue; 
run; 
  
To assess the assumption of proportional hazards for Cox models, Kaplan-Meier curves for each treatment 
arm will be produced (PH assumption supported if curves do not cross). Restricted mean survival time along 
with its 95% CI will be reported to assess whether the results change if the PH assumption is not satisfied. 
 
Proportional Odds analysis without MI: 
The following SAS pseudocode will be used to perform the proportional odds analysis with treatment, 
baseline ordinal score and baseline steroid use as covariates to generate the treatment odds ratio, p-value, and 
predicted probabilities of the ordinal scale levels by treatment and ordinal score using complete data 
proc logistic data=dataset out=imp_parms plots(only)=effect(x= ordscore_d8  
 
sliceby =baseordscorevar*trtvar individual connect);  
  
class baseordscorevar (param=ref ref=5) basesteroidusevar (param=ref ref=no 
steroid use) trtvar (param=ref ref=placebolabel); 
 
 model ordscore_d8 = trtvar baseordscorevar basesteroidusevar; 
  
oddsratio trtvar; 
  
ods output oddsratioswald = orest; 
run; 
 
For the endpoints analyzed by proportional odds, odds ratios between the binary progression strata will be 
computed, to support data understanding. For example, odds ratio, confidence intervals from logistic 
regression will be reported for treatment effect for the binary endpoint of OS= 1-7 vs 8, then OS= 1-6 vs 7-8, 
etc. Similar odds ratios across these 7 2x2 tables will support the proportional odds assumption.  
 
95% Blaker confidence intervals for proportions/percentages: 
 
proc freq; 
 
by analysisvariable; 
 
table trtvar/alpha=0.05 binomial (cl=blaker); 
  
ods output binomialcls=outputdsn2; 
run; 
 
Risk differences and 95% CI Using Miettinen-Nurminen: 
  
proc freq data = analysis;tables trtvar*aval/ out=mncidat;run; 
 
proc sort data=mncidat;by  trtvar;run; 
 
ods select  PdiffCLs; 
ods output PdiffCLs=mnci_d5v; 
proc freq data=mncidat order=data; 
    tables trtvar*aval /riskdiff (CL=( MN )); 
    weight count; 
run; 
 
 
 


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Odds ratios from logistic regression without MI: 
 
proc logistic data=dataset out=imp_parms; 
  
class baseordscorevar (param=ref ref=5) basesteroidusevar (param=ref ref=no 
steroid use) trtvar (param=ref ref=placebolabel); 
 
 model aval (event=’Yes’) = trtvar baseordscorevar basesteroidusevar; 
  
oddsratio trtvar; 
  
ods output oddsratioswald = orest; 
run; 
 
Risk differences from logistic regression using the approach described in Ge et. Al [2]: 
 
proc logistic data = dataset outmodel=pout; 
 
class trtvar ; 
 
model surv(event=’1’) = trtvar othercovariates  ; 
run; 
 
*Create dataset tempa to contain all subjects and assign them the active treatment and 
dataset tempp which include all subjects assigned the placebo treatment; 
 
proc logistic inmodel=pout; 
  score data = tempa out=preda(keep=id P_a rename= (P_1=P_a))) ; 
run; 
 
proc logistic inmodel=pout; 
  score data = tempp out=predp(keep=id P_1 rename= (P_1=P_p)) ; 
run; 
  
proc sort data=pred1;by subjectid;run; 
proc sort data=pred2;by subjectid;run; 
 
*Combine to obtain risk differences in probabilities for each subject; 
 
data comb; 
 
merge predp preda; 
 
by subjectid; 
 
diff=P_a-P_p; 
run; 
 
proc means data=comb;var diff;run; 
To obtain the CI for the risk difference, use bootstrap with the following steps: 
1. Sample with replacement from the dataset. 
2. Obtain risk difference estimate for each bootstrap sample. 
3. Repeat this step the above step 1000 times and use the 25th and 975th values from the sorted list of the 
1000 risk estimates as the limits for the 95% CI for the risk difference. The risk difference estimate 
from bootstrap can be estimated as the mean of the 1000 risk estimates and should be equal to the risk 
difference obtained prior to performing bootstrap. 
All statistical analyses and summaries will be performed on the mITT, ITT, and/or Safety populations. In 
general, the efficacy analysis will be performed mITT population and the safety analysis will be conducted on 
the Safety population. Any exceptions will be stated in the stage-specific appendix. 


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6.2. 
Timing of Analyses 
6.2.1. 
Interim Analyses 
A Data and Safety Monitoring Board (DSMB) will monitor ongoing results to ensure subject well-being and 
safety as well as study integrity. The DSMB will be asked to recommend early termination or modification 
only when there is clear and substantial evidence of a treatment difference. Interim analyses for a given stage 
will be conducted after each intervention arm and the comparison control arm has approximately 50 subjects 
with Study Day 8 assessments. The DSMB may use the following guidelines: 
• consider an arm futile at the interim evaluation if the odds ratio point estimate for the primary 
endpoint is <1. 
• consider an intervention arm efficacious if the p-value after 50 subjects per arm is <0.001 and OR 
estimate >1. 
• consider to not recommend discontinuing an arm if the p-value is <0.001, if members judge it would 
be more beneficial to collect more data before announcing the results.  
Any time-to-event outcomes for the interim analyses will be analyzed through Study Day 29. The efficacy 
boundary follows a Haybittle-Peto approach. Given that the statistical adjustment for multiplicity due to this 
0.001 boundary would be very minimal, no adjustment to the final p-value will be made, in this proof of 
concept study. 
Safety analyses will evaluate Grade 2 (drug related hypersensitivity only), 3 and 4 AE, AESIs, and SAEs by 
treatment arm and baseline ordinal score. Safety monitoring will be ongoing (see study protocol Section 
10.1.6) and evaluate safety results weekly. The unblinded statistical team will prepare these reports by 
baseline ordinal score with treatment groups collapsed for review by the DSMB. The unblinded statistical 
team may also prepare these reports by blinded treatment arm for review by the DSMB, if requested.  
The unblinded statistical team will prepare the closed reports for DSMB review and recommendations. 
Analyses will be presented with blinded codes for treatment arms to protect against the possibility that the 
DSMB report may fall into the wrong hands. A DSMB charter will further describe procedures and 
membership. 
6.2.2. 
Final Analyses 
The final analyses of outcomes and planned summaries/listings will be performed on the final locked database 
through Day 60 and provided in the final report. If data for some of the exploratory endpoints is available, 
results will also be included in the final report. 
6.3. 
Analysis Populations 
The default primary analysis will be based on a modified intention-to-treat (mITT) population, including all 
subjects who were randomized and received at least one dose of an investigational product administration for 
all proof of concept stages. If a stage requires a different population for the primary analysis, the appropriate 
population will be identified in the stage-specific appendix. Safety analyses will be based on the safety 
population and will use actual treatment received. For some stages an intention-to-treat (ITT) population, 
which includes all subjects randomized and is analyzed according to the randomized treatment assignment, 
will be considered. For all populations, actual ordinal score at baseline will be used to classify subjects into 
baseline ordinal score category. 


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Stage-specific appendices will denote the appropriate analysis populations to be used if different from the 
master SAP. 
6.3.1. 
Intention-to-Treat Analysis (ITT) Population 
The Intention-to-treat population will include all randomized subjects, and the population will be analyzed 
using randomized treatment group. Demographics and disposition tables will be based on this population. 
6.3.2. 
Modified Intention-to-Treat (mITT) Population 
The mITT population will include all randomized subjects who received at least one dose of an investigational 
product other than standard of care therapies, and the population will be analyzed using randomized treatment 
group. 
6.3.3. 
Safety Population 
The safety population will include all randomized subjects who received at least one dose of an 
investigational product other than standard of care therapies, and the population will be analyzed using actual 
treatment group.  
6.4. 
Covariates and Subgroups 
6.4.1. 
Covariates for the Primary Endpoint 
The primary analysis model of ordinal score at Day 8 will use a proportional odds model with baseline steroid 
use (yes/no) and actual baseline ordinal score (5 vs 6/7) as covariates. A sensitivity analysis of the primary 
endpoint will include baseline steroid use, actual baseline ordinal score, and categorical variables for sites. 
Sites will be pooled into categories by grouping sites based on the major US regions (Northeast, Southeast, 
Midwest, Southwest, and West) groupings include at least 25 subjects who were randomized. A region with 
less than 25 subjects will be combined with the neighboring region with the fewest subjects. A supplemental 
analysis of the primary endpoint will include baseline steroid use, actual baseline ordinal score, continuous 
covariate age, and continuous duration of symptoms prior to enrollment as covariates in the model.  
Additional supplemental analyses of the primary endpoint for ordinal score at Day 8 will include baseline 
steroid use, actual baseline ordinal score, and baseline use (yes/no) of each emerging COVID-19 treatment 
category listed in Section 6.4.3 as covariates.  
A detailed list of covariates and subgroup analyses to be performed for the primary endpoint is also provided 
in Table 6. 
6.4.2. 
Covariates for Secondary Endpoints 
The main analysis for time to sustained recovery will use baseline steroid use and actual baseline ordinal 
score as covariates in a Cox regression model. P-value from the score test of this adjusted Cox model will be 
used to compare the covariate adjusted time to sustained recovery between treatment arms. This analysis will 
be referred to as the primary analysis of the time to sustained recovery endpoint. In the supplemental analysis, 
time to sustained recovery endpoint will be analyzed using baseline steroid use, actual baseline ordinal score, 
continuous age, and continuous duration of symptoms prior to enrollment as covariates in the Cox model. 
Survival without respiratory failure up to and including Study Day 29 will be analyzed only for subjects with 
an actual baseline ordinal score of 5 or 6. The main analysis for this endpoint will use a logistic regression 
model adjusted for baseline ordinal score (5 vs 6/7), baseline dexamethasone use (yes or no), continuous 


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baseline CRP value, and continuous age as covariates. Additionally, the proportion of subjects who are alive 
and without respiratory failure up to and including Study Day 29 will be presented by treatment along with 
95% and 80%  CI estimated from Kaplan Meier. As a sensitivity analysis, survival without respiratory failure 
will be analyzed using a logistic regression model adjusting for baseline steroid use and actual baseline 
ordinal score as covariates. A supplemental analysis of this endpoint will use a logistic regression model 
adjusting for baseline steroid use, actual baseline ordinal, continuous age, and continuous duration of 
symptoms prior to enrollment. 
The analysis of the time to mechanical ventilation or death will include baseline ordinal score (5 vs 6/7), 
baseline dexamethasone use (yes or no), baseline CRP value and age as covariates in the Cox regression 
model. 
A detailed list of covariates and subgroup analyses to be performed for secondary endpoints is also provided 
in Table 6. 
6.4.3. 
Subgroups 
The following subgroups will be considered for the different subgroup analyses: 
• Severity of disease using actual baseline ordinal score 
o Actual baseline ordinal score 5: Hospitalized and requiring supplemental oxygen 
o Actual baseline ordinal score 6 or 7: Hospitalized, on non-invasive ventilation or high-flow oxygen 
devices; or Hospitalized, on invasive mechanical ventilation or ECMO 
• Baseline steroid use (Yes; No) 
• Baseline use of emerging COVID-19 treatments (Yes; No): Defined by the sponsor based on a blinded 
review of WHODrug coded medications. 
• Duration of symptoms prior to enrollment 
o Quartiles 
o <= Median; > Median 
• Race (White; Black/African American; Asian; Other) 
• Ethnicity (Hispanic or Latino; Not Hispanic or Latino) 
• Comorbidities 
o None; Any 
o One, Two or more 
o Obese; Non-Obese 
• Age (<40; 40-64; 65 and older), 
• Sex (Female; Male) 
Refer to Table 6 for details of which specific subgroup variables will be considered for a given endpoint.  
Interaction tests will be conducted to evaluate whether the effect of treatment is different among subgroups 
described above for primary and key secondary endpoints. The type III p-value for the interaction term from 
the primary analysis of the primary endpoint, the primary analysis of the time to sustained recovery endpoint, 


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and the primary analysis of the survival without respiratory failure endpoint with the addition of the 
interaction term(s) will be reported. 
A review of the concomitant medications will be performed by the study sponsor using the 202003 version of 
WHODrug to identify emerging COVID-19 treatments focusing on medications that fall into the following 
categories: 
• Other drugs used to treat COVID (off-label, experimental use) 
o Monoclonal antibodies targeting the spike protein of SARS-CoV-2 including casirivimab, 
imdevimab and bamlanivimab 
• Corticosteroids 
• Other anti-inflammatory drugs: 
o JAK inhibitors: Tofacitinib, Baricitinib,etc 
o Tyrosine kinase inhibitors: Ruxolitinib, etc 
o Interleukin inhibitors 
Additional details regarding covariates used in primary, sensitivity and supplemental analyses along with 
subgroup analyses to be performed for each endpoint are provided below in Table 6. 
 
 


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Table 6: 
Covariates and Subgroup Analyses for Each Endpoint 
Endpoint 
Analysis 
Covariates/Subgroups 
Primary Endpoint 
1. Ordinal Score at Day 8 
Primary 
1. Adjust for the following covariates: 
• 
Baseline steroid use  
• 
Actual baseline ordinal score  
Sensitivity 
1. Repeat primary analysis with the following covariates: 
• 
Baseline steroid use   
• 
Actual baseline ordinal score  
• 
Site pooled by geographic regions (Categorical)  
2. Repeat primary analysis on ITT population with the following 
covariates: 
• 
Baseline steroid use  
• 
Actual baseline ordinal score 
Supplemental 
1. Adjust for the following covariates: 
• 
Baseline steroid use 
• 
Actual baseline ordinal score  
• 
Continuous Age  
• 
Continuous duration of symptoms prior to enrollment 
2. Repeat primary model with the following covariates: 
• 
Baseline steroid use  
• 
Actual baseline ordinal score  
• 
Baseline use of emerging COVID-19 treatment by treatment 
categories   
Subgroup 
Repeat the primary analysis for this endpoint within each of the following 
subgroups:  
• 
Actual baseline ordinal score  
• 
Baseline steroid use  
• 
Baseline use of emerging COVID-19 treatments   
• 
Duration of symptoms prior to enrollment  
• 
Race   
• 
Ethnicity 
• 
Comorbidities  
• 
Age (categorical) 
• 
Sex 
Baseline steroid use and baseline ordinal score will be included in the 
subgroup analysis as covariates unless the covariate is the subgroup. 
Key Secondary Endpoints  
1. Time to Sustained 
Recovery 
Primary 
1. Adjust for the following covariates: 
• 
Baseline steroid use 
• 
Actual baseline ordinal score  
Supplementary 
1. Adjust for the following covariates: 
• 
Baseline steroid use  
• 
Actual baseline ordinal score  
• 
Age (continuous) 
• 
Duration of symptoms prior to enrollment (continuous) 


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Endpoint 
Analysis 
Covariates/Subgroups 
Subgroup 
Repeat the primary analysis for this endpoint within each of the following 
subgroups: 
• 
Actual baseline ordinal score  
• 
Baseline steroid use   
• 
Baseline use of emerging COVID-19 treatments   
• 
Duration of symptoms prior to enrollment  
• 
Race 
• 
Ethnicity 
• 
Comorbidities  
• 
Age (categorical) 
• 
Sex 
Baseline steroid use and baseline ordinal score should be included in the 
subgroup analysis as covariates unless the covariate is the subgroup. 
2. Survival without 
respiratory failure up to 
and including Study Day 
29 
Primary 
1. Adjust for the following covariates: 
• 
Baseline dexamethasone use   
• 
Actual baseline ordinal score  
• 
Baseline CRP value (continuous) 
• 
Age (continuous) 
Sensitivity 
1. Adjust for the following covariates: 
• 
Baseline steroid use 
• 
Actual baseline ordinal score 
Supplementary 
1. Adjust for the following covariates: 
• 
Actual baseline ordinal score  
• 
Baseline dexamethasone use 
• 
Age (continuous) 
• 
Duration of symptoms prior to enrollment (continuous) 
Subgroup 
Repeat the primary analysis for this endpoint within each of the following 
subgroups: 
• 
Actual baseline ordinal score  
• 
Baseline steroid use  
• 
Baseline dexamethasone use 
• 
Baseline use of emerging COVID-19 treatments  
• 
Duration of symptoms prior to enrollment 
• 
Race  
• 
Ethnicity 
• 
Comorbidities 
• 
Age (categorical) 
• 
Sex 
• 
Baseline CRP <150 
Baseline dexamethasone use, baseline CRP, age, and baseline ordinal score 
will be included in the subgroup analysis as covariates unless the covariate 
is the subgroup. 


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Endpoint 
Analysis 
Covariates/Subgroups 
Other Secondary Endpoints: Efficacy 
1. Time to 1-point 
improvement by Day 60 
Primary 
Adjust for the following covariates: 
• 
Baseline steroid use  
• 
Actual baseline ordinal score  
Subgroup 
Repeat the primary analysis for this endpoint within each of the following 
subgroups:  
• 
Actual baseline ordinal score  
• 
Baseline steroid use  
• 
Baseline use of emerging COVID-19 treatments   
• 
Duration of symptoms prior to enrollment  
Baseline steroid use and baseline ordinal score will be included in the 
subgroup analysis as covariates unless the covariate is the subgroup. 
2. Time to 2- points 
improvement by Day 60 
Primary 
Adjust for the following covariates: 
• 
Baseline steroid use  
• 
Actual baseline ordinal score  
Subgroup 
Repeat the primary analysis for this endpoint within each of the following 
subgroups:  
• 
Actual baseline ordinal score  
• 
Baseline steroid use  
• 
Baseline use of emerging COVID-19 treatments   
• 
Duration of symptoms prior to enrollment  
Baseline steroid use and baseline ordinal score will be included in the 
subgroup analysis as covariates unless the covariate is the subgroup. 
3. Clinical status assessed 
using ordinal scale on 
Study Days 1, 3, 5, 8, 11, 
15, 22, and 29; Change in 
clinical status using 
change in ordinal scale 
from Study Day 1 to 
Study Days 3, 5, 8,11, 15, 
22 and 29. 
Primary 
• 
No covariate adjustment 
Subgroup 
Repeat the primary analysis for this endpoint within each of the following 
subgroups:  
• 
Actual baseline ordinal score  
4. Days of supplemental 
oxygen by Study Day 29; 
Primary  
• 
No covariate adjustment 
Subgroup 
Repeat the primary analysis for this endpoint within each of the following 
subgroups: 
• 
Actual baseline ordinal score  
• 
Baseline steroid use   
• 
Baseline use of emerging COVID-19 treatment 
• 
Duration of symptoms prior to enrollment (only using the <= 
Median; > Median classification) 
5. Days of non-invasive 
ventilation/high-flow 
oxygen by Study Day 29; 
Primary 
• 
No covariate adjustment for this analysis  
Subgroup 
Repeat the primary analysis for this endpoint within each of the following 
subgroups: 
• 
Actual baseline ordinal score  
• 
Baseline steroid use   
• 
Baseline use of emerging COVID-19 treatment 


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Endpoint 
Analysis 
Covariates/Subgroups 
• 
Duration of symptoms prior to enrollment (only using the <= 
Median; > Median classification) 
6. Incidence of new non-
invasive oxygen use 
(clinical status > 5) during 
the study up to and 
including Study Day 29 
for subject with baseline 
clinical status of 5; 
Primary 
• 
No covariate adjustment for this analysis 
7. Days a subject who has a 
baseline clinical status of 
5 has a clinical status > 5 
up to and including Study 
Day 29; 
Primary 
• 
No covariate adjustment for this analysis 
Subgroup 
Repeat the primary analysis for this endpoint within each of the following 
subgroups: 
• 
Actual baseline ordinal score  
• 
Baseline steroid use   
• 
Baseline use of emerging COVID-19 treatment 
• 
Duration of symptoms prior to enrollment (only using the <= 
Median; > Median classification) 
8. Days of invasive 
mechanical 
ventilation/ECMO by 
Study Day 29; 
Primary 
• 
No covariate adjustment for this analysis 
Subgroup 
Repeat the primary analysis for this endpoint within each of the following 
subgroups: 
• 
Actual baseline ordinal score  
• 
Baseline steroid use 
• 
Baseline use of emerging COVID-19 treatments  
• 
Duration of symptoms prior to enrollment (only using the <= 
Median; > Median classification) 
9. Incidence of new invasive 
ECMO use through study 
Day 29 for subjects with 
baseline clinical status of 
5 or 6; 
Primary 
• 
No covariate adjustment 
10. Days a subject who has a 
baseline clinical status of 
5 or 6 has a clinical status 
> 6 up to and including 
Study Day 29; 
Primary 
• 
No covariate adjustment 
Subgroup 
Repeat the primary analysis for this endpoint within each of the following 
subgroups: 
• 
Actual baseline ordinal score  
• 
Baseline steroid use   
• 
Baseline use of emerging COVID-19 treatment 
• 
Duration of symptoms prior to enrollment (only using the <= 
Median; > Median classification) 
11. Proportion of subjects 
alive and without 
respiratory failure at 
Study Day 29; 
Primary 
• 
No covariate adjustment 
12. Time (days) to death or  
ventilation up to and 
Including Day 29 
Primary 
Adjust for the following covariates: 
• 
Baseline dexamethasone use   
• 
Actual baseline ordinal score  
• 
Baseline CRP value (Continuous) 
• 
Age (continuous) 


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Endpoint 
Analysis 
Covariates/Subgroups 
13. Days of hospitalization 
from date of admission by 
Study Day 29. 
Primary 
• 
No covariate adjustment for this analysis 
Subgroup 
Repeat the primary analysis for this endpoint within each of the following 
subgroups: 
• 
Actual baseline ordinal score  
• 
Baseline steroid use   
• 
Baseline use of emerging COVID-19 treatment 
• 
Duration of symptoms prior to enrollment (only using the <= 
Median; > Median classification) 
Other Secondary Endpoints: Safety 
1. Values of CRP ferritin, D-
dimer, LDH, and 
fibrinogen on Study Day 
1: Study Days 3, 5, 8, 
11,15 and 29 
Primary 
• 
 No covariate adjustment 
2.  14-day Mortality 
Primary 
1. Adjust for the following covariates: 
• 
Actual baseline ordinal score  
• 
Baseline steroid use 
3. 28-day Mortality 
Primary 
1. Adjust for the following covariates: 
• 
Actual baseline ordinal score  
• 
Baseline steroid use  
4. 59-day Mortality 
Primary 
1. Adjust for the following covariates: 
• 
Actual baseline ordinal score  
• 
Baseline steroid use 
Sensitivity 
1. Adjust for the following covariates: 
• 
Actual baseline ordinal score  
• 
Baseline steroid use 
5. Time to death by Day 29 
Primary  
• 
No covariate adjustment 
Sensitivity 
• 
No covariate adjustment  
6. SAEs by Day 60 
Primary  
• 
No covariate adjustment 
7. Grade 3 or 4 AE by Day 
60 
Primary  
• 
No covariate adjustment 
8. Time to Death, SAE or 
Grade 3 or 4 TEAE 
Primary  
• 
No covariate adjustment 
9. Episodes of early 
discontinuation or 
interruption of study 
product administration; 
Primary  
• 
No covariate adjustment 
10. Values of WBC with 
differential, hemoglobin, 
platelets, creatinine, total 
bilirubin, ALT, AST, and 
INR on Study Day 1; 
Study Days 3, 5, 8, and 11 
(while hospitalized); and 
Study Days 15 and 29 (if 
Primary  
• 
No covariate adjustment 


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Endpoint 
Analysis 
Covariates/Subgroups 
attends in-person visit or 
still hospitalized). 
Exploratory Endpoints 
1. Concomitant COVID-19 
treatments (e.g., steroids) 
post-baseline up to and 
including Study Day 29. 
Primary  
• 
No covariate adjustment 
6.5. 
Missing Data 
6.5.1. 
General Guidelines Regarding Handling of Missing Data 
All attempts will be made to collect all data per the protocol. Efforts to minimize loss-to-follow-up will be 
considerable. Chart review will be performed for lost-to-follow-up subjects to obtain data related to the 
subjects’ clinical status, oxygen use, or death status after discharge. However, small amounts of missing data 
may occur. In order to conduct mITT and ITT analyses for primary and secondary outcomes, missing data 
will be imputed in the manners described below in Table 7. Prior to applying the imputation rules described in 
Table 7, an endpoint review committee (ERC) may meet to adjudicate the primary endpoint and the key 
secondary endpoints for each study stage, such as Day 8 ordinal scores for subjects discharged to hospice, 
another hospital, or long-term care facilities. Any ERC reviews will be performed prior to database lock and 
all committee members will be blinded to treatment assignments. If an ERC is used, an ERC charter will be 
prepared prior to any reviews.   
For the primary analysis of ordinal score at Day 8, the following imputations will be performed prior to 
multiple imputation:  
• If a subject is discharged from the hospital to another location other than LTAC, hospice care or other 
hospital, has intermittent missing ordinal score and reported an ordinal score of 1 or 2 after the missing 
score then: 
o The intermittent missing ordinal score is imputed as 1 if the scores reported before and after 
the missing value are both 1 and no change in oxygen use or hospitalization status after 
discharge to a location other than hospice, long term acute care or other hospital. 
o The intermittent missing ordinal score is imputed as 2 after discharge to a location other than 
hospice, long term acute care or other hospital if the subject doesn’t fall into the category 
above and subject is not hospitalized at the time point. 
• LOCF will be used for remaining intermittent missingness of ordinal scores for the next planned 
assessment. 
• All missing scores after death will be assigned an ordinal score of 8. 
• Subjects that terminated from the study with known discharge to a location other than hospice, LTAC 
or other hospital at their last assessment will be assigned a score of 2 for all timepoints after last 
assessment. 
Remaining missing ordinal scores for subjects that terminated early from the study and were still hospitalized 
at the time of their last assessment or with discharge to a location of hospice, LTAC or other hospital at the 
time of last contact will be imputed using multiple imputation. A sensitivity analysis of this analysis will be 


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performed using multiple imputation for all subjects missing ordinal after their last assessment regardless of 
their discharge status at the last assessment. Details of multiple Imputation are provided in Section 6.5.2.  
Some analyses of ordinal score such as those reported in Table 17, Table 18, Table 20, Table 21, Table 24, 
Table 25, Table 26, Table 27, Table 34, Table 35, Figure 4, Figure 5, Figure 6, Figure 7, and Figure 18 will be 
based on complete ordinal score data created using the following steps: 
• If a subject is discharged from the hospital to a location other than LTAC, Hospice care or other 
hospital, has intermittent missing ordinal score and reported an ordinal score of 1 or 2 after the missing 
score then: 
o Impute the intermittent missing ordinal score as 1 if the scores reported before and after the 
missing value are both 1 and no change in oxygen use or hospitalization status after discharge to a 
location other than hospice, long term acute care or other hospital. 
o Impute the intermittent missing ordinal score as 2 after discharge to a location other than hospice, 
long term acute care or other hospital if the subject doesn’t fall into the category above and subject 
is not hospitalized at the time point. 
• LOCF will be used for remaining intermittent missingness of ordinal scores for the next planned 
assessment. 
• All missing scores after death will be assigned an ordinal score of 8. 
• Subjects discharged from the hospital to a location other than LTAC, hospice care or other hospital at 
their last assessment will be assigned a score of 2 for all timepoints after last assessment. 
• Impute all remaining missing data after last assessment using last observation carried forward. 
Analysis of time to event endpoints (i.e., sustained recovery, time to improvement, time to mechanical 
ventilation or death) will be based on observed ordinal score without imputation along with discharge and 
death information. Refer to Table 7 for additional details regarding censoring and handling of missing data for 
all endpoints. As handling of missing data might differ for different stages of this study, stage-specific SAPs 
will provide additional details if handling of missing data for an endpoint for that stage differ from what is in 
the master SAP. 
Table 7: 
Imputation Method for Each Endpoint and Analysis Type 
Endpoint 
Analysis 
Imputation Method 
Primary Endpoint 
1. 
Ordinal Score at Day 8 
Primary 
• 
If a subject is discharged from the hospital to another location other than 
LTAC, hospice care or other hospital, has intermittent missing ordinal score 
and reported an ordinal score of 1 or 2 after the missing score then: 
o 
Impute the intermittent missing ordinal score as 1 if the scores reported 
before and after the missing value are both 1 and no change in oxygen use 
or hospitalization status after discharge to a location other than hospice, 
long term acute care or other hospital. 
o 
Impute the intermittent missing ordinal score as 2 after discharge to a 
location other than hospice, long term acute care or other hospital if the 
subject doesn’t fall into the category above and subject is not hospitalized 
at the time point. 
• 
LOCF will be used for remaining intermittent missingness of ordinal scores for 
the next planned assessment. 
• 
All missing scores after death will be assigned an ordinal score of 8. 


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Endpoint 
Analysis 
Imputation Method 
• 
Subjects discharged from the hospital to a location other than LTAC, hospice 
care or other hospital at their last assessment will be assigned a score of 2 for 
all timepoints after last assessment. 
• 
Multiple imputation will be used to impute missing ordinal scores after last 
assessment for subjects still hospitalized or discharged to hospice, other 
hospital, or long-term care facility at their last assessment. See Section 6.5.2 
for more details. 
Primary with 
Sensitivity 
Imputation 1 
• 
Use similar imputation methods for intermittent missingness and missing data 
after death. 
• 
Multiple Imputation will be used for all subjects missing data after last 
assessment regardless of their discharge status at the last assessment. 
Primary with 
Sensitivity 
Imputation 2 
Use complete data defined as follow: 
• 
If a subject is discharged from the hospital to another location other than 
LTAC, hospice care or other hospital, has intermittent missing ordinal score 
and reported an ordinal score of 1 or 2 after the missing score then: 
o 
Impute the intermittent missing ordinal score as 1 if the scores reported 
before and after the missing value are both 1 and no change in oxygen use 
or hospitalization status after discharge to a location other than hospice, 
long term acute care or other hospital. 
o 
Impute the intermittent missing ordinal score as 2 after discharge to a 
location other than hospice, long term acute care or other hospital if the 
subject doesn’t fall into the category above and subject is not hospitalized 
at the time point. 
• 
LOCF will be used for remaining intermittent missingness of ordinal scores for 
the next planned assessment. 
• 
All missing scores after death will be assigned an ordinal score of 8 
• 
Subjects discharged from the hospital to a location other than LTAC, hospice 
care or other hospital at their last assessment will be assigned a score of 2 for 
all timepoints after last assessment. 
• 
Impute all remaining missing data after last assessment using last observation 
carried forward. 
Sensitivity 
• 
Same imputation as the primary analysis 
Supplemental 
• 
Same imputation as the primary analysis  
Subgroup   
• 
Repeat analysis for each subgroup using same imputation as primary analysis 
for this endpoint. 
Key Secondary Endpoints 
1. 
Time to Sustained Recovery 
Primary 
• 
Use the complete data for ordinal score to derive sustained recovery.  
• 
Subjects whose last assessment in the study is prior to Day 57 (beginning of 
Day 60 window) will be considered not recovered and censored at the date of 
their last assessment. 
• 
Death prior to recovery will be considered not recovered and censored at 
expected study Day 60.  
Primary with 
Sensitivity 
Imputation 1 
• 
Use the complete data for ordinal score to derive sustained recovery.  
• 
Subjects whose last assessment in the study is prior to Day 57 (beginning of 
Day 60 window) after discharge from the hospital to a location other than 
LTAC, hospice care or other hospital will be treated as recovered by Day 60. 
Their time to recovery will be the day of their first observed/imputed recovery 
score (i.e., 1, 2, 3) or the day of discharge, whichever comes first. 
• 
Subjects whose last assessment in the study is prior to Day 57 (beginning of 
Day 60 window) without being discharged from the hospital to a location other 
than LTAC, Hospice care or other hospital at their last assessment will be 
considered not recovered and censored at the date of their last assessment. 


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Endpoint 
Analysis 
Imputation Method 
• 
Death prior to recovery will be considered not recovered and censored at 
expected study Day 60. 
Supplementary 
• 
Same imputation method as primary analysis for time to sustained recovery. 
Subgroup 
• 
Repeat analysis for each subgroup using same imputation as primary analysis 
for this endpoint. 
2. 
Survival without respiratory 
failure up to and including 
Study Day 29 
Primary 
• 
Subjects who complete follow-up without mechanical ventilation or death or 
who have the event after Day 29 will be considered non-events and censored at 
Day 29.  
• 
Subjects whose last assessment in the study is before Day 26 (beginning of 
Day 29 window) and before experiencing death or progression to mechanical 
ventilation will be considered non-events and censored at the last assessment. 
• 
Subjects whose last assessment in the study is before Day 29 but within 
window for Day 29 (i.e., Day 26, 27, 28) and before experiencing death or 
progression to mechanical ventilation will be considered non-events regardless 
of their discharge status and censored at Day 29. 
Primary with 
Sensitivity 
Imputation 
• 
Subjects who complete follow-up without mechanical ventilation or death or 
who have the event after Day 29 will be considered non-events and censored at 
Day 29.  
• 
Subjects whose last assessment in the study is before Day 26 (beginning of 
Day 29 window) and before experiencing death or progression to mechanical 
ventilation and were discharged to a location other than LTAC, hospice care, 
or other hospital will be considered non-events and censored at Day 29. 
• 
Subjects whose last assessment in the study is before Day 26 (beginning of 
Day 29 window) and before experiencing death or progression to mechanical 
ventilation without being discharged to a location other than LTAC, hospice 
care, or other hospital will be considered non-events and censored at the last 
assessment. 
• 
Subjects whose last assessment in the study is before Day 29 but within 
window for Day 29 (i.e., Day 26, 27, 28) and before experiencing death or 
progression to mechanical ventilation will be considered non-events regardless 
of their discharge status and censored at Day 29. 
Sensitivity 
• 
Same imputation method as primary analysis of this endpoint 
Supplementary 
• 
Same imputation method as primary analysis of this endpoint 
Subgroup 
• 
Repeat analysis for each subgroup using same imputation as primary analysis 
for this endpoint  
Other Secondary Endpoints: Efficacy 
1. 
Time to 1-point improvement 
by Day 60 
Primary 
• 
Use the complete data for ordinal score to define time to improvement. 
• 
Subjects whose last assessment in the study is prior to an observed 
improvement will be censored at the day of their last assessment. 
• 
Subjects who complete follow-up but do not experience improvement will be 
censored at the day of their Study Day 60. 
• 
Death prior to improvement will be considered not improved and censored at 
expected study Day 60.  
Subgroup   
• 
Repeat analysis for each subgroup using same imputation as primary analysis 
for this endpoint. 
2. 
Time to 2-points improvement 
by Day 60 
Primary 
• 
Use the complete data for ordinal score to define time to improvement. 
• 
Subjects whose last assessment in the study is prior to an observed 
improvement will be censored at the day of their last assessment. 
• 
Subjects who complete follow-up but do not experience improvement will be 
censored at the day of their Study Day 60. 


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Endpoint 
Analysis 
Imputation Method 
• 
Death prior to improvement will be considered not improved and censored at 
expected study Day 60. 
Subgroup   
• 
Repeat analysis for each subgroup using same imputation as primary analysis 
for this endpoint. 
3. 
Clinical status assessed using 
ordinal scale on Study Days 1, 
3, 5, 8, 11, 15, 22, and 
29;Change in clinical status 
using change in ordinal scale 
from Study Day 1 to Study 
Days 3, 5, 8,11, 15, 22 and 29. 
Primary 
• 
Use complete data for ordinal score. 
Subgroup 
• 
Repeat analysis for each subgroup using same imputation as primary analysis 
for this endpoint. 
4. 
Days of supplemental oxygen 
by Study Day 29; 
Primary  
• 
If the subject’s clinical status scale is 6 or above at the last observed 
assessment, then the subject will be considered to be on supplemental oxygen 
use through Day 29. The endpoint will be total days when assessments are 
available plus all imputed days following the last observed assessment. 
• 
If the subject’s clinical status is less than 6 at the last observed assessment, 
then the subject will be considered to not be on supplemental oxygen use for 
the remainder of follow-up. Thus, no additional imputed days will be added to 
the number of days recorded on available assessments. 
Subgroup 
• 
Repeat analysis for each subgroup using same imputation as primary analysis 
for this endpoint. 
5. 
Days of non-invasive 
ventilation/high-flow oxygen 
by Study Day 29; 
Primary 
• 
If the subject’s clinical status scale is 6 or above at the last observed 
assessment, then the subject will be considered to be on non-invasive 
ventilation/high-flow oxygen through Day 29. The endpoint will be total days 
when assessments are available plus all imputed days following the last 
observed assessment. 
• 
If the subject’s clinical status is less than 6 at the last observed assessment, 
then the subject will be considered to not be on non- invasive ventilation/high-
flow oxygen for the remainder of follow-up. Thus, no additional imputed days 
will be added to the number of days recorded on available assessments. 
Subgroup 
• 
Repeat analysis for each subgroup using same imputation as primary analysis 
for this endpoint. 
6. 
Incidence of new non-invasive 
oxygen use (clinical status > 5) 
during the study up to and 
including Study Day 29 for 
subject with baseline clinical 
status of 5 
Primary 
• 
If the subject’s clinical status scale is 6 or above at the last observed 
assessment, then the subject will be considered to be on non-invasive 
ventilation/high-flow oxygen through Day 29. The endpoint will be total days 
when assessments are available plus all imputed days following the last 
observed assessment. 
• 
If the subject’s clinical status is less than 6 at the last observed assessment, 
then the subject will be considered to not be on non- invasive ventilation/high-
flow oxygen for the remainder of follow-up. Thus, no additional imputed days 
will be added to the number of days recorded on available assessments. 
7. 
Days a subject who has a 
baseline clinical status of 5 has 
a clinical status > 5 up to and 
including Study Day 29; 
Primary 
• 
Use complete data for ordinal score to define this endpoint. 
Subgroup 
• 
Use complete data for ordinal score to define this endpoint. 
8. 
Days of invasive mechanical 
ventilation/ECMO by Study 
Day 29; 
Primary 
• 
If the subject’s clinical status scale is 7 or above at the last observed 
assessment, then the subject will be considered to be on invasive mechanical 
ventilation/ECMO through Day 29. The endpoint will be total days when 
assessments are available plus all imputed days following the last observed 
assessment. 
• 
If the subject’s clinical status is less than 7 at the last observed assessment, 
then the subject will be considered to not be on invasive ventilation/ECMO for 
the remainder of follow-up. Thus, no additional imputed days will be added to 
the number of days recorded on available assessments. 
Subgroup 
• 
Repeat analysis for each subgroup using same imputation as primary analysis 
for this endpoint. 


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Endpoint 
Analysis 
Imputation Method 
9. 
Incidence of new invasive 
ECMO use through study Day 
29 for subjects with baseline 
clinical status of 5 or 6; 
Primary 
• 
If the subject’s clinical status scale is 7 or above at the last observed 
assessment, then the subject will be considered to be on invasive mechanical 
ventilation/ECMO through Day 29. The endpoint will be total days when 
assessments are available plus all imputed days following the last observed 
assessment. 
• 
If the subject’s clinical status is less than 7 at the last observed assessment, 
then the subject will be considered to not be on invasive ventilation/ECMO for 
the remainder of follow-up. Thus, no additional imputed days will be added to 
the number of days recorded on available assessments. 
10. Days a subject who has a 
baseline clinical status of 5 or 6 
has a clinical status > 6 up to 
and including Study Day 29; 
Primary 
• 
Use complete data for ordinal score to define this endpoint. 
Subgroup 
• 
Repeat analysis for each subgroup using the complete dataset for ordinal score. 
11. Proportion of subjects alive and 
without respiratory failure at 
Study Day 29; 
Primary 
• 
Use the complete data for ordinal score to define survival without respiratory 
failure. 
• 
Subjects will be considered events at Day 29 if they are dead or are on 
invasive mechanical ventilation/ECMO anytime between Day 26 and Day 32 
(Window for Day 29) regardless of their baseline ordinal score.   
• 
All subjects who died before Day 26 (beginning of Day 29 visit window) will 
be considered events. 
• 
All subjects who died after Day 32 or those who were not on invasive 
mechanical ventilation/ECMO between Day 26 and Day 32 will be considered 
non-events. 
12. Time (days) to ventilation or 
death up to and Including Day 
29; 
Primary 
• 
Use the complete data for ordinal score to define survival without respiratory 
failure. 
• 
All subjects whose last assessment in the study is before Day 26 and before 
progression to mechanical ventilation or death will be considered non-events 
and censored at the date of their last observed assessment. 
• 
Subjects who complete follow-up without mechanical ventilation or death will 
be censored at the expected study Day 29.  
• 
Subjects whose last assessment in the study is before Day 29 but within 
window for Day 29 (i.e., Day 26, 27, 28) and before experiencing death or 
progression to mechanical ventilation will be considered non-events regardless 
of their discharge status at Day 29. 
Primary with 
Sensitivity 
Imputation 
• 
Use the complete data for ordinal score to define survival without respiratory 
failure. 
• 
Subjects whose last assessment in the study is before Day 26 and were 
discharged to a location other than LTAC, hospice care or other hospital, or 
progressed to mechanical ventilation or death after Day 29 will be considered 
non-events and censored at Day 29. 
• 
Subjects whose last assessment in the study is before Day 26 and before 
progression to mechanical ventilation or death and without being discharged to 
a location other than LTAC, hospice care or other hospital at their last 
assessment will be considered non-events and censored at the date of their last 
observed assessment. 
• 
Subjects who complete follow-up without mechanical ventilation or death will 
be censored at the expected study Day 29. 
13. Days of hospitalization from 
date of admission by Study 
Day 29. 
Primary 
• 
If a subject is discharged and no further hospitalization data are available, 
consider the subject as not readmitted, no additional imputed days will be 
added. 
• 
If a subject dies while hospitalized, the number of days of hospitalization will 
be imputed as the number of days between the date of admission and the 
expected date of subject’s Study Day 29 visit+1. 
Subgroup 
• 
Use complete data for ordinal score to define this endpoint. 


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Endpoint 
Analysis 
Imputation Method 
Other Secondary Endpoints: Safety 
1. 
Values of CRP, ferritin, D-
dimer, LDH, and fibrinogen on 
Study Day 1: Study Days 3, 5, 
8, 11,15 and 29 
Primary 
• 
If results are not available for any visit day(s) but are available for visits before 
or after that visit, the average of the two nearest visits will be imputed for all 
missing visits between them. 
• 
 If a subject dies or is otherwise terminated early from the study, their last 
available observation will be carried forward. If baseline is missing, another 
pre-treatment dose will be used, or the earliest post treatment dose will be 
used. 
2. 
14-day Mortality 
Primary 
• 
Subjects whose last assessment in the study is before Day 13 (beginning of 
Day 29 window) and before death will be considered not dead and censored at 
the date of their last observed assessment.   
• 
Subjects who complete follow-up will be censored at Day 15. 
• 
Deaths that occur after Day 15 will be censored at Day 15. 
Primary with 
Sensitivity 
Imputation 
• 
Subjects whose last assessment in the study is before Day 13 (beginning of 
Day 15 window) and were discharged to a location other than LTAC, hospice 
care or other hospital, or subjects died after Day 15 will be considered non-
events and censored at Day 15. 
• 
Subjects whose last assessment in the study is before Day 13 (beginning of 
Day 15 window) and before death and without being discharged to a location 
other than LTAC, hospice care or other hospital at their last assessment will be 
considered non-events and censored at the date of their last observed 
assessment. 
• 
Subjects who complete follow-up will be censored at Day 15.  
3. 
28-day Mortality 
Primary 
• 
Subjects whose last assessment in the study is before Day 26 (beginning of 
Day 29 window) and before death will be considered not dead and censored at 
the date of their last observed assessment.   
• 
Subjects who complete follow-up will be censored at Day 29. 
• 
Deaths that occur after Day 29 will be censored at Day 29. 
Primary with 
Sensitivity 
Imputation 
• 
Subjects whose last assessment in the study is before Day 26 (beginning of 
Day 29 window) and were discharged to a location other than LTAC, hospice 
care or other hospital, or subjects died after Day 29 will be considered non-
events and censored at Day 29. 
• 
Subjects whose last assessment in the study is before Day 26 (beginning of 
Day 29 window) and before death and without being discharged to a location 
other than LTAC, hospice care or other hospital at their last assessment will be 
considered non-events and censored at the date of their last observed 
assessment. 
• 
Subjects who complete follow-up will be censored at Day 29. 
4. 
59-day Mortality 
Primary 
• 
Subjects whose last assessment in the study is before Day 57 (beginning of 
Day 60 window) and before death will be considered not dead and censored at 
the date of their last observed assessment.   
• 
Subjects who complete follow-up will be censored at Day 60. 
• 
Deaths that occur after Day 60 will be censored at Day 60. 
Primary with 
Sensitivity 
Imputation 
• 
Subjects whose last assessment in the study is before Day 57 (beginning of 
Day 60 window) and were discharged to a location other than LTAC, hospice 
care or other hospital, or subjects died after Day 60 will be considered non-
events and censored at Day 60. 
• 
Subjects whose last assessment in the study is before Day 57 (beginning of 
Day 60 window) and before death and without being discharged to a location 
other than LTAC, hospice care or other hospital at their last assessment will be 
considered non-events and censored at the date of their last observed 
assessment. 
• 
Subjects who complete follow-up will be censored at Day 60. 


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Endpoint 
Analysis 
Imputation Method 
5. 
Time to death by Day 29 
Primary  
• 
Subjects whose last assessment in the study is before Day 26 (beginning of 
Day 29 window) and before death will be considered not dead and censored at 
the date of their last observed assessment.   
• 
Subjects who complete follow-up will be censored at Day 29. 
• 
Deaths that occur after Day 29 will be censored at Day 29. 
Primary with 
Sensitivity 
Imputation 
• 
Subjects whose last assessment in the study is before Day 26 (beginning of 
Day 29 window) and were discharged to a location other than LTAC, hospice 
care or other hospital, or subjects died after Day 29 will be considered non-
events and censored at Day 29. 
• 
Subjects whose last assessment in the study is before Day 26 (beginning of 
Day 29 window) and before death and without being discharged to a location 
other than LTAC, hospice care or other hospital at their last assessment will be 
considered non-events and censored at the date of their last observed 
assessment. 
• 
Subjects who complete follow-up will be censored at Day 29. 
6. 
SAEs by Day 60 
Primary  
• 
No imputation of missing data will be performed. 
7. 
Grade 3 or 4 AE by Day 60 
Primary  
• 
No imputation of missing data will be performed. 
8. 
Time to Death, SAE or Grade 3 
or 4 TEAE by Day 60 
Primary  
• 
Subjects whose last assessment in the study is prior to death or SAE or Grade 
3 or 4 TEAE will be censored at the date of their last observed assessment. 
• 
Subjects who complete follow-up will be censored at Day 60. 
• 
Deaths that occur after Day 60 will be censored at Day 60. 
9. 
Episodes of early 
discontinuation or interruption 
of study product 
administration; 
Primary  
• 
No imputation of missing data will be performed. 
10. Values of WBC with 
differential, hemoglobin, 
platelets, creatinine, total 
bilirubin, ALT, AST, and INR 
on Study Day 1; Study Days 3, 
5, 8, and 11 (while 
hospitalized); and Study Days 
15 and 29 (if attends in-person 
visit or still hospitalized). 
Primary  
• 
No imputation of missing data will be performed. 
Exploratory Endpoints 
1. 
Concomitant COVID-19 
treatments (e.g., steroids) post-
baseline up to and including 
Study Day 29. 
Primary  
• 
No imputation of missing data will be performed. Details regarding imputation 
of missing dates are provided in Table 8. 
6.5.2. 
Multiple Imputation 
Multiple imputation will be performed for the primary endpoint of the Day 8 ordinal score for subjects whose 
last assessment in the study is before Day 8 and missing ordinal scores after their last assessment for the 
following two scenarios: 
• For the primary analysis of the primary endpoint, assign a score of 2 for subjects missing Day 8 score 
after last assessment for subjects with a good discharge status (i.e., discharged to a location other than 
LTAC, hospice care, other hospital) at last assessment and use multiple imputation to impute missing 
data at Day 8 only for subjects without a good discharge status (i.e., subjects with no post baseline 
data or still hospitalized or those discharged to LTAC, hospice care, or other hospital) at their last 
assessment  


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• As a sensitivity analysis of the primary endpoint, use multiple imputation to impute missing ordinal 
scores for all subjects missing Day 8 ordinal scores after last assessment regardless of their good 
discharge status at last assessment. 
For analyses based on multiple imputation, remaining missing ordinal scores will be imputed for Day 8 using 
the PROC MI procedure in SAS. Treatment group (trtvar), baseline ordinal score (basesteroidusevar), baseline 
steroid use (basesteroidvar), duration of symptoms prior to randomization (dursymp), age, indicator for black 
or Hispanic ethnicity (blackhispfl), presence of 2 or more comorbidities (comorb2fl), baseline CRP 
(basescrp), and indicator for discharge to a location other than long term care facility (LTAC), hospice care or 
another hospital (i.e., good discharge status) at the last assessment of the subject being imputed will be 
included as covariates in the multiple imputation model for ordinal scores at each timepoint using monotone 
logistic regression. The good discharge status variable at last assessment variable (goodischstat) will vary 
from subject to subject and will be defined as the discharge status for all subjects at the last assessed timepoint 
of the subject being imputed. For example, if the subject being imputed had their last assessment at Day 5, the 
good discharge status variable for all subjects will be defined as their discharge status at Day 5. The timing for 
the discharge status variable will be defined according to the last assessment timepoint of the subjects being 
imputed. The treatment group variable (trtvar) represents the randomized treatment group. Each imputation 
model will include all subjects with complete data plus all subject with missing ordinal score at Day 8 to be 
imputed who have the same last assessment day. The procedure will loop through all possible last assessment 
days (i.e., day 1 through day 8) imputing data for subjects missing data who were last assessed on the same 
day. 
Since missing data in any of these baseline characteristics may cause issues with the monotone missing data 
patterns, the following methods will be used to fill in missing baseline covariates data: 
• For continuous baseline covariates (age, CRP, duration of symptoms), mean imputation will be used to 
replace missing values with the overall mean value from all randomized subjects for the given 
covariate.  
• For indicator variables of baseline steroid use, black or Hispanic ethnicity, and presence of two or 
more comorbidities, subjects with missing values will be given the value with the greatest number of 
subjects among all randomized subjects. 
• We do not anticipate any missing data for actual baseline ordinal score. 
Twenty imputation sets will be generated, and final results from these 20 imputed datasets will be aggregated. 
Pseudocode: 
• Define ordscore_d8 as the ordinal score: 
• DEFINE ordscore_d8 as the ordinal score value at Day 8. 
• DEFINE j: as the last time assessment for the subjects being imputed used to define the good 
discharge status variable in the model. Possible values for j are from 1 to 8. 
• DEFINE jMax= Maximum time of last assessment observed during the study. 
• DEFINE g&j=analysis dataset containing predictors and ordinal score for complete data subjects as 
well as subjects missing Day 8 score who were last assessed on the same day.   
• DEFINE &&modelVars = list of covariates to be used in the imputation model: trtvar baseordscorevar 
basesteroidusevar dursymp age blackhispfl comorb2fl basecrp goodischstat_j. 


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• DEFINE imp_g&j = g&j with 20 imputed values for the missing ordinal score added by PROC MI. 
 
 
%do j=1 %to &jMax; 
 
proc mi data=g&j out= imp_g&j impute=20 seed = 300&j noprint; 
class trtvar baseordscorevar basesteroidusevar  blackhispfl comorb2fl  
goodischstat_j ordscore_d8;  
var trtvar baseordscorevar basesteroidusevar dursymp age blackhispfl comorb2fl 
basecrp goodischstat_j ordscore_d8; 
monotone logistic(ordscore_d8 = trtvar baseordscorevar basesteroidusevar dursymp 
age blackhispfl comorb2fl basecrp goodischstat_j; 
run; 
 %end; 
imp_g&j will be subset to contain only rows for the subjects with imputed ordinal scores and merged 
together with data from subjects with complete data to form twenty complete multiply imputed datasets. The 
final dataset imp_g will contain 20 replicates for complete subjects and data from the 20 imputation datasets 
for imputed subjects. 
Proportional Odds analysis with multiple imputation: 
The following SAS pseudocode will be used to perform the proportional odds analysis with treatment, 
baseline ordinal score and baseline steroid use as covariates to generate the treatment odds ratio, p-value, and 
predicted probabilities of the ordinal scale levels by treatment and ordinal score using data from multiple 
imputation: 
proc logistic data=imp_g out=imp_parms plots(only)=effect(x= ordscore_d8  
 
sliceby =baseordscorevar*trtvar individual connect);  
 
by _imputation_; 
  
class baseordscorevar (param=ref ref=5) basesteroidusevar (param=ref ref=no 
steroid use) trtvar (param=ref ref=placebolabel); 
 
 model ordscore_d8 = trtvar baseordscorevar basesteroidusevar; 
  
oddsratio trtvar; 
  
ods output oddsratioswald = orest parameterestimates=pars; 
run; 
 
*Keep only estimates for the treatment variable; 
data pars1;set pars;where Variable='Treatment variable';run; 
*Combine estimates; 
PROC MIANALYZE DATA=pars1;  
 
ODS OUTPUT PARAMETERESTIMATES= logor;  
 
MODELEFFECTS estimate ;  
 
STDERR stderr ;  
RUN;  
*Transform estimates from the log(OR) scale to the OR scale; 
data OR;  
  
SET logor;  
 
OR_estimate = EXP(ESTIMATE);  
 
OR_LCL_95 =OR_estimate*EXP(-1.96*STDERR);  
 
OR_UCL_95 =OR_estimate*EXP(+1.96*STDERR);  
OR_LCL_80 =OR_estimate*EXP(-1.28*STDERR);  
 
OR_UCL_80 =OR_estimate*EXP(+1.28*STDERR);  
 
RUN; 


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Similar pseudocode for odds ratio between the binary progression strata will use used for the Day 8 ordinal 
score endpoint analyzed by proportional odds using multiple imputation.  
If the primary analysis results are at least borderline significant with a p-value < 0.10 and more than 5% of 
subjects have missing primary endpoint data, additional analyses will be performed to evaluate the effect of 
the missing data assumptions on the results. Using a tipping point strategy, these analyses will vary the Day 8 
ordinal score independently across groups to determine if there is a distribution of missing data that would 
result in a change of conclusion.   
6.6. 
Data Handling and Transformations 
By-subject listings will be presented and sorted by treatment group, actual baseline ordinal score, subject 
number, and study day (if applicable). Data collected on log forms, such as AEs, will be presented in 
chronological order and alphabetical order using the preferred term within subject. The intervention stage and 
treatment arm to which subjects were randomized will be used in the listings.  
In general, age (in years) on the date of Study Day 1 will be used for analyses and presentation in 
demographic data listings. If an enrolled subject was not dosed with study product at all, the date baseline 
assessment was conducted will be used instead of the first dosing date of study product. For screen failures, 
the date the informed consent was signed will be used for age calculation. If only the birth year is collected on 
the case report form (CRF), “01 January” will be used for the unknown birthday and month for the purpose of 
age calculation, unless age is captured on the CRF.  
The conventions for missing dates (adverse event [AE], concomitant medication [CM], medical history [MH]) 
are provided in Table 8.  
 
 


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Table 8: 
Partial Date Imputation for Adverse Events (AEs), Concomitant medications (CMs), and 
Medical History (MH) 
Type of Date 
Scenario 
Impute strategy 
 
Month 
Day 
Year 
 
AE Dates 
AE Start Date 
UNK 
UNK 
UNK 
IMPUTE with FIRST_DOSE; Default to making AE start date/time a treatment emergent 
event and earliest possible date. Impute with randomization date if not treated, or 
informed consent date for other subjects. In case that imputed start date is after stop date, 
impute as stop date. 
AE Start Date 
UNK 
UNK 
YYYY 
IMPUTE with 01/01/YYYY, or FIRST_DOSE (or randomization date if not treated) date 
if in same year. In case that imputed start date is after AE stop date, impute as stop date. 
AE Start Date 
MM 
UNK 
YYYY 
IMPUTE with MM/01/YYYY, or FIRST_DOSE (or randomization date if not treated) if 
it is in same month/year. In case that imputed start date is after AE stop date, impute as 
stop date. 
AE Stop Date 
UNK 
UNK 
UNK 
IMPUTE with discharge date, or last assessment date if never discharged or last 
assessment is after discharge date 
AE Stop Date 
UNK 
UNK 
YYYY 
If discharge date or last assessment date is YYYY, IMPUTE with discharge date if 
discharged, or last assessment date if never discharged.  If discharge date or last 
assessment date is YYYY+1 then IMPUTE AE Stop date as 12/31/YYYY. 
AE Stop Date 
MM 
UNK 
YYYY 
IMPUTE with last day of MM/YYYY or last assessment day if never discharged or last 
assessment month/year is the same as MM/YYYY 
CM Dates 
CM Start Date 
UNK 
UNK 
UNK 
IMPUTE with FIRST_DOSE date; Default = make CM start date/time a CM with earliest 
possible date; Impute with randomization date if not treated, or informed consent date for 
other subjects. In cases with imputed start date after stop date, impute start date as stop 
date. 
CM Start Date 
UNK 
UNK 
YYYY 
IMPUTE with 01/01/YYYY, or FIRST_DOSE date (or randomization date if not treated) 
if in same year; if first dose is later in that year, start date= 01/01/YYYY. In cases with 
imputed start date after CM stop date, impute start date as stop date. 
CM Start Date 
MM 
UNK 
YYYY 
IMPUTE with MM/01/YYYY, or FIRST_DOSE (or randomization date if not treated) if 
it is in same month/year. In case that imputed start date is after CM stop date, impute start 
date with stop date. 
CM Stop Date 
UNK 
UNK 
UNK 
IMPUTE with discharge date, or last assessment date if never discharged or last 
assessment date is after discharge date 
CM Stop Date 
UNK 
UNK 
YYYY 
If discharge date or last assessment date is YYYY, IMPUTE with discharge date if 
discharged, or last assessment date if never discharged.  If discharge date or last 
assessment date is YYYY+1 then IMPUTE AE Stop date as 12/31/YYYY. 
CM Stop Date 
MM 
UNK 
YYYY 
IMPUTE with last day of MM/YYYY or last assessment day if never discharged or last 
assessment month/year is the same as MM/YYYY 
MH Dates 
MH Start Date 
UNK 
UNK 
UNK 
IMPUTE with FIRST_DOSE date; Default = make MH start date/time a MH with earliest 
possible date. Impute with randomization date if not treated, or informed consent date for 
other subjects. In case that imputed start date is after stop date, impute start date with stop 
date. 
MH Start Date 
UNK 
UNK 
YYYY 
IMPUTE with 01/01/YYYY 
MH Start Date 
MM 
UNK 
YYYY 
IMPUTE with MM/01/YYYY 
MH Stop Date 
UNK 
UNK 
UNK 
IMPUTE with discharge date, or last assessment date if never discharged or last 
assessment date is after discharge date 
MH Stop Date 
UNK 
UNK 
YYYY 
IMPUTE with 12/31/YYYY 
MH Stop Date 
MM 
UNK 
YYYY 
IMPUTE with last day of MM/YYYY 


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Listings should not present imputed dates; listings should present partial dates or “.” if date is entirely 
missing. 
6.7. 
Multicenter Studies 
Data will be pooled across all clinical sites. Center effects are not anticipated because the sites are using 
standardized procedures for collection of data. 
Nevertheless, to guard against the potential for regional differences, a sensitivity analysis for the primary 
endpoint will adjust for site effects pooling sites together based on their geographic region. 
6.8. 
Multiple Comparisons/Multiplicity 
Analyses related to primary and key secondary endpoints will be conducted without adjustment for multiple 
endpoints and multiple arms. That is, all planned analyses will be conducted without statistical adjustment for 
multiplicity, with the main focus on the primary and secondary endpoints for each intervention versus placebo 
comparison.  
However, a possible set of supplementary analyses described in the remainder of this section adjusting for 
multiplicity might be performed, but only if their inclusion appears likely to be helpful in interpreting the 
primary and secondary analyses results.  
For this approach, adjusted p-values for multiple endpoints (primary and secondary continuous and binary 
endpoints) will be computed using the Westfall-Young permutation approach (specifically, the free step-down 
resampling method procedure that produces adjusted p-values that preserves the order of the endpoints for the 
unadjusted p-values) and results will be reported in Table 44. Two analyses will be performed both based on 
complete data, one treating Day 8 ordinal score as a continuous variable and the other excluding Day 8 
endpoint from the Westfall-Young analysis. Time-to-event endpoints will be excluded from both models.   
A third analysis will provide adjusted P-values using Hochberg method. This analysis will include p-values 
from endpoints and will use p-value from multiple imputation where applicable. Results will be reported in 
Table 45. 
An additional global analysis will calculate Z-scores for all primary and secondary efficacy endpoints 
applicable to all subjects in the analysis population [3] and a global p-value will be calculated from the 
permutation test using z-scores from the linear model for continuous endpoints, cox model for time-to-event 
data, logistic regression for binary, and ordinal logistic regression model for continuous. For the logistic and 
log-rank test, the z-score can be calculated as the square root of the chi-square statistic of the treatment group 
variable from the adjusted model. A global test statistic vector will be constructed where each element is a Z 
score calculated from an endpoint in Table 9. 
The mean of the z-scores for all the endpoints will be calculated. A global p-value can then be obtained 
through a permutation test. Results of this global test will be reported in Table 45. 


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Table 9: 
Endpoints to be included in the global analysis 
Endpoint type 
Endpoint 
Primary 
Ordinal score at Study Day 8 
Key Secondary 
Time (days) to sustained recovery 
Key Secondary 
Sustained survival without respiratory failure (binary: 1=Yes or 0=No) 
Secondary 
Time (days) to at least 1 units improvement from baseline/Time (days) to at least 2 units 
improvement from baseline 
Secondary 
Difference from baseline ordinal score at Days 3, 5, 8, 11, 15, 22, 29 
Secondary 
Number of days ordinal score > 4 
Secondary 
Number of days ordinal score > 5 
Secondary 
Number of days ordinal score > 6 
Secondary 
Number of days of hospitalization 
Secondary 
Value of CRP, ferritin, D-dimer, LDH, fibrinogen 
Secondary (safety) 
14-Day mortality, 28-Day mortality,59-Day morality (binary: 1=Yes or 0=No) 
Secondary (safety) 
Time (days) to death 
Pseudocode:  
Method 1: Obtain Adjusted P-values from Westfall-Young for Continuous and Binary Endpoints using 
observed data 
 
proc multtest data=dataset perm stepboot n=100000 seed=1234;  
 
class trt;  
 
test  mean (C1 C2 C3/uppertailed) ;  
             test  mean (C4 C5 … Cx/lowertailed) ; 
 
test fisher(B1 B2 B3 B4/lowertailed); 
 
test fisher(B5 B6 … Bx/uppertailed); 
 
contrast 'Trt vs Placebo' -1 1;  
 
ods output pValues=pvals; 
run;   
Where C1 C2 … Cx is a list of all continuous covariates and C1 C2 … Cx is the list of all binary covariates. 
The contrast should be updated as needed so that the placebo group is the reference. Note that the variables 
are grouped depending on the direction of the hypothesis test. 
Method 2: Obtain Adjusted P-values using Hochberg method: Use raw p-values as input from the primary 
analysis for all the endpoints in Table 9. 
 
proc multtest data=rawpvalues hoc out=adj_pvals; 
run;   
 


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7. 
STUDY SUBJECTS 
7.1. 
Disposition of Subjects 
A summary of subject disposition and study milestones will be provided by treatment and actual baseline 
ordinal score in Table 13. This summary will present the number of subjects screened, enrolled, randomized, 
completed all infusions of investigational agents, had any investigational infusions slowed or stopped, 
completed all expected blood draws, completed all expected NP swabs, completed Study Day 8, completed 
Study Day 15 visit, completed Study Day 22 visit, completed Study Day 29 visit, completed Study Day 60, 
and the number of subjects in each of the categories listed below. 
• Safety Population  
• ITT Population 
• mITT Population 
• Discontinuation of Treatment with reasons for discontinuation 
• Completed the Study 
• Did not complete the study with reasons for discontinuation of study 
The denominator for the percentage calculation will be the total number of subjects who were in the analysis 
population corresponding to that treatment and ordinal score category.  
A flowchart showing the disposition of study subjects, adapted from the Consort Statement [4] will be 
generated (Figure 1). This figure will present the number of subjects screened, randomized, lost to follow-up, 
and analyzed, by treatment group and actual baseline ordinal score (ordinal scale 5, 6, 7). 
A listing will be provided by subject number, treatment assignment, actual baseline ordinal score, completion 
status and reasons for discontinuation of study product or study (Listing 1). 
A listing of subjects who failed screening and reasons that subjects were screened but not randomized is 
provided in Listing 2. 
7.2. 
Protocol Deviations 
A summary of subject-specific protocol deviations will be provided by treatment and actual baseline ordinal 
score (Table 11). Summaries will include the reason for the deviation and the deviation category for all 
subjects. All subject-specific protocol deviations and non-subject specific protocol deviations will be included 
in listings (Listing 3 and Listing 4). 
7.3. 
Investigational Product Exposure and Compliance 
The number of subjects with halted, slowed, or missed investigational doses will be summarized for the 
investigational product by treatment and actual baseline ordinal score (Table 12). 
For subjects with doses missed, halted or slowed, a listing of treatment exposure will be provided by subject 
number, treatment start/end dates, treatment duration in days, volume administered, and the number of 
missed, halted or slowed doses as well as the corresponding reasons (Listing 10). Total duration of exposure 
will be defined as last dosing date of investigational product – first dosing date of investigational product + 1, 
regardless of any temporary interruptions in study product administration, and will be expressed in days using 
up to 1 decimal place (e.g., 5.5 days). 


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8. 
EFFICACY EVALUATION 
All efficacy analyses will be summarized and performed on the mITT and/or ITT populations by treatment 
and baseline ordinal score. Each stage will be summarized and listed separately. If the handling of any 
subject’s primary or key secondary endpoint data is unclear, the subject’s data may be reviewed by a blinded 
endpoint review committee (ERC), see Section 6.5 for more details on the ERC. 
8.1. 
Primary Efficacy Analysis 
Analysis of the primary endpoint, clinical status (8-point ordinal scale) on Study Visit (not necessarily actual) 
Study Day 8, will be analyzed using a proportional odds model with baseline steroid use and baseline ordinal 
score as covariates (primary analysis of the primary endpoint) after multiple imputation. See Section 6.5 for 
details regarding handling of missing ordinal score data. 
The null hypothesis for active treatment over control is: 
 
H0: OR =1 
and the alternative hypothesis is: 
 
HA: OR ≠ 1 
where: 
OR = common odds ratio 
The treatment odds ratio at Day 8 estimated from the model will be presented along with the corresponding 
95% and 80% confidence intervals, and the p-value (Table 16). Subjects in the shared control arm can only be 
used in comparison of any given intervention ‘A’, if they were eligible for ‘A’ and consented to 
randomization to ‘A’; thus controls randomized at clinics where ‘A’ is not currently being studied are not 
compared to subjects in the ‘A’ arm. Odds ratios between the binary progression strata from the proportional 
odds model are reported in Table 22 for mITT population and Table 23 for ITT population at Day 8.  
Refer to Table 6 for a list of covariates and subgroup analyses for this endpoint. Refer to Table 7 for 
imputation methods to be applied to this endpoint.  
Results of the sensitivity, supplemental and subgroup analyses for ordinal score at Day 8 are provided in 
Table 16. Adjusted odds ratios of inferior clinical status at Day 8 along with their 95% CIs and 80% CIs are 
presented overall ad within each subgroup in Figure 2 and Figure 3. These analyses will be repeated for the 
ITT population and results will be in Table 19. 
Individual listing of ordinal score and its components will be provided in Listing 13. 
8.2. 
Secondary Efficacy Analyses 
8.2.1. 
Key Secondary Efficacy Analyses 
Recovery will be defined as having a value of 1, 2, or 3 on the clinical status 8-point ordinal scale. The time to 
sustained recovery will be defined as the elapsed time (in days) from Study Day 1 to the day prior to the 
earliest recorded day at which a subject reaches recovery or hospital discharge and doesn’t worsen (ordinal 
score > 3) up to and including Study Day 60. For example, a hospitalized subject with an ordinal score of 3 on 
Study Day 7 and doesn’t worsen up to and including Day 60 will have a time to sustained recovery of 6 days, 
since ordinal score is reflective of the prior 24-hours.  


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For the primary analysis of sustained recovery endpoint, any subjects whose last assessment in the study is 
prior to an observed recovery will be censored at the day of their last observed assessment. For the sensitivity 
analysis of this endpoint, subjects whose last assessment in the study is prior to an observed recovery before 
Day 57 (beginning of Day 60 window) and who were discharged to a location other than LTAC, hospice care, 
or other hospital will be considered recovered and censored at Day 60. For both primary and sensitivity 
analysis of this endpoint, subjects who complete follow-up but do not experience sustained recovery will be 
censored at the day of their Study Day 60. All deaths that occur on or before Study Visit Day 60 will be 
considered not recovered and censored at Day 60. Note that we do not expect many subjects to worsen after 
discharge.  
If a subject’s last assessment is before Day 57 and is discharged to a location other than hospice, another 
hospital, or long-term care facilities, the subject will be considered recovered at the time of discharge for the 
sensitivity analysis but may be reviewed by the Endpoint Review Committee, if other data suggests the 
subject may not be recovered (e.g., to a location other than a private residence or discharged on high flow 
oxygen). If a subject is discharged to hospice or another hospital, or is a special case where recovery handling 
may be unclear, the subject’s data may be reviewed by the Endpoint Review Committee to make the 
determination of whether the subject should be considered to have sustained recovery and, if so, at what time 
point in the analyses. Subject data to be reviewed as part of this determination will include the reported 
clinical status scores while hospitalized, where the subject was discharged to (e.g., private residence, 
rehabilitation facility, long-term care/nursing home, comfort care), and any information regarding 
readmittance. Additional information may be solicited to assess recovery. 
Refer to Table 6 for a list of covariates and subgroup analyses for this endpoint. Refer to Table 7 for 
imputation methods to be applied to this endpoint.  
The main analysis of the first key secondary endpoint (time to sustained recovery up to and including Study 
Day 60) conducts a score test to compare treatment to control up to and including Study Day 60. The 
treatment median survival time, confidence intervals and p-value from the score test will be presented 
(Table 28). Restricted mean recovery time estimates will be provided for each treatment group and actual 
baseline ordinal score stratum as well as the difference in restricted mean recovery time between treatment 
groups within each of the baseline ordinal score strata (Table 29). 
Kaplan-Meier curves for each treatment arm will be presented and supplemented with the hazard ratio 
estimate, p-value, and the number of subjects at risk in each treatment at Study Day (not necessarily actual 
Study Days 1, 3, 5, 8, 11, 15, 22, 29, and 60) (Figure 8).  
If the key secondary endpoint is different than what is covered in this SAP, it will be highlighted for each 
individual stage in the corresponding stage-specific appendix along with the subsequent analysis. 
Each subgroup from Table 6 will be considered separately, and the tabular and graphical summaries described 
above will be replicated for each subgroup (Table 20). A forest plot will be generated to display 95% and 80% 
CIs for hazard ratios from each of the subgroup analyses (Figure 16, Figure 17). 
Proportion of Subjects Alive and Without Respiratory Failure up to and Including Study Day 29 
Any subjects whose last assessment is prior to death or progression to respiratory failure and prior to Day 26 
(beginning of Day 29 window) will be censored at the date of their last observed assessment. For the 
sensitivity analysis of this endpoint, subjects whose last assessment is prior to obtaining the event and who 
were discharged to a location other than LTAC, hospice care, or other hospital will be considered recovered 
and censored at Day 29. For both primary and sensitivity analysis of this endpoint, subjects who complete 
follow-up will be censored Day 29. Events that occur after Day 29 will be censored at Day 29. 


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Kaplan-Meier estimates for the proportion of subjects with baseline ordinal score 5 or 6, who are alive and 
without respiratory failure up to and including Study Day 29 will be presented by treatment along with 95% 
CI from Kaplan-Meier (Table 30). Odds ratios and a p-value from an adjusted logistic regression model 
adjusting for covariates [2] detailed in Table 6 will be presented in Table 30. Risk differences and 
corresponding CIs obtained through bootstrap will also be generated using the approach discussed in [2] and 
results will be reported in Table 30. This analysis will be referred to as the primary analysis for the survival 
without respiratory failure endpoint.  
Refer to Table 6 for a list of covariates and subgroup analyses for this endpoint. Refer to Table 7 for 
imputation methods to be applied to this endpoint.   
Results of the primary, sensitivity, and subgroup analyses for this endpoint are reported in Table 30. 
8.2.2. 
Other Secondary Efficacy Analyses 
This section describes the planned analyses for the secondary efficacy outcome measures. Analyses of 
mortality will be described in Section 9.4 and analyses of markers of inflammation and coagulation will be 
described in Section 9.7. 
Analyses of the other secondary outcome measures will be performed by treatment only and repeated for 
specified subgroups described in Table 6. As with the analyses described in Section 8.2.1, tabular summaries 
will mimic the structure of the main tabular summaries planned for each outcome with the modification that 
stratified estimates will be provided in separate rows. Forest plots will display confidence intervals of 
outcomes/estimates across subgroups, where applicable. 
Ordinal Scale Outcomes 
Analyses will evaluate the time to improvement of at least one point on the clinical status 8-point ordinal 
scale. The time to 1 point improvement (at least 1 point drop from baseline) will be defined as the elapsed 
time (in days) from Study Day 1 to the day prior to the earliest recorded day at which a subject reaches at least 
a 1-point improvement up to and including Study Day 60. Any subjects whose last assessment in the study is 
prior to an observed improvement will be censored at the day of their last observed Clinical Status score. 
Subjects who complete follow-up but do not experience improvement will be censored at the day of their 
Study Day 60. All deaths that occur on or before Study Day 60 (and prior to any observed improvement) will 
be considered censored at Day 60. 
Refer to Table 6 for a list of covariates and subgroup analyses for this endpoint. Refer to Table 7 for 
imputation methods to be applied to this endpoint.  
An alternative definition of improvement will also be used where improvement will be defined as a decrease 
of at least two points on the 8-point scale compared to the baseline value (e.g., from 5 to 3; from 5 to 2). The 
timing and censoring definitions will follow a strategy similar to the above one-point improvement.  
The Cox proportional hazards model will be performed to test whether the survival curves differ between 
treatments (with respect to improvement endpoints). The median time to event and CI in each treatment group 
will be summarized along with the treatment hazard ratio estimate and p-value (Table 32). Differences in 
time-to-event endpoints by treatment will also be summarized with Kaplan-Meier curves (Figure 9). Number 
at risk, hazard ratio and log rank test p-values will be presented on the figures.  
The analyses (and tabular and graphical summaries) will be repeated using the outcome of time to 
improvement in two categories of the ordinal scale (Table 33, Figure 10).  


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The number and proportion of subjects in each ordinal score by baseline ordinal score will be presented by 
treatment at Baseline and Study Visit (not necessarily actual) Study Days 3, 5, 8, 11, 15, 22, 29, 60 
(Table 35). Additionally, the change from baseline in ordinal scale (e.g., proportion who have a 1-, 2-, 3-, or 
4-point improvement or 1-, 2-, 3-, or 4-point worsening), or no change, will be presented at all post-dose 
Study Visit Days (Table 34). Figures by study day visits will present grouped bar charts by point changes with 
side-by-side bars for each treatment (Figure 18). 
The mean change from baseline at Study Days 3, 5, 8, 11, 15, 22, 29, and 60 will be summarized by treatment 
(Table 35).  
The main analysis of the primary endpoint will be repeated using the ordinal score on Study Days 15 and 29 
instead of Day 8 using complete data, adjusting for baseline severity and steroid use. The analysis will be 
repeated for baseline severity of disease, baseline steroid use, baseline use of emerging COVID-19 treatments, 
and duration of symptoms subgroups. Each subgroup will be considered separately, and the estimated 
treatment odds ratio from the proportional odds model with corresponding 95% and 80% confidence intervals 
and the p-value will be presented for each subgroup. A forest plot will be generated to display the overall 
treatment odds ratio and CI from each of the within-stratum analyses. Results for Day 15 will be presented in 
Table 17, Figure 4, and Figure 5 while results for Day 29 will be presented in Table 18, Figure 6, and 
Figure 7. These analyses will be repeated for the ITT population and results will be presented in Table 20 and 
Table 21. Odds ratios between the binary progression strata from the proportional odds model are reported in 
Table 24, Table 25, Table 26, Table 27 for mITT population and ITT population for Study Days 15 and 29. 
Oxygenation 
Oxygen days will be defined as the number of days where the ordinal score > 4 up to and including Study Day 
29. The total number of days will be the sum of all reported days, regardless of whether the days occur 
consecutively or in disjoint intervals. For planned gaps between study days, the day of the qualifying Study 
Day and the days to the next planned Study Day will be included in the total number of days. The Post-
Discharge Supplemental Oxygen CRF questions regarding days of oxygenation (including ECMO, invasive 
ventilation, non-invasive ventilation, high-flow oxygen devices, and all other oxygen delivery devices) will be 
used for any time period the subject is not hospitalized at the study hospital. See Section 6.5 for the plan for 
handling subjects who do not have data through Study Day 29 or die prior to Study Day 29.  
Duration of oxygenation days will be summarized in a table using medians and quartiles by treatment 
(Table 36). Bee swarm plots of oxygen days by treatment will be generated (Figure 19). 
Refer to Table 6 for a list of covariates and subgroup analyses for this endpoint. Refer to Table 7 for 
imputation methods to be applied to this endpoint.  
Non-Invasive Ventilation/High-Flow Oxygen 
Non-invasive ventilation/high flow-oxygen days or worse will be defined as the number of days where the 
ordinal score is > 5 up to and including Study Day 29. The total number of days will be the sum of all 
reported days, regardless of whether the days occur consecutively or in disjoint intervals. For planned gaps 
between study days, the day of the qualifying Study Day and the days to the next planned Study Day will be 
included in the total number of days. The Post-Discharge Supplemental Oxygen CRF questions regarding 
days of non-invasive ventilation or high-flow oxygen will be used for any time period the subject is not 
hospitalized at the study hospital. See Section 6.5 for the plan for handling subjects who do not have data 
through Study Day 29 or die prior to Study Day 29.  


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Duration of non-invasive ventilation/high flow oxygen days or worse will be summarized in a table using 
medians and quartiles by treatment (Table 37). Bee swarm plots of non-invasive ventilation/high flow oxygen 
days by treatment will be generated (Figure 20). 
The incidence and duration of new Non-Invasive Ventilation/High-Flow Oxygen use or worse will be 
analyzed by treatment (Table 40). The numerator will include only subjects in category 5 or below at 
enrollment who change to a category 6, 7, or 8. The denominator will only include subjects with an actual 
baseline ordinal score of 5 or below at enrollment. The number of subjects reporting new use of Non-Invasive 
Ventilation/High-Flow Oxygen and the incidence rate along with 95% and 80% CIs estimated using the 
Blaker method will be reported.   
Refer to Table 6 for a list of covariates and subgroup analyses for this endpoint. Refer to Table 7 for 
imputation methods to be applied to this endpoint.  
Invasive Mechanical Ventilation/ECMO 
Ventilator / ECMO days will be defined as the number of days where the ordinal score > 6 up to and 
including Study Day 29. The total number of days will be the sum of all reported days, regardless of whether 
the days occur consecutively or in disjoint intervals. For planned gaps between study days, the day of the 
qualifying Study Day and the days to the next planned Study Day will be included in the total number of days. 
The Post-Discharge Supplemental Oxygen CRF questions regarding days of ECMO or invasive ventilation 
will be used for any time period the subject is not hospitalized at the study hospital. See Section 6.5 for the 
plan for handling subjects who do not have data through Study Day 29 or die prior to Study Day 29.  
Duration of Invasive Mechanical Ventilation/ECMO days will be summarized in a table using medians and 
quartiles by treatment (Table 38). Bee swarm plots of Invasive Mechanical Ventilation/ECMO days, and days 
hospitalized by treatment will be generated (Figure 21). 
The incidence of new Invasive Mechanical Ventilation/ECMO use will be analyzed by treatment (Table 41). 
The numerator will only include subjects in category 6 or below at enrollment who change to a category 7 or 
8. The denominator will include subjects with a baseline ordinal score of 6 or below. The number of subjects 
reporting new use of Invasive Mechanical Ventilation/ECMO and the incidence rate along with 95% and 80% 
CIs estimated using the Blaker method will be reported.   
Refer to Table 6 for a list of covariates and subgroup analyses for this endpoint. Refer to Table 7 for 
imputation methods to be applied to this endpoint.  
Proportion of Subjects Alive and Without Respiratory Failure at Study Day 29 
The proportion of subjects alive and without respiratory failure at Study Day 29 will be defined as the 
proportion of subjects with an ordinal score < 7 at any time between Day 26 through Day 32 (Visit window 
for Study Day 29 Visit). The proportion of subjects with respiratory Failure or death at Day 29 will also be 
provided. These proportions will be presented by treatment along with 95% and 80% Blaker CIs. Treatment 
differences will be evaluated using a logistic regression and the p-value will be presented (Table 31).  
Refer to Table 6 for a list of covariates and subgroup analyses for this endpoint. Refer to Table 7 for 
imputation methods to be applied to this endpoint.  
Time to Mechanical Ventilation or Death up to and Including Day 29 
The time to mechanical ventilation or death up to and including Day 29 will be defined as the elapsed time (in 
days) from Study Day 1 to date of mechanical ventilation or death. Any subjects whose last assessment is 
prior to obtaining the event and prior to Day 26 (beginning of Day 29 window) will be censored at the date of 
their last observed assessment. For the sensitivity analysis of this endpoint, subjects whose last assessment is 


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prior to obtaining the event and who were discharged to a location other than LTAC, hospice care, or other 
hospital will be considered recovered and censored at Day 29. For both primary and sensitivity analysis of this 
endpoint, subjects who complete follow-up will be censored Day 29. Events that occur after Day 29 will be 
censored at Day 29. A table will present median time to event along with corresponding 95% and 80% 
confidence intervals for each treatment along with the hazard ratio estimate and score test p-value from  
a Cox-proportional hazard model (Table 42). The Cox model will include as covariates baseline ordinal score, 
baseline CRP value, continuous age, and baseline dexamethasone use. Differences in time-to-event endpoints 
by treatment will be summarized with Kaplan-Meier curves (Figure 11). Analyses will be performed on the 
mITT population for those subjects who at baseline have an ordinal score of 5 or 6, CRP<150 mg/L, and 
age<85 years and results will be reported in Table 42. This analysis will be repeated for all subjects in the 
mITT population and results will be reported in Table 43. 
Refer to Table 6 for a list of covariates and subgroup analyses for this endpoint. Refer to Table 7 for 
imputation methods to be applied to this endpoint.  
Hospitalization 
Duration (in days) of hospitalization will be defined as the number of days subject is hospitalized for COVID-
19-related reasons starting from the date of randomization. It will be calculated as the total number of days 
hospitalized, including readmissions for COVID-19-related reasons. It will also be calculated as the total 
number of days hospitalized, including any readmissions regardless of cause. See Section 6.5 for the plan for 
handling subjects who do not have data through Day 29 or die prior to Day 29.  
Duration of hospitalization days will be summarized in a table using medians and quartiles by treatment 
(Table 39). Bee swarm plots of days hospitalized by treatment will be generated, where subjects whose days 
are imputed due to death are grouped separately from subjects who do not die (Figure 22). 
Refer to Table 6 for a list of covariates and subgroup analyses for this endpoint. Refer to Table 7 for 
imputation methods to be applied to this endpoint.  
Individual listing of all primary and secondary endpoints is provided in Listing 14. 
8.3. 
Exploratory Efficacy Analyses 
Key Concomitant COVID-19 Treatments 
The post-baseline usage, onset, and duration of treatment of key concomitant COVID-19 treatments will be 
summarized by treatment for each concomitant medication/therapy category (Table 78). If no concomitant 
COVID-19 treatment has been applied up to Study Day 60, day of onset will be censored at Study Day 60 for 
descriptive statistics (means, medians). Duration will be defined as the number of days between day of onset 
and end of medication. For ongoing medication at the end of the study, the medication end date will be 
imputed based on rules in Table 8.  
Steroid Usage 
Steroid usage and steroid type for indications other than COVID-19 post-baseline will be summarized by 
treatment group (Table 87). If no concomitant COVID-19 treatment has been applied up to Study Day 60, day 
of onset will be censored at Study Day 60 for descriptive statistics (means, medians). Duration will be defined 
as the number of days between day of onset and end of medication. For ongoing medication at the end of the 
study, the medication end date will be imputed based on rules in Table 8. 
Details of analyses for virology and markers of inflammation and immune response will be covered in a 
separate SAP. 


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9. 
SAFETY EVALUATION 
9.1. 
Demographic and Other Baseline Characteristics 
Subject demographic variables (i.e., age, sex, race, and ethnicity) will be summarized by treatment and overall 
using descriptive statistics for age, and using number and percentage of subjects for sex, race, and ethnicity 
(Table 14). Age at Study Day 1 is calculated in years at the first dosing date of study product and will be 
rounded down to an integer. Age group (<40; 40-64; 65 or older) will be summarized by using summary 
statistics for categorical variables. If a subject did not receive study product after enrollment, the subject’s age 
will be calculated from the date of randomization unless stated otherwise in a stage-specific appendix.  
A demographic listing, including the informed consent date, will be provided Listing 5. 
Baseline characteristics include body weight (in kg), height (in cm), body mass index (BMI; in kg/m2), 
duration of symptoms prior to enrollment, steroid use, baseline viral measures and ordinal score. These 
baseline characteristics will be summarized by the treatment group and overall using descriptive statistics for 
continuous variables and using number and percentage of subjects for categorical variables (Table 15). No 
formal statistical testing is planned. 
A listing of baseline characteristics will be provided (Listing 5). 
9.1.1. 
Prior and Concurrent Medical Conditions 
Focused medical history is obtained at the screening visit that includes the following: 
• Day of onset of COVID-19 signs and symptoms. 
• Prior enrollment in ACTIV-5/BET. 
• History of vaccinations within 4 weeks prior to screening, including SARS-CoV-2 vaccination. 
o Exclusionary vaccine history includes any live vaccine (that is, live attenuated) within 4 weeks 
prior to screening 
• History of chronic medical conditions including chronic oxygen requirement prior to onset of 
COVID-19. 
• History of medication allergies. 
• Medications and therapies for this current illness taken in the 7 days prior to Study Day 1. 
• Whether subject is participating in another clinical trial or plan to enroll in another clinical trial in the 
next 30 days. 
Medical history is limited to the following conditions: asthma, cancer, cardiac vascular disease, chronic 
kidney disease, chronic liver disease, chronic oxygen requirement, chronic respiratory disease, coagulopathy, 
congestive heart failure, coronary artery disease, current nicotine consumption, diabetes type I and II, 
hypertension, immune deficiency, and obesity. Summaries of subjects’ medical history will be presented by 
treatment group and overall (Table 14, Table 15). 
A listing of medical history will be provided by subject number. Additional medial history other than the 
diagnoses listed above will be included in the listing (Listing 6). 


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9.1.2. 
Prior and Concomitant Medications  
Concomitant medications will be coded to the Anatomical Therapeutic Classification using the WHODrug 
Dictionary. The use of prior and concomitant medications taken during the study will be recorded on the 
CRFs.  
Prior medications are defined as any medications begun and stopped before a subject took the first dose of 
study product. If a partial stop date is entered, the month and year (if day is missing) or year (if day and month 
are missing) of the stop date are prior to the first dosing date will be considered prior (See Table 8). 
Concomitant medications are defined as medications taken while a subject took study product. Therefore, any 
medications started prior to or during the first dosing date of study product and continued after the first dosing 
date or started after the first dosing date will be considered concomitant medications. If a partial start date is 
entered, any medication with the month and year (if day is missing) or year (if day and month are missing) 
after the date of first study product administration will be included in the concomitant medication summary. 
Medications with completely missing start and stop dates will be included in the concomitant medication 
summary (Table 8). 
Prior and concomitant medications reported on the concomitant medication form will be summarized 
separately WHO Drug Level 1 and 2 Codes, actual baseline ordinal score, and treatment group using the 
number and percentage of subjects for each treatment, actual baseline ordinal score, and overall (Table 84, 
Table 85). Concomitant COVID-19 treatments are reported in Table 86 while steroids used for indications 
other than COVID-19 are reported in Table 87. A subject reporting the same medication more than once will 
be counted only once when calculating the number and percentage of subjects who received that medication. 
The summary will be ordered alphabetically by WHO Drug level 1code then by WHO Drug level 2 code in 
order of descending overall frequency within each WHO Drug level code. For drugs with the same frequency, 
sorting will be done alphabetically. 
Summaries of prior and concomitant medications will be based on the Safety population and individual 
subject listing of all prior and concomitant medications including those reported on the SAE form is provided 
in Listing 9, Listing 10 for steroids, and Listing 11 for other medication of interest. 
9.2. 
Measurements of Treatment Compliance 
Section 7 provides the descriptions of summaries of key treatment compliance milestones/variables. 
Individual subject listings will be presented for all subjects who discontinued dosing (Listing 1). Individual 
subject listings will be presented for all subjects who missed, halted or slowed any dose (Listing 12). 
9.3. 
Adverse Events 
All safety analyses will be summarized and performed on the Safety population by treatment and ordinal 
score, as appropriate.  
Clinical and laboratory adverse events (AEs) will be coded using the version 23.0 of MedDRA. System organ 
class (SOC) and preferred term (PT) will be provided in the AE dataset.  
AEs are graded by the investigator as Grade 2 (moderate), Grade 3 (severe), Grade 4 (severe/potentially life-
threatening), or Grade 5 (fatal/death) according to the NIAID Division of AIDS (DAIDS) Table for Grading 
the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1 [5].The severity grade of events 
for which the investigator did not record severity will be categorized as “missing” for tabular summaries and 
data listings. The missing category will be listed last in summary presentation.  


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The relationship of an adverse event to the component of the investigational product should be assessed using 
clinical judgment by the investigator, describing the event as either unrelated or related. Events for which the 
investigator did not record relationship to study product will be considered related to study product for 
summary purposes. However, data listings will show relationship as missing. Relationship to COVID-19 and 
other medical conditions is also collected and will be reported in data listings. 
Treatment-emergent adverse events (TEAEs) are defined as any AE with an onset date on or after the study 
product start date. 
If the onset date of the AE is incomplete and the AE stop date is not prior to the first dosing date of study 
product, then the month and year (or year alone if month is not recorded) of onset determine whether an AE is 
treatment emergent. The event is considered treatment emergent if the AE onset is the same as or after the 
month and year (or year) of the first dosing date of study product. 
An AE with completely missing onset and stop dates, or with the onset date missing and a stop date later than 
the first dosing date of study product, will be considered to be treatment emergent. In addition, an AE with the 
onset date missing and incomplete stop date with the same or later month and year (or year alone if month is 
not recorded) as the first dosing date of study product will be considered treatment emergent. For additional 
details on imputation of partial or missing dates, see Table 8.  
For the calculation of incidence of TEAEs each subject will only be counted once per category (Any TEAEs, 
Any SOC, Any PT within SOC) and any repetitions of TEAEs within a subject will be ignored; the 
denominator will be the number of subjects in the Safety population. 
An overall summary of TEAEs by treatment, actual baseline ordinal score, severity, and relatedness of TEAEs 
will be presented in Table 46 and will include subjects with at least one: 
• TEAE 
• Grade ≥3 TEAE 
• TEAE related to study treatment 
• Grade ≥3 TEAE related to study treatment 
• Treatment-emergent SAE 
• Treatment-emergent SAE related to study treatment 
• TEAE leading to early termination of study product 
• TEAE leading to study discontinuation 
• TEAE leading to death. 
The following summaries for TEAEs will be presented by MedDRA system organ class, preferred term, 
severity and relatedness (when applicable) of TEAE, ordinal score and treatment: 
• Subject listing of non-serious AEs (Listing 15); 
• Bar chart of non-serious related AEs by severity and MedDRA system organ class (beginning at 
Figure 23 and continuing through Figure 30);  
The proportion of subjects reporting at least one TEAE will be summarized by MedDRA system organ class 
and preferred term for each treatment (Table 47), by baseline ordinal score (Table 48), by baseline steroid use 
(Table 49), by baseline use of Emerging COVID-19 treatments (Table 50), and by duration of symptoms prior 
to enrollment (Table 51). Denominators for percentages are the number of subjects in the Safety population. 


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Similarly, the proportion of subjects reporting at least one treatment-emergent SAE will be summarized by 
MedDRA system organ class and preferred term for each treatment, ordinal score and overall (Table 52, 
Table 53). 
Separate listings of non-serious TEAEs, all TEAEs, related TEAEs, treatment-emergent SAEs, and TEAEs 
leading to early termination of study product, TEAEs leading to study discontinuation or death will be 
presented (beginning at Listing 15 and continuing through Listing 21). 
9.4. 
Deaths, Serious Adverse Events and other Significant Adverse Events 
The time to death up to and including Day 60 will be defined as the elapsed time (in days) from Study Day 1 
to date of death. Any subjects whose last assessment is prior to death will be censored at the date of their last 
observed assessment.  For the sensitivity analysis of this endpoint, subjects discharged to a location other than 
LTAC, hospice care, or other hospital will be considered non-events and censored at Day 60. For both 
analyses, subjects who complete follow-up will be censored at Day 60. Deaths that occur after Day 60 will be 
censored at Day 60. The Kaplan-Meier estimates of mortality rates along with corresponding 80% CI and 
95% CI will be presented by treatment group and baseline ordinal score. Difference in Kaplan-Meier 
estimates of mortality rates between treatment arms along with corresponding 80% CI, 95% CI will be 
presented. Additionally, hazard ratios along with corresponding 80% CI, 95% CI and score test p-value 
calculated from the Cox proportional hazard model adjusted from baseline ordinal score and baseline steroid 
use will be presented (Table 54).  
This analysis will be repeated for deaths through Day 15 and deaths through Day 29 and results will be 
reported in Table 54. Restricted mean mortality time estimates will be provided for each treatment group and 
actual baseline ordinal score stratum as well as the difference in restricted mean mortality time between 
treatment groups within each of the baseline ordinal score strata (Table 55). 
Differences in time-to-event endpoints by treatment will be summarized with Kaplan-Meier curves 
(Figure 12, Figure 13, Figure 14). Analyses of mortality will be performed on the Safety population at risk. 
A safety composite endpoint will be defined as the occurrence of at least one of the following up to and 
including Study Day 60:  
1. Death  
2. Treatment-emergent SAE  
3. Grade 3 or 4 TEAE  
The time to this composite endpoint will be defined as the elapsed time (in days) from Study Day 1 to the 
earliest date of any of the events. Any subjects whose last assessment in the study is prior to experiencing any 
of the events will be censored at the day of their last observed assessment. Subjects who complete follow-up 
but do not experience any of the events will be censored at the expected date of their Study Day 60 visit. 
Rates death, SAE, and Grade ≥ 3 TEAEs occurrence up to and including expected date of the Study Day 60 
visit will be presented for each treatment arm. Further, the composite endpoint of the occurrence of death, 
treatment-emergent SAE, or Grade 3 or 4 TEAE will be analyzed as a time-to-event outcome. A table will 
present Kaplan-Meier estimates of the event rates along with corresponding 80%, 95% confidence intervals 
for each treatment. Difference in event rates along with corresponding 80%, 95% confidence intervals will 
also be presented. Hazard ratio estimates and score test p-value from the Cox model will also be presented 
(Table 56). Differences in time-to-event endpoints by treatment will also be summarized with Kaplan-Meier 
curves (Figure 18).  


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9.5. 
Pregnancies 
For any subjects in the Safety population who become pregnant during the study, every attempt will be made 
to follow these subjects to completion of pregnancy to document the outcome, including information 
regarding any complications with pregnancy and/or delivery. Note that the clinical study report (CSR) will not 
be delayed to wait for outcomes of any pregnancies; an addendum to the CSR would be provided in such a 
scenario. A set of listings of pregnancies and outcomes will be presented beginning at Listing 22 and 
continuing through Listing 26. 
9.6. 
Clinical Laboratory Evaluations 
Clinical safety laboratory AEs are collected Study Days 1, 3, 5, 8, and 11 (while hospitalized); and outpatient 
Study Days 15 and 29 (if attends in-person visit or still hospitalized). Parameters evaluated include WBC, 
differential, Hgb, PLT, creatinine, (and calculate an estimated glomerular filtration rate (eGFR); the formula 
used is determined by the sites, but should be consistent throughout the study), total bilirubin, AST, ALT, and 
INR. Additional laboratory parameters may be summarized based on each intervention’s safety profile. 
Laboratory safety parameters will be graded according to the NIAID Division of AIDS (DAIDS) Table for 
Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1 (July 2017). 
The distribution of Grade 3 and 4 chemistry and hematology laboratory results by maximum severity, time 
point, ordinal score and treatment group will be presented in Table 62 through Table 66 for chemistry and 
Table 76 through Table 81 for hematology. Absolute values and change from baseline of laboratory values 
will be summarized by mean, SD, median, minimum, and maximum results at Study Days 1, 3, 5, 8, 11, 15 
and 29 in Table 57, through Table 61 for chemistry and Table 67 through Table 75 for hematology. Individual 
laboratory results are provided in Listing 27 for chemistry and hematology and Listing 29 for urine pregnancy 
results. 
Markers of inflammation and coagulation results for CRP, ferritin, d-dimer, LDH, and fibrinogen will be 
summarized by mean, SD, median, minimum, and maximum results at Study Day 1 and Study Visit (not 
necessarily actual) Study Days 3, 5, 8, 11, 15 and 29 by treatment as well as change from baseline at each 
post-Study Day 1 visit (Table 82). Figures with mean and SD over time will also be presented by treatment 
(Figure 31, Figure 32, Figure 33, Figure 34, Figure 35). Individual results for markers of inflammation are 
presented in Listing 28. 
9.7. 
Vital Signs and Physical Evaluations 
Vital sign measurements include pulse, systolic blood pressure, respiratory rate, blood oxygen saturation 
(SpO2) and oral temperature. Vital signs were assessed as part of the NEW score at baseline and will be listed 
(Listing 7). Descriptive statistics for baseline vital signs (i.e., NEWS components) collected will be presented 
by treatment (Table 83). 
Targeted physical examinations are performed at Study Day 1 and are performed post-baseline only when 
needed to evaluate possible adverse events. At the screening visit, the targeted physical examination is 
focused on lung auscultation. Physical exam findings per subject will be detailed in a listing (Listing 8). 
9.8. 
Concomitant Medications 
Concomitant medications will be coded to the Anatomical Therapeutic Classification using the WHODrug 
Dictionary. The use of prior and concomitant medications taken during the study will be recorded on the 
CRFs. 


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Summaries of prior and concomitant medications will be based on the Safety population and are provided in 
Table 84, Table 85, Table 86, and Table 87. An individual subject listing of all concomitant medications is 
provided in Listing 9. 
9.9. 
Other Safety Measures 
No additional safety analyses are planned. 


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10. 
PHARMACOKINETICS 
Details for PK analysis will be provided in a separate SAP. 


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11. 
IMMUNOGENICITY 
Not Applicable. 


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12. 
OTHER ANALYSES 
Not Applicable. 


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13. 
REPORTING CONVENTIONS 
P-values ≥0.001 and ≤0.999 will be reported to 3 decimal places; p-values less than 0.0005 will be reported as 
“<0.001” and p-values greater than 0.9995 will be reported as “>0.999”. 
The mean, confidence intervals, median, IQR, and other statistics will be reported to 1 decimal place greater 
than the original data. The minimum and maximum will use the same number of decimal places as the 
original data. 
Proportions will be presented as 2 decimal places; values greater than zero but <0.01 will be presented as 
“<0.01”. Percentages will be reported to the nearest whole number; values greater than 0.5% but < 1% will be 
presented as “<1”; values greater than 99.5% but less than 100% will be reported as “>99”. 
For all other estimators, the NEJM statistical reporting guidelines will be followed: results will be presented 
with no more precision than is of scientific value and is meaningful. For example, measures of association, 
such as odds ratios, will be reported to two or three significant digits. Results derived from models will be 
limited to the appropriate number of significant digits. 


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14. 
TECHNICAL DETAILS 
SAS version 9.4 or above, or R language and environment for statistical computing 3.6.1 or above, will be 
used to generate all tables, figures and listings. 


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15. 
SUMMARY OF CHANGES IN THE CONDUCT OF THE STUDY OR 
PLANNED ANALYSES 
15.1. 
Changes from Planned analyses for BET-B 
The BET-B protocol and SAP inadvertently did not include analysis of Day 8 ordinal score endpoint. As this 
endpoint is the primary endpoint for BET-A and BET-C, the BET-B planned analyses are updated as 
described in this section to include Day 8 ordinal score as a secondary endpoint for BET-B. The Day 8 ordinal 
score analysis will only be based on complete data only, without the use of multiple imputation. Imputations 
for intermittent missingness described in Section 6.5 will be used. Subjects missing Day 8 score after last 
assessment for subjects with a good discharge status (i.e., discharged to a location other than LTAC, hospice 
care, other hospital) at last assessment will be assigned a score of 2 and last observation carried forward will 
be used for subjects missing data at Day 8 without a good discharge status (i.e., subjects with no post baseline 
data or still hospitalized or those discharged to LTAC, hospice care, or other hospital) at their last assessment.  
Tables similar to Table 16, Table 22 will be presented for the primary subgroup (ITT Population with 
Baseline Ordinal Score of 5 or 6, CRP<150 mg/L, and age<85 years ) and for the full ITT population. Only 
complete data and subgroup rows from Table 22 will be presented. Results will also be presented graphically 
in a figure similar to Figure 2 using complete data. 
15.2. 
Changes from Version 1.0 to Version 2.0 of the Master SAP 
• Version 1.0 of the SAP was written by Social & Scientific Systems, Inc. Version 2.0 of the SAP was 
updated by Emmes and revised to follow Emmes standard formats. 
• The SAP was updated to clarify the statistical methods and imputations to be used including clear 
details regarding multiple imputation and multiplicity testing. 
• For the analysis of primary endpoint and key secondary endpoints, baseline ordinal score and baseline 
steroid use were updated to be used as the covariates instead of the stratification variables. 
• For time to event endpoints, the analyses were updated to report the p-value from the score test in the 
adjusted Cox model instead of unadjusted p-value from the log rank test. 
• For the analysis of proportion alive and without respiratory failure through Day 29, the analysis was 
updated to use an adjusted regression model to match what is being done for BET-B. 
• For binary endpoints, the analyses were updated to report a p-value from a logistic regression instead 
of a p-value from the Chi-square test. 
• Updated language for time to recovery to use time to sustained recovery. 
• Updated language throughout the SAP to use baseline ordinal score for disease severity at baseline 
instead of using moderate, severe categories.  
• Major formatting updates to TFL shells and clarification changes   
• Removed PK and virology exploratory endpoints from the master SAP. These endpoints will be 
covered in a separate SAP. 
• Added a table and figure for LDH. 
• Ethnicity was added as a subgroup. 


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• Added an endpoint review committee to review and adjudicate if a subject’s primary or key secondary 
endpoint data is unclear. 
• The SAP was updated to note that the DSMB report will not be done by a blinded team. 
• The method for multiplicity adjustment was updated to use Westfall-Young only for binary and 
continuous endpoints using complete data. An additional analysis was added to use the Hochberg 
approach to adjust p-values from all endpoints. 
15.3. 
Changes from Version 2.0 to Version 3.0 of the Master SAP 
• All analyses of time to events (e.g., time to sustained recovery, time to death, time to mechanical 
ventilation or death) endpoints were updated to censor subjects without events at last assessment.  
• A sensitivity analysis was added for time to recovery endpoint that considers subjects whose last 
assessment in the study is prior to Day 60 after discharge from the hospital to a location other than 
LTAC, hospice care or other hospital as recovered by Day 60. Their time to recovery will be the day 
the time of their first observed/imputed recovery score (i.e., 1, 2, 3) or the day of discharge, whichever 
comes first. 
• A sensitivity analysis was added for survival without respiratory failure and time to mechanical 
ventilation or death that considers subjects lost to follow-up before Day 26 (beginning of Day 29 
window) before event who were discharged to a location other than LTAC, hospice care, or other 
hospital as non-events and censors them at Day 29.  
• The analyses for mortality were updated to use Kaplan Meier estimates instead of crude estimates for 
mortality rates. All subjects lost to follow up before death were censored at their last assessment.  
• A sensitivity analysis was added for the 14-day mortality and time to death through Day 15 endpoints 
that consider subjects lost to follow-up before Day 13 (beginning of Day 15 window) before event 
who were discharged to a location other than LTAC, hospice care, or other hospital as non-events and 
censors them at Day 15. Similar sensitivity analyses were added for 28-day mortality, 59-day 
mortality, time to death by Day 29, and time to death by Day 60 endpoints.  
• The definition for survival without respiratory failure at Day 29 was updated count respiratory failure 
events and deaths that occurred within the Day 29 visit window (Day 26 through Day 32) and to count 
all deaths that occurred before Day 29. 
• The method for handling ties in time to event analyses was updated from Breslow to the Efron method 
for analyses based on Cox regression model. 
• Tables for laboratory parameters without grading ranges (Eosinophils, monocytes, basophils) were 
removed. 
• The previous SAP version used a subject-specific multiple imputation approach that only used 
covariates with non-missing values. This MI method was updated to first impute continuous covariates 
(baseline CRP, baseline duration of symptoms, age) with missing values using the overall mean 
among all randomized subjects and impute indicator variables of baseline steroid use, black or 
Hispanic ethnicity, and presence of two or more comorbidities, subjects with missing values using the 
value with the greatest number of subjects among all randomized subjects. Moreover, this updated 
multiple imputation will use one model to impute all subjects missing Day 8 ordinal score and with the 
same last assessment time in the study. The number of MI models fit will correspond to the number of 
observed last assessment times prior to Day 8.  


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16. 
REFERENCES 
1. G. B. Smith, D. R. Prytherch, P. E. Schmidt and P. I. Featherstone, "The ability of the National Early 
Warning Score (NEWS) to discriminate patients at risk of early cardiac arrest, unanticipated intensive 
care unit admission, death.," Resuscitation, pp. 465-470, 2013. 
2. M. Ge, L. K. Durham, R. D. Meyer, W. Xie and N. Thomas, "Covariate-Adjusted difference in 
proportions from clincal trials using logistic regression and weighted risk differences.," Ther Innov 
Regul Sci, vol. 45, pp. 481-493, 2011.  
3. Pocock SJ, Geller NL, Tsiatis AA. The analysis of multiple endpoints in clinical trials. Biometrics. 1987 
Sep;43(3):487-98. PMID: 3663814. 
4. Drummond R. CONSORT Revised: Improving the Reporting of Randomized Clinical Trials. JAMA. 
2001; 285(15):2006-2007.   
5. Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, 
Corrected Version 2.1," U.S. Department of Health and Human Services, National Institutes of Health, 
National Institute of Allergy and Infectious Diseases, Division of AIDS, 2017.[Online].Available: 
https://rsc.niaid.nih.gov/sites/default/files/daidsgadingcorrectedv21.pdf. [Accessed July 2020]. 
 


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17. 
LISTING OF TABLES, FIGURES, AND LISTINGS  
Table, figure, and listing shells are presented in Appendices 1, 2, and 3. 
 


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APPENDICES 


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APPENDIX 1. TABLE MOCK-UPS 
Tables below will be presented for final reports of all stages. Additional stage-specific tables will 
be added to each stage-specific SAP appendix as needed. 
LIST OF TABLES 
Table 1: 
Clinical Status Study Day Windows ...........................................................................16 
Table 2: 
Lab Sample Collection Study Day Windows .............................................................16 
Table 3: 
National Early Warning Score (NEWS) .....................................................................22 
Table 4: 
Expected distribution of ordinal outcomes for the control arm at Study Day 8 .........24 
Table 5: 
Simulated early stopping probabilities at the interim review (n=50/arm), and 
power calculations for the final study size (n=100/arm) for Study Day 8 
Ordinal Score ..............................................................................................................25 
Table 6: 
Covariates and Subgroup Analyses for Each Endpoint ..............................................33 
Table 7: 
Imputation Method for Each Endpoint and Analysis Type ........................................39 
Table 8: 
Partial Date Imputation for Adverse Events (AEs), Concomitant medications 
(CMs), and Medical History (MH) .............................................................................49 
Table 9: 
Endpoints to be included in the global analysis ..........................................................51 
Table 10: Schedule of Study Procedures ....................................................................................80 
Table 11: Protocol Deviations—mITT Population .....................................................................82 
Table 12: Treatment Exposure and Compliance by Baseline Ordinal Score — Safety 
Population ...................................................................................................................84 
Table 13: Subject Disposition by Baseline Ordinal Score – ITT Population .............................85 
Table 14: Categorical Demographics and Medical History – ITT Population ...........................89 
Table 15: Continuous Demographics and Medical History – ITT Population ...........................92 
Table 16: Global Odds Ratios for Inferior Clinical Status Score at Study Visit Day 8 
Using a Proportional Odds Model — mITT Population ............................................95 
Table 17: Global Odds Ratios for Inferior Clinical Status Score at Study Visit Day 15 
Using a Proportional Odds Model — mITT Population ............................................98 
Table 18: Global Odds Ratios for Inferior Clinical Status Score at Study Visit Day 29 
Using a Proportional Odds Model — mITT Population ............................................98 
Table 19: Global Odds Ratios for Inferior Clinical Status Score at Study Visit Day 8 
Using a Proportional Odds Model — ITT Population................................................98 
Table 20: Global Odds Ratios for Inferior Clinical Status Score at Study Visit Day 15 
Using a Proportional Odds Model  — ITT Population...............................................98 
Table 21: Global Odds Ratios for Inferior Clinical Status Score at Study Visit Day 29 
Using a Proportional Odds Model — ITT Population................................................98 


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Table 22: Proportional Odds Model for Clinical Status Score at Study Visit 8 – Odds 
Ratios Between the Binary Progression Strata with Multiple Imputation — 
mITT Population .........................................................................................................99 
Table 23: Proportional Odds Model for Clinical Status Score at Study Visit 8 – Odds 
Ratios Between the Binary Progression Strata with Multiple Imputation — 
ITT Population ............................................................................................................99 
Table 24: Proportional Odds Model for Clinical Status Score at Study Visit 15 – Odds 
Ratios Between the Binary Progression Strata without Multiple Imputation 
— mITT Population ....................................................................................................99 
Table 25: Proportional Odds Model for Clinical Status Score at Study Visit 15 – Odds 
Ratios Between the Binary Progression Strata without Multiple Imputation 
— ITT Population .......................................................................................................99 
Table 26: Proportional Odds Model for Clinical Status Score at Study Visit 29 – Odds 
Ratios Between the Binary Progression Strata without Multiple Imputation 
— mITT Population ....................................................................................................99 
Table 27: Proportional Odds Model for Clinical Status Score at Study Visit 29 – Odds 
Ratios Between the Binary Progression Strata without Multiple Imputation 
— ITT Population .......................................................................................................99 
Table 28: Time to Sustained Recovery through Day 60 — mITT Population .........................100 
Table 29: Time to Sustained Recovery through Day 60 by Treatment Group, Actual 
Baseline Ordinal Score, and Analysis Population: Restricted Mean Survival 
Time Analysis ...........................................................................................................104 
Table 30: Proportion of Subjects Alive and Without Respiratory Failure through Day 
29 — mITT Population .............................................................................................105 
Table 31: Proportion of Subjects Alive and Without Respiratory Failure at Study Day 
29 — mITT Population .............................................................................................106 
Table 32: Time to Improvement by at Least One Category through Day 60 in the 8-
point Ordinal Scale — mITT Population ..................................................................107 
Table 33: Time to Improvement by at Least Two Categories through Day 60 in the 8-
point Ordinal Scale — mITT Population ..................................................................108 
Table 34: Summary of Change from Baseline of Ordinal Score by Study Day — mITT 
Population .................................................................................................................109 
Table 35: Disease Severity Distribution as Measured by Ordinal Score for Study Day 
— mITT Population ..................................................................................................110 
Table 36: Summary of Continuous Secondary Outcomes through Day 29 – Oxygen 
Days — mITT Population ........................................................................................111 
Table 37: Summary of Continuous Secondary Outcomes through Day 29 – Non-
Invasive Ventilation/High Flow Oxygen Free Days or Worse — mITT 
Population .................................................................................................................111 


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Table 38: Summary of Continuous Secondary Outcomes through Day 29 – 
Ventilator/ECMO Days or Worse — mITT Population ...........................................111 
Table 39: Summary of Continuous Secondary Outcomes through Day 29 – Duration of 
Hospitalization — mITT Population ........................................................................111 
Table 40: Incidence of Secondary Outcomes – Non-Invasive Ventilation/High Flow 
Oxygen Free Days or Worse through Day 29 — mITT Population .........................112 
Table 41: Incidence of Secondary Outcomes – Ventilator/ECMO Days or Worse 
through Day 29 — mITT Population ........................................................................113 
Table 42: Time to Mechanical Ventilation or Death through Day 29 — mITT 
Population with Baseline Ordinal Score of 5 or 6, CRP<150 mg/L, and 
age<85 years .............................................................................................................114 
Table 43: Time to Mechanical Ventilation or Death through Day 29 — mITT 
Population .................................................................................................................114 
Table 44: Z-Scores and Westfall-Young Permutation P-Value Adjustment — mITT 
Population .................................................................................................................115 
Table 45: Hochberg P-Value Adjustment — mITT Population ...............................................116 
Table 46: Overall Summary of Treatment Emergent Adverse Events by Baseline 
Ordinal Score — Safety Population .........................................................................117 
Table 47: Treatment Emergent Adverse Events by System Organ Class, Preferred 
Term and Treatment Group — Safety Population ....................................................118 
Table 48: Treatment Emergent Adverse Events by System Organ Class, Preferred 
Term, and Baseline Ordinal Score — Safety Population .........................................119 
Table 49: Treatment Emergent Adverse Events by System Organ Class, Preferred 
Term, and Baseline Steroid Use — Safety Population .............................................119 
Table 50: Treatment Emergent Adverse Events by System Organ Class, Preferred 
Term, and Baseline Use of Emerging Covid-19 Treatments — Safety 
Population .................................................................................................................119 
Table 51: Treatment Emergent Adverse Events by System Organ Class, Preferred 
Term, and Duration of Symptoms Prior to Enrollment — Safety Population ..........119 
Table 52: Treatment Emergent Serious Adverse Events by System Organ Class, 
Preferred Term and Treatment Group — Safety Population ....................................120 
Table 53: Treatment Emergent Serious Adverse Events by System Organ Class, 
Preferred Term, and Baseline Ordinal Score — Safety Population .........................121 
Table 54: Mortality Rates — Safety Population .......................................................................122 
Table 55: Time to Death through Day 15, 29, or 60 by Treatment Group: Restricted 
Mean Survival Time Analysis — Safety Population ................................................125 
Table 56: Time to Death, SAE or Grade ≥3 TEAEs through Day 60 — Safety 
Population .................................................................................................................126 


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Table 57: Summary of ALT Results Values and Change from Baseline by Study Days 
— Safety Population .................................................................................................127 
Table 58: Summary of AST Results Values and Change from Baseline by Study Days 
— Safety Population .................................................................................................127 
Table 59: Summary of Bilirubin Results Values and Change from Baseline by Study 
Days — Safety Population ........................................................................................127 
Table 60: Summary of Creatinine Values and Change from Baseline by Study Days — 
Safety Population ......................................................................................................127 
Table 61: Summary of eGFR Results Values and Change from Baseline by Study Days 
— Safety Population .................................................................................................127 
Table 62: ALT Results by Baseline Ordinal Score, Severity and Study Days — Safety 
Population .................................................................................................................128 
Table 63: AST Results by Baseline Ordinal Score, Severity and Study Days — Safety 
Population .................................................................................................................129 
Table 64: Bilirubin Results by Baseline Ordinal Score, Severity and Study Days — 
Safety Population ......................................................................................................129 
Table 65: Creatinine Results by Baseline Ordinal Score, Severity and Study Days — 
Safety Population ......................................................................................................129 
Table 66: eGFR Results by Baseline Ordinal Score, Severity and Study Days — Safety 
Population .................................................................................................................129 
Table 67: Summary of White Blood Cells Results Values and Change from Baseline 
by Study Days — Safety Population ........................................................................130 
Table 68: Summary of Platelets Results Values and Change from Baseline by Study 
Days — Safety Population ........................................................................................130 
Table 69: Summary of Hemoglobin Results Values and Change from Baseline by 
Study Days — Safety Population .............................................................................130 
Table 70: Summary of INR Results Values and Change from Baseline by Study Days 
— Safety Population .................................................................................................130 
Table 71: Summary of Neutrophils Results Values and Change from Baseline by Study 
Days — Safety Population ........................................................................................130 
Table 72: Summary of Eosinophils Results Values and Change from Baseline by Study 
Days — Safety Population ........................................................................................130 
Table 73: Summary of Basophils Results Values and Change from Baseline by Study 
Days — Safety Population ........................................................................................130 
Table 74: Summary of Lymphocytes Results Values and Change from Baseline by 
Study Days — Safety Population .............................................................................130 
Table 75: Summary of Monocytes Results Values and Change from Baseline by Study 
Days — Safety Population ........................................................................................130 


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Table 76: White Blood Cell Results by Baseline Ordinal Score, Severity and Study 
Days — Safety Population ........................................................................................131 
Table 77: Platelets Results by Baseline Ordinal Score, Severity and Study Days — 
Safety Population ......................................................................................................132 
Table 78: Hemoglobin Results by Baseline Ordinal Score, Severity and Study Days — 
Safety Population ......................................................................................................132 
Table 79: INR Results by Baseline Ordinal Score, Severity and Study Days — Safety 
Population .................................................................................................................132 
Table 80: Neutrophils Results by Baseline Ordinal Score, Severity and Study Days — 
Safety Population ......................................................................................................132 
Table 81: Lymphocytes Results by Baseline Ordinal Score, Severity and Study Days 
— Safety Population .................................................................................................132 
Table 82: Summary of Continuous Markers of Inflammation and Immune Response by 
Study Day — Safety Population ...............................................................................133 
Table 83: Summary Statistics of Baseline Vital Signs by Actual Baseline Ordinal 
Score and Treatment Group — Safety Population ...................................................134 
Table 84: Number and Percentage of Subjects with Prior Medications by WHO Drug 
Classification, Actual Baseline Ordinal Score, and Treatment Group — 
Safety Population ......................................................................................................136 
Table 85: Number and Percentage of Subjects with Concomitant Medications by WHO 
Drug Classification, Actual Baseline Ordinal Score, and Treatment Group — 
Safety Population ......................................................................................................136 
Table 86: Summary of Concomitant COVID-19 Treatments — Safety Population ................137 
Table 87: Summary of Steroid Usage for Indications Other than COVID-19 by 
Treatment of Indication — Safety Population ..........................................................138 
 
  


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9.5.1 Efficacy and Safety Measurements Assessed and Flow Chart 
Table 10: 
Schedule of Study Procedures  
  
Screen 
Baseline 
Study Intervention Period 
Follow-up Visits 
Day +/- Window 
−1 or 1 
115 
Daily until hospital discharge (up to Day 29) 
810 
± 2 
156  
± 2 
2210 
± 3 
296 
± 3 
6010 
± 3 
ELIGIBILITY 
 
 
 
 
 
 
 
 
Informed consent 
X 
 
 
 
 
 
 
 
Demographics & Medical History 
X 
 
 
 
 
 
 
 
Targeted physical exam 
X 
 
 
 
 
 
 
 
Review SARS-CoV-2 results 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
STUDY INTERVENTION 
 
 
 
 
 
 
 
 
Randomization 
 
X 
 
 
 
 
 
 
Administration of investigational 
agent 
 
• Risankizumab or placebo: one infusion on Day 1 
• Remdesivir: IV daily for 5-10 days or until discharge.  
 
 
 
 
 
 
 
 
 
 
 
 
 
STUDY PROCEDURES 
 
 
 
 
 
 
 
 
Vital sign and NEWS score 1 
 
X3 
 
 
 
 
 
 
Clinical data collection1  
 
X3 
Daily until discharge 
X 
X 
X 
X 
X13 
Adverse event evaluation 
 
X3 
Daily until discharge 
X 
X 
X 
X 
X 
Concomitant medication review12 
 
X3 
Day -7 until discharge 
X 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
SAFETY LABORATORY 
 
 
 
 
 
 
 
 
Safety hematology, chemistry, 
and liver tests4 
X2 
X3 
Day 3, 5, 8, 11 (all ± 1 day) if hospitalized5 
 
X 
 
X 
 
Pregnancy test for females of 
childbearing potential 
X2 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
RESEARCH LABORATORY16  
 
 
 
 
 
 
 
 
Oropharyngeal swab7 
 
X3 
Day 3, 5, 8, 11 (all ± 1 day) if hospitalized 
 
X 
 
X 
 
Blood draw for serum and 
plasma. Specific testing is as 
follows: 
 
X3 
Day 3, 5, 8, 11 (all ± 1 day) if hospitalized  
 
X 
 
X 
 
PCR SARS-CoV-2 
 
X3 
Day 3, 5, 8, 11 (all ± 1 day) if hospitalized  
 
 
 
 
 
Proteomic analysis (including 
specifically for Risankizumab IL-
17A, IL-22, and IL-1b) 
 
X3 
Day 3, 8, (all ± 1 day) if hospitalized  
 
X 
 
X 
 
Risankizumab pharmacokinetics11 
 
X8 
Day 5 (± 1 day) if hospitalized 
 
X 
 
X 
 
Risankizumab immunogenicity11 
 
X8 
 
 
 
 
X 
 
Serum for secondary research 
 
X3 
Day 3, 5, 8, 11 (all ± 1 day) if hospitalized. 
 
X 
 
X 
 
Blood for RNA 
 
X3 
Day 3, 8 (all ± 1 day) if hospitalized 
 
X 
 
X 
 
Blood for PBMC11  
 
X3 
Day 3, 8 (all ± 1 day) if hospitalized 
 
X 
 
X 
 
1 Refer to Section 8.1 of the protocol for details of clinical data to be collected including ordinal score, NEWS, oxygen requirement, mechanical 
ventilator requirement, etc. 
2 Screening laboratory tests include: ALT, AST, creatinine (and calculate an estimated glomerular filtration rate (eGFR) the formula used is 
determined by the sites, but should be consistent throughout the study), and urine or serum pregnancy test for females of child-bearing 
potential. Laboratory tests performed as part of routine clinical care in the 48 hours prior to enrollment will be accepted for determination of 
eligibility. 
3 Baseline assessments should be performed prior to first infusion. Laboratory tests performed as part of routine clinical care in the 24 hours 
prior to first dose will be accepted for the baseline safety laboratory tests. Baseline may be the same as the screening laboratory tests if 
obtained in the 24 hours prior to first dose. 
4 Safety laboratory tests include WBC with differential, hemoglobin, platelets, creatinine, total bilirubin, ALT, AST, and INR. 
5 Any laboratory tests performed as part of routine clinical care within the specified visit window can be used for safety laboratory testing. 


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PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
6 In-person visits are preferred but recognizing quarantine and other factors may limit the subject’s ability to return to the site for the visit. In 
this case, the visit may be performed by phone. 
• If still hospitalized at Day 15 and 29 or returns to the site for an in-person visit: assess adverse events, collect clinical data, vital signs, 
safety laboratory tests, and research laboratory samples (OP swab and blood) as able.  
• If phone call only on Days 15 and 29 and all Day 22 and Day 60 visits: assess adverse events, clinical status (ordinal scale), readmission 
to a hospital, and mortality only. 
7 Oropharyngeal swabs are preferred, but if these are not obtainable, saliva or nasopharyngeal or nasal swabs may be substituted.  
8 Pre-dose serum sample collections for PK and immunogenicity.  
9 To include markers of inflammation and coagulation: CRP, ferritin, fibrinogen, LDH, d-dimer.  
10 Day 8, 22 and 60 visits performed by phone if discharged from the site hospital: assess adverse events, clinical status (ordinal scale), 
readmission to a hospital, and mortality only. 
11 Only collected at selected sites capable of processing. 
12 Steroids and other concomitant therapies intended as specific treatment of COVID-19, as well as all biologics, will be assessed from 7 days 
prior to enrollment to Day 29. All other concomitant medications will be assessed from 7 days prior to enrollment to Day 15 or upon 
discharge, whichever comes first. 
13 Ordinal score only. 
14 Vital signs include temperature, systolic blood pressure, heart rate, respiratory rate, O2 saturation and level of consciousness. In addition, 
height and weight are obtained only at baseline (height can be self-reported). Vital signs collected as part of standard care may be used. 
15 Day 1 is defined as the calendar day of randomization. 
16 Blood draws for research labs may be omitted on any given study day if inappropriate for a subject’s clinical status per site investigator 
judgment. 


Statistical Analysis Plan - DMID Protocol: 20-0013  
Version 3.0 
23 May 2022 
- 82 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
10.2 
Protocol Deviations  
Table 11: 
Protocol Deviations—mITT Population 
Category 
Deviation Type 
Treatment A 
(N=X) 
Treatment B 
(N=X) 
Baseline Ordinal Scorea 
Baseline Ordinal Scorea 
5 
(N=x) 
6 
(N=x) 
7 
(N=x) 
Any BOSb 
(N=x) 
5 
(N=x) 
6 
(N=x) 
7 
(N=x) 
Any BOSb 
(N=x) 
# of 
Subj. 
# of 
Dev. 
# of 
Subj. 
# of 
Dev. 
# of 
Subj. 
# of 
Dev. 
# of 
Subj. 
# of 
Dev. 
# of 
Subj. 
# of 
Dev. 
# of 
Subj. 
# of 
Dev. 
# of 
Subj. 
# of 
Dev. 
# of 
Subj. 
# of 
Dev. 
Major Deviations 
Eligibility/randomization 
Any type 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
Did not meet inclusion criterion 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
Met exclusion criterion 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
ICF not signed prior to study 
procedures 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
Other 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Treatment administration 
schedule 
Any type 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
Out of window visit 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
Missed visit/visit not conducted 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
Missed treatment administration 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
Delayed treatment 
administration 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
Other 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Follow-up visit schedule 
Any type 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
Out of window visit 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
Missed visit/visit not conducted 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
Other 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Protocol procedure/ 
assessment 
Any type 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
Incorrect version of ICF signed 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
Blood not collected 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 


Statistical Analysis Plan - DMID Protocol: 20-0013  
Version 3.0 
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PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Category 
Deviation Type 
Treatment A 
(N=X) 
Treatment B 
(N=X) 
Baseline Ordinal Scorea 
Baseline Ordinal Scorea 
5 
(N=x) 
6 
(N=x) 
7 
(N=x) 
Any BOSb 
(N=x) 
5 
(N=x) 
6 
(N=x) 
7 
(N=x) 
Any BOSb 
(N=x) 
# of 
Subj. 
# of 
Dev. 
# of 
Subj. 
# of 
Dev. 
# of 
Subj. 
# of 
Dev. 
# of 
Subj. 
# of 
Dev. 
# of 
Subj. 
# of 
Dev. 
# of 
Subj. 
# of 
Dev. 
# of 
Subj. 
# of 
Dev. 
# of 
Subj. 
# of 
Dev. 
 
Oropharyngeal swab not 
collected 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
Other specimen not collected 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
Specimen result not obtained 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
Required procedure not 
conducted 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
Required procedure done 
incorrectly 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
Study product temperature 
excursion 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
Specimen temperature excursion 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
Stratification error 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
Other 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Treatment administration 
Any type 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
Required procedure done 
incorrectly 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
Study product temperature 
excursion 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
Other 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Blinding 
policy/procedure 
Any type 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
Treatment unblinded 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
Other 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Repeat for Minor Deviations 
BOS= Baseline Ordinal Score. 
N=Number of subjects in the modified intent-to-treat (mITT) population. n= Number of unique subjects that satisfies the row criteria.  
a There were X additional subjects with an Actual Baseline Ordinal Score of 4 that are included in the ‘Any BOS’ summaries. 


Statistical Analysis Plan - DMID Protocol: 20-0013  
Version 3.0 
23 May 2022 
- 84 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 12: 
Treatment Exposure and Compliance by Baseline Ordinal Score — Safety Population 
 
Treatment A 
(N=X) 
Treatment B 
(N=X) 
Baseline Ordinal Scorea 
Baseline Ordinal Scorea 
5 
(N=X) 
6 
(N=X) 
7 
(N=X) 
Any BOSb 
(N=X) 
5 
(N=X) 
6 
(N=X) 
7 
(N=X) 
Any BOSb 
(N=X) 
Number of Subjects Halted, Missed, or Slowed Doses 
 
 
 
 
 
 
 
 
Number of Subjects with Halted Doses 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
Number of Subjects with Slowed Doses 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
Number of Subjects with Missed Dosesc 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
BOS= Baseline Ordinal Score.  
N=Number of subjects in the Safety population. 
a Baseline Ordinal Score defined as: 5 (Moderate), 6 or 7 (Severe).   
b There were X additional subjects with an Actual Baseline Ordinal Score of 4 that are included in the ‘Any BOS’ summaries. 
c Missed doses refer to intermittent missing doses and do not include doses missed after treatment discontinuation. 
 


Statistical Analysis Plan - DMID Protocol: 20-0013  
Version 3.0 
23 May 2022 
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PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
14.1 
Description of Study Subjects 
14.1.1 Disposition of Subjects  
Table 13: 
Subject Disposition by Baseline Ordinal Score – ITT Population  
Subject Disposition  
Treatment A 
(N=X) 
Treatment B 
(N=X) 
All Subjects 
(N=X) 
5 
(N=X) 
6 
(N=X) 
7 
(N=X) 
Any BOSa 
(N=X) 
5 
(N=X) 
6 
(N=X) 
7 
(N=X) 
Any BOSa 
(N=X) 
5 
(N=X) 
6 
(N=X) 
7 
(N=X) 
Any BOSa 
(N=X) 
n/N 
% 
n/N 
% 
n/N 
% 
n/N 
% 
n/N 
% 
n/N 
% 
n/N 
% 
n/N 
% 
n/N 
% 
n/N 
% 
n/N 
% 
n/N 
% 
Randomized/Enrolledb 
x/x 
100 
x/x 
100 
x/x 
100 
x/x 
100 
x/x 
100 
x/x 
100 
x/x 
100 
x/x 
100 
x/x 
100 
x/x 
100 
x/x 
100 
x/x 
100 
Safety Populationc 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
x 
Discharged from Hospital 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
x 
Died During Follow-up 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
x 
Completed Follow-up (Study 
Day 1) – Hospitalized 
Subjects in Studyf 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
x 
Ordinal Scale Data 
Available 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
x 
Safety Laboratory Blood 
Draw 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
x 
Secondary Research Blood 
Draw 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
 
OP Swab Collection 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
x 
PCR or Proteomic Assays 
Blood Draw 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
x 
Serum Blood Draw 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
x 
Repeat for Days 3, 5, 8, 11 
Completed Follow-up (Study 
Day 15) – All Subjects in 
Studyf 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
x 
Ordinal Scale Data 
Available 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
x 


Statistical Analysis Plan - DMID Protocol: 20-0013  
Version 3.0 
23 May 2022 
- 86 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Subject Disposition  
Treatment A 
(N=X) 
Treatment B 
(N=X) 
All Subjects 
(N=X) 
5 
(N=X) 
6 
(N=X) 
7 
(N=X) 
Any BOSa 
(N=X) 
5 
(N=X) 
6 
(N=X) 
7 
(N=X) 
Any BOSa 
(N=X) 
5 
(N=X) 
6 
(N=X) 
7 
(N=X) 
Any BOSa 
(N=X) 
n/N 
% 
n/N 
% 
n/N 
% 
n/N 
% 
n/N 
% 
n/N 
% 
n/N 
% 
n/N 
% 
n/N 
% 
n/N 
% 
n/N 
% 
n/N 
% 
Safety Laboratory Blood 
Draw 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
x 
Secondary Research Blood 
Draw 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
 
OP Swab Collection 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
x 
PCR or Proteomic Assays 
Blood Draw 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
x 
Serum Blood Draw 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
x 
RNA Blood Draw 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
x 
PBMC Blood Draw 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
x 
Completed Follow-up (Study 
Day 22) – All Subjects in 
Study 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
x 
Ordinal Scale Data 
Available 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
x 
Completed Follow-up (Study 
Day 29) – All Subjects in 
Studyf 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
x 
Ordinal Scale Data 
Available 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
x 
Safety Laboratory Blood 
Draw 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
x 
Secondary Research Blood 
Draw 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
x 
OP Swab Collection 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
x 
PCR or Proteomic Assays 
Blood Draw 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
x 
Serum Blood Draw 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
x 


Statistical Analysis Plan - DMID Protocol: 20-0013  
Version 3.0 
23 May 2022 
- 87 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Subject Disposition  
Treatment A 
(N=X) 
Treatment B 
(N=X) 
All Subjects 
(N=X) 
5 
(N=X) 
6 
(N=X) 
7 
(N=X) 
Any BOSa 
(N=X) 
5 
(N=X) 
6 
(N=X) 
7 
(N=X) 
Any BOSa 
(N=X) 
5 
(N=X) 
6 
(N=X) 
7 
(N=X) 
Any BOSa 
(N=X) 
n/N 
% 
n/N 
% 
n/N 
% 
n/N 
% 
n/N 
% 
n/N 
% 
n/N 
% 
n/N 
% 
n/N 
% 
n/N 
% 
n/N 
% 
n/N 
% 
RNA Blood Draw 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
x 
PBMC Blood Draw 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
x 
Completed Follow-up (Study 
Day 60) – All Subjects in 
Studyf 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
x 
Ordinal Scale Data 
Available 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
x 
Treatment Completion 
Discontinued Treatmentd 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
x 
Reasons for Discontinuation 
of Treatmente 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
XXXX 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
x 
XXXX 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
x 
Study Completion 
 
 
 
 
 
 
 
 
Completed Study 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
x 
Did not Complete Study 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
x 
Reasons for Discontinuation 
of Study 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
XXXX 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
x 
XXXX 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
xx 
x/x 
x 
BOS= Baseline Ordinal Score. 
N=Number of subjects randomized/enrolled and in study for visits 1, 15, 22, 29, 60 and the number of subjects hospitalized and in study for visits 3,5, 8, and 11. Subjects that died or terminated early 
from the study on or prior to the study visit are not included in the denominators. n= Number of unique subjects that satisfy the row criteria. 
aThere were X additional subjects with an Actual Baseline Ordinal Score of 4 that are included in the ‘Any BOS’ summaries. 
b Represents the number of subjects who were randomized to either treatment arm. 
c Represents the number of subjects who received any amount of investigational agent.    
d Refers to the discontinuation of the investigational agent or placebo.  
eRefer to Listing 1 for the individual reasons subjects discontinued or terminated early.   
f Visit completion is as completing a visit for that day or another day that is in window for the corresponding visit. 


Statistical Analysis Plan - DMID Protocol: 20-0013  
Version 3.0 
23 May 2022 
- 88 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
 
Programming 
• Update milestones for each visit based on stage-specific schedule of events.  
• Had any infusions stopped or slowed:  if the question “Was full infusion administered successfully?” is marked “slowed or stopped” for either 
treatment, subject will be counted in this row. 
• Completed all Required Investigational Infusions: if treatment was not discontinued, then subject will be counted in this row. 
• Completed all Blood Draws: If there are not any blood draws that were “Not done”, then subject will be counted in this row.  
 


Statistical Analysis Plan - DMID Protocol: 20-0013  
Version 3.0 
23 May 2022 
- 89 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
14.1.2 Demographic Data by Study Group  
Table 14: 
Categorical Demographics and Medical History – ITT Population 
Demographic Category 
Characteristic 
Treatment A 
(N=X) 
Treatment B 
(N=X) 
All Subjects 
(N=X) 
5 
(N=X) 
6 
(N=X) 
7 
(N=X) 
Any 
BOSa 
(N=X) 
5 
(N=X) 
6 
(N=X) 
7 
(N=X) 
Any 
BOSa 
(N=X) 
5 
(N=X) 
6 
(N=X) 
7 
(N=X) 
Any 
BOSa 
(N=X) 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Age 
<40 years old 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
40-64 years old 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
≥65 years old 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Sex  
Male 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Female 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Ethnicity  
Not Hispanic or Latino 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Hispanic or Latino 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Not Reported 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Unknown 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Race  
American Indian or Alaska Native 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Asian 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Native Hawaiian or Other Pacific Islander 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Black or African American 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
White 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Multi-Racial 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Unknown 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Baseline Ordinal Score 
4 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
5 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
6 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
7 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Any BOS 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 


Statistical Analysis Plan - DMID Protocol: 20-0013  
Version 3.0 
23 May 2022 
- 90 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Demographic Category 
Characteristic 
Treatment A 
(N=X) 
Treatment B 
(N=X) 
All Subjects 
(N=X) 
5 
(N=X) 
6 
(N=X) 
7 
(N=X) 
Any 
BOSa 
(N=X) 
5 
(N=X) 
6 
(N=X) 
7 
(N=X) 
Any 
BOSa 
(N=X) 
5 
(N=X) 
6 
(N=X) 
7 
(N=X) 
Any 
BOSa 
(N=X) 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Steroid Use 
Yes 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
No 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Comorbidities 
History of Medication Allergies 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Diabetes Type I 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Diabetes Type II 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Obesity 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Chronic Kidney Disease 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Chronic Liver Disease (e.g., chronic 
hepatitis, cirrhosis) 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Chronic Respiratory Disease (e.g., COPD, 
emphysema) 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Respiratory Support (e.g., CPAP, BiPAP) 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Asthma 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Current Nicotine Consumption (any 
amount daily) 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Chronic Oxygen Requirement 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Coronary Artery Disease 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Cardiac Valvular Disease 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Hypertension 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Congestive Heart Failure 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Cancer 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Immune Deficiency (acquired or innate) 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Coagulopathy 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 


Statistical Analysis Plan - DMID Protocol: 20-0013  
Version 3.0 
23 May 2022 
- 91 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Demographic Category 
Characteristic 
Treatment A 
(N=X) 
Treatment B 
(N=X) 
All Subjects 
(N=X) 
5 
(N=X) 
6 
(N=X) 
7 
(N=X) 
Any 
BOSa 
(N=X) 
5 
(N=X) 
6 
(N=X) 
7 
(N=X) 
Any 
BOSa 
(N=X) 
5 
(N=X) 
6 
(N=X) 
7 
(N=X) 
Any 
BOSa 
(N=X) 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Participating in another clinical trial 
or plan to enroll in another trial in 
next 30 days 
Yes 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
No 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Baseline NEW Score 
0 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
1 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
2 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
3 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
[Add the rest of observed NEW score 
values] 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
N = Number of enrolled subjects in the ITT population.  
n = Number of subjects that satisfy the row criteria. 
a There were X additional subjects with an Actual Baseline Ordinal Score of 4 that are included in the ‘Any BOS’ summaries. 
 
 


Statistical Analysis Plan - DMID Protocol: 20-0013  
Version 3.0 
23 May 2022 
- 92 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 15: 
Continuous Demographics and Medical History – ITT Population 
Variable 
Statistic 
Treatment A 
(N=X) 
Treatment B 
(N=X) 
All Subjects 
(N=X) 
5 
(N=X) 
6 
(N=X) 
7 
(N=X) 
Any BOSa 
(N=X) 
5 
(N=X) 
6 
(N=X) 
7 
(N=X) 
Any BOSa 
(N=X) 
5 
(N=X) 
6 
(N=X) 
7 
(N=X) 
Any BOSa 
(N=X) 
Age (years) 
n 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Mean  
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Standard Deviation 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Median 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Minimum 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Maximum 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Height (cm) 
n 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Mean 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Standard Deviation 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Median 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Minimum 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Maximum 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Weight (kg) 
n 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Mean 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Standard Deviation 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Median 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Minimum 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Maximum 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
BMI (kg/m2) 
n 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Mean 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Standard Deviation 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Median 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Minimum 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Maximum 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 


Statistical Analysis Plan - DMID Protocol: 20-0013  
Version 3.0 
23 May 2022 
- 93 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Variable 
Statistic 
Treatment A 
(N=X) 
Treatment B 
(N=X) 
All Subjects 
(N=X) 
5 
(N=X) 
6 
(N=X) 
7 
(N=X) 
Any BOSa 
(N=X) 
5 
(N=X) 
6 
(N=X) 
7 
(N=X) 
Any BOSa 
(N=X) 
5 
(N=X) 
6 
(N=X) 
7 
(N=X) 
Any BOSa 
(N=X) 
Duration of Symptoms Prior to 
Randomization (days) 
n 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Mean 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Standard Deviation 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Minimum 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Maximum 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Baseline CRP 
n 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Mean  
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Standard Deviation 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Median 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Minimum 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Maximum 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Baseline Ferritin 
n 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Mean  
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Standard Deviation 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Median 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Minimum 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Maximum 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Baseline D-Dimer  
n 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Mean  
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Standard Deviation 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Median 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Minimum 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Maximum 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 


Statistical Analysis Plan - DMID Protocol: 20-0013  
Version 3.0 
23 May 2022 
- 94 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Variable 
Statistic 
Treatment A 
(N=X) 
Treatment B 
(N=X) 
All Subjects 
(N=X) 
5 
(N=X) 
6 
(N=X) 
7 
(N=X) 
Any BOSa 
(N=X) 
5 
(N=X) 
6 
(N=X) 
7 
(N=X) 
Any BOSa 
(N=X) 
5 
(N=X) 
6 
(N=X) 
7 
(N=X) 
Any BOSa 
(N=X) 
Baseline Fibrinogen 
n 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Mean  
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Standard Deviation 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Median 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Minimum 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Maximum 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Baseline LDH 
Mean  
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Standard Deviation 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Median 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Minimum 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Maximum 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
SD=Standard Deviation. BMI=Body Mass Index. LDH= Lactate Dehydrogenase. CRP=C-Reactive Protein. 
N=Number of subjects in the ITT population. n=number of subjects with a non-missing assessment. 
 
 


Statistical Analysis Plan - DMID Protocol: 20-0013  
Version 3.0 
23 May 2022 
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PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
14.2 
Efficacy Data  
Table 16: 
Global Odds Ratios for Inferior Clinical Status Score at Study Visit Day 8 Using a Proportional Odds Model — mITT Population 
Analysis/Subgroup 
Category 
Treatment A 
(N=x) 
Treatment B 
(N=x) 
Odds Ratio 
P-value 
n 
n 
Estimate 
95% CI 
80% CI 
Initial model, MI for subjects without a discharge to a location other than 
LTAC, hospice or other hospitala 
- 
x 
X 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
Sensitivity/Supplemental Analyses 
Primary with Sensitivity Imputation 1: MI for All Subjects with Missing Datab 
- 
x 
x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
Primary with Sensitivity Imputation 2: Complete Datac 
- 
x 
x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
Sensitivity Analysis 1: Impact of Investigational site, MId 
- 
x 
x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
Supplemental Analysis 1: Impact of age and duration of symptoms prior to 
enrollment, MIe 
- 
x 
x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
Supplemental Analysis 2: Baseline Use of Emerging Covid-19 Treatment, MIf 
 
 
 
 
 
 
 
Any Baseline Use of Emerging Covid-19 Treatments 
- 
x 
x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
Corticosteroids Use 
- 
x 
x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
Monoclonal Antibodies Use 
- 
x 
x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
Other Anti-Inflammatory Drugs Use 
- 
x 
x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
Subgroup Analyses, Complete Datag 
Baseline Ordinal Score 
5 
x 
x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
6 or 7 
x 
x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
P-value for interactionh 
 
 
 
 
 
0.xxx 
Baseline Use of Steroid 
Yes 
x 
x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
No 
x 
x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
P-value for interactionh 
 
 
 
 
 
0.xxx 
Baseline Use of Emerging Covid-19 Treatments 
Yes 
x 
x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
No 
x 
x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
P-value for interactionh 
x 
x 
 
 
 
0.xxx 


Statistical Analysis Plan - DMID Protocol: 20-0013  
Version 3.0 
23 May 2022 
- 96 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Analysis/Subgroup 
Category 
Treatment A 
(N=x) 
Treatment B 
(N=x) 
Odds Ratio 
P-value 
n 
n 
Estimate 
95% CI 
80% CI 
Duration of Symptoms Prior to Enrollment Group 1 
≤ Median 
x 
x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
> Median 
x 
x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
P-value for interactionh 
 
 
 
 
 
0.xxx 
Duration of Symptoms Prior to Enrollment Group 2 
< 25th percentile 
x 
x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
25<75th percentile 
x 
x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
≥75th percentile 
x 
x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
P-value for interactionh 
 
 
 
 
 
0.xxx 
Race 
White 
x 
x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
Black/African 
American 
x 
x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
Asian 
x 
x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
Other 
x 
x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
P-value for interactionh 
 
 
 
 
 
0.xxx 
Ethnicity  
Hispanic or Latino 
x 
x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
Not Hispanic or Latino 
x 
x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
P-value for interactionh 
 
 
 
 
 
0.xxx 
Comorbidities Group 1 
None 
x 
x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
Any 
x 
x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
P-value for interactionh 
 
 
 
 
 
0.xxx 
Comorbidities Group 2 
One 
x 
x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
Two or More 
x 
x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
P-value for interactionh 
 
 
 
 
 
0.xxx 
Comorbidities Group 3 
Obese 
x 
x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
Non-obese 
x 
x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
P-value for interactionh 
 
 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 


Statistical Analysis Plan - DMID Protocol: 20-0013  
Version 3.0 
23 May 2022 
- 97 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Analysis/Subgroup 
Category 
Treatment A 
(N=x) 
Treatment B 
(N=x) 
Odds Ratio 
P-value 
n 
n 
Estimate 
95% CI 
80% CI 
Age Group 
< 40 
x 
x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
41-64 
x 
x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
65 and older 
x 
x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
P-value for interactionh 
 
 
 
 
 
0.xxx 
Sex 
Male 
x 
x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
Female 
x 
x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
P-value for interactionh 
 
 
 
 
 
0.xxx 
CI=Confidence Internals. OR=Odds Ratios. NA=Not applicable. MI=Multiple Imputation. 
N=Number of subjects in the modified-intent-to-treat (mITT) population. 
n=Number of subjects with non-missing Day 8 ordinal score for each treatment group. 
a Odds Ratios calculated for the odds of moving down the ordinal score using a proportional odds model where the clinical status (8- point ordinal scale) is the dependent variable, odds ratios compare 
Active treatment vs Placebo. Subjects discharged to a location other than LTAC, hospice or other hospital at their last assessment were assigned a score of 2 for all timepoints after last assessment, and 
MI will be used to impute data for remaining subjects missing ordinal score data without a good discharge status after their last assessment. 
b Primary with Sensitivity Imputation 1:  Multiple imputation was used to impute missing data after last assessment for all subjects. The model described in a was used to estimate the OR, 95% CI, 80% 
CI and p-values. 
c Primary with Sensitivity Imputation 2: The model described in a was used to estimate the OR, 95% CI, 80% CI and p-values using complete data. 
d Sensitivity Analysis 1 (impact of investigational site): In addition to the variable included in the model described in a, the investigational site was added to the model when estimating the OR, 95% CI 
and p-values using the same multiple imputation approach as the primary analysis in a. 
 e Supplemental Analysis 1 (age and duration of symptoms prior to enrollment): In addition to the variable included in the model described in a, age and duration of symptoms prior to enrollment as 
additional covariates were added to the model when estimating the OR, 95% CI, 80% CI, and p-values using the same multiple imputation approach as the primary analysis in a. 
f Supplemental Analysis 2 (by Baseline COVID-19 treatment category): In addition to the variable included in the model described in a, baseline use of COVID-19 treatment as additional covariates were 
added to the model when estimating the OR, 95% CI, 80% CI, and p-values using the same multiple imputation approach as the primary analysis in a. Additional models using use of each COVID-19 
treatment category as a covariate separately. 
g For the subgroup analyses, the model described in a using complete data was performed for each level of the subgroup. 
h P-Value for treatment difference or P-value from interaction Type III test in subgroup analysis where the interaction between subgroup and treatment is being added to the model. 
 


Statistical Analysis Plan - DMID Protocol: 20-0013  
Version 3.0 
23 May 2022 
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PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Tables with similar format:  
[Implementation notes: For analyses using Day 15 and Day 29, perform all the analyses using complete data. Delete Primary with Sensitivity 
Imputation 1 and Primary with Sensitivity Imputation 2 analyses.] 
Table 17: 
Global Odds Ratios for Inferior Clinical Status Score at Study Visit Day 15 Using a Proportional Odds Model — mITT 
Population 
Table 18: 
Global Odds Ratios for Inferior Clinical Status Score at Study Visit Day 29 Using a Proportional Odds Model — mITT 
Population 
Table 19: 
Global Odds Ratios for Inferior Clinical Status Score at Study Visit Day 8 Using a Proportional Odds Model — ITT Population 
Table 20: 
Global Odds Ratios for Inferior Clinical Status Score at Study Visit Day 15 Using a Proportional Odds Model  — ITT Population 
Table 21: 
Global Odds Ratios for Inferior Clinical Status Score at Study Visit Day 29 Using a Proportional Odds Model — ITT Population 
 


Statistical Analysis Plan - DMID Protocol: 20-0013  
Version 3.0 
23 May 2022 
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PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 22: 
Proportional Odds Model for Clinical Status Score at Study Visit 8 – Odds Ratios 
Between the Binary Progression Strata with Multiple Imputation — mITT Population 
OS Table 
Comparison 
Treatment 
Lower OS 
Higher OS 
Odds Ratio 
OR (80% CI) 
Odds Ratio 
OR (95% CI) 
P-value X2 
P-value 
Fisher’s Exact 
n 
% 
n 
% 
1 vs 2-8 
Treatment A (N=X) 
x 
xx.x 
x 
xx.x 
x.xx (x.xx, x.xx) 
x.xx (x.xx, x.xx) 
0.xxx 
0.xxx 
Treatment B (N=X) 
x 
xx.x 
x 
xx.x 
1-2 vs 3-8 
Treatment A (N=X) 
x 
xx.x 
x 
xx.x 
x.xx (x.xx, x.xx) 
x.xx (x.xx, x.xx) 
0.xxx 
0.xxx 
Treatment B (N=X) 
x 
xx.x 
x 
xx.x 
1-3 vs 4-8 
Treatment A (N=X) 
x 
xx.x 
x 
xx.x 
x.xx (x.xx, x.xx) 
x.xx (x.xx, x.xx) 
0.xxx 
0.xxx 
Treatment B (N=X) 
x 
xx.x 
x 
xx.x 
1-4 vs 5-8 
Treatment A (N=X) 
x 
xx.x 
x 
xx.x 
x.xx (x.xx, x.xx) 
x.xx (x.xx, x.xx) 
0.xxx 
0.xxx 
Treatment B (N=X) 
x 
xx.x 
x 
xx.x 
1-5 vs 6-8 
Treatment A (N=X) 
x 
xx.x 
x 
xx.x 
x.xx (x.xx, x.xx) 
x.xx (x.xx, x.xx) 
0.xxx 
0.xxx 
Treatment B (N=X) 
x 
xx.x 
x 
xx.x 
1-6 vs 7-8 
Treatment A (N=X) 
x 
xx.x 
x 
xx.x 
x.xx (x.xx, x.xx) 
x.xx (x.xx, x.xx) 
0.xxx 
0.xxx 
Treatment B (N=X) 
x 
xx.x 
x 
xx.x 
1-7 vs 8 
Treatment A (N=X) 
x 
xx.x 
x 
xx.x 
x.xx (x.xx, x.xx) 
x.xx (x.xx, x.xx) 
0.xxx 
0.xxx 
Treatment B (N=X) 
x 
xx.x 
x 
xx.x 
OS= Ordinal Score. CI= Confidence Interval. N=Number of subjects in modified intent-to-treat (mITT) population. n= Number of unique 
subjects that satisfies the row criteria. 
 
Tables with similar format 
[Implementation note: For analyses using Day 15 and Day 29, repeat the analysis using complete data.] 
Table 23: 
Proportional Odds Model for Clinical Status Score at Study Visit 8 – Odds Ratios 
Between the Binary Progression Strata with Multiple Imputation — ITT Population 
Table 24: 
Proportional Odds Model for Clinical Status Score at Study Visit 15 – Odds Ratios 
Between the Binary Progression Strata without Multiple Imputation — mITT Population 
Table 25: 
Proportional Odds Model for Clinical Status Score at Study Visit 15 – Odds Ratios 
Between the Binary Progression Strata without Multiple Imputation — ITT Population 
Table 26: 
Proportional Odds Model for Clinical Status Score at Study Visit 29 – Odds Ratios 
Between the Binary Progression Strata without Multiple Imputation — mITT Population 
Table 27: 
Proportional Odds Model for Clinical Status Score at Study Visit 29 – Odds Ratios 
Between the Binary Progression Strata without Multiple Imputation — ITT Population 
 


Statistical Analysis Plan - DMID Protocol: 20-0013  
Version 3.0 
23 May 2022 
- 100 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 28: 
Time to Sustained Recovery through Day 60 — mITT Population 
Analysis/Subgroup 
Treatment 
Number of Recovered Subjects 
Median Time Until Recovery 
Hazard Ratio 
P-valuee 
n 
% 
Estimate 
80% CI 
95% CI 
Estimate 
95% CI 
Initial Model a 
Treatment A (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
0.xxx 
Treatment B (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
Sensitivity Analyses 
Primary with Sensitivity Imputation 1: Imputation for good 
dischargesb 
Treatment A (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
0.xxx 
Treatment B (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
Supplemental Analysis 1: Impact of age and duration of 
symptomsc 
Treatment A (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
0.xxx 
Treatment B (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
Subgroup Analysesd 
Baseline Ordinal Score 
5 
Treatment A (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
0.xxx 
Treatment B (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
6 or 7 
Treatment A (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
0.xxx 
Treatment B (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
 
P-value for interactione 
 
 
 
 
 
 
 
0.xxx 
Baseline Steroid Use 
Yes 
Treatment A (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
0.xxx 
Treatment B (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
No 
Treatment A (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
0.xxx 
Treatment B (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
P-value for interactione 
 
 
 
 
 
 
 
0.xxx 
Baseline Use of Emerging Covid-19 Treatments 
Yes 
Treatment A (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
 
Treatment B (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
No 
Treatment A (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
0.xxx 
Treatment B (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 


Statistical Analysis Plan - DMID Protocol: 20-0013  
Version 3.0 
23 May 2022 
- 101 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Analysis/Subgroup 
Treatment 
Number of Recovered Subjects 
Median Time Until Recovery 
Hazard Ratio 
P-valuee 
n 
% 
Estimate 
80% CI 
95% CI 
Estimate 
95% CI 
P-value for interactione 
 
 
 
 
 
 
 
0.xxx 
Duration of Symptoms Prior to Enrollment Group 1 
≤ Median 
Treatment A (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
0.xxx 
Treatment B (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
> Median 
Treatment A (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
0.xxx 
Treatment B (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
P-value for interactione 
 
 
 
 
 
 
 
0.xxx 
Duration of Symptoms Prior to Enrollment Group 2 
< 25th percentile 
Treatment A (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
0.xxx 
Treatment B (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
25 ≤ 75th percentile 
Treatment A (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
0.xxx 
Treatment B (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
≥ 75th percentile 
Treatment A (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
0.xxx 
Treatment B (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
P-value for interactione 
x 
x.x 
 
 
 
 
 
0.xxx 
Race 
White 
Treatment A (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
0.xxx 
Treatment B (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
Black/African American 
Treatment A (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
0.xxx 
Treatment B (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
Asian 
Treatment A (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
0.xxx 
Treatment B (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
Other 
Treatment A (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
0.xxx 
Treatment B (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
P-value for interactione 
 
 
 
 
 
 
 
0.xxx 


Statistical Analysis Plan - DMID Protocol: 20-0013  
Version 3.0 
23 May 2022 
- 102 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Analysis/Subgroup 
Treatment 
Number of Recovered Subjects 
Median Time Until Recovery 
Hazard Ratio 
P-valuee 
n 
% 
Estimate 
80% CI 
95% CI 
Estimate 
95% CI 
Ethnicity 
Hispanic or Latino 
Treatment A (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
x.x  
x.x, x.x  
0.xxx  
Treatment A (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
Not Hispanic or Latino 
Treatment A (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
x.x  
x.x, x.x  
0.xxx  
Treatment A (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
P-value for interactione 
 
 
 
 
 
 
 
0.xxx 
Comorbidities Group 1 
None 
Treatment A (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
0.xxx 
Treatment B (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
Any 
Treatment A (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
0.xxx 
Treatment B (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
P-value for interactione 
 
 
 
 
 
0.xxx 
Comorbidities Group 2 
One 
Treatment A (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
0.xxx 
Treatment B (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
Two or More 
Treatment A (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
0.xxx 
Treatment B (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
P-value for interactione 
 
 
 
 
 
 
 
 
Comorbidities Group 3 
Obese 
Treatment A (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
0.xxx 
Treatment B (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
Non-obese 
Treatment A (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
0.xxx 
Treatment B (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
P-value for interactione 
 
 
 
 
 
 
 
0.xxx 


Statistical Analysis Plan - DMID Protocol: 20-0013  
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Analysis/Subgroup 
Treatment 
Number of Recovered Subjects 
Median Time Until Recovery 
Hazard Ratio 
P-valuee 
n 
% 
Estimate 
80% CI 
95% CI 
Estimate 
95% CI 
Age Group 
< 40 
Treatment A (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
0.xxx 
Treatment B (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
41-64 
Treatment A (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
0.xxx 
Treatment B (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
65 and older 
Treatment A (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
0.xxx 
Treatment B (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
P-value for interactione 
 
 
 
 
 
 
 
0.xxx 
Sex 
Male 
Treatment A (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
0.xxx 
Treatment B (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
Female 
Treatment A (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
0.xxx 
Treatment B (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
P-value for interactione 
 
 
 
 
 
 
 
0.xxx 
CI=Confidence Intervals. N=Number of subjects in modified intent-to-treat (mITT) population. n= Number of unique recovered subjects that satisfies the row criteria.  
a Hazard Ratio (HR) is the hazard ratio calculated from the Cox Proportional Hazard Model comparing Active treatment vs Placebo.  All subjects lost to follow-up before recovery are censored at last 
assessment date. 
b Primary with Sensitivity Imputation 1: Subjects discharged to a location other than LTAC, hospice care, or other hospital are considered recovered at Day 60. The rest of lost to follow-up subjects are 
censored at last assessment date. Model a was fit to estimate the HR, 95% CI and p-values. 
c Supplemental Analysis 1 (age and duration of symptoms prior to enrollment): In addition to the variable included in the model described in a, age and duration of symptoms prior to enrollment as 
additional covariates were added to the model when estimating the HR, 95% CI and p-values. Same censoring as in model a. 
d For the subgroup analyses, the model described in a was performed for each level of the subgroup.   
e P-value is based on the Cox adjusted model or P-value from interaction Type III test in subgroup analysis where the interaction between subgroup and treatment is being added to the Cox Proportional 
Hazard Model.  
 


Statistical Analysis Plan - DMID Protocol: 20-0013  
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Table 29: 
Time to Sustained Recovery through Day 60 by Treatment Group, Actual Baseline Ordinal Score, and Analysis Population: 
Restricted Mean Survival Time Analysis  
Analysis Population 
Treatment Group 
Actual Baseline 
Ordinal Score 
n 
Taua 
Restricted Mean Recovery Time (Days) 
Difference 
Estimate 
95% CI 
80% CI 
Estimate 
95% CI 
80% CI 
mITT 
Treatment A (N=X) 
5 
x 
x 
x.x 
x.x, x.x 
x.x, x.x 
x.xx 
 
x.xx, x.xx 
 
x.xx, x.xx 
 
Treatment B (N=X) 
x 
x 
x.x 
x.x, x.x 
x.x, x.x 
Treatment A (N=X) 
6 
x 
x 
x.x 
x.x, x.x 
x.x, x.x 
x.xx 
x.xx, x.xx 
x.xx, x.xx 
Treatment B (N=X) 
x 
x 
x.x 
x.x, x.x 
x.x, x.x 
Treatment A (N=X) 
7 
x 
x 
x.x 
x.x, x.x 
x.x, x.x 
x.xx 
x.xx, x.xx 
x.xx, x.xx 
Treatment B (N=X) 
x 
x 
x.x 
x.x, x.x 
x.x, x.x 
Treatment A (N=X) 
Any BOS 
x 
x 
x.x 
x.x, x.x 
x.x, x.x 
x.xx 
x.xx, x.xx 
x.xx, x.xx 
Treatment B (N=X) 
x 
x 
x.x 
x.x, x.x 
x.x, x.x 
ITT 
Treatment A (N=X) 
5 
x 
x 
x.x 
x.x, x.x 
x.x, x.x 
x.xx 
x.xx, x.xx 
x.xx, x.xx 
Treatment B (N=X) 
x 
x 
x.x 
x.x, x.x 
x.x, x.x 
Treatment A (N=X) 
6 
x 
x 
x.x 
x.x, x.x 
x.x, x.x 
x.xx 
x.xx, x.xx 
x.xx, x.xx 
Treatment B (N=X) 
x 
x 
x.x 
x.x, x.x 
x.x, x.x 
Treatment A (N=X) 
7 
x 
x 
x.x 
x.x, x.x 
x.x, x.x 
x.xx 
x.xx, x.xx 
x.xx, x.xx 
Treatment B (N=X) 
x 
x 
x.x 
x.x, x.x 
x.x, x.x 
Treatment A (N=X) 
Any BOS 
x 
x 
x.x 
x.x, x.x 
x.x, x.x 
x.xx 
x.xx, x.xx 
x.xx, x.xx 
Treatment B (N=X) 
x 
x 
x.x 
x.x, x.x 
x.x, x.x 
N = Number of subjects in the specified treatment group, actual baseline ordinal score, and analysis population.  
n = Number of recovered subjects.  
Difference is the difference in the restricted mean recovery time between active treatment to placebo. 
a Tau is the truncation time point for the Restricted Mean Survival Time analysis and is equal to the minimum of the largest observed times in each group. 
Programming  
Within an actual baseline ordinal score stratum: 
proc lifetest data=enrevent plots=(rmst) method=breslow rmst(cl); 
by stratum; 
time evntday * Censor(1); 
strata trtcode /diff=all; 
ods output  rmst=rmst; 
run; 


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Table 30: 
Proportion of Subjects Alive and Without Respiratory Failure through Day 29 — mITT Population 
Analysis/Subgroup 
Category 
Treatment A 
(N=x) 
Treatment B 
(N=x) 
Odds Ratio 
Risk Differenceg 
P-valueh 
n 
% 
(95%CI)f 
n 
% (95%CI)f Estimate 
95% CI 
80% 
CI 
Estimate 
95% CI 
80% 
CI 
Initial model, Age, Baseline OS, 
Dexamethasone Use, and CRPa 
- 
x 
x.x (x.x, x.x) 
X 
x.x (x.x, x.x) 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
Primary with Sensitivity Imputation 1b 
- 
x 
x.x (x.x, x.x) 
X 
x.x (x.x, x.x) 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
Sensitivity Analysis 1: Baseline OS and 
Steroid Usec 
- 
x 
x.x (x.x, x.x) 
x 
x.x (x.x, x.x) 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
Supplemental Analysis 1: Impact of age 
and duration of symptoms prior to 
enrollmentd 
- 
x 
x.x (x.x, x.x) 
x 
x.x (x.x, x.x) 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
Subgroup Analysese 
Baseline Ordinal Score 
5 
x 
x.x (x.x, x.x) 
x 
x.x (x.x, x.x) 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
6 or 7 
x 
x.x (x.x, x.x) 
x 
x.x (x.x, x.x) 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
Repeat for all subgroups from Table 6 
 
x 
x.x (x.x, x.x) 
x 
x.x (x.x, x.x) 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
CI=Confidence Internals. OR=Odds Ratios. NA=Not applicable.  
N=Number of subjects in the modified-intent-to-treat (mITT) population. n=Number of subjects without respiratory failure or death through Day 29.  
a Odds Ratios of Active treatment vs Placebo calculated from the logistic regression model adjusted for baseline dexamethasone use, baseline OS, age, and baseline CRP. Subjects lost to follow-up 
before Day 26 (beginning of Day 29 window) and before experiencing death or progression to mechanical ventilation will be considered non-events and censored at the last assessment. 
b Primary with Sensitivity Imputation 1: Subjects lost to follow-up before Day 26 (beginning of Day 29 window) and before experiencing death or progression to mechanical ventilation who were 
discharged to a location other than LTAC, hospice care, or other hospital were considered non-events and censored at Day 29 while those still hospitalized or discharged to LTAC, hospice care, or 
other hospital were censored at the last assessment. 
c Sensitivity Analysis 1: Same analysis as in the initial model but only using baseline ordinals score and baseline steroid use as covariates in the logistic regression model. 
d Supplemental Analysis 1 (age and duration of symptoms prior to enrollment): In addition to the variable included in the model described in a, age and duration of symptoms prior to enrollment as 
additional covariates were added to the model when estimating the OR, 95% CI and p-values  
e For the subgroup analyses, the model described in a was performed for each level of the subgroup.  
f Kaplan-Meier estimates and confidence intervals are reported. All subjects whose last assessment in the study is before Day 29 and before experiencing death or progression to mechanical ventilation 
were considered non-events and censored at last assessment. 
g Risk Differences calculated using the approach described in Ge.et al [2]. CIs calculated using bootstrap. 
h P-Value from the logistic regression model. 
 


Statistical Analysis Plan - DMID Protocol: 20-0013  
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Table 31: 
Proportion of Subjects Alive and Without Respiratory Failure at Study Day 29 — mITT Population 
Status 
Treatment A 
(N=X) 
Treatment B 
(N=X) 
P-value 
n  
% 
80% CI 
95% CI 
n 
% 
80% CI 
95% CI 
Initial Analysisa 
Alive and Without Respiratory Failure 
x 
xx 
x.x, x.x 
x.x, x.x 
x 
xx 
x.x, x.x 
x.x, x.x 
0.xxx  
Respiratory Failure or Death 
x 
xx 
x.x, x.x 
x.x, x.x 
x 
xx 
x.x, x.x 
x.x, x.x 
Subgroup Analyses: Alive and Without Respiratory Failureb 
Baseline Ordinal Score 
 
 
 
 
 
 
 
 
 
5 
x 
xx 
x.x, x.x 
x.x, x.x 
x 
xx 
x.x, x.x 
x.x, x.x 
0.xxx 
6 or 7 
x 
xx 
x.x, x.x 
x.x, x.x 
x 
xx 
x.x, x.x 
x.x, x.x 
0.xxx 
Repeat for the subgroups presented in Table 6 
 
 
 
 
 
 
 
 
 
CI= Confidence Interval. N=Number of subjects in modified intent-to-treat (mITT) population. n= Number of unique subjects that satisfies the row criteria. 
a The table includes 80% and 95% Blaker confidence intervals and p-value from the logistic regression with treatment group as the only covariate.  
b For the subgroup analyses, only the values for the “Alive and Without Respiratory Failure” are presented and analyses similar to those in a were performed.  
 


Statistical Analysis Plan - DMID Protocol: 20-0013  
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Table 32: 
Time to Improvement by at Least One Category through Day 60 in the 8-point Ordinal Scale — mITT Population 
Analysis/Subgroup 
Treatment 
Number of Recovered Subjects 
Median Time to Recovery 
Hazard Ratio 
P-valuec 
n 
% 
Estimate 
80% CI 
95% CI 
Estimate 
80% CI 
95% CI 
Initial Modela 
Treatment A (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
Treatment B (N=X) 
x  
x.x 
x.x 
x.x, x.x 
x.x, x.x 
Subgroup Analysesb 
Baseline Ordinal Score 
5 
Treatment A (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
Treatment B (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
6 or 7 
Treatment A (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
Treatment B (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
Other 
Treatment A (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
Treatment B (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
Baseline Steroid Use 
Yes 
Treatment A (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
Treatment B (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
No 
Treatment A (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
Treatment B (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
Baseline Use of Emerging Covid-19 Treatments 
Yes 
Treatment A (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
x.x, x.x 
 
Treatment B (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
No 
Treatment A (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
Treatment B (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
Duration of Symptoms Prior to Enrollment Group 1 
≤ Median 
Treatment A (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
Treatment B (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
> Median 
Treatment A (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
Treatment B (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 


Statistical Analysis Plan - DMID Protocol: 20-0013  
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Analysis/Subgroup 
Treatment 
Number of Recovered Subjects 
Median Time to Recovery 
Hazard Ratio 
P-valuec 
n 
% 
Estimate 
80% CI 
95% CI 
Estimate 
80% CI 
95% CI 
Duration of Symptoms Prior to Enrollment Group 2 
< 25th percentile 
Treatment A (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
Treatment B (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
25 ≤ 75th percentile 
Treatment A (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
Treatment B (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
≥ 75th percentile 
Treatment A (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
Treatment B (N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
CI=Confidence Intervals. Improvement is defined by an Improvement by at least One Category in the 8-point Ordinal Scale. N=Number of subjects in modified intent-to-treat (mITT) population. n= 
Number of unique subjects that satisfies the row criteria.  
a Hazard Ratio (HR) is the hazard ratio calculated from the Cox Proportional Hazard Model comparing Active treatment to placebo adjusting for baseline ordinal score and baseline steroid use.    
b For the subgroup analyses, the model described in a was performed for each level of the subgroup. The subgroup variable was removed from the model where applicable. 
c P-value is based on the Score test from Cox model.    
 
Table with similar format:  
Table 33: 
Time to Improvement by at Least Two Categories through Day 60 in the 8-point Ordinal Scale — mITT Population 
 


Statistical Analysis Plan - DMID Protocol: 20-0013  
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Table 34: 
Summary of Change from Baseline of Ordinal Score by Study Day — mITT Population 
Subgroup 
Study 
Day 
Treatment 
Categories Worsening 
Same 
Category Improvement 
3 
2 
1 
1 
2 
3 
4 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Primary analysis 
Day 3 
Treatment A (N=X) 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
Treatment B (N=X) 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
Day X 
Treatment A (N=X) 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
Treatment B (N=X) 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
X 
x.x 
x 
x.x 
x 
x.x 
Subgroup Analysis 
Baseline Ordinal Score 
5 
Day 3 
Treatment A (N=X) 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
Treatment B (N=X) 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
Day X 
Treatment A (N=X) 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
Treatment B (N=X) 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
Repeat the above rows for Change from Baseline and Study Days 5, 8, 11, 15, 22, 29, and 60. Repeat for all subgroups specified in Table 6. 
N=Number of subjects in modified intent-to-treat (mITT) population. n= Number of unique subjects that satisfies the row criteria.  
 


Statistical Analysis Plan - DMID Protocol: 20-0013  
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Table 35: 
Disease Severity Distribution as Measured by Ordinal Score for Study Day — mITT Population 
Subgroup 
Study 
Day 
Treatment 
Ordinal Scorea 
8 
7 
6 
5 
4 
3 
2 
1 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Primary Analysis 
Day 3 
Treatment A (N=X) 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
Treatment B (N=X) 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
Day X 
Treatment A (N=X) 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
Treatment B (N=X) 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
X 
x.x 
x 
x.x 
x 
x.x 
Subgroup Analysis 
Baseline Ordinal Score 
5 
Day 3 
Treatment A (N=X) 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
Treatment B (N=X) 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
Day X 
Treatment A (N=X) 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
Treatment B (N=X) 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
Repeat the above rows for Study Days 5, 8, 11, 15, 22, 29, and 60, Repeat for each subgroup as shown in Table 6  
N=Number of subjects in modified intent-to-treat (mITT) population. n= Number of unique subjects that satisfies the row criteria with non-missing data.  
 


Statistical Analysis Plan - DMID Protocol: 20-0013  
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PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 36: 
Summary of Continuous Secondary Outcomes through Day 29 – Oxygen Days — mITT Population 
Outcomes 
Treatment 
n 
% 
Minimum 
25th Percentile 
Median 
75th Percentile 
Maximum 
Primary Analysis 
Treatment A (N=X) 
x 
x 
x 
x.x 
x.x 
x.x 
x 
Treatment B (N=X) 
x 
x 
x 
x.x 
x.x 
x.x 
x 
Subgroup Analyses 
Baseline Ordinal Score 
5 
Treatment A (N=X) 
x 
x 
x 
x.x 
x.x 
x.x 
x 
Treatment B (N=X) 
x 
x 
x 
x.x 
x.x 
x.x 
x 
Repeat for each subgroup analyses as shown in Table 6.  
N=Number of subjects in modified intent-to-treat (mITT) population. n= Number of unique subjects that satisfies the row criteria with non-missing data. 
 
Tables with similar format: 
Table 37: 
Summary of Continuous Secondary Outcomes through Day 29 – Non-Invasive Ventilation/High Flow Oxygen Free Days or 
Worse — mITT Population 
Table 38: 
Summary of Continuous Secondary Outcomes through Day 29 – Ventilator/ECMO Days or Worse — mITT Population 
Table 39: 
Summary of Continuous Secondary Outcomes through Day 29 – Duration of Hospitalization — mITT Population 
[Implementation note: For duration of hospitalization, remove rows for multiple imputation.] 
 


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Table 40: 
Incidence of Secondary Outcomes – Non-Invasive Ventilation/High Flow Oxygen Free 
Days or Worse through Day 29 — mITT Population 
Outcomes 
Treatment 
Population at 
Riska 
New Casesb 
Incidence Rate  
n 
% 
n 
% 
Estimatec 
 95% CId 
80% CId 
Primary Analysis 
Treatment A (N=X) 
x 
x.x 
x 
x.x 
x.xxx 
x.xxx, x.xxx 
x.xxx, x.xxx 
Treatment B (N=X) 
x 
x.x 
x 
x.x 
x.xxx 
x.xxx, x.xxx 
x.xxx, x.xxx 
Subgroup Analysis 
Repeat for each sensitivity and subgroup category as detailed in Table 6 and Table 7. 
N=Number of subjects in modified intent-to-treat (mITT) population. n= Number of unique subjects that satisfies the row criteria.  
a Population at risk is defined as all subjects with a baseline ordinal score of 5 or below. 
bNew cases are defined as subjects with a baseline ordinal score of 5 or below that progress to an ordinal score of 6, 7, or 8. 
cThe incidence rate is the proportion of the population at risk that have new cases. 
d Confidence intervals for the incidence rate estimated using Blaker method. 
 


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Table 41: 
Incidence of Secondary Outcomes – Ventilator/ECMO Days or Worse through Day 29 — 
mITT Population 
Outcomes 
Treatment 
Population at 
Riska 
New Casesb 
Incidence Rate  
n 
% 
n 
% 
Estimatec 
 95% CId 
80% CId 
Primary Analysis 
Treatment A (N=X) 
x 
x.x 
x 
x.x 
x.xxx 
x.xxx, x.xxx 
x.xxx, x.xxx 
Treatment B (N=X) 
x 
x.x 
x 
x.x 
x.xxx 
x.xxx, x.xxx 
x.xxx, x.xxx 
Subgroup Analysis 
Repeat for each sensitivity and subgroup category as detailed in Table 6 and Table 7. 
N=Number of subjects in modified intent-to-treat (mITT) population. n= Number of unique subjects that satisfies the row criteria.  
a Population at risk is defined as all subjects with a baseline ordinal score of 6 or below. 
bNew cases are defined as subjects with a baseline ordinal score of 6 or below that progress to an ordinal score of 7 or 8. 
cThe incidence rate is the proportion of the population at risk that have new cases. 
d Confidence intervals for the incidence rate estimated using Blaker method. 
 


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Table 42: 
Time to Mechanical Ventilation or Death through Day 29 — mITT Population with 
Baseline Ordinal Score of 5 or 6, CRP<150 mg/L, and age<85 years 
Analysis/Subgroup 
Treatment 
Number of Subjects to 
Mechanical 
Ventilation or Deathd 
Median Time Until Event 
Hazard Ratio 
P-
valuee 
n 
% 
Estimate 
80% 
CI 
95% CI 
Estim
ate 
80% 
CI 
95% 
CI 
Initial Modela 
Treatment A 
(N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
x.x, 
x.x 
0.xxx 
Treatment B 
(N=X) 
x  
x.x 
x.x 
x.x, x.x 
x.x, x.x 
Primary with 
Sensitivity Imputationb 
Treatment A 
(N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
x.x, 
x.x 
0.xxx 
Treatment B 
(N=X) 
x  
x.x 
x.x 
x.x, x.x 
x.x, x.x 
Subgroup Analysesc 
Baseline Ordinal Score 
5 
Treatment A 
(N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
x.x, 
x.x 
0.xxx 
Treatment B 
(N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
6 
Treatment A 
(N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
x.x, 
x.x 
0.xxx 
Treatment B 
(N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
5 or 6 
Treatment A 
(N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
x.x, 
x.x 
0.xxx 
Treatment B 
(N=X) 
x 
x.x 
x.x 
x.x, x.x 
x.x, x.x 
Repeat for the rest of the subgroups in Table 6. 
CI=Confidence Intervals.  
N=Number of subjects in modified intent-to-treat (mITT) population. n= Number of unique subjects who progressed to mechanical ventilation 
or death that satisfies the row criteria. 
a Hazard Ratio (HR) is the hazard ratio calculated from the Cox Proportional Hazard Model comparing Active treatment vs Placebo and 
adjusting for the baseline dexamethasone use (yes, no), Baseline Ordinal Score (5, 6 or 7), age, and baseline CRP as covariates. All subjects 
whose last assessment was before Day 29 and were missing the event were censored at the date of last assessment.  
b Primary with Sensitivity Imputation: Same analysis as the initial model but subjects missing event and whose last assessment is before Day 29 
are non-events for good discharges and censored at Day 29 or at last assessment for subjects still hospitalized or discharged to LTAC, 
hospice care, or other hospital. 
c For the subgroup analyses, the model described in a was performed for each level of the subgroup.  
d Number of subjects who progressed to a clinical status of 7 or 8 through Day 29. 
e P-value is based on the adjusted cox model.    
 
Table with similar format: 
Table 43: 
Time to Mechanical Ventilation or Death through Day 29 — mITT Population 
[Implementation note: Add subgroup category for baseline ordinal score 7 and baseline ordinal score ‘6 or 7’ 
to Table 43.]


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Table 44: 
Z-Scores and Westfall-Young Permutation P-Value Adjustment — mITT Population 
[Implementation note: This analysis is option and will be performed only if its inclusion appears likely to be 
helpful in interpreting the primary and secondary analyses results.] 
Endpoint 
Raw P-value 
Westfall-Young Adjusted P-Value 
Analysis Including Day 8 OS as a Continuous Endpoint 
Clinical Status at Study Day 8 
0.xxx 
0.xxx 
Sustained Survival Without Respiratory Failure 
0.xxx 
0.xxx 
Difference from Baseline Clinical Status at Days 3 
0.xxx 
0.xxx 
Difference from Baseline Clinical Status at Days 5 
0.xxx 
0.xxx 
Difference from Baseline Clinical Status at Days 8 
0.xxx 
0.xxx 
Difference from Baseline Clinical Status at Days 11 
0.xxx 
0.xxx 
Difference from Baseline Clinical Status at Days 15 
0.xxx 
0.xxx 
Difference from Baseline Clinical Status at Days 22 
0.xxx 
0.xxx 
Difference from Baseline Clinical Status at Days 29 
0.xxx 
0.xxx 
Number of Days Clinical Status >4 
0.xxx 
0.xxx 
Number of Days Clinical Status>5 
0.xxx 
0.xxx 
Number of Days Clinical Status>6 
0.xxx 
0.xxx 
Value of CRP 
0.xxx 
0.xxx 
Value of Ferritin 
0.xxx 
0.xxx 
Value of D-dimer 
0.xxx 
0.xxx 
Value of Fibrinogen 
0.xxx 
0.xxx 
Value of LDH 
0.xxx 
0.xxx 
14-Day Mortality 
0.xxx 
0.xxx 
28-Day Mortality 
0.xxx 
0.xxx 
59-Day Mortality 
0.xxx 
0.xxx 
Repeat above analyses excluding the Day 8 OS endpoint 
Note: This analysis will be based on complete data. 
 


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Table 45: 
Hochberg P-Value Adjustment — mITT Population 
[Implementation note: This analysis is option and will be performed only if its inclusion appears likely to be 
helpful in interpreting the primary and secondary analyses results.] 
Endpoint 
Raw P-valuea 
Hochberg Adjusted P-Value 
Z-Scores 
Global P-Value 
Clinical Status at Study Day 8 
0.xxx 
0.xxx 
x.xx 
0.xxx 
Time (days) to Sustained Recovery 
0.xxx 
0.xxx 
x.xx 
Sustained Survival Without 
Respiratory Failure 
0.xxx 
0.xxx 
x.xx 
Time (days) to at least 1 point 
Improvement from Baseline 
0.xxx 
0.xxx 
x.xx 
Time (days) to at least 2 point 
Improvement from Baseline 
0.xxx 
0.xxx 
x.xx 
Difference from Baseline Clinical 
Status at Days 3 
0.xxx 
0.xxx 
x.xx 
Difference from Baseline Clinical 
Status at Days 5 
0.xxx 
0.xxx 
x.xx 
Difference from Baseline Clinical 
Status at Days 8 
0.xxx 
0.xxx 
x.xx 
Difference from Baseline Clinical 
Status at Days 11 
0.xxx 
0.xxx 
x.xx 
Difference from Baseline Clinical 
Status at Days 15 
0.xxx 
0.xxx 
x.xx 
Difference from Baseline Clinical 
Status at Days 22 
0.xxx 
0.xxx 
x.xx 
Difference from Baseline Clinical 
Status at Days 29 
0.xxx 
0.xxx 
x.xx 
Number of Days Clinical Status >4 
0.xxx 
0.xxx 
x.xx 
Number of Days Clinical Status>5 
0.xxx 
0.xxx 
x.xx 
Number of Days Clinical Status>6 
0.xxx 
0.xxx 
x.xx 
Value of CRP 
0.xxx 
0.xxx 
x.xx 
Value of Ferritin 
0.xxx 
0.xxx 
x.xx 
Value of D-dimer 
0.xxx 
0.xxx 
x.xx 
Value of Fibrinogen 
0.xxx 
0.xxx 
x.xx 
Value of LDH 
0.xxx 
0.xxx 
x.xx 
14-Day Mortality 
0.xxx 
0.xxx 
x.xx 
28-Day Mortality 
0.xxx 
0.xxx 
x.xx 
59-Day Mortality 
0.xxx 
0.xxx 
x.xx 
Time (days) to Death 
0.xxx 
0.xxx 
x.xx 
a Raw p-values and Z-scores will come from analysis of these endpoints using multiple imputation for Day 8 Ordinal Score and 
using complete data for the rest of the endpoints. 
 


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14.3 
Safety Data 
14.3.1 Displays of Adverse Events  
Table 46: 
Overall Summary of Treatment Emergent Adverse Events by Baseline Ordinal Score — Safety Population 
Adverse Event 
Categories 
Treatment A (N=X) 
Treatment B (N=X) 
Baseline Ordinal Score 
Baseline Ordinal Score 
5 
6 
7 
Any BOSa 
5 
6 
7 
Any BOSa 
n 
% 
Events 
n 
% 
Events 
n 
% 
Events 
n 
% 
Events 
n 
% 
Events 
n 
% 
Events 
n 
% 
Events 
n 
% 
Events 
At least one TEAE 
x 
x.x 
xxx 
x 
x.x 
xxx 
x 
x.x 
xxx 
x x.x 
xxx 
x 
x.x 
xxx 
x 
x.x 
xxx 
x 
x.x 
xxx 
x 
x.x 
xxx 
At least one TEAE 
grade ≥ 3 
x 
x.x 
xxx 
x 
x.x 
xxx 
x 
x.x 
xxx 
x x.x 
xxx 
x 
x.x 
xxx 
x 
x.x 
xxx 
x 
x.x 
xxx 
x 
x.x 
xxx 
At least one related 
TEAE 
x 
x.x 
xxx 
x 
x.x 
xxx 
x 
x.x 
xxx 
x x.x 
xxx 
x 
x.x 
xxx 
x 
x.x 
xxx 
x 
x.x 
xxx 
x 
x.x 
xxx 
At least one related 
TEAE grade ≥ 3 
x 
x.x 
xxx 
x 
x.x 
xxx 
x 
x.x 
xxx 
x x.x 
xxx 
x 
x.x 
xxx 
x 
x.x 
xxx 
x 
x.x 
xxx 
x 
x.x 
xxx 
At least one treatment-
emergent SAE 
x 
x.x 
xxx 
x 
x.x 
xxx 
x 
x.x 
xxx 
x x.x 
xxx 
x 
x.x 
xxx 
x 
x.x 
xxx 
x 
x.x 
xxx 
x 
x.x 
xxx 
At least one TEAE 
leading to early 
termination of study 
x 
x.x 
xxx 
x 
x.x 
xxx 
x 
x.x 
xxx 
x x.x 
xxx 
x 
x.x 
xxx 
x 
x.x 
xxx 
x 
x.x 
xxx 
x 
x.x 
xxx 
At least one TEAE 
leading to study drug 
discontinuation 
x 
x.x 
xxx 
x 
x.x 
xxx 
x 
x.x 
xxx 
x x.x 
xxx 
x 
x.x 
xxx 
x 
x.x 
xxx 
x 
x.x 
xxx 
x 
x.x 
xxx 
Death 
x 
x.x 
xxx 
x 
x.x 
xxx 
x 
x.x 
xxx 
x x.x 
xxx 
x 
x.x 
xxx 
x 
x.x 
xxx 
x 
x.x 
xxx 
x 
x.x 
xxx 
BOS= Baseline Ordinal Score. 
TEAE= Treatment-emergent Adverse Event. N=Number of subjects in the Safety population. n= Number of unique subjects that satisfies the row criteria. 
a There were X additional subjects with an Actual Baseline Ordinal Score of 4 that are included in the ‘Any BOS’ summaries. 


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Table 47: 
Treatment Emergent Adverse Events by System Organ Class, Preferred Term and Treatment Group — Safety Population 
MedDRA Classification 
Treatment A (N=X) 
Treatment B (N=X) 
Risk Difference 
System Organ Class 
Preferred Term 
n 
% 
Events 
n 
% 
Events 
Estimate 
95% CIa 
Any SOC 
Any PT 
x 
x.x 
xxx 
x 
x.x 
xxx 
x.x 
x.x 
SOC 1 
Any PT 
x 
x.x 
xxx 
x 
x.x 
xxx 
x.x 
x.x 
PT 1 
x 
x.x 
xxx 
x 
x.x 
xxx 
x.x 
x.x 
PT 2 
x 
x.x 
xxx 
x 
x.x 
xxx 
x.x 
x.x 
SOC 2 
Any PT 
x 
x.x 
xxx 
x 
x.x 
xxx 
x.x 
x.x 
PT 1 
x 
x.x 
xxx 
x 
x.x 
xxx 
x.x 
x.x 
PT 2 
x 
x.x 
xxx 
x 
x.x 
xxx 
x.x 
x.x 
TEAE= Treatment-emergent Adverse Event. n= Number of unique subjects that satisfies the row criteria. N=Number of subjects in the Safety population. n= Number of unique subjects that satisfies 
the row criteria. 
Denominators are the number of subjects in the Safety population. 
If a subject has multiple occurrences of an adverse event, the subject is counted only once in the preferred term/system organ class category. 
All adverse events were coded using the Medical Dictionary for Regulatory Activities (MedDRA) version 23.0. 
a 95% CI for risk differences calculated using the Miettinen-Nurminen method. 
 


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Table 48: 
Treatment Emergent Adverse Events by System Organ Class, Preferred Term, and Baseline Ordinal Score — Safety Population 
MedDRA Classification 
Treatment A (N=X) 
Treatment B (N=X) 
Baseline Ordinal Score 
Baseline Ordinal Score 
5 
6 
7 
Any BOSa 
5 
6 
7 
Any BOSa 
n 
% 
Events 
n 
% 
Events 
n 
% 
Events 
n 
% 
Events 
n 
% 
Events 
n 
% 
Events 
n 
% 
Events 
n 
% 
Events 
System 
Organ 
Class 
Preferred 
Term 
Any SOC 
Any PT 
x 
x.x 
xxx 
x x.x 
xxx 
x 
x.x 
xxx 
x 
x.x 
xxx 
x x.x 
xxx 
x 
x.x 
xxx 
x 
x.x 
xxx 
x 
x.x 
xxx 
SOC 1 
Any PT 
x 
x.x 
xxx 
x x.x 
xxx 
x 
x.x 
xxx 
x 
x.x 
xxx 
x x.x 
xxx 
x 
x.x 
xxx 
x 
x.x 
xxx 
x 
x.x 
xxx 
PT 1 
x 
x.x 
xxx 
x x.x 
xxx 
x 
x.x 
xxx 
x 
x.x 
xxx 
x x.x 
xxx 
x 
x.x 
xxx 
x 
x.x 
xxx 
x 
x.x 
xxx 
PT 2 
x 
x.x 
xxx 
x x.x 
xxx 
x 
x.x 
xxx 
x 
x.x 
xxx 
x x.x 
xxx 
x 
x.x 
xxx 
x 
x.x 
xxx 
x 
x.x 
xxx 
SOC 2 
Any PT 
x 
x.x 
xxx 
x x.x 
xxx 
x 
x.x 
xxx 
x 
x.x 
xxx 
x x.x 
xxx 
x 
x.x 
xxx 
x 
x.x 
xxx 
x 
x.x 
xxx 
PT 1 
x 
x.x 
xxx 
x x.x 
xxx 
x 
x.x 
xxx 
x 
x.x 
xxx 
x x.x 
xxx 
x 
x.x 
xxx 
x 
x.x 
xxx 
x 
x.x 
xxx 
PT 2 
x 
x.x 
xxx 
x x.x 
xxx 
x 
x.x 
xxx 
x 
x.x 
xxx 
x x.x 
xxx 
x 
x.x 
xxx 
x 
x.x 
xxx 
x 
x.x 
xxx 
TEAE= Treatment-emergent Adverse Event. n= Number of unique subjects that satisfies the row criteria. N=Number of subjects in the Safety population. 
Denominators are the number of subjects in the Safety population. 
If a subject has multiple occurrences of an adverse event, the subject is counted only once in the preferred term/system organ class category. 
All adverse events were coded using the Medical Dictionary for Regulatory Activities (MedDRA) version 23.0.  
a There were X additional subjects with an Actual Baseline Ordinal Score of 4 that are included in the ‘Any BOS’ summaries. 
 
Table with similar format: 
Table 49: 
Treatment Emergent Adverse Events by System Organ Class, Preferred Term, and Baseline Steroid Use — Safety Population 
Table 50: 
Treatment Emergent Adverse Events by System Organ Class, Preferred Term, and Baseline Use of Emerging Covid-19 
Treatments — Safety Population  
Table 51: 
Treatment Emergent Adverse Events by System Organ Class, Preferred Term, and Duration of Symptoms Prior to Enrollment 
— Safety Population 
 


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Table 52: 
Treatment Emergent Serious Adverse Events by System Organ Class, Preferred Term and Treatment Group — Safety 
Population 
MedDRA Classification 
Treatment A (N=X) 
Treatment B (N=X) 
Risk Difference 
System Organ Class 
Preferred Term 
n 
% 
Events 
n 
% 
Events 
Estimate 
95% CIa 
Any SOC 
Any PT 
x 
x.x 
xxx 
x 
x.x 
xxx 
x.x 
x.x 
SOC 1 
Any PT 
x 
x.x 
xxx 
x 
x.x 
xxx 
x.x 
x.x 
PT 1 
x 
x.x 
xxx 
x 
x.x 
xxx 
x.x 
x.x 
PT 2 
x 
x.x 
xxx 
x 
x.x 
xxx 
x.x 
x.x 
SOC 2 
Any PT 
x 
x.x 
xxx 
x 
x.x 
xxx 
x.x 
x.x 
PT 1 
x 
x.x 
xxx 
x 
x.x 
xxx 
x.x 
x.x 
PT 2 
x 
x.x 
xxx 
x 
x.x 
xxx 
x.x 
x.x 
TEAE= Treatment-emergent Adverse Event. n= Number of unique subjects that satisfies the row criteria. N=Number of subjects in the Safety population.  
Denominators are the number of subjects in the Safety population. 
If a subject has multiple occurrences of an adverse event, the subject is counted only once in the preferred term/system organ class category. 
All adverse events were coded using the Medical Dictionary for Regulatory Activities (MedDRA) version 23.0. 
a 95% CI for risk differences calculated using the Miettinen-Nurminen method. 
 


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Table 53: 
Treatment Emergent Serious Adverse Events by System Organ Class, Preferred Term, and Baseline Ordinal Score — Safety 
Population 
MedDRA Classification 
Treatment A (N=X) 
Treatment B (N=X) 
Baseline Ordinal Score 
Baseline Ordinal Score 
5 
6 
7 
Any BOSa 
5 
6 
7 
Any BOSa 
n 
% 
Events 
n 
% 
Events 
n 
% 
Events 
n 
% 
Events 
n 
% 
Events 
n 
% 
Events 
n 
% 
Events 
n 
% 
Events 
System 
Organ Class 
Preferred 
Term 
Any SOC 
Any PT 
x 
x.x 
xxx 
x x.x 
xxx 
x x.x 
xxx 
x x.x 
xxx 
x x.x 
xxx 
x x.x 
xxx 
x x.x 
xxx 
x 
x.x 
xxx 
SOC 1 
Any PT 
x 
x.x 
xxx 
x x.x 
xxx 
x x.x 
xxx 
x x.x 
xxx 
x x.x 
xxx 
x x.x 
xxx 
x x.x 
xxx 
x 
x.x 
xxx 
PT 1 
x 
x.x 
xxx 
x x.x 
xxx 
x x.x 
xxx 
x x.x 
xxx 
x x.x 
xxx 
x x.x 
xxx 
x x.x 
xxx 
x 
x.x 
xxx 
PT 2 
x 
x.x 
xxx 
x x.x 
xxx 
x x.x 
xxx 
x x.x 
xxx 
x x.x 
xxx 
x x.x 
xxx 
x x.x 
xxx 
x 
x.x 
xxx 
SOC 2 
Any PT 
x 
x.x 
xxx 
x x.x 
xxx 
x x.x 
xxx 
x x.x 
xxx 
x x.x 
xxx 
x x.x 
xxx 
x x.x 
xxx 
x 
x.x 
xxx 
PT 1 
x 
x.x 
xxx 
x x.x 
xxx 
x x.x 
xxx 
x x.x 
xxx 
x x.x 
xxx 
x x.x 
xxx 
x x.x 
xxx 
x 
x.x 
xxx 
PT 2 
x 
x.x 
xxx 
x x.x 
xxx 
x x.x 
xxx 
x x.x 
xxx 
x x.x 
xxx 
x x.x 
xxx 
x x.x 
xxx 
x 
x.x 
xxx 
TEAE= Treatment-emergent Adverse Event. n= Number of unique subjects that satisfies the row criteria. N=Number of subjects in the Safety population.  
Denominators are the number of subjects in the Safety population. 
If a subject has multiple occurrences of an adverse event, the subject is counted only once in the preferred term/system organ class category. 
All adverse events were coded using the Medical Dictionary for Regulatory Activities (MedDRA) version 23.0.  
a There were X additional subjects with an Actual Baseline Ordinal Score of 4 that are included in the ‘Any BOS’ summaries. 
 


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Table 54: 
Mortality Rates — Safety Population 
Analysis Type 
Baseline 
Ordinal Score 
Treatment Group 
Number of 
Deaths 
Mortality Rate (CI)c 
Difference in Mortality Rates at the 
Specified Time Pointd 
HRe 
P-valuef 
n 
% 
Estimate 
80% CI 
95% 
CI 
Estimate 
80% CI 
95% CI 
Estimate 
80% CI 95% CI 
Time to Death by Day 15 
Primarya 
5 
Treatment A (N=X) 
X 
x.x 
x.x 
x.x, x.x 
x.xxx 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
Treatment B (N=X) 
X 
x.x 
x.xx 
x.x, x.x 
x.xxx 
 
 
 
 
 
 
 
6 
Treatment A (N=X) 
X 
x.x 
x.x 
x.x, x.x 
x.xxx 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
Treatment B (N=X) 
X 
x.x 
x.xx 
x.x, x.x 
x.xxx 
 
 
 
 
 
 
 
7 
Treatment A (N=X) 
X 
x.x 
x.x 
x.x, x.x 
x.xxx 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
Treatment B (N=X) 
X 
x.x 
x.xx 
x.x, x.x 
x.xxx 
 
 
 
 
 
 
 
Any BOS 
Treatment A (N=X) 
X 
x.x 
x.x 
x.x, x.x 
x.xxx 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
Treatment B (N=X) 
X 
x.x 
x.xx 
x.x, x.x 
x.xxx 
 
 
 
 
 
 
 
Primary with 
Sensitivity 
Imputationb 
5 
Treatment A (N=X) 
X 
x.x 
x.x 
x.x, x.x 
x.xxx 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
Treatment B (N=X) 
X 
x.x 
x.xx 
x.x, x.x 
x.xxx 
 
 
 
 
 
 
 
6 
Treatment A (N=X) 
X 
x.x 
x.x 
x.x, x.x 
x.xxx 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
Treatment B (N=X) 
X 
x.x 
x.xx 
x.x, x.x 
x.xxx 
 
 
 
 
 
 
 
7 
Treatment A (N=X) 
X 
x.x 
x.x 
x.x, x.x 
x.xxx 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
Treatment B (N=X) 
X 
x.x 
x.xx 
x.x, x.x 
x.xxx 
 
 
 
 
 
 
 
Any BOS 
Treatment A (N=X) 
X 
x.x 
x.x 
x.x, x.x 
x.xxx 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
Treatment B (N=X) 
X 
x.x 
x.xx 
x.x, x.x 
x.xxx 
 
 
 
 
 
 
 
Time to Death by Day 29 
Primarya 
5 
Treatment A (N=X) 
X 
x.x 
x.xx 
x.x, x.x 
x.xxx 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
Treatment B (N=X) 
X 
x.x 
x.xx 
x.x, x.x 
x.xxx 
 
 
 
 
 
 
 
6 
Treatment A (N=X) 
X 
x.x 
x.x 
x.x, x.x 
x.xxx 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
Treatment B (N=X) 
X 
x.x 
x.xx 
x.x, x.x 
x.xxx 
 
 
 
 
 
 
 
7 
Treatment A (N=X) 
X 
x.x 
x.x 
x.x, x.x 
x.xxx 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 


Statistical Analysis Plan - DMID Protocol: 20-0013  
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Analysis Type 
Baseline 
Ordinal Score 
Treatment Group 
Number of 
Deaths 
Mortality Rate (CI)c 
Difference in Mortality Rates at the 
Specified Time Pointd 
HRe 
P-valuef 
n 
% 
Estimate 
80% CI 
95% 
CI 
Estimate 
80% CI 
95% CI 
Estimate 
80% CI 95% CI 
Treatment B (N=X) 
X 
x.x 
x.xx 
x.x, x.x 
x.xxx 
 
 
 
 
 
 
 
Any BOS 
Treatment A (N=X) 
X 
x.x 
x.x 
x.x, x.x 
x.xxx 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
Treatment B (N=X) 
X 
x.x 
x.xx 
x.x, x.x 
x.xxx 
 
 
 
 
 
 
 
Primary with 
Sensitivity 
Imputationb 
5 
Treatment A (N=X) 
X 
x.x 
x.xx 
x.x, x.x 
x.xxx 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
Treatment B (N=X) 
X 
x.x 
x.xx 
x.x, x.x 
x.xxx 
 
 
 
 
 
 
 
6 
Treatment A (N=X) 
X 
x.x 
x.x 
x.x, x.x 
x.xxx 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
Treatment B (N=X) 
X 
x.x 
x.xx 
x.x, x.x 
x.xxx 
 
 
 
 
 
 
 
7 
Treatment A (N=X) 
X 
x.x 
x.x 
x.x, x.x 
x.xxx 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
Treatment B (N=X) 
X 
x.x 
x.xx 
x.x, x.x 
x.xxx 
 
 
 
 
 
 
 
Any BOS 
Treatment A (N=X) 
X 
x.x 
x.x 
x.x, x.x 
x.xxx 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
Treatment B (N=X) 
X 
x.x 
x.xx 
x.x, x.x 
x.xxx 
 
 
 
 
 
 
 
Time to Death by Day 60 
Primarya 
5 
Treatment A (N=X) 
X 
x.x 
x.xx 
x.x, x.x 
x.xxx 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
Treatment B (N=X) 
X 
x.x 
x.xx 
x.x, x.x 
x.xxx 
 
 
 
 
 
 
 
6 
Treatment A (N=X) 
X 
x.x 
x.x 
x.x, x.x 
x.xxx 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
Treatment B (N=X) 
X 
x.x 
x.xx 
x.x, x.x 
x.xxx 
 
 
 
 
 
 
 
7 
Treatment A (N=X) 
X 
x.x 
x.x 
x.x, x.x 
x.xxx 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
Treatment B (N=X) 
X 
x.x 
x.xx 
x.x, x.x 
x.xxx 
 
 
 
 
 
 
 
Any BOS 
Treatment A (N=X) 
X 
x.x 
x.x 
x.x, x.x 
x.xxx 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
Treatment B (N=X) 
X 
x.x 
x.xx 
x.x, x.x 
x.xxx 
 
 
 
 
 
 
 
Primary with 
Sensitivity 
Imputationb 
5 
Treatment A (N=X) 
X 
x.x 
x.xx 
x.x, x.x 
x.xxx 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
Treatment B (N=X) 
X 
x.x 
x.xx 
x.x, x.x 
x.xxx 
 
 
 
 
 
 
 
6 
Treatment A (N=X) 
X 
x.x 
x.x 
x.x, x.x 
x.xxx 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
Treatment B (N=X) 
X 
x.x 
x.xx 
x.x, x.x 
x.xxx 
 
 
 
 
 
 
 
7 
Treatment A (N=X) 
X 
x.x 
x.x 
x.x, x.x 
x.xxx 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 


Statistical Analysis Plan - DMID Protocol: 20-0013  
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Analysis Type 
Baseline 
Ordinal Score 
Treatment Group 
Number of 
Deaths 
Mortality Rate (CI)c 
Difference in Mortality Rates at the 
Specified Time Pointd 
HRe 
P-valuef 
n 
% 
Estimate 
80% CI 
95% 
CI 
Estimate 
80% CI 
95% CI 
Estimate 
80% CI 95% CI 
Treatment B (N=X) 
X 
x.x 
x.xx 
x.x, x.x 
x.xxx 
 
 
 
 
 
 
 
Any BOS 
Treatment A (N=X) 
X 
x.x 
x.x 
x.x, x.x 
x.xxx 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
Treatment B (N=X) 
X 
x.x 
x.xx 
x.x, x.x 
x.xxx 
 
 
 
 
 
 
 
CI= Confidence Intervals. N=Number of subjects in the Safety population. n= Number of unique subjects that satisfies the row criteria. 
a For the primary endpoint, all subjects whose last assessment was before the corresponding timepoint (Day 15 Visit, Day 29 Visit, Day 60 Visit) and were missing the event were censored at the date of 
last assessment.  
b Primary with Sensitivity Imputation: Same analysis as the initial model but subjects missing event and whose last assessment is before the corresponding timepoint (Day 15 Visit, Day 29 Visit, Day 60 
Visit) are non-events for good discharges and censored at Day 15, Day 29, Day 60 respectively or at last assessment for subjects still hospitalized or discharged to LTAC, hospice care, or other hospital. 
c Mortality Rates are the Kaplan-Meier estimates. 
d Difference in mortality rates (80%, 95% CI) obtained from Kaplan Meier. 
e HR is the hazard ratio from the Cox Proportional Hazard Model adjusted for baseline ordinal score and baseline steroid use. 
f P-value is based on the Cox adjusted model. 
 


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Table 55: 
Time to Death through Day 15, 29, or 60 by Treatment Group: Restricted Mean Survival Time Analysis — Safety Population  
Study Day 
Treatment Group 
Actual Baseline Ordinal Score 
n 
Restricted Mean Mortality Time (Days) 
Difference 
Estimate 
95% CI 
Estimate 
95% CI 
Day 15 
Treatment A (N=X) 
5 
x 
x.x 
x.x, x.x 
x.xx 
 
x.xx, x.xx 
 
Treatment B (N=X) 
x 
x.x 
x.x, x.x 
Treatment A (N=X) 
6 
x 
x.x 
x.x, x.x 
x.xx 
x.xx, x.xx 
Treatment B (N=X) 
x 
x.x 
x.x, x.x 
Treatment A (N=X) 
7 
x 
x.x 
x.x, x.x 
x.xx 
x.xx, x.xx 
Treatment B (N=X) 
x 
x.x 
x.x, x.x 
Treatment A (N=X) 
Any BOS 
x 
x.x 
x.x, x.x 
x.xx 
x.xx, x.xx 
Treatment B (N=X) 
x 
x.x 
x.x, x.x 
Repeat for Day 29 and Day 60 
N= Number of subjects in the specified treatment group, actual baseline ordinal score, and analysis population.  
n = Number of subjects who died by the specified study day.  
Difference is the difference in the restricted mean mortality time between Active treatment and Placebo. 
 


Statistical Analysis Plan - DMID Protocol: 20-0013  
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Table 56: 
Time to Death, SAE or Grade ≥3 TEAEs through Day 60 — Safety Population 
Baseline Ordinal 
Score 
Treatment Group 
Number of Deaths 
or Grade >3 
TEAEs 
Event Rate (CI)a 
Difference in Event Rates at the 
Specified Time Pointb 
HRc 
P-valued 
n 
% 
Estimate 
80% CI 
95% CI 
Estimate 
80% CI 
95% CI 
Estimate 80% CI 
95% CI 
5 
Treatment A (N=X) 
X 
x.x 
x.x 
x.x, x.x 
x.xxx 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
Treatment B (N=X) 
X 
x.x 
x.xx 
x.x, x.x 
x.xxx 
 
 
 
 
 
 
 
6 
Treatment A (N=X) 
X 
x.x 
x.x 
x.x, x.x 
x.xxx 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
Treatment B (N=X) 
X 
x.x 
x.xx 
x.x, x.x 
x.xxx 
 
 
 
 
 
 
 
7 
Treatment A (N=X) 
X 
x.x 
x.x 
x.x, x.x 
x.xxx 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
Treatment B (N=X) 
X 
x.x 
x.xx 
x.x, x.x 
x.xxx 
 
 
 
 
 
 
 
Any BOS 
Treatment A (N=X) 
X 
x.x 
x.x 
x.x, x.x 
x.xxx 
x.x 
x.x, x.x 
x.x, x.x 
x.x 
x.x, x.x 
x.x, x.x 
0.xxx 
Treatment B (N=X) 
X 
x.x 
x.xx 
x.x, x.x 
x.xxx 
 
 
 
 
 
 
 
CI= Confidence Intervals. N=Number of subjects in the Safety population. n= Number of unique subjects that satisfies the row criteria. 
a Event rates are the Kaplan-Meier estimates. 
b Difference in event rates (80%, 95% CI) obtained from Kaplan Meier. 
c HR is the hazard ratio from the Cox Proportional Hazard Model adjusted for baseline ordinal score and baseline steroid use. 
d P-value is based on the Cox adjusted model. 
 


Statistical Analysis Plan - DMID Protocol: 20-0013  
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14.3.5 Displays of Laboratory Results 
14.3.5.1 
Chemistry Results  
Table 57: 
Summary of ALT Results Values and Change from Baseline by Study Days — Safety Population 
Study Day 
Treatment Group 
Value at Visit 
Change from Baseline 
n 
Mean 
SD 
Median 
Min 
Max 
n 
Mean 
SD 
Median 
Min 
Max 
Day 1 
Treatment A (N=X) 
x 
x.x 
x.xx 
x.x 
x.x 
x.x 
- 
- 
- 
- 
- 
- 
Treatment B (N=X) 
x 
x.x 
x.xx 
x.x 
x.x 
x.x 
- 
- 
- 
- 
- 
- 
Repeat Rows for Study Days 3, 
5, 8, 11, 15, and 29 
 
x 
x.xx 
x.xx 
x.xx 
x.x 
x.x 
x 
x.x 
x.xx 
x.x 
x.x 
x.x 
 
x 
x.xx 
x.xx 
x.xx 
x.x 
x.x 
x 
x.x 
x.xx 
x.x 
x.x 
x.x 
SD= Standard Deviation. Min- Minimum. Max= Maximum. N=Number of subjects in the Safety population.  
 
Tables with similar format:  
Table 58: 
Summary of AST Results Values and Change from Baseline by Study Days — Safety Population 
Table 59: 
Summary of Bilirubin Results Values and Change from Baseline by Study Days — Safety Population  
Table 60: 
Summary of Creatinine Values and Change from Baseline by Study Days — Safety Population 
Table 61: 
Summary of eGFR Results Values and Change from Baseline by Study Days — Safety Population 
[Implementation note: Add footnote that eGFR values reported as >60 are analyzed as 61 and those reported as >90 are analyzed as 91.] 
 


Statistical Analysis Plan - DMID Protocol: 20-0013  
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Table 62: 
ALT Results by Baseline Ordinal Score, Severity and Study Days — Safety Population 
Study Day 
Baseline Ordinal Score 
N 
Severitya 
None-Grade 2 
Grade 3 
Life Threatening/ Grade 4 
Missing 
n 
% 
n 
% 
n 
% 
n 
Baseline 
Treatment A  
5 
x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
6 
 
 
 
 
 
 
 
 
7 
x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
Any BOS 
x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
Treatment B 
5 
x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
6 
 
 
 
 
 
 
 
 
7 
x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
Any BOS 
x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
Repeat Rows or Study Days 
3, 5, 8, 11, 15, 29 
 
 
 
 
 
 
 
 
 
Maximum Severity Post Baseline 
Treatment A  
5 
x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
6 
 
 
 
 
 
 
 
 
7 
x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
Any BOS 
x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
Treatment B  
5 
x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
6 
 
 
 
 
 
 
 
 
7 
x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
Any BOS 
x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
N=Number of subjects in the Safety population with a non-missing lab value at the respective time point. n= Number of unique subjects that satisfies the row criteria and have the corresponding lab 
severity. The "Maximum Severity Post Baseline" rows indicate the maximum severity experienced by each subject at any time point post baseline, including unscheduled assessments. 
a Severity as per NIAID Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1 (July 2017). 


Statistical Analysis Plan - DMID Protocol: 20-0013  
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Tables with similar format:  
Table 63: 
AST Results by Baseline Ordinal Score, Severity and Study Days — Safety Population 
Table 64: 
Bilirubin Results by Baseline Ordinal Score, Severity and Study Days — Safety Population  
Table 65: 
Creatinine Results by Baseline Ordinal Score, Severity and Study Days — Safety Population 
Table 66: 
eGFR Results by Baseline Ordinal Score, Severity and Study Days — Safety Population 
[Implementation note: Add footnote that eGFR values reported as >60 are analyzed as 61 and those reported as >90 are analyzed as 91.] 
 


Statistical Analysis Plan - DMID Protocol: 20-0013  
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14.3.5.1 
Hematology Results  
Table 67: 
Summary of White Blood Cells Results Values and Change from Baseline by Study Days — Safety Population 
Study Day 
Treatment Group 
Value at Visit 
Change from Baseline 
n 
Mean 
SD 
Median 
Min 
Max 
n 
Mean 
SD 
Median 
Min 
Max 
Day 1 
Treatment A (N=X) 
x 
x.xx 
x.xx 
x.xx 
x.x 
x.x 
- 
- 
- 
- 
- 
- 
Treatment B (N=X) 
x 
x.xx 
x.xx 
x.xx 
x.x 
x.x 
- 
- 
- 
- 
- 
- 
Repeat Rows for Study Days 3, 
5, 8, 11, 15, and 29 
 
x 
x.xx 
x.xx 
x.xx 
x.x 
x.x 
x 
x.x 
x.xx 
x.x 
x.x 
x.x 
 
x 
x.xx 
x.xx 
x.xx 
x.x 
x.x 
x 
x.x 
x.xx 
x.x 
x.x 
x.x 
SD= Standard Deviation. Min- Minimum. Max= Maximum. N=Number of subjects in the Safety population.  
 
Tables with similar format:  
Table 68: 
Summary of Platelets Results Values and Change from Baseline by Study Days — Safety Population 
Table 69: 
Summary of Hemoglobin Results Values and Change from Baseline by Study Days — Safety Population 
Table 70: 
Summary of INR Results Values and Change from Baseline by Study Days — Safety Population 
Table 71: 
Summary of Neutrophils Results Values and Change from Baseline by Study Days — Safety Population 
Table 72: 
Summary of Eosinophils Results Values and Change from Baseline by Study Days — Safety Population 
[Implementation note: Add footnote that Eosinophils values reported as <0.03 are analyzed as 0.02.] 
Table 73: 
Summary of Basophils Results Values and Change from Baseline by Study Days — Safety Population 
Table 74: 
Summary of Lymphocytes Results Values and Change from Baseline by Study Days — Safety Population 
Table 75: 
Summary of Monocytes Results Values and Change from Baseline by Study Days — Safety Population 
 


Statistical Analysis Plan - DMID Protocol: 20-0013  
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Table 76: 
White Blood Cell Results by Baseline Ordinal Score, Severity and Study Days — Safety Population 
Study Day 
Baseline Ordinal Score 
N 
Severitya 
None-Grade 2 
Grade 3 
Life Threatening/ Grade 4 
Missing 
n 
% 
n 
% 
n 
% 
n 
Baseline 
Treatment A  
5 
x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
6 
 
 
 
 
 
 
 
 
7 
x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
Any BOS 
x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
Treatment B  
5 
x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
6 
 
 
 
 
 
 
 
 
7 
x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
Any BOS 
x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
Repeat Rows or Study Days 
3, 5, 8, 11, 15, 29 
 
 
 
 
 
 
 
 
 
Maximum Severity Post Baseline 
Treatment A  
5 
x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
6 
 
 
 
 
 
 
 
 
7 
x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
Any BOS 
x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
Treatment B  
5 
x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
6 
 
 
 
 
 
 
 
 
7 
x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
Any BOS 
x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
N=Number of subjects in the Safety population. n= Number of unique subjects that satisfies the row criteria. 
a Severity as per NIAID Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1 (July 2017). 


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Tables with similar format:   
Table 77: 
Platelets Results by Baseline Ordinal Score, Severity and Study Days — Safety Population 
Table 78: 
Hemoglobin Results by Baseline Ordinal Score, Severity and Study Days — Safety Population 
Table 79: 
INR Results by Baseline Ordinal Score, Severity and Study Days — Safety Population 
Table 80: 
Neutrophils Results by Baseline Ordinal Score, Severity and Study Days — Safety Population 
Table 81: 
Lymphocytes Results by Baseline Ordinal Score, Severity and Study Days — Safety Population 
 


Statistical Analysis Plan - DMID Protocol: 20-0013  
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Table 82: 
Summary of Continuous Markers of Inflammation and Immune Response by Study Day — Safety Population 
Study Day 
Immune Response Measure 
Treatment A 
(N=X) 
Treatment B 
(N=X) 
P-valuea  
 
n 
Mean 
SD 
Median 
Min 
Max 
Mean 
SD 
Median 
Min 
Max 
Day 3 
C-reactive protein 
xx 
x.x 
x.xx 
x.x 
x 
x 
x.x 
x.xx 
x.x 
x 
x 
0.xxx 
Ferritin 
xx 
x.x 
x.xx 
x.x 
x 
x 
x.x 
x.xx 
x.x 
x 
x 
0.xxx 
D-Dimer 
xx 
x.x 
x.xx 
x.x 
x 
x 
x.x 
x.xx 
x.x 
x 
x 
0.xxx 
Fibrinogen 
xx 
x.x 
x.xx 
x.x 
x 
x 
x.x 
x.xx 
x.x 
x 
x 
0.xxx 
 
LDH 
xx 
x.x 
x.xx 
x.x 
x 
x 
x.x 
x.xx 
x.x 
x 
x 
0.xxx 
Rows should be repeated for 
Study Days 1, 5, 8, 11, 15, and 29  
 
 
 
 
 
 
 
 
 
 
 
 
SD= Standard Deviation. Min= Minimum. Max= Maximum. N=Number of subjects in Safety population. 
Values of D-Dimer reported as <220 were analyzed as 219 and values of CRP reported as <3.0 were analyzed as 2.9. 
a P-value of tests of two sample means. 
  


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14.3.6 Displays of Vital Signs  
Table 83: 
Summary Statistics of Baseline Vital Signs by Actual Baseline Ordinal Score and Treatment Group — Safety Population 
Variable 
Statistic 
Treatment A 
(N=X) 
Treatment B 
(N=X) 
All Subjects 
(N=X) 
BOS 5 
(N=X) 
BOS 6 
(N=X) 
BOS 7 
(N=X) 
Any BOSa 
(N=X) 
BOS 5 
(N=X) 
BOS 6 
(N=X) 
BOS 7 
(N=X) 
Any BOSa 
(N=X) 
BOS 5 
(N=X) 
BOS 6 
(N=X) 
BOS 7 
(N=X) 
Any BOSa 
(N=X) 
Pulse 
n 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Mean  
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Standard Deviation 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Median 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Minimum 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Maximum 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Diastolic Blood 
Pressure 
n 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Mean 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Standard Deviation 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Median 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Minimum 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Maximum 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Respiratory Rate 
n 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Mean 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Standard Deviation 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Median 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Minimum 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Maximum 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Blood oxygen 
Saturation 
n 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Mean 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Standard Deviation 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Median 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Minimum 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Maximum 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 


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Variable 
Statistic 
Treatment A 
(N=X) 
Treatment B 
(N=X) 
All Subjects 
(N=X) 
BOS 5 
(N=X) 
BOS 6 
(N=X) 
BOS 7 
(N=X) 
Any BOSa 
(N=X) 
BOS 5 
(N=X) 
BOS 6 
(N=X) 
BOS 7 
(N=X) 
Any BOSa 
(N=X) 
BOS 5 
(N=X) 
BOS 6 
(N=X) 
BOS 7 
(N=X) 
Any BOSa 
(N=X) 
Oral Temperature 
n 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Mean 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Standard Deviation 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Minimum 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Maximum 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
N=Number of subjects in the Safety population. n=number of subjects with a non-missing assessment. 
a There were X additional subjects with an Actual Baseline Ordinal Score of 4 that are included in the ‘Any BOS’ summaries. 


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14.4 
Summary of Concomitant Medications  
Table 84: 
Number and Percentage of Subjects with Prior Medications by WHO Drug Classification, Actual Baseline Ordinal Score, and 
Treatment Group — Safety Population 
WHO Drug 
Code 
Level 1, 
Anatomic 
Group 
WHO Drug 
Code 
Level 2, 
Therapeutic 
Subgroup 
Treatment A 
(N=X) 
Treatment B 
(N=X) 
All Subjects 
(N=X) 
BOS 5 
(N=X) 
BOS 6 
(N=X) 
BOS 7 
(N=X) 
Any BOSa 
(N=X) 
BOS 5 
(N=X) 
BOS 6 
(N=X) 
BOS 7 
(N=X) 
Any BOSa 
(N=X) 
BOS 5 
(N=X) 
BOS 6 
(N=X) 
BOS 7 
(N=X) 
Any BOSa 
(N=X) 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Any Level 1 
Codes 
Any Level 2 
Codes 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
ATC 1 
Any ATC 2 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
ATC 2 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
ATC 2 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
ATC 1 
Any ATC 2 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
ATC 2 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
ATC 2 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Prior medications are defined as any medications begun before a subject took the first dose of study product. Medications are coded using the WHO Drug Dictionary version 202003. 
ATC=Anatomical Therapeutic Chemical. 
BOS= Baseline Ordinal Score. 
N=Number of subjects in the Safety population.  
n= Number of subjects reporting taking at least one medication in the specific ATC Class. 
a There were X additional subjects with an Actual Baseline Ordinal Score of 4 that are included in the ‘Any BOS’ summaries. 
 
Table with similar format: 
Table 85: 
Number and Percentage of Subjects with Concomitant Medications by WHO Drug Classification, Actual Baseline Ordinal Score, 
and Treatment Group — Safety Population 
[Implementation note: Update the footnote to state ‘Concomitant medications are defined as any medications that begun after a subject took the first 
dose of study product or that begun before the first dose and continued after the subject took the first dose of study product.’] 
 


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Table 86: 
Summary of Concomitant COVID-19 Treatments — Safety Population 
Type 
Summary Measure 
Treatment A 
(N=X) 
Treatment B 
(N=X) 
n 
Mean 
SD 
Median 
Min 
Max 
n 
Mean 
SD 
Median 
Min 
Max 
[COVID-19 Treatment 1] 
Number of Subjects 
x 
- 
- 
- 
- 
 
x 
- 
- 
- 
- 
- 
Study Day Onseta 
x 
x.x 
x.xx 
x.x 
x 
x 
x 
x.x 
x.xx 
x.x 
x 
x 
Duration (days) 
x 
x.x 
x.xx 
x.x 
x 
x 
x 
x.x 
x.xx 
x.x 
x 
x 
Concomitant COVID-19 Treatments are defined as medications that started before dose 1 of study product and continued throughout the study or those started after a subject took study product. 
SD=Standard Deviation. Min=Minimum. Max=Maximum.  
N=Number of subjects in the Safety population. 
n=Number of subjects reporting at least one of the concomitant COVID-19 treatments. Refer to Section 6.4 for a list of COVID-19 treatments of interest. 
a Study day onset is defined as the start day of the concomitant medication. 
 


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Table 87: 
Summary of Steroid Usage for Indications Other than COVID-19 by Treatment of Indication — Safety Population 
Type 
Summary Measure 
Treatment A 
(N=X) 
Treatment B 
(N=X) 
n 
Mean 
SD 
Median 
Min 
Max 
n 
Mean 
SD 
Median 
Min 
Max 
[COVID-19 Treatment 1] 
Number of Subjects 
x 
- 
- 
- 
- 
 
x 
- 
- 
- 
- 
- 
Study Day Onseta 
x 
x.x 
x.xx 
x.x 
x 
x 
x 
x.x 
x.xx 
x.x 
x 
x 
Duration (days) 
x 
x.x 
x.xx 
x.x 
x 
x 
x 
x.x 
x.xx 
x.x 
x 
x 
Concomitant Steroid Treatments are defined as steroids for indications other than COVID-19 that started before dose 1 of study product and continued throughout the study or those started after a 
subject took study product.  
SD=Standard Deviation. Min=Minimum. Max=Maximum.  
N=Number of subjects in the Safety population. 
n=Number of subjects reporting steroid usage for indications other than COVID-19. Refer to Section 6.4 for a list of steroids of interest. 
a Study day onset is defined as the start day of the concomitant medication. 
 


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APPENDIX 2.  FIGURE MOCK-UPS 
General Programming Notes for figures: 
• Treatment group labeling will vary by stage. Abbreviations will be used if the treatment 
group labels need to be abbreviated to improve fit. 
• All figures will be based on complete data analyses without multiple imputation. 
• Use the same color for a treatment on the different graphs (SAS standard colors): 
o Active Treatment = Blue 
o Placebo = Red 
• For severity graphs (SAS standard colors): 
o 5 = green 
o 6 = blue 
o 7 = red 
o Death = black 


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LIST OF FIGURES 
Figure 1: 
CONSORT Flow Diagram .......................................................................................142 
Figure 2: 
Adjusted Odds Ratios and 95% Confidence Interval of Inferior Clinical 
Status Score at Study Visit Day 8 Using a Proportional Odds Model: Overall 
and for each Subgroup — mITT Population ............................................................143 
Figure 3: 
Adjusted Odds Ratios and 80% Confidence Interval of Inferior Clinical 
Status Score at Study Visit Day 8 Using a Proportional Odds Model: Overall 
and for each Subgroup — mITT Population ............................................................144 
Figure 4: 
Adjusted Odds Ratios and 95% Confidence Interval of Inferior Clinical 
Status Score at Study Visit Day 15 Using a Proportional Odds Model: 
Overall and for each Subgroup — mITT Population ...............................................144 
Figure 5: 
Adjusted Odds Ratios and 80% Confidence Interval of Inferior Clinical 
Status Score at Study Visit Day 15 Using a Proportional Odds Model: 
Overall and for each Subgroup — mITT Population ...............................................144 
Figure 6: 
Adjusted Odds Ratios and 95% Confidence Interval of Inferior Clinical 
Status Score at Study Visit Day 29 Using a Proportional Odds Model: 
Overall and for each Subgroup — mITT Population ...............................................144 
Figure 7: 
Adjusted Odds Ratios and 80% Confidence Interval of Inferior Clinical 
Status Score at Study Visit Day 29 Using a Proportional Odds Model: 
Overall and for each Subgroup — mITT Population ...............................................144 
Figure 8: 
Kaplan-Meier Plot for Time to Sustained Recovery through Day 60 defined 
by 8-point Ordinal Scale — mITT Population .........................................................145 
Figure 9: 
Kaplan-Meier Plot for Time to Improvement by at least One Category in the 
Ordinal Scale through Day 60 — mITT Population .................................................145 
Figure 10: Kaplan-Meier Plot for Time to Improvement by at least Two Categories in 
the Ordinal Scale through Day 60 — mITT Population ...........................................145 
Figure 11: Kaplan-Meier Plot for Time to Mechanical Ventilation or Death through 
Day 29 — mITT Population .....................................................................................146 
Figure 12: Kaplan-Meier Plot for Time to Death through Day 15 — Safety Population ..........146 
Figure 13: Kaplan-Meier Plot for Time to Death through Day 29 — Safety Population ..........146 
Figure 14: Kaplan-Meier Plot for Time to Death through Day 60 — Safety Population ..........146 
Figure 15: Kaplan-Meier Plot for Time to Death, SAE or Grade ≥3 TEAEs through Day 
60 — Safety Population ............................................................................................146 
Figure 16: Adjusted Hazard Ratios and 95% Confidence Intervals of Time to Sustained 
Recovery through Study Visit Day 60 Using a Cox Proportional Hazard 
Model Overall and for each Subgroup — mITT Population ....................................147 


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Figure 17: Adjusted Hazard Ratios and 80% Confidence Interval of Time to Sustained 
Recovery through Study Visit Day 60 Using a Cox Proportional Hazard 
Model Overall and for each Subgroup — mITT Population ....................................147 
Figure 18: Distribution of Ordinal Scores by Study Days — mITT Population........................148 
Figure 19: Bee Swarm Plot of Oxygenation Days through Day 29 — mITT Population .........149 
Figure 20: Bee Swarm Plot of Non-Invasive/High-Flow Oxygen Days through Day 29 
— mITT Population ..................................................................................................149 
Figure 21: Bee Swarm Plot of Invasive Mechanical Ventilation/ECMO Days through 
Day 29 — mITT Population .....................................................................................149 
Figure 22: Bee Swarm Plot of Hospitalization Days through Day 29 — mITT 
Population .................................................................................................................149 
Figure 23: Frequency of Non-Serious Related AEs by MedDRA System Organ Class 
and Severity — Safety Population, All Subjects ......................................................150 
Figure 24: Frequency of Non-Serious Related AEs by MedDRA System Organ Class 
and Severity — Safety Population, Actual Baseline Ordinal Score 5 ......................150 
Figure 25: Frequency of Non-Serious Related AEs by MedDRA System Organ Class 
and Severity — Safety Population, Actual Baseline Ordinal Score 6 ......................150 
Figure 26: Frequency of Non-Serious Related AEs by MedDRA System Organ Class 
and Severity — Safety Population, Actual Baseline Ordinal Score 7 ......................150 
Figure 27: Incidence of Non-Serious Related AEs by MedDRA System Organ Class 
and Severity — Safety Population, All Subjects ......................................................151 
Figure 28: Incidence of Non-Serious Related AEs by MedDRA System Organ Class 
and Severity — Safety Population, Actual Baseline Ordinal Score 5 ......................151 
Figure 29: Incidence of Non-Serious Related AEs by MedDRA System Organ Class 
and Severity — Safety Population, Actual Baseline Ordinal Score 6 ......................151 
Figure 30: Incidence of Non-Serious Related AEs by MedDRA System Organ Class 
and Severity — Safety Population, Actual Baseline Ordinal Score 7 ......................151 
Figure 31: Mean and Standard Deviations of CRP by Study Days — Safety Population .........152 
Figure 32: Mean and Standard Deviations of Ferritin by Study Days — Safety 
Population .................................................................................................................152 
Figure 33: Mean and Standard Deviations of D-Dimer by Study Days — Safety 
Population .................................................................................................................152 
Figure 34: Mean and Standard Deviations of Fibrinogen by Study Days — Safety 
Population .................................................................................................................152 
Figure 35: Mean and Standard Deviations of LDH by Study Days — Safety Population ........152 
 


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10.1 
Disposition of Subjects 
Figure 1: 
CONSORT Flow Diagram  
[Implementation note: Update final CONSORT diagram to include only the two treatment groups applicable to each stage.] 
Allocated to Group 1 (n=x) 
Received allocated intervention (n=x) 
Did not receive allocated intervention (n=x) 
[Reason 1] (x), [Reason 2] (x) 
Discontinued Intervention (n=x) 
[Reason 1] (x), [Reason 2] (x) 
 
Early Termination (n=32) 
[Reason 1] (x), [Reason 2] (x) 
Analysed in mITT (n=x) 
Excluded from immuno analyses (n=x) 
[Reason 1] (x), [Reason 2] (x) 
Analyzed for safety (n=x) 
Excluded from safety analyses (n=x) 
[Reason 1] (x), [Reason 2] (x) 
Assessed for Eligibility (n=x) 
Excluded* (n=x) 
   [Reason 1] (n=x) 
   Concern of potential risk (n=x) 
Randomized (n=x) 
Allocation 
Analysis 
Follow-Up 
Enrollment 
Allocated to Group 1 (n=x) 
Received allocated intervention (n=x) 
Did not receive allocated intervention (n=x) 
[Reason 1] (x), [Reason 2] (x) 
Allocated to Group 1 (n=x) 
Received allocated intervention (n=x) 
Did not receive allocated intervention (n=x) 
[Reason 1] (x), [Reason 2] (x) 
Discontinued Intervention (n=x) 
[Reason 1] (x), [Reason 2] (x) 
Early Termination (n=32) 
[Reason 1] (x), [Reason 2] (x) 
Discontinued Intervention (n=x) 
[Reason 1] (x), [Reason 2] (x) 
Early Termination (n=32) 
[Reason 1] (x), [Reason 2] (x) 
Analysed in mITT (n=x) 
Excluded from immuno analyses (n=x) 
[Reason 1] (x), [Reason 2] (x) 
Analyzed for safety (n=x) 
Excluded from safety analyses (n=x) 
[Reason 1] (x), [Reason 2] (x) 
Analysed in mITT (n=x) 
Excluded from immuno analyses (n=x) 
[Reason 1] (x), [Reason 2] (x) 
Analyzed for safety (n=x) 
Excluded from safety analyses (n=x) 
[Reason 1] (x), [Reason 2] (x) 


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Figure 2: 
Adjusted Odds Ratios and 95% Confidence Interval of Inferior Clinical Status Score at 
Study Visit Day 8 Using a Proportional Odds Model: Overall and for each Subgroup — 
mITT Population 
[Implementation note: The reference group for odds ratio calculation is the placebo group.] 
 


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Figures with similar format:  
Figure 3: 
Adjusted Odds Ratios and 80% Confidence Interval of Inferior Clinical Status Score at 
Study Visit Day 8 Using a Proportional Odds Model: Overall and for each Subgroup — 
mITT Population 
Figure 4: 
Adjusted Odds Ratios and 95% Confidence Interval of Inferior Clinical Status Score at 
Study Visit Day 15 Using a Proportional Odds Model: Overall and for each Subgroup — 
mITT Population 
Figure 5: 
Adjusted Odds Ratios and 80% Confidence Interval of Inferior Clinical Status Score at 
Study Visit Day 15 Using a Proportional Odds Model: Overall and for each Subgroup — 
mITT Population 
Figure 6: 
Adjusted Odds Ratios and 95% Confidence Interval of Inferior Clinical Status Score at 
Study Visit Day 29 Using a Proportional Odds Model: Overall and for each Subgroup — 
mITT Population 
Figure 7: 
Adjusted Odds Ratios and 80% Confidence Interval of Inferior Clinical Status Score at 
Study Visit Day 29 Using a Proportional Odds Model: Overall and for each Subgroup — 
mITT Population 
 


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Figure 8: 
Kaplan-Meier Plot for Time to Sustained Recovery through Day 60 defined by 8-point 
Ordinal Scale — mITT Population 
[Implementation note: For time to sustained recovery, create individual figures 8A through 8F for all 
subjects, baseline steroid use=Yes, No and baseline ordinals score=5,6,7]  
 
 
Figures with Similar Format:  
Figure 9: 
Kaplan-Meier Plot for Time to Improvement by at least One Category in the Ordinal 
Scale through Day 60 — mITT Population 
Figure 10: 
Kaplan-Meier Plot for Time to Improvement by at least Two Categories in the Ordinal 
Scale through Day 60 — mITT Population 
[Implementation note: For time to improvement KM figures, create one figure for all subjects in the analysis 
population.] 
 


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Figure 11: 
Kaplan-Meier Plot for Time to Mechanical Ventilation or Death through Day 29 — 
mITT Population 
[Implementation note: For time to mechanical ventilation or death, create individual figures 11A through 11F 
for all baseline dexamethasone use=Yes, No and Baseline ordinal score=5,6,7.]  
 
 
Figures with similar format: 
[Implementation note: For the figures below, create only one figure for all subjects in the analysis 
population.]  
Figure 12: 
Kaplan-Meier Plot for Time to Death through Day 15 — Safety Population 
Figure 13: 
Kaplan-Meier Plot for Time to Death through Day 29 — Safety Population 
Figure 14: 
Kaplan-Meier Plot for Time to Death through Day 60 — Safety Population 
Figure 15: 
Kaplan-Meier Plot for Time to Death, SAE or Grade ≥3 TEAEs through Day 60 — 
Safety Population 
 


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Figure 16: 
Adjusted Hazard Ratios and 95% Confidence Intervals of Time to Sustained Recovery 
through Study Visit Day 60 Using a Cox Proportional Hazard Model Overall and for 
each Subgroup — mITT Population 
 
 
Figure with Similar Format:  
Figure 17: 
Adjusted Hazard Ratios and 80% Confidence Interval of Time to Sustained Recovery 
through Study Visit Day 60 Using a Cox Proportional Hazard Model Overall and for 
each Subgroup — mITT Population 
 


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Figure 18: 
Distribution of Ordinal Scores by Study Days — mITT Population 
 
 


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Figure 19: 
Bee Swarm Plot of Oxygenation Days through Day 29 — mITT Population 
[Implementation note: Update colors for treatment groups to match colors used for KM curves.] 
 
 
Figures with similar format: 
Figure 20: 
Bee Swarm Plot of Non-Invasive/High-Flow Oxygen Days through Day 29 — mITT 
Population 
Figure 21: 
Bee Swarm Plot of Invasive Mechanical Ventilation/ECMO Days through Day 29 — 
mITT Population 
Figure 22: 
Bee Swarm Plot of Hospitalization Days through Day 29 — mITT Population 
 
0
Treatment A
Treatment B
Treatment Group
0
5
10
15
20
25
30
Number of Days of Oxygenation


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Figure 23: 
Frequency of Non-Serious Related AEs by MedDRA System Organ Class and Severity — 
Safety Population, All Subjects 
 
 
Figures with similar format:  
Figure 24: 
Frequency of Non-Serious Related AEs by MedDRA System Organ Class and Severity — 
Safety Population, Actual Baseline Ordinal Score 5 
Figure 25: 
Frequency of Non-Serious Related AEs by MedDRA System Organ Class and Severity — 
Safety Population, Actual Baseline Ordinal Score 6 
Figure 26: 
Frequency of Non-Serious Related AEs by MedDRA System Organ Class and Severity — 
Safety Population, Actual Baseline Ordinal Score 7  
 


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Figure 27: 
Incidence of Non-Serious Related AEs by MedDRA System Organ Class and Severity — 
Safety Population, All Subjects 
 
 
Figures with similar format: 
Figure 28: 
Incidence of Non-Serious Related AEs by MedDRA System Organ Class and Severity — 
Safety Population, Actual Baseline Ordinal Score 5 
Figure 29: 
Incidence of Non-Serious Related AEs by MedDRA System Organ Class and Severity — 
Safety Population, Actual Baseline Ordinal Score 6 
Figure 30: 
Incidence of Non-Serious Related AEs by MedDRA System Organ Class and Severity — 
Safety Population, Actual Baseline Ordinal Score 7 
 


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Figure 31: 
Mean and Standard Deviations of CRP by Study Days — Safety Population 
 
 
Figures with similar format: 
Figure 32: 
Mean and Standard Deviations of Ferritin by Study Days — Safety Population 
Figure 33: 
Mean and Standard Deviations of D-Dimer by Study Days — Safety Population 
Figure 34: 
Mean and Standard Deviations of Fibrinogen by Study Days — Safety Population 
Figure 35: 
Mean and Standard Deviations of LDH by Study Days — Safety Population 
 


Statistical Analysis Plan - DMID Protocol: 20-0013  
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APPENDIX 3. LISTINGS MOCK-UPS 
LIST OF LISTINGS 
Listing 1: Subjects Who Early Terminated or Discontinued Treatment ...................................155 
Listing 2: Screen Failures — Screen Failed Subjects ...............................................................156 
Listing 3: Subject-Specific Protocol Deviations .......................................................................157 
Listing 4: Non Subject-Specific Protocol Deviations ...............................................................158 
Listing 5: Demographics and Baseline Characteristics .............................................................159 
Listing 6: Medical History ........................................................................................................160 
Listing 7: NEW Score Individual Components and Overall NEW Score for Study Day 
1 (Baseline) ...............................................................................................................161 
Listing 8: Physical Examinations ..............................................................................................162 
Listing 9: Prior and Concomitant Medications .........................................................................163 
Listing 10: Steroid Use ................................................................................................................164 
Listing 11: Medications of Interest .............................................................................................165 
Listing 12: Treatment Exposure ..................................................................................................166 
Listing 13: Individual Components and Ordinal Score ...............................................................167 
Listing 14: Primary and Secondary Efficacy Endpoints .............................................................168 
Listing 15: Non-Serious Treatment Emergent Adverse Events ..................................................169 
Listing 16: Treatment Emergent Adverse Events Leading to Early Termination of Study 
Drug ..........................................................................................................................169 
Listing 17: Treatment Emergent Adverse Events Resulting in Death ........................................169 
Listing 18: All Treatment Emergent Adverse Events .................................................................169 
Listing 19: Related Treatment Emergent Adverse Events ..........................................................169 
Listing 20: Serious Treatment Emergent Adverse Events ..........................................................169 
Listing 21: Treatment Emergent Adverse Events Leading to Early Termination of Study ........169 
Listing 22: Pregnancy Reports - Maternal Information ..............................................................170 
Listing 23: Pregnancy Reports - Gravida and Para .....................................................................171 
Listing 24: Pregnancy Reports - Live Birth Outcomes ...............................................................172 
Listing 25: Pregnancy Reports - Still Birth Outcomes ................................................................173 
Listing 26: Pregnancy Reports - Spontaneous, Elective, or Therapeutic Abortion 
Outcomes ..................................................................................................................174 
Listing 27: Clinical Laboratory Test Results ..............................................................................175 


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Listing 28: Markers of Inflammation and Coagulation Test Results ..........................................175 
Listing 29: Urine Pregnancy Test Results ...................................................................................175 
 


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Listing 1: 
Subjects Who Early Terminated or Discontinued Treatment  
Actual Treatment 
Group 
Actual Baseline 
Ordinal Score 
Subject ID 
Study Day 
Last Date of 
Study Treatment 
Category 
Treatment Discontinued 
Reason for Early Termination or 
Treatment Discontinuation 
Treatment A or B 
7/6/5 
XXXXX 
xxxx 
 
Early Termination/Treatment 
Discontinuation 
NA/Infusions/RDV/ Risankizumab  
xxxxx 
 
Programming  
Include randomized subjects only.  
Sort Order = Treatment Group, Actual Baseline Ordinal Score (descending order, i.e., 6, then 5 then 4), USUBJID, category where Treatment 
discontinuation is sorted prior to Early termination. If there are multiple treatment discontinuations (i.e., distinct dates for each product type) the order 
will be sorted by Study day. If both treatments were discontinued at the same time “Infusions + Injections” will be displayed in the Treatment 
Discontinued column. If subjects were randomized and not dosed are categorized as “Not Treated” and sorted after PBO + Dexamethasone + RDV if 
applicable. 
 


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Listing 2: 
Screen Failures — Screen Failed Subjects 
Subject ID 
Inclusion/Exclusion Not Met 
XXXXX 
 
 
Programming  
Include screen failure subjects only. Sort Order = USUBJID.  
 


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Listing 3: 
Subject-Specific Protocol Deviations 
Actual Treatment 
Group 
Actual 
Baseline 
Ordinal Score 
Subject 
ID 
DV 
Number Deviation 
Deviation 
Classification 
Deviation 
Category 
Study 
Day 
Reason 
for 
Deviation 
Deviation 
Resulted 
in AE? 
Deviation Resulted 
in Subject 
Termination? 
Deviation 
Affected Product 
Stability? 
Planned or 
Unplanned? 
Treatment A or B 
7/6/5 
Xxxxx 
xx 
xxx 
Major/Minor 
xxx 
x 
xxxx 
Yes/No 
Yes/No 
Yes/No 
Planned, 
Approved/ 
Planned, Not 
Approved /Not 
Planned  
 
Programming  
Sort Order = Treatment Group, Actual Baseline Ordinal Score (descending order, i.e., 6, then 5 then 4), USUBJID, Deviation Number. Concatenate all 
the specify fields as appropriate. If the columns do not fit within the eCTD specified margins, then Actual Treatment Group, Actual Baseline Ordinal 
Score, Subject ID will be placed in a header row as in the AE listings. 
 


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Listing 4: 
Non Subject-Specific Protocol Deviations 
Site 
Start Date  
End Date 
Deviation 
Deviation 
Classification 
Reason for 
Deviation 
Deviation Resulted in 
Subject Termination? 
Deviation Affected 
Product Stability? 
Deviation 
Category 
Planned or Unplanned? 
xxxx 
xxxx 
xxxx 
xxxx 
Major/Minor 
xxxx 
Yes/No 
Yes/No 
xxxx 
Planned, Approved/ Planned, Not 
Approved /Not Planned  
 
Programming  
Sort Order = Site (use site name and not the 5 alphanumeric site code), start date, deviation. Concatenate all the specify fields as appropriate.  
 


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Listing 5: 
Demographics and Baseline Characteristics  
Actual Treatment 
Group 
Randomized 
Treatment Group 
Baseline 
Ordinal Score Subject ID 
Site ID 
Sex 
Age 
(years) 
Ethnicity 
Race 
Eligibility 
Date of Informed Consent  
xx 
Treatment A or B 
7/6/5 
xxxxx 
xx 
xxx 
xx 
xxx 
xxx 
xx 
DDMMMYYYY 
 
Programming  
Sort Order = Actual Treatment Group, Baseline Ordinal Score (descending order, i.e., 6, then 5, then 4), USUBJID. 
For date of informed consent, use the date the subject signed the informed consent for corresponding stage being analyzed.  
 


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Listing 6: 
Medical History  
Subject ID 
Screen Date 
Date of Onset COVID-
19 Symptoms 
List of 
Comorbidities 
Concomitant Medications for Any 
Comorbidities 7 Days Prior to Enrollment 
Concomitant Medications for Current SARS-
CoV-2 Infection 7 Days Prior to Enrollment 
Relevant Medical 
History 
xx 
 
 
 
 
 
 
Medications were coded to the Anatomical Therapeutic Classification using the WHO Drug Dictionary (WHODRUG) version 202003. 
 
Programming   
Sort Order = USUBJID, Screen Date, Comorbidities. 
 


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Listing 7: 
NEW Score Individual Components and Overall NEW Score for Study Day 1 (Baseline) 
Actual Treatment 
Group 
Baseline 
Ordinal Score 
Subject 
ID 
Assessment 
Date (Day) 
Respiratory Rate  
(bpm) 
O2 Saturation 
(%) 
Any 
Supplemental O2 
Temperature 
(°C) 
Systolic BP 
(mmHg) 
Heart Rate 
(bpm) 
Level of 
Consciousness 
Total NEW 
Score 
Treatment A or B 
7/6/5 
xx 
DDMMYYYY 
(xx) 
xx 
xx 
Yes/No 
xx.x 
xxx 
xx 
A/N 
xx 
 
Programming  
Sort Order = Actual Treatment Group, Baseline Ordinal Score (descending order, i.e., 6, then 5, then 4), USUBJID, Assessment Date. 
 


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Listing 8: 
Physical Examinations  
Actual Treatment Group 
Actual Baseline 
Ordinal Score 
Subject ID 
Study Day 
Date (Day) of Assessment 
Body System 
Abnormal 
Finding 
Treatment A or B 
7/6/5/4 
xxx 
xx 
DDMMYYYY (xx) 
xxxx 
xxxxxx 
 
Programming  
For respiratory findings denoted as 'Yes' on the Physical Exam CRF, denote the Body System as "Respiratory Finding' and denote the Abnormal Finding 
as the symptom name, e.g., if Wheezing is reported, the Abnormal Finding will be 'Wheezing'.  Each reported respiratory finding will appear in its own 
row.   
Sort order will be Treatment Group, Actual Baseline Ordinal Score (descending order, i.e., 6, then 5 then 4), USUBJID, Study Day, and Body System. 
 


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Listing 9: 
Prior and Concomitant Medications  
Actual 
Treatment 
Group 
Actual Baseline 
Ordinal Score 
Subject 
ID 
Medication 
Number 
Medication 
Start Date (Day) 
Stop Date 
(Day) 
Indication 
Taken for a condition on 
Medical History? (MH 
Description; Number) 
Taken for AE? 
(AE Description; 
Number) 
ATC Level 1 
(ATC Level 2) 
Treatment A 
or B 
7/6/5/4 
xxx 
xx 
xxxx 
DDMMYYYY 
(xx) 
DDMMYYY 
(xx) 
xxxxx 
Yes/No 
Yes/No 
xxxx 
 
Programming  
Sort Order = Treatment Group, Actual Baseline Ordinal Score (descending order, i.e., 6, then 5 then 4), USUBJID, CM number 
If medication started prior to enrollment and there is no date, then Medication Start Day = Prior to Enrollment 
If medication is ongoing at end of study, the Medication End Day = Ongoing 
 


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Listing 10: 
Steroid Use 
Actual Treatment 
Group 
Actual Baseline 
Ordinal Score 
Subject ID 
Medication 
Number 
Medication 
Medication 
Start Day 
Medication 
End Day 
Dose / Route 
Frequency 
Indication 
Taken for an AE? 
(AE Description; Number) 
Treatment A or B 
7/6/5/4/ 
xxx 
xx 
xxxx 
x 
x 
xx / xx 
xx 
xxxx 
Yes/No 
 
Programming Notes: Sort Order = Treatment Group, Actual Baseline Ordinal Score (descending order, i.e., 6, then 5 then 4), USUBJID, CM number. If 
medication started prior to enrollment and there is no date, then Medication Start Day = Prior to Enrollment. If medication is ongoing at end of study, the 
Medication End Day = Ongoing 
 


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Listing 11: 
Medications of Interest 
Actual Treatment 
Group 
Actual Baseline 
Ordinal Score 
Subject ID 
Medication 
Number 
Medication 
Medication 
Start Day 
Medication 
End Day 
Indication 
Medication of 
Interest Category 
Medication of Interest 
Subcategory 
ATC Level 1 
(ATC Level 2) 
Treatment A or B 
7/6/5/4/ 
xxx 
xx 
xxxx 
x 
x 
xxxx 
xxxx 
xxxx 
xxxx / xxxx 
 
Programming Notes: Sort Order = Treatment Group, Actual Baseline Ordinal Score (descending order, i.e., 6, then 5 then 4), USUBJID, CM number 
Note: If medication started prior to enrollment and there is no date, then Medication Start Day = Prior to Enrollment 
If medication is ongoing at end of study, the Medication End Day = Ongoing 
If the medication does not have an applicable subcategory, then display ‘N/A’ 
 
 


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Listing 12: 
Treatment Exposure 
Actual Treatment 
Group 
Actual Baseline 
Ordinal Score 
Subject ID 
Treatment Administration 
Start Date (day) 
Treatment Administration 
End Date (day) 
Treatment 
Duration (days) 
Dose Status 
Reason for 
Halting/Slowing/Missing 
Treatment A or B 
7/6/5/4 
xxxx 
DDMMYYYY 
(xx) 
DDMMYYYY 
(xx) 
xx 
Halted/Slowed/Missing 
xxxxx 
 
Programming  
Sort Order = Treatment Group, Actual Baseline Ordinal Score (descending order, i.e., 6, then 5 then 4), USUBJID, Treatment Administration Start Date. 
 


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Listing 13: 
Individual Components and Ordinal Score  
Treatment 
Group 
Actual 
Baseline 
Ordinal Score 
Subject 
ID 
Visit 
Number 
Study Visit 
Date (day) of 
Assessment 
Death Date 
(day) 
Hospitalization 
Date 
Reason for 
Hospitalization 
If Hospitalized: New 
or Increased 
Supplemental 
Oxygen 
If Not 
Hospitalized: 
Increased 
Limitation of 
Physical Activities 
If Not 
Hospitalized: 
New or 
Increased 
Home Oxygen 
Ordinal 
Score 
Treatment 
A or B 
7/6/5/4 
xxxx 
xx 
DDMMYYYY 
(xx) 
DDMMYYYY 
(xx) 
DDMMYYYY 
(xx) 
 
 
 
 
 
 
Programming  
Sort Order = Treatment Group, Baseline Ordinal Score (descending order, i.e., 6, then 5 then 4), USUBJID, Visit Number.   
 


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Listing 14: 
Primary and Secondary Efficacy Endpoints 
Treatment 
Group 
Baseline Ordinal 
Score 
Subject ID 
Visit Number 
Study Visit Date (day) of 
Assessment 
Parameter 
Result 
Change from 
Baseline 
Analysis Type 
Analysis Flag 
01 
Treatment A or B 
7/6/5/4 
xxxx 
xx 
DDMMYYYY 
(xx) 
 
 
 
 
 
Analysis Flag identified the record used in the analysis in case of more than one record is present by parameter and visit. 
 
Programming  
Sort Order = Treatment Group, Baseline Ordinal Score (descending order, i.e., 6, then 5 then 4), USUBJID, Study Day.   
 


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Listing 15: 
Non-Serious Treatment Emergent Adverse Events  
Start Date 
(day) 
End Date 
(day) 
Adverse 
Event 
Number 
Adverse 
Event 
Reported 
Term 
MedDRA 
System 
Organ 
Class 
MedDRA 
Preferred 
Term 
Severity 
Relationship to 
Study Treatment 
Relationship 
to COVID-19 
Relationship 
to Other 
Medical 
Conditions 
Subject 
Discontinued 
Due to AE 
Action Taken 
with Study 
Treatment 
Subject ID: , Treatment Group: , Baseline Ordinal Score: 
DDMMYYYY 
(xx) 
DDMMYYYY 
(xx) 
 
 
 
 
xxxx 
Not Related/Related  
Related/Not 
Related 
Related/Not 
Related 
Yes/No 
For each of 
Remdesivir, 
Risankizumab, 
or Placebo 
 
Programming  
Sort order will be Treatment Group, Actual Baseline Ordinal Score (descending order, i.e., 6, then 5 then 4), USUBJID, AE Number. For relationship to 
study treatment, list either Not Related or each study treatment it is related to. For Action taken, separately list actions for each treatment. 
 
Listings with similar format: 
Listing 16: 
Treatment Emergent Adverse Events Leading to Early Termination of Study Drug  
Listing 17: 
Treatment Emergent Adverse Events Resulting in Death  
Listing 18: 
All Treatment Emergent Adverse Events  
Listing 19: 
Related Treatment Emergent Adverse Events  
Listing 20: 
Serious Treatment Emergent Adverse Events  
Listing 21: 
Treatment Emergent Adverse Events Leading to Early Termination of Study 
 


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Listing 22: 
Pregnancy Reports - Maternal Information 
Actual 
Treatment 
Group 
Actual 
Baseline 
Ordinal 
Score 
Subject 
ID 
Pregnancy 
Number 
Study Day 
Corresponding 
to Estimated 
Date of 
Conception 
Source of 
Maternal 
Information 
Pregnancy 
Status 
Mother’s 
Pre-
Pregnancy 
BMI 
Mother’s 
Weight 
Gain 
During 
Pregnancy 
Tobacco, 
Alcohol, or 
Drug Use 
During 
Pregnancy? 
Medications 
During 
Pregnancy? 
Maternal 
Complications 
During 
Pregnancy? 
Maternal 
Complications 
During Labor, 
Delivery, or 
Post-Partum? 
Treatment A 
or B 
7/6/5/4 
xxxx 
xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Maternal Complications are included in the Adverse Event listing. Medications taken during pregnancy are included in the Concomitant Medications Listing. 
 
Programming notes: 
Sort order will be Treatment Group, Actual Baseline Ordinal Score, USUBJID, Pregnancy Number. 
 


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Listing 23: 
Pregnancy Reports - Gravida and Para 
Gravida 
Extremely 
PBa 
Very Early 
PBa 
Early 
PBa 
Late PBa 
Early 
TBb 
Full 
TBb 
Late 
TBb 
Post 
TBb 
Still 
Births 
Spontaneous 
Abortion/ 
Miscarriage 
Elective 
Abortions 
Therapeutic 
Abortions 
Major 
Congenital 
Anomaly with 
Previous 
Pregnancy? 
Treatment Group: , Actual Baseline Ordinal Score: , Subject ID: , Pregnancy Number:  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Gravida includes the current pregnancy, para events do not. 
a Preterm Birth 
b Term Birth 
 
 
Programming notes: 
Sort order will be Treatment Group, Actual Baseline Ordinal Score, USUBJID, Pregnancy Number. 
 


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Listing 24: 
Pregnancy Reports - Live Birth Outcomes 
Treatment 
Group 
Actual 
Baseline 
Ordinal 
Score 
Subject 
ID 
Pregnancy 
Number 
Fetus 
Number 
Pregnancy 
Outcome 
(for this 
Fetus) 
Fetal 
Distress 
During 
Labor 
and 
Delivery? 
Delivery 
Method 
Gestational 
Age at Live 
Birth  
Size for 
Gestational 
Age 
Apgar 
Score, 
1 
minute 
Apgar 
Score, 5 
minutes 
Cord 
pH 
Congenital 
Anomalies? 
Illnesses/ 
Hospitalizations 
within 1 Month 
of Birth? 
Treatment A 
or B 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Congenital Anomalies are included in the Adverse Event listing. 
 


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Listing 25: 
Pregnancy Reports - Still Birth Outcomes 
Treatment 
Group 
Actual 
Baseline 
Ordinal 
Score 
Subject 
ID 
Date of 
Initial 
Report 
Fetus 
Number 
Pregnancy 
Outcome 
(for this 
Fetus) 
Fetal 
Distress 
During 
Labor and 
Delivery? 
Delivery 
Method 
Gestational 
Age at Still 
Birth 
Size for 
Gestational 
Age 
Cord 
pH 
Congenital 
Anomalies? 
Autopsy 
Performed? 
If Autopsy, 
Etiology for Still 
Birth Identified? 
Treatment A 
or B 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Listing 26: 
Pregnancy Reports - Spontaneous, Elective, or Therapeutic Abortion Outcomes 
Treatment Group 
Actual Baseline 
Ordinal Score 
Subject ID 
Date of Initial 
Report 
Fetus 
Number 
Pregnancy Outcome 
(for this Fetus) 
Gestational Age 
at Termination 
Abnormality in Product 
of Conception? 
Reason for Therapeutic 
Abortion 
Treatment A or B 
 
 
 
 
 
 
 
 


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Listing 27: 
Clinical Laboratory Test Results 
Treatment Group 
Actual Baseline 
Ordinal Score 
Subject ID 
Planned 
Study Day 
Actual 
Study Day 
Date (Day) of 
Sample 
Laboratory 
Parameter (Units) 
Result 
(Toxicity Grade) 
Change from 
Baseline 
Reference 
Range Low 
Reference 
Range High 
Treatment A or B 
7/6/5/4 
xxx 
xx 
xx 
DDMMMYYYY 
(xx) 
xxx (xxx) 
xxx (xxxx) 
xxx 
xxxx 
xxxx 
 
Programming notes: 
Sort order will be Treatment Group, Baseline Ordinal Score, USUBJID, Planned Study Day. If subjects were randomized and not dosed “Not Treated” 
will be used for the actual treatment category and will be sorted after PBO + Dexamethasone + RDV. All parameters will be included in the listing. 
 
Listings with similar format:  
Listing 28: 
Markers of Inflammation and Coagulation Test Results  
Listing 29: 
Urine Pregnancy Test Results  

Prot_004.pdf: 
Protocol 20-0013A 
Version 6 
ACTIV-5/Big Effect Trial (BET) 
21 September 2021 
Appendix A – BET-A: Risankizumab/Remdesivir vs. Placebo/Remdesivir 
1 
 
APPENDIX A – ACTIV-5/BET-A: RISANKIZUMAB/REMDESIVIR VS. 
PLACEBO/REMDESIVIR 
 
 
 
 
 
 


Protocol 20-0013A 
Version 6 
ACTIV-5/Big Effect Trial (BET) 
21 September 2021 
Appendix A – BET-A: Risankizumab/Remdesivir vs. Placebo/Remdesivir 
2 
 
 
TABLE OF CONTENTS  
Appendix A – ACTIV-5/BET-A: Risankizumab/Remdesivir vs. Placebo/Remdesivir ................. 1 
TABLE OF CONTENTS ................................................................................................................ 2 
LIST OF TABLES .......................................................................................................................... 3 
1. 
PROTOCOL SUMMARY ...................................................................................................... 4 
1.1 
Synopsis .......................................................................................................................... 4 
1.2 
Schedule of Assessments ................................................................................................ 6 
2. 
INTRODUCTION .................................................................................................................. 7 
2.1 
Study Rationale ............................................................................................................... 7 
2.2 
Background ..................................................................................................................... 7 
2.2.1 
Purpose of Study ..................................................................................................... 7 
2.2.2 
Potential Therapeutic Agents .................................................................................. 7 
2.3 
Risk/Benefit Assessment ................................................................................................ 8 
2.3.1 
Known Overall Risks .............................................................................................. 8 
2.3.2 
Potential Risks of Remdesivir ................................................................................. 9 
2.3.3 
Potential Risks of Risankizumab ............................................................................ 9 
2.3.4 
Known Potential Benefits ..................................................................................... 10 
3. 
OBJECTIVES AND ENDPOINTS ...................................................................................... 10 
4. 
STUDY DESIGN.................................................................................................................. 14 
4.1 
Overall Design .............................................................................................................. 14 
4.2 
Justification for Dose .................................................................................................... 14 
4.2.1 
Justification for Dose of Remdesivir .................................................................... 14 
4.2.2 
Justification for Dose of Risankizumab ................................................................ 14 
5. 
STUDY POPULATION ....................................................................................................... 15 
5.1 
Inclusion Criteria .......................................................................................................... 15 
5.2 
Exclusion Criteria ......................................................................................................... 15 
5.2.1 
Exclusion of Specific Populations ........................................................................ 16 
5.3 
Inclusion of Vulnerable Subjects .................................................................................. 17 
5.4 
Lifestyle Considerations ............................................................................................... 17 
5.5 
Screen Failures .............................................................................................................. 18 
5.6 
Strategies for Recruitment and Retention ..................................................................... 18 
6. 
STUDY PRODUCT.............................................................................................................. 18 
6.1 
Study Product(s) and Administration –Remdesivir, Risankizumab, and Placebo ........ 18 
6.1.1 
Study Product Description .................................................................................... 18 
6.1.2 
Dosing and Administration ................................................................................... 18 
6.1.3 
Dose Escalation ..................................................................................................... 19 
6.1.4 
Dose Modifications ............................................................................................... 19 
6.1.5 
Overdosage ........................................................................................................... 19 


Protocol 20-0013A 
Version 6 
ACTIV-5/Big Effect Trial (BET) 
21 September 2021 
Appendix A – BET-A: Risankizumab/Remdesivir vs. Placebo/Remdesivir 
3 
 
6.2 
Preparation/Handling/Storage/Accountability .............................................................. 20 
6.2.1 
Acquisition and Accountability ............................................................................ 20 
6.2.2 
Formulation, Appearance, Packaging, and Labeling ............................................ 20 
6.2.3 
Product Storage and Stability................................................................................ 21 
6.2.4 
Preparation ............................................................................................................ 21 
6.3 
Measures to Minimize Bias: Randomization and Blinding .......................................... 21 
6.4 
Study Intervention Compliance .................................................................................... 22 
6.5 
Concomitant Therapy.................................................................................................... 22 
6.5.1 
Permitted Concomitant Therapy and Procedures ................................................. 22 
6.5.2 
Prohibited Concomitant Therapy .......................................................................... 24 
6.5.3 
Rescue Medicine ................................................................................................... 24 
6.5.4 
Non-Research Standard of Care ............................................................................ 24 
7. 
STUDY INTERVENTION DISCONTINUATION AND SUBJECT 
DISCONTINUATION/WITHDRAWAL ..................................................................................... 24 
7.1 
Halting Criteria and Discontinuation of Study Intervention ......................................... 25 
7.1.1 
Individual Infusion Halting ................................................................................... 25 
7.1.2 
Study Halting ........................................................................................................ 25 
7.2 
Withdrawal from the Study ........................................................................................... 25 
7.3 
Readmission .................................................................................................................. 25 
7.4 
Lost to Follow-Up ......................................................................................................... 25 
8. 
STUDY ASSESSMENTS AND PROCEDURES ................................................................ 26 
8.1 
Screening and Efficacy Assessments ............................................................................ 26 
8.1.1 
Screening Procedures ............................................................................................ 26 
8.1.2 
Efficacy Assessments ............................................................................................ 27 
8.1.2.1 
Measures of Clinical Support, Limitations, and Infection Control ................... 27 
8.1.2.2 
Ordinal Scale ..................................................................................................... 28 
8.1.3 
Exploratory Assessments ...................................................................................... 28 
8.2 
Safety and Other Assessments ...................................................................................... 29 
8.3 
Adverse Events and Serious Adverse Events ............................................................... 29 
9. 
STATISTICAL CONSIDERATIONS.................................................................................. 29 
10. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS ....... 29 
11. REFERENCES ..................................................................................................................... 29 
 
LIST OF TABLES 
Table 1. BET-A Schedule of Assessments ..................................................................................... 6 
Table 2. Summary of Adverse Reaction Rates in Subjects with Mild, Moderate, or Severe 
COVID-19 in ACTT-1 .................................................................................................................... 9 
Table 3. BET-A Study Objectives ................................................................................................ 10 
 


Protocol 20-0013A 
Version 6 
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1. 
PROTOCOL SUMMARY 
1.1 
Synopsis 
Rationale for Proposed Clinical Study 
Studies have shown that moderate to severe cases of COVID-19 are characterized by marked 
inflammation and cytokine storm.(1-5) Over the course of the SARS-CoV2 pandemic, the TH17 
pathway has specifically been identified as a potentially important contributor to disease 
pathophysiology.(6, 7) Evaluation of a patient with severe COVID-19 showed an increased 
concentration of TH17 cells in peripheral blood.(8) The role of TH17 immune responses in 
COVID-19 pathogenesis appears to be comparable to its roles in SARS and MERS.(9, 10) 
 
In light of these data, drugs that inhibit TH17 immune responses hold promise for COVID-19 
treatment. Since IL-23 has an essential role in the differentiation and expansion of TH17 cells, 
inhibition of IL-23 is expected to dampen COVID-19 immunopathogenesis.(11, 12) According 
to findings from The Inflammatory Bowel Diseases Surveillance Epidemiology of Coronavirus 
Under Research Exclusion (Secure-IBD) database,(13) patients on IL-12/-23 inhibitors had 
milder COVID-19 disease courses than those on most other classes of medication, with 116/139 
(83%) managed as outpatients and only 5/139 (4%) meeting the combined endpoint of either 
ICU admission, mechanical ventilation or death (compared to 284/481 (59%) and 60/481 (12%) 
who were taking sulfasalazine or mesalamine for their baseline IBD control. This suggests that 
inhibition of the IL-23 pathway, at least early in infection, may be useful in modulating disease 
severity. Thus, we hypothesize that treatment of COVID-19 patients with risankizumab, an IL-23 
antagonist, will improve clinical outcomes. 
 
Study Design 
See the Master protocol document for a description of the study design. 
 
Study Objectives  
See Table 3 in Section 3. 
 
Study Population 
This trial will study risankizumab in a hospitalized adult population (≥18 years old) with COVID-
19. See Sections 5.1 and 5.2 for inclusion and exclusion criteria. 
 
Study Phase 
• Phase 2 
 
Study Sites 
There will be up to 70 domestic sites and 5 international sites. 
 
Study Interventions 
All subjects will receive remdesivir as a 200-mg intravenous (IV) loading dose on Day 1, 
followed by a 100-mg once-daily IV maintenance dose during hospitalization up to a maximum 
of 10 total doses (i.e., loading + maintenance doses received during study and pre-study if 


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applicable). The duration of dosing may be adjusted by the site similar to what is described in the 
product label and based on a subject’s clinical course and ultimate disease severity.  
 
In addition to receiving remdesivir, subjects in the BET-A stage will be randomized to receive 
risankizumab or placebo as follows:  
• Risankizumab 1200-mg IV infusion once on Day 1. 
• Placebo will be given at an equal volume at the same schedule.  
  
Study Duration 
This stage is anticipated to enroll over 3 months, with an additional 1 month of follow-up, and 2 
months to lock the database.  
 
Participant Duration 
An individual subject will complete the study in about 60 days, from screening at Day -1 or 1 to 
completion of follow-up on Day 60 ± 3 days.  
 
DSMB 
See Section 10.1.6.2 of the Master protocol document. 
 


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1.2 
Schedule of Assessments 
Table 1. BET-A Schedule of Assessments 
  
Screen 
Baseline  Study Intervention Period 
Follow-up Visits 
Day +/- Window 
−1 or 1 
115 
Daily until hospital 
discharge (up to Day 29) 
810 
± 2 
156  
± 2 
2210 
± 3 
296 
± 3 
6010 
± 3 
ELIGIBILITY 
 
 
 
 
 
 
 
 
Informed consent 
X 
 
 
 
 
 
 
 
Demographics & Medical History 
X 
 
 
 
 
 
 
 
Targeted physical exam 
X 
 
 
 
 
 
 
 
Review SARS-CoV-2 results 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
STUDY INTERVENTION 
 
 
 
 
 
 
 
 
Randomization 
 
X 
 
 
 
 
 
 
Administration of investigational 
agent 
 
• Risankizumab or placebo: one 
infusion on Day 1 
• Remdesivir: IV daily for 5-10 days or 
until discharge.  
 
 
 
 
 
 
 
 
 
 
 
 
 
STUDY PROCEDURES 
 
 
 
 
 
 
 
 
Vital signs and NEWS score 1, 14 
 
X3 
 
 
 
 
 
 
Clinical data collection1  
 
X3 
Daily until discharge 
X 
X 
X 
X 
X13 
Adverse event evaluation 
 
X3 
Daily until discharge 
X 
X 
X 
X 
X 
Concomitant medication review12 
 
X3 
Day -7 until discharge 
X 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
SAFETY LABORATORY 
 
 
 
 
 
 
 
 
Safety hematology, chemistry, 
and liver tests4, 9 
X2 
X3 
Day 3, 5, 8, 11 (all ± 1 
day) if hospitalized5 
 
X 
 
X 
 
Pregnancy test for females of 
childbearing potential 
X2 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
RESEARCH LABORATORY16  
 
 
 
 
 
 
 
 
Oropharyngeal swab7 
 
X3 
Day 3, 5, 8, 11 (all ± 1 
day) if hospitalized 
 
X 
 
X 
 
Blood draw for serum and plasma.  
Specific testing is as follows: 
 
X3 
Day 3, 5, 8, 11 (all ± 1 
day) if hospitalized  
 
X 
 
X 
 
PCR SARS-CoV-2 
 
X3 
Day 3, 5, 8, 11 (all ± 1 
day) if hospitalized  
 
 
 
 
 
Proteomic analysis (including 
specifically for risankizumab 
IL-17A, IL-22, and IL-1b) 
 
X3 
Day 3, 8, (all ± 1 day) if 
hospitalized  
 
X 
 
X 
 
Risankizumab 
pharmacokinetics11 
 
X8 
Day 5 (± 1 day) if 
hospitalized 
 
X 
 
X 
 
Risankizumab 
immunogenicity11 
 
X8 
 
 
 
 
X 
 
Serum for secondary research 
 
X3 
Day 3, 5, 8, 11 (all ± 1 
day) if hospitalized. 
 
X 
 
X 
 
Blood for RNA 
 
X3 
Day 3, 8 (all ± 1 day) if 
hospitalized 
 
X 
 
X 
 
Blood for PBMC11  
 
X3 
Day 3, 8 (all ± 1 day) if 
hospitalized 
 
X 
 
X 
 
Notes: 


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1 Refer to Section 8.1 of the protocol for details of clinical data to be collected including ordinal score, NEWS, oxygen requirement, 
mechanical ventilator requirement, etc. 
2 Screening laboratory tests include: ALT, AST, creatinine (and calculate an estimated glomerular filtration rate (eGFR) the formula used 
is determined by the sites, but should be consistent throughout the study), and urine or serum pregnancy test for females of child-bearing 
potential. Laboratory tests performed as part of routine clinical care in the 48 hours prior to enrollment will be accepted for 
determination of eligibility. 
3 Baseline assessments should be performed prior to first infusion. Laboratory tests performed as part of routine clinical care in the 24 
hours prior to first dose will be accepted for the baseline safety laboratory tests. Baseline may be the same as the screening laboratory 
tests if obtained in the 24 hours prior to first dose. 
4 Safety laboratory tests include WBC with differential, hemoglobin, platelets, creatinine, total bilirubin, ALT, AST, and INR. 
5 Any laboratory tests performed as part of routine clinical care within the specified visit window can be used for safety laboratory testing. 
6 In-person visits are preferred but recognizing quarantine and other factors may limit the subject’s ability to return to the site for the 
visit. In this case, the visit may be performed by phone. 
• 
If still hospitalized at Day 15 and 29 or returns for an in-person visit: assess adverse events, collect clinical data, vital signs, 
safety laboratory tests, and research laboratory samples (OP swab and blood) as able.  
• 
If phone call only on Days 15 and 29 and all Day 22 and Day 60 visits: assess adverse events, clinical status (ordinal scale), 
readmission to a hospital, and mortality only. 
7 Oropharyngeal swabs are preferred, but if these are not obtainable, saliva or nasopharyngeal or nasal swabs may be substituted.  
8 Pre-dose serum sample collections for PK and immunogenicity.  
9 To include markers of inflammation and coagulation: CRP, ferritin, fibrinogen, d-dimer.  
10 Day 8, 22 and 60 visits performed by phone call or home visit if discharged from the site hospital: assess adverse events, clinical status 
(ordinal scale), readmission to a hospital, and mortality only. 
11 Only collected at selected sites capable of processing. 
12 Steroids and other concomitant therapies intended as specific treatment of COVID-19, as well as all biologics, will be assessed from 7 
days prior to enrollment to Day 29. All other concomitant medications will be assessed from 7 days prior to enrollment to Day 15 or upon 
discharge, whichever comes first. 
13 Ordinal score only. 
14 Vital signs include temperature, systolic blood pressure, heart rate, respiratory rate, O2 saturation and level of consciousness. In 
addition, height and weight are obtained only at baseline (height can be self-reported). Vital signs collected as part of standard care may 
be used. 
15 Day 1 is defined as the calendar day of randomization. 
16 Blood draws for research labs may be omitted on any given study day if inappropriate for a subject’s clinical status per site investigator 
judgment. 
 
2. 
INTRODUCTION 
2.1 
Study Rationale 
See Section 1.1 of this Appendix. 
2.2 
Background 
2.2.1 
Purpose of Study 
See Section 1.1 of this Appendix. 
2.2.2 
Potential Therapeutic Agents 
Remdesivir is a broad-spectrum nucleotide prodrug that inhibits RNA-dependent RNA 
polymerase. Remdesivir is licensed for the treatment of COVID-19 requiring hospitalization. In 
the ACTT-1 trial, remdesivir has been demonstrated to decrease the time to recovery from 15 to 
10 days (recovery rate ratio 1.29 (1.12 to 1.49); P<0.001).(14) All subjects in the trial will be 
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Risankizumab is a humanized immunoglobulin G1 (IgG1) monoclonal antibody that antagonizes 
IL-23. It is indicated for the treatment of moderate-to-severe plaque psoriasis,  
and is currently under investigation in patients with ulcerative colitis, Crohn’s disease, and 
hidradenitis suppurativa. 
2.3 
Risk/Benefit Assessment 
2.3.1 
Known Overall Risks 
Potential risks of participating in this stage are those associated with having blood drawn, the IV 
catheterization, possible reactions to remdesivir and risankizumab (as noted in Sections 2.3.2-
2.3.3), and breach of confidentiality. 
 
Drawing blood may cause transient discomfort and fainting. Fainting is usually transient and 
managed by having the subject lie down and elevate his/her legs. Bruising at the blood collection 
sites may occur but can be prevented or lessened by applying pressure to the blood draw site for 
a few minutes after the blood is taken. IV catheterization may cause insertion site pain, phlebitis, 
hematoma formation, and infusate extravasation; less frequent but significant complications 
include bloodstream and local infections. The use of aseptic (sterile) technique will make 
infection at the site where blood will be drawn or at catheter site less likely. Rarely, severe 
allergic reactions (called anaphylaxis) can occur and may cause heart attacks and, if untreated, 
even death. 
 
Risks to Privacy 
Subjects will be asked to provide personal health information (PHI). All attempts will be made to 
keep this PHI confidential within the limits of the law. However, there is a chance that 
unauthorized persons will see the subject’s PHI. All study records will be kept in a locked file 
cabinet or maintained in a locked room at the participating clinical site. Electronic files will be 
password protected. Only people who are involved in the conduct, oversight, monitoring, or 
auditing of this trial will be allowed access to the PHI that is collected. Any publication from this 
trial will not use information that will identify subjects. Organizations that may inspect and/or 
copy research records maintained at the participating site for quality assurance and data analysis 
include groups such as the IRB, NIAID and applicable regulatory agencies (e.g., FDA). For more 
information about confidentiality and privacy see Section 10.1.3 in the Master protocol 
document. 
 
Risks of Genetic Testing 
Genetic findings can have emotional and psychological consequences as well as implications for 
health, employability, and insurability for the subject and family members. However, state and 
federal laws provide protections against genetic discrimination. Samples and the resulting data 
will be coded and kept private. Additionally, to protect confidentiality, results will be entered 
into a password-protected database restricted to the PI or appointed designees. Genetic 
information would only be divulged if a subject signs a waiver on an insurance application. 
Study analyses will not result in discoveries about identity or paternity. 
 


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2.3.2 
Potential Risks of Remdesivir 
Remdesivir is an FDA approved antiviral and may be obtained as part of standard care outside 
the clinical trial. For the purpose of the BET-A study, remdesivir is still considered a study 
product being used as part of an investigational trial and it will be tracked and monitored 
accordingly. 
 
Transaminase elevations have been observed in healthy volunteers who received remdesivir; the 
transaminase elevations were mild (Grade 1) to moderate (Grade 2) in severity and resolved 
upon discontinuation of remdesivir. Transaminase elevations have also been reported in patients 
with COVID-19 who received remdesivir.  
 
In ACTT-1, the collection of adverse event (AE) data in this trial was limited to severe (Grade 3) 
or potentially life-threatening (Grade 4) AEs, serious adverse events (SAEs), AEs leading to 
study drug discontinuation, and moderate (Grade 2) severity or higher hypersensitivity reactions. 
Rates of adverse reactions (≥ Grade 3), serious adverse reactions, and adverse reactions leading 
to treatment discontinuation are presented in Table 2. 
 
Table 2. Summary of Adverse Reaction Rates in Subjects with Mild, Moderate, or Severe 
COVID-19 in ACTT-1 
Types of Adverse Reactions 
Remdesivir N=532 n (%) 
Placebo N=516 n (%) 
Adverse reactions, Grades ≥3 
41 (8%) 
46 (9%) 
Serious adverse reactions 
2 (0.4%)a 
3 (0.6%) 
Adverse reactions leading to 
treatment discontinuation 
11 (2%)b 
15 (3%) 
a Seizure (n=1), infusion-related reaction (n=1).  
b. Seizure (n=1), infusion-related reaction (n=1), transaminases increased (n=3), ALT increased and AST 
increased (n=1), GFR decreased (n=2), acute kidney injury (n=3). 
 
There is the potential of the SARS-CoV-2 developing resistance to remdesivir, which could 
result in decreased efficacy. The clinical impact of the development of resistance is not clear at 
this time.  
 
Coadministration of remdesivir and chloroquine phosphate or hydroxychloroquine sulfate is not 
recommended based on cell culture data demonstrating an antagonistic effect of chloroquine on 
the intracellular metabolic activation and antiviral activity of remdesivir. 
 
See Package Insert for full discussion of clinical experience and risks.  
2.3.3 
Potential Risks of Risankizumab  
Potential risks include upper respiratory infection, fungal skin infection, headache, and tiredness. 
A total of 2234 subjects were treated with risankizumab in clinical studies for plaque psoriasis. 
In the first 16 weeks of treatment, infections occurred in 22.1% of the risankizumab group (90.8 
events per 100 subject-years) compared to 14.7% of the placebo group (56.5 events per 100 
subject-years) and did not lead to discontinuation of risankizumab. The rates of serious infections 
for both the risankizumab and placebo groups were ≤0.4%. Serious infections in the 
risankizumab-treated group included cellulitis, osteomyelitis, sepsis, and herpes zoster. In 


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ULTIMMA-1 and ULTIMMA-2 trials, through Week 52, the rate of infections (73.9 events per 
100 subject-years) was similar to the rate observed during the first 16 weeks of treatment. 
Through Week 52, no new adverse reactions were observed, and the rates of the adverse 
reactions were similar to those identified during the first 16 weeks of treatment. During this time 
period, serious infections that led to study discontinuation included pneumonia. 
 
In the Phase 2 ulcerative colitis study, 49% of patients treated with up to three doses of 1200 mg 
of risankizumab IV over a 3-month period and 41% of patients in the placebo arm were on 
concomitant steroids. There was no difference in the overall safety profile of patients that were 
on corticosteroid medication and received either risankizumab 1200 mg or placebo, indicating no 
safety concerns with concomitant use of risankizumab with steroids. 
2.3.4 
Known Potential Benefits 
Individual subjects with COVID-19 participating in this stage may or may not experience 
improved clinical outcomes. However, there is potential benefit to society from their 
participation in this study resulting from insights gained about the therapeutic agent under study 
as well as the natural history of the disease. While there may not be benefits for an individual 
subject, there may be benefits to society if a safe, efficacious therapeutic agent can be identified 
during this global COVID-19 outbreak.  
3. 
OBJECTIVES AND ENDPOINTS 
Table 3. BET-A Study Objectives 
OBJECTIVES 
ENDPOINTS  
(OUTCOME MEASURES) 
Primary 
 
To evaluate the clinical efficacy of 
risankizumab relative to the control arm in 
adults hospitalized with COVID-19 according 
to clinical status (8-point ordinal scale) at 
Day 8. 
 
 
 
1. Not hospitalized, no new or increased** 
limitations on activities; 
2. Not hospitalized, but new or increased 
limitation on activities and/or requiring new 
or increased home oxygen, CPAP or BiPAP; 
3. Hospitalized, not requiring new or 
increased supplemental oxygen - no longer 
requires ongoing medical care; 
4. Hospitalized, not requiring new or 
increased supplemental oxygen - requiring 
ongoing medical care (COVID-19 related or 
otherwise); 
5. Hospitalized, requiring new or increased 
supplemental oxygen; 
6. Hospitalized, requiring new or increased 
non-invasive ventilation or high-flow oxygen 
devices; 
7. Hospitalized, on invasive mechanical 
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OBJECTIVES 
ENDPOINTS  
(OUTCOME MEASURES) 
oxygenation (ECMO); 
8. Death. 
Key Secondary 
 
1. To evaluate the clinical efficacy of 
risankizumab as assessed by time to recovery 
compared to the control arm. 
 
 
Day of recovery is defined as the first day on 
which the subject satisfies 1 of the following 
3 categories from the ordinal scale (and does 
not return to a score of 4 or higher for the 
remainder of the study period): 
1. Not hospitalized, no new or increased 
limitations on activities; 
2. Not hospitalized, but new or increased 
limitation on activities and/or 
requiring new or increased home 
oxygen, CPAP, or BiPAP; 
3. Hospitalized, not requiring new or 
increased supplemental oxygen - no 
longer requires ongoing medical care. 
2. To evaluate the proportion of subjects alive 
and without respiratory failure through Day 
29. 
 
Subjects in ordinal scale 5 or 6 at baseline 
who did not meet either of the following two 
categories at any point through Day 29: 
7. Hospitalized, on invasive mechanical 
ventilation or ECMO; 
8. Death. 
Other Secondary 
 
1. To evaluate the clinical efficacy of 
risankizumab as compared to the control arm 
as assessed by: 
• Clinical Severity 
o Ordinal scale: 
 Clinical status using ordinal scale at 
Days 15 and 29. 
 Time to an improvement of one 
category and two categories from 
Day 1 (baseline) using an ordinal 
scale. 
 Mean change in the ordinal scale 
from Day 1 to Days 3, 5, 8, 11, 15, 
22, and 29. 
 
 
 
• Clinical outcome assessed using ordinal 
scale daily while hospitalized and on Days 
15, 22, and 29. 
 
o Oxygenation: 
 Supplemental oxygen use up to Day 
• Days of supplemental oxygen (if 
applicable) up to Day 29. 


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OBJECTIVES 
ENDPOINTS  
(OUTCOME MEASURES) 
29. 
o Non-invasive ventilation/high-flow 
oxygen: 
 Non-invasive ventilation/high-flow 
oxygen use up to Day 29. 
 Incidence and duration of new non-
invasive ventilation or high-flow 
oxygen use through Day 29. 
• Days of non-invasive ventilation/high-
flow oxygen (if applicable) up to Day 29. 
o Invasive Mechanical Ventilation/ 
ECMO: 
 Ventilator/ECMO use up to Day 29. 
 Incidence and duration of new 
mechanical ventilation or ECMO 
use through Day 29. 
• Days of invasive mechanical 
ventilation/ECMO (if applicable) up to 
Day 29. 
 
o Proportion of subjects alive and 
without respiratory failure at Day 29. 
Proportion of subjects who did not meet 
either of the following two categories on Day 
29: 
7. Hospitalized, on invasive mechanical 
ventilation or ECMO; 
8. Death. 
• Hospitalization: 
o Duration of hospitalization (days).  
• Days of hospitalization up to Day 29. 
• Mortality: 
o 14-day mortality. 
o 29-day mortality. 
o Time to death up to Day 29. 
o 60-day mortality. 
• Date and cause of death (if applicable). 
 
• Markers of inflammation and 
coagulation. 
• C-reactive protein (CRP), ferritin, D-
dimer, and fibrinogen on Day 1; Days 3, 
5, 8, and 11 (while hospitalized); and 
Days 15 and 29 (if attends in-person visit 
or still hospitalized). 
2. To evaluate the safety of risankizumab as 
compared to the control arm as assessed by: 
• Cumulative incidence of SAEs through 
Day 60. 
• Cumulative incidence of Grade 3 and 4 
clinical and/or laboratory AEs through 
Day 60. 
 
 
 
• SAEs. 
 
• Grade 3 and 4 AEs.  
 


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OBJECTIVES 
ENDPOINTS  
(OUTCOME MEASURES) 
• Discontinuation or temporary 
suspension of study product 
administration (for any reason). 
• Changes in white blood cell (WBC) 
count with differential, hemoglobin, 
platelets, creatinine, total bilirubin, 
alanine aminotransferase (ALT), 
aspartate aminotransferase (AST), and 
international normalized ratio (INR) 
over time (analysis of lab values in 
addition to AEs noted above).  
• Episodes of early discontinuation or 
interruption of study product 
administration. 
 
• WBC with differential, hemoglobin, 
platelets, creatinine, total bilirubin, ALT, 
AST, and INR on Day 1; Days 3, 5, 8, and 
11 (while hospitalized); and Days 15 and 
29 (if attends in-person visit or still 
hospitalized). 
 
Exploratory  
 
1. To evaluate the virologic efficacy of 
risankizumab as compared to the control arm 
as assessed by: 
• Percent of subjects with SARS-CoV-2 
detectable in saliva (or best technology) 
sample at Days 3, 5, 8, 11, 15, and 29.  
• Quantitative SARS-CoV-2 virus in 
saliva (or best technology) sample at 
Days 3, 5, 8, 11, 15, and 29. 
• Quantitative SARS-CoV-2 virus in 
blood at Days 3, 5, 8, and 11. 
• Qualitative and quantitative polymerase 
chain reaction (PCR) for SARS-CoV-2 in 
OP swab on Day 1; Days 3, 5, 8, and 11 
(while hospitalized); and Days 15 and 29 
(if attends in-person visit or still 
hospitalized). 
 
• Qualitative and quantitative PCR for 
SARS-CoV-2 in blood on Day 1; Days 3, 
5, 8, and 11 (while hospitalized). 
2. To evaluate the impact of study 
interventions on markers of inflammation and 
immune response. 
• Proteomic analysis of plasma cytokines 
and markers of inflammation including 
IL-17A, IL-22 and IL-1b.  
• Transcription, epigenetic, and molecular 
profiles of mRNA in peripheral blood 
mononuclear cells (PBMC). 
• Phenotypic and responsiveness markers in 
PBMC. 
3. To evaluate post-baseline usage of key 
concomitant COVID-19 treatments (e.g., 
steroids) in investigational therapeutic arms 
as compared to the control arm. 
 
• Use of concomitant COVID-19 treatments 
up to Day 29.  
 


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OBJECTIVES 
ENDPOINTS  
(OUTCOME MEASURES) 
Stage-specific 
objective/endpoint 
4. To evaluate risankizumab 
pharmacokinetics (PK) and 
immunogenicity in subjects 
with COVID-19. 
• Serum samples for PK (at pre-dose, Day 
5, Day 15, and Day 29) and serum 
samples for anti-drug antibodies and 
neutralizing antibodies at pre-dose and 
Day 29. 
 
 ** “New or increased” is relative to pre-COVID status 
4. 
STUDY DESIGN 
4.1 
Overall Design 
See Section 1.1 of the Master protocol document. 
4.2 
Justification for Dose 
4.2.1 
Justification for Dose of Remdesivir 
The dose of remdesivir used in this study will be the same dose shown to be efficacious in the 
ACTT-1 clinical trial,(14) and are the US FDA approved doses. The duration of dosing may be 
adjusted by the site according to clinical severity. The maximum number of doses to be given 
during hospitalization is ten doses. This includes the loading dose and all maintenance doses 
given during the study and pre-study if applicable.  
4.2.2 
Justification for Dose of Risankizumab 
The dose of risankizumab used in this stage will be 1200 mg administered as a single dose 
intravenously (IV). This is the same dose level as the highest dose used in the multiple dose 
induction Phase 3 clinical trials for inflammatory bowel diseases. The 1200 mg IV dose given 
once every 4 weeks for 3 doses has been evaluated in a dose-ranging Phase 2 clinical study in 
subjects with UC 
 
. The same dosing regimen is also the highest dose being tested in the ongoing 
Phase 3 study in subjects with CD. Available data from these studies showed that the 1200 mg 
risankizumab dose is well tolerated and dose-ranging data including higher and lower doses 
 did not reveal any exposure-dependent safety issues. Therefore, given 
the novel setting of COVID-19 and the acute nature of the disease onset in the target patient 
population of the study, 1200 mg IV is selected to provide best opportunity for efficacy in this 
POC study. The dose is expected to be safe and well tolerated in COVID-19 patients. It is also 
expected to provide a quick onset of drug exposure following IV administration and duration of 
exposure long enough to cover the 29 days of the main study thanks to the long elimination half-
life (approximately 28 days) of risankizumab.  


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5. 
STUDY POPULATION 
Approximately 200 (100 treatment and 100 shared placebo) male and non-pregnant female adults 
≥18 years of age or older with COVID-19 and who meet all eligibility criteria will be enrolled at 
up to 70 domestic sites and 5 international sites. The target population should reflect the 
community at large. The estimated time from screening (Day -1 or Day 1) to end of study for an 
individual subject is approximately 60 days.  
 
Subject inclusion and exclusion criteria must be confirmed by a clinician named on the 
delegation log. If there is any uncertainty, the site PI may consult the DMID Medical Officer on 
whether a potential subject is eligible for study enrollment; the site PI is ultimately responsible 
for making the final decision. There is no exclusion for receipt of SARS-CoV-2 vaccine 
(experimental or licensed). 
5.1 
Inclusion Criteria 
1. Admitted to a hospital with symptoms suggestive of COVID-19 and requires ongoing 
medical care. 
2. Subject (or legally authorized representative) provides informed consent prior to 
initiation of any study procedures. 
3. Subject (or legally authorized representative) understands and agrees to comply with 
planned study procedures. 
4. Male or non-pregnant female adult ≥18 years of age at time of enrollment. 
5. Illness of any duration and has laboratory-confirmed SARS-CoV-2 infection as 
determined by PCR or other commercial or public health assay (e.g., Nucleic Acid 
Amplification Test [NAAT], antigen test) in any respiratory specimen or saliva ≤14 days 
prior to randomization.  
6. Illness of any duration, and requiring, just prior to randomization, supplemental oxygen 
(any flow), mechanical ventilation or ECMO (ordinal score 5, 6, or 7).  
7. Women of childbearing potential must agree to either abstinence or use at least one 
acceptable method of contraception from the time of screening through 5 months post 
study IP dosing. 
Note: Acceptable methods include barrier contraceptives (condoms or diaphragm) with spermicide, 
intrauterine devices (IUDs), hormonal contraceptives, oral contraceptive pills, and surgical 
sterilization.  
8. Agrees not to participate in another blinded clinical trial (both pharmacologic and other 
types of interventions) for the treatment of COVID-19 through Day 29 (see Section 5.4 
for more information about concurrent trial participation).  
5.2 
Exclusion Criteria 
1. ALT or AST > 5 times the upper limit of normal. 
2. Subjects with a low glomerular filtration rate (eGFR), specifically: 
a. Subjects with an eGFR 20-30 mL/min are excluded unless in the opinion of the 
PI, the potential benefit of participation outweighs the potential risk of study 
participation. 
b. All subjects with an eGFR <20 mL/min (including hemodialysis and 
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3. Pregnancy or breast feeding. 
4. Anticipated discharge from the hospital or transfer to another hospital which is not a 
study site within 72 hours of enrollment. 
5. Allergy to any study medication. 
6. Received five or more doses of remdesivir prior to screening.  
7. Received two or more doses of > 60 mg of prednisone or equivalent in the 7 days prior to 
screening  
8. Received small molecule tyrosine kinase inhibitors, including Janus kinase (JAK) 
inhibitors (e.g., baricitinib, ibrutinib, acalabrutinib, imatinib, gefitinib), in the 4 weeks 
prior to screening.* 
9. Received monoclonal antibodies targeting cytokines (e.g., TNF inhibitors, anti-IL-1 [e.g., 
anakinra, canakinumab], anti-IL-6 [e.g., tocilizumab, sarilumab, sitlukimab]), or T-cells 
(e.g., abatacept) in the 4 weeks prior to screening.* 
10. Received monoclonal antibodies targeting B-cells (e.g., rituximab, and including any 
targeting multiple cell lines including B-cells) in the 3 months prior to screening.* 
11. Received GM-CSF agents (e.g., sargramostim) within 2 months prior to screening.* 
12. Received other immunosuppressants in the 4 weeks prior to screening and in the 
judgment of the investigator, the risk of immunosuppression with risankizumab is larger 
than the risk of COVID-19.*  
13. Received any live vaccine in the 4 weeks prior to screening. 
14. Known active tuberculosis. 
15. Known history of HIV, Hepatitis B (HBV) or untreated hepatitis C (HCV) infection. 
16. History of pulmonary alveolar proteinosis (PAP).* 
17. Has a malignancy and currently receiving immunosuppressive chemotherapy, 
immunodeficiency, uncontrolled opportunistic infection, or uncontrolled cirrhosis. 
18. Has a medical condition that could, in the judgment of the investigator, limit the 
interpretation and generalizability of trial results. 
19. Positive test for influenza virus during the current illness (influenza testing is not 
required by protocol). 
20. Previous participation in an ACTIV-5/BET trial. 
 
* Stage-specific criteria.  
5.2.1 
Exclusion of Specific Populations 
Children and adolescents will not be included in this trial. Remdesivir has only been used in a 
small number of pediatric patients. Initial information about the epidemiology of COVID-19 
indicates that the overwhelming burden of severe disease occurs among older adults, especially 
those with comorbidities. The safety and efficacy of risankizumab in pediatric patients less than 
18 years of age have not yet been established. Given significant gaps in knowledge in this 
population, and a low incidence of severe morbidity/mortality in children, the risk/benefits do 
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Remdesivir and risankizumab have not been studied in pregnant women. Because the effects on 
the fetus and the pregnant woman are not fully known, pregnant women will not be eligible for 
the trial.  
 
It is not known whether remdesivir or risankizumab is secreted in human milk. Because the 
effects of remdesivir and risankizumab on the breastfeeding infant is not known, women who are 
breast feeding will not be eligible for the trial. 
5.3 
Inclusion of Vulnerable Subjects 
Certain human subjects are categorized as vulnerable populations and require special treatment 
with respect to safeguards of their well-being. For this clinical trial, examples include cognitively 
impaired or mentally disabled persons and intubated individuals who are sedated. When it is 
determined that a potential research subject is cognitively impaired, federal and institutional 
regulations permit researchers to obtain consent from a legally authorized representative (LAR). 
The study team will obtain consent from these vulnerable subjects using an IRB-approved 
protocol-specific process for consent using a LAR. 
 
For subjects for whom a LAR gave consent, during the course of the study, if the subject regains 
the capacity to consent, informed consent must be obtained from the subject and the subject 
offered the ability to leave the study if desired. 
5.4 
Lifestyle Considerations 
During this study, subjects are asked to: 
• Refrain from drinking alcohol through Day 15.  
• Avoid getting pregnant during the study from the time of screening through 5 months 
post study IP dosing. 
• Subject’s participation in other trials for COVID-19 or SARS-CoV-2 infection are 
restricted/permitted as follows:  
o Blinded trials of interventions of antiviral or immunomodulatory agents for 
treatment of COVID-19 are prohibited through Day 29. 
o Co-enrollment in non-blinded (open-label) interventional studies that evaluate 
how to apply a standard of care intervention or strategy for patients with COVID-
19 (e.g., comparing dose, duration or schedule of VTE prophylaxis regimens; ICU 
strategies such as proning, etc.) is permitted.  
o Co-enrollment in natural history studies of COVID-19 and/or studies of SARS-
CoV-2 diagnostics is permitted.  
o Participation in both ACTIV-5/BET and these studies can only occur if the 
recommended blood collection volumes are not exceeded. 
o If a subject is co-enrolled in a prohibited study noted above, this should be 
reported as a protocol deviation, but the subject should not be withdrawn from 
this trial to participate in the other study. Full follow-up should occur per 
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5.5 
Screen Failures 
Following consent, after the screening evaluations have been completed, the investigator or 
designee is to review the inclusion/exclusion criteria and determine the subject’s eligibility for 
the study stage. If there is any uncertainty, the PI should make the decision on whether a 
potential subject is eligible for study enrollment.  
 
Only basic demographic information and the reason(s) for ineligibility will be collected on 
screen failures. Subjects who are found to be ineligible will be told the reason(s) for ineligibility. 
 
Individuals who do not meet the criteria for participation in this study (screen failure) because of 
an abnormal laboratory finding may be rescreened once. 
5.6 
Strategies for Recruitment and Retention 
See Section 5.4 of the Master protocol document. 
6. 
STUDY PRODUCT  
6.1 
Study Product(s) and Administration –Remdesivir, Risankizumab, 
and Placebo 
6.1.1 
Study Product Description  
Remdesivir Component: 
Remdesivir is a single diastereomer monophosphoramidate prodrug designed for the intracellular 
delivery of a modified adenine nucleoside analog GS-441524. In addition to the active 
ingredient, the solution and lyophilized formulations of remdesivir contains the following 
inactive ingredients: water for injection (solution only), betadex sulfobutyl ether sodium, and 
hydrochloric acid and/or sodium hydroxide. 
 
Risankizumab Component: 
Risankizumab is a humanized immunoglobulin (Ig) G1 antagonistic monoclonal 
antibody (mAb) directed against the p19 subunit of the human cytokine 
interleukin-23. Risankizumab is formulated in a buffer of 4.4 mM disodium succinate 
hexahydrate/succinic acid, 225 mM sorbitol, 0.2 mg/mL polysorbate 20, and WFI in a 6R vial.  
 
Risankizumab matching placebo solution for infusion is available in a 6R vial containing 
Disodium Succinate, Succinic Acid, Sorbitol, Polysorbate 20, and water for injection with a pH 
of 6.2  
6.1.2 
Dosing and Administration 
All subjects will receive remdesivir as a 200 mg IV loading dose on Day 1, followed by a 100 
mg once-daily IV maintenance dose for the duration of the hospitalization up to a 10-day total 
course. If subjects already received the loading dose prior to study enrollment, then start at 100 
mg/day on Day 1. Any doses of remdesivir given within 1 week of enrollment will be counted, 
so that the total duration of remdesivir (i.e. pre-enrollment + on this trial) is up to 10 days (i.e., a 
maximum of 10 total infusions). Any doses of remdesivir were administered prior to study 


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enrollment should be documented in on the eCRF as a concomitant medication given prior to 
Day 1. The duration of dosing may be adjusted by the site similar to what is described in the 
package insert and based on a subject’s clinical course and ultimate disease severity.  
 
Any dose of remdesivir that is delayed may be given later that calendar day. Any dose or 
remdesivir that is missed (not given that calendar day) is not made up. The treatment course 
continues as described above even if the subject becomes PCR negative.  
 
In addition to receiving remdesivir, subjects in the BET-A trial will be randomized to receive 
risankizumab or placebo as follows:  
• Risankizumab 1200-mg IV infusion (300 mg x 4 vials) once on Day 1. 
• Placebo will be given at an equal volume at the same schedule.  
 
At least 20 minutes between administration of remdesivir and risankizumab or placebo are 
preferred if possible (to allow attribution of any infusion related adverse reactions). However, 
timely administration of both products is most important, and if the interval between products is 
likely to cause delays for either products, it can be omitted. See MOP for details.  
 
If the dose of risankizumab is delayed, it should be given as soon as practical. 
6.1.3 
Dose Escalation 
Not Applicable 
6.1.4 
Dose Modifications 
Remdesivir component: 
The infusion should be held and not given if the subject is found to have any of the following 
laboratory values: 
• eGFR decreases to < 20 mL/min 
o Remdesivir infusion will resume when the eGFR increases to ≥ 20 mL/min and the 
potential benefit of giving remdesivir outweighs the potential risk.  
o If renal function worsens during the study to the point that they require hemodialysis 
or hemofiltration, remdesivir will be discontinued. 
• ALT and/or AST increases to > 5 times upper limits of normal (ULN); resume remdesivir 
infusions when ALT and AST ≤ 5 times ULN. 
 
Risankizumab component: No dosing adjustment needed. 
6.1.5 
Overdosage 
There is no known antidote for remdesivir. In the case of overdose, the subject should receive 
supportive therapy based on the subject´s signs and symptoms. 
 
In the event of risankizumab overdosage, monitor the patient for any signs or symptoms of adverse 
reactions and administer appropriate symptomatic treatment immediately. 


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6.2 
Preparation/Handling/Storage/Accountability 
6.2.1 
Acquisition and Accountability 
Investigational products (IP) will be shipped to the site either directly from participating 
companies, from the Sponsor, or from other regional or local drug repositories. All other supplies 
should be provided by the site. Multiple lots of each IP may be supplied. 
 
Study products received at the sites will be open label and not kit specific, unless specified in the 
stage-specific Manual of Procedures (MOP). Drug preparation will be performed by the 
participating site’s research pharmacist on the same day of administration to the subject. See the 
MOP for detailed information on the preparation, labeling, storage, and administration of 
remdesivir, risankizumab, and placebo.  
 
Accountability 
The site PI is responsible for study product distribution and disposition and has ultimate 
responsibility for study product accountability. The site PI may delegate to the participating 
site’s research pharmacist responsibility for study product accountability. The participating site’s 
research pharmacist will be responsible for maintaining complete records and documentation of 
study product receipt, accountability, dispensation, storage conditions, and final disposition of 
the study product(s). Time of study drug administration to the subject will be recorded on the 
appropriate data collection form (CRF). All study product(s), whether administered or not, must 
be documented on the appropriate study product accountability record or dispensing log. The 
Sponsor’s monitoring staff will verify the participating site’s study product accountability 
records and dispensing logs per the site monitoring plan. Refer to the protocol-specific MOP for 
details on storing study medications.  
 
Destruction 
After the study treatment period has ended or as appropriate over the course of the study after 
study product accountability has been performed, used active and placebo vials can be destroyed 
on-site following applicable site procedures with a second staff member observing and verifying 
the destruction.  
 
Unused vials at the end of the study should be saved until instructed by the Sponsor. 
6.2.2 
Formulation, Appearance, Packaging, and Labeling 
Remdesivir component 
Remdesivir may be supplied in two formulations: 
• The concentrated solution of remdesivir is supplied as a single dose in a Type 1 clear 
glass vial containing 100 mg/20 mL (5 mg/mL) of remdesivir per vial for dilution into 
0.9% sodium chloride infusion bag. It is a sterile, preservative-free, clear, colorless to 
yellow, aqueous-based concentrated solution that is to be diluted into 0.9% sodium 
chloride infusion bag prior to administration by intravenous infusion. In addition to the 
active ingredient, the solution formulation of remdesivir contains the following inactive 
ingredients: water for injection, betadex sulfobutyl ether sodium, hydrochloric acid, 
and/or sodium hydroxide. For more information, refer to the MOP. 
 


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• The lyophilized formulation of remdesivir is a sterile, preservative-free, white to off-
white to yellow powder containing 100 mg of remdesivir to be reconstituted with 19 mL 
of sterile water for injection and diluted into IV infusion fluids prior to IV infusion. 
Following reconstitution, each vial contains a 5 mg/mL remdesivir concentrated solution 
with sufficient volume to allow withdrawal of 20 mL (100 mg of remdesivir). It is 
supplied in a single-use, Type 1 clear glass vial. In addition to the active ingredient, the 
lyophilized formulation of remdesivir contains the following inactive ingredients: water 
for injection, betadex sulfobutyl ether sodium, hydrochloric acid, and/or sodium 
hydroxide. For more information, refer to the MOP. 
 
Remdesivir will be labeled according to manufacturer specifications. 
 
Risankizumab component 
Risankizumab 
 is a sterile isotonic aqueous solution for IV administration contained 
in a 
. Risankizumab drug 
product 
 is a colorless to slightly yellow, clear to slightly opalescent solution, with an 
 
 
Placebo  
The supplied matching placebo of risankizumab is identical in physical appearance to the active 
IV formulation and contains the same inactive ingredients. The IV formulation of matching 
placebo is filled in a 
 
. Each single-use vial 
contains sufficient volume to allow withdrawal of 3.3 mL of placebo. 
 
Each of the study products will be labeled according to manufacturer specifications and include 
the statement “Caution: New Drug Limited by Federal Law to Investigational Use.” 
6.2.3 
Product Storage and Stability 
Refer to the MOP for instructions regarding the stability and storage of remdesivir, 
risankizumab, and placebo. 
6.2.4 
Preparation 
Refer to the MOP for details about preparation and handling of remdesivir, risankizumab, and 
placebo.  
 
Remdesivir and risankizumab do not meet the criteria for a hazardous compound as defined by 
NIOSH and ASHP hazard classification systems. The study products may be prepared in a clean 
room but do not need to be prepared or handled in a fume hood. 
 
Measures that minimize drug contact with the body should always be considered during 
handling, preparation, and disposal procedures as indicated in the MOP.  
6.3 
Measures to Minimize Bias: Randomization and Blinding 
Randomization will be a two-step process. Patients will first be randomized to one of the stages 
to which they are eligible (e.g., risankizumab or other interventions) with equal allocation. Then 


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patients are randomized to the active or placebo version of that intervention with allocation k:1, 
where k is the number of eligible stages the study site is currently randomizing. All eligible 
subjects will receive backbone therapy comprising remdesivir. Patients randomized to 
risankizumab in the first stage will be randomized to receive either risankizumab/remdesivir or 
placebo/remdesivir in the second stage. Randomization will be stratified by: 
• Site 
• Severity of illness at enrollment: baseline Ordinal Score 5 versus Ordinal Score 6 or 7 
combined 
 
The randomization procedure will be described in the MOP. 
6.4 
Study Intervention Compliance 
Each dose of study product will be administered by a blinded member of the clinical research 
team who is qualified and licensed to administer the study product. Administration and date, and 
time, will be entered into the case report form (CRF). 
6.5 
Concomitant Therapy 
6.5.1 
Permitted Concomitant Therapy and Procedures 
For patients that are eligible for the study, other therapy received prior to enrollment with any 
other experimental treatment or off-label use of marketed medications that are intended as 
specific treatment for COVID-19 or the SARS-CoV-2 infection (i.e., post-exposure prophylaxis 
[PEP]) are permitted but must be discontinued on enrollment. There is no waiting period 
between discontinuation of these treatments and administration of study products. However, 
these prior treatments and their end date should be documented on the concomitant medication 
form in the EDC system.  
Steroids for the treatment of COVID-19 may be used per the local institution’s written standard 
of care (i.e., not just an individual clinician decision) or NIH COVID-19 Treatment Guidelines 
(https://www.covid19treatmentguidelines.nih.gov/). NIH COVID-19 Treatment Guidelines 
provide current evidence-based information about the optimal management of COVID-19. NIH 
COVID-19 Treatment Guidelines were updated on June 25, 2020 to include a Grade AI 
recommendation for using dexamethasone (6 mg per day for up to 10 days) in patients with 
COVID-19 who are mechanically ventilated and a Grade B1 recommendation for patients with 
COVID-19 who require supplemental oxygen but who are not mechanically ventilated based on 
preliminary data from the RECOVERY trial. The NIH Guidelines also recommend against using 
dexamethasone in COVID-19 patients who do not require supplemental oxygen.  
Steroid regimens for other standard indications including asthma exacerbation, ARDS, COPD, 
laryngeal edema, adrenal insufficiency, shock, etc. are allowable up to a maximum of prednisone 
60 mg daily or equivalent. All steroid use regardless of indication until Day 29 will be recorded 
in the EDC system.  
Subjects who are taking another antiviral for a concurrent infection (e.g. oseltamivir for an 
influenza virus) or another existing medical condition (e.g. hydroxychloroquine for lupus) may 


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continue with the treatment. Note that these treatments may be thought of as an off-label 
medication for COVID-19, however, because they were being used prior to study enrollment for 
another indication, they are allowable. 
Outpatient experimental treatment or off-label use of marketed medications that are intended as 
specific treatment for COVID-19 do not need to be discontinued if there is a written policy or 
guideline for the local standard of care and treatment of COVID-19 patients or SARS-CoV-2 
infection (i.e., not just an individual clinician decision). In the absence of a local written standard 
of care, the National Institutes of Health (NIH) COVID-19 Treatment Guidelines may be used. If 
concomitant medications are used, there should be plans on how the concomitant drugs are 
stopped in case of additive toxicities. 
Steroids and other concomitant therapies intended as specific treatment of COVID-19, as well as 
all biologics, will be assessed from 7 days prior to enrollment to Day 29. All other concomitant 
medications will be assessed from 7 days prior to enrollment to Day 15 or upon discharge, 
whichever comes first. All prescription medications should be recorded during this time period 
with the exceptions listed in the bullets below. All medications, except biologics, convalescent 
plasma and corticosteroids, can be recorded once regardless of the number of times it was given 
during the time period. For example, vasopressors should be recorded when first dose given (as 
the start date) and the last dose given (as the end date) during the period of assessment. 
Sites do not need to record any of the following categories of medications  
as concomitant medications: 
o All topical medications: ointments, creams, and lotions; 
o All intranasal medications: nasal decongestants, nasal allergy medications, nasal steroids, 
and nasal saline drops/sprays;  
o All ophthalmic medications: ophthalmic allergy medication, ophthalmic medications for 
infection, and ophthalmic medications for eye dryness (e.g., saline eye drops); 
o Antiseptic mouth wash, lozenges; 
o Cough medication: mucolytics, cough suppressants, and expectorates; 
o GI medications: H2 blockers, proton pump inhibitors, GI stimulants, prokinetics, 
laxatives, stool softeners, antacids, anti-diarrheal and anti-nausea medications; 
o Insulin and medications for diabetic control; 
o Symptomatic care medications: antipyretics, antihistamines, decongestants, and NSAIDs;  
o Vitamins, minerals or herbal supplements, dietary supplements, iron/ferrous sulfate, 
magnesium, calcium, electrolyte replacement; 
o Albumin infusions; 
o Melatonin; 
o Nicotine patch, lozenge, gum, or nasal spray, or other product to treat tobacco 
dependence; 
o Dyes: iodine-based dye, barium sulfate, and diatrizoate sodium. 
 
See the MOP for more information about recording concomitant medications. 


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6.5.2 
Prohibited Concomitant Therapy 
Receipt of any exclusionary treatments or medications prior to screening will be assessed at 
screening to determine eligibility as described in the exclusion criteria.  
 
The following medications are prohibited during this study: 
• 
Small molecule tyrosine kinase inhibitors (e.g., baricitinib, ibrutinib, acalabrutinib, 
imatinib, gefitinib).  
• 
Monoclonal antibodies targeting cytokines (e.g., TNF inhibitors, anti-IL-1 [e.g., anakinra, 
canakinumab], anti-IL-6 [e.g., tocilizumab, sarilumab, sitlukimab]), or T-cells (e.g., 
abatacept). 
• 
Monoclonal antibodies targeting B-cells (e.g., rituximab, and including any targeting 
multiple cell lines including B-cells). 
• 
GM-CSF agents (e.g., sargramostim). 
• 
Other immunosuppressants which, in the judgment of the investigator, pose risk of 
immunosuppression in combination with risankizumab that is larger than the risk of 
COVID-19. 
• 
Chloroquine or hydroxychloroquine use for the treatment of COVID-19 
 
A recent study found that chloroquine antagonizes remdesivir in a dose dependent manner as 
evidenced by an increase in the median effective dose (EC50) for remdesivir with increasing 
chloroquine concentration. Another in vitro study found that chloroquine induces a dose 
dependent inhibition of the formation of the active nucleoside triphosphate metabolite of 
remdesivir. Thus, chloroquine or hydroxychloroquine use for the treatment of COVID-19 is 
prohibited during the study. 
 
Concomitant use of any other experimental treatment or off-label use of marketed medications 
intended as specific treatment for COVID-19 or SARS-CoV-2 infection, and not specified in 
local written guidelines or the NIH COVID-19 Treatment Guidelines are prohibited.  
 
Overall, the risk of potential drug-drug interactions between risankizumab and concomitant 
medications is low. As a monoclonal antibody, risankizumab is not expected to undergo 
metabolism by hepatic enzymes or renal elimination. Drug interactions between risankizumab 
and substrates/inhibitors/inducers of drug metabolizing enzymes are not expected. Drugs with 
immunosuppressant effects such as methotrexate might reduce the immunogenicity to 
risankizumab but given the short duration of the study and the single dose administration, the 
potential impact of reduced immunogenicity on risankizumab safety or efficacy is expected to be 
low. 
6.5.3 
Rescue Medicine 
Not Applicable 
6.5.4 
Non-Research Standard of Care 
Not Applicable 
7. 
STUDY INTERVENTION DISCONTINUATION AND 


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SUBJECT DISCONTINUATION/WITHDRAWAL 
7.1 
Halting Criteria and Discontinuation of Study Intervention 
7.1.1 
Individual Infusion Halting 
See Section 6.1.4 for information about dosing modifications due to laboratory abnormalities. 
 
For an individual subject, an individual infusion must be stopped if they have a suspected drug-
related event of hypersensitivity (Grade 2 or higher) during the infusion. While there are no 
criteria for grading “hypersensitivity” in the Division of AIDS (DAIDS) Table for Grading the 
Severity of Adverse Events,(15) sites should use Acute Allergic Reaction from that toxicity 
table. Subjects who have an IV infusion stopped for a safety related issues will not continue with 
dosing.  
 
The treatment of any given subject may be stopped for SAEs, clinically significant AEs, severe 
laboratory abnormalities, or any other medical conditions that indicate to the site Investigator 
that continued dosing is not in the best interest of the patient. 
 
In addition, a subject in this clinical study may discontinue study drug at their request for any 
reason. Every effort should be made to encourage subjects to remain in the study for the duration 
of their planned outcome assessments. Subjects should be educated on the continued scientific 
importance of their data, even if they discontinue study drug.  
 
Unless the subject withdraws consent, those who discontinue study drug early will remain in the 
study. The reason for subject discontinuation of study drug should be documented in the case 
report form. 
7.1.2 
Study Halting 
Given the potential severity of COVID-19, there are no pre-specified study stopping rules. 
Instead there will be close oversight by the protocol team and frequent DSMB reviews of the 
safety data.  
7.2 
Withdrawal from the Study 
See Section 7.2 of the Master protocol document. 
7.3 
Readmission 
See Section 7.3 of the Master protocol document. 
7.4 
Lost to Follow-Up 
See Section 7.4 of the Master protocol document. 


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8. 
STUDY ASSESSMENTS AND PROCEDURES 
8.1 
Screening and Efficacy Assessments 
8.1.1 
Screening Procedures 
Screening procedures may be done from Day -1 to Day 1 (Day 1 is the calendar day of 
randomization). However, in many cases all the screening assessments can be done in less than 
24 hours. If that is the case, Day 1 pre-study product administration baseline assessments, 
specimen collection and the initial study product administration can occur on the same calendar 
day as the screening procedures.  
 
After the informed consent, the following assessments are performed to determine eligibility: 
• 
Confirm the positive SARS-CoV-2 test result (per inclusion criteria).  
• 
Confirm that patient does not have a positive influenza test during the current illness for 
which they are being screened. (Influenza testing is not required per protocol.)  
• 
Take a focused medical history, including the following information:  
• Day of onset of COVID-19 signs and symptoms. 
• Prior enrollment in ACTIV-5/BET. 
• History of vaccinations within 4 weeks prior to screening, including SARS-CoV-2 
vaccination. 
• Exclusionary vaccine history includes any live vaccine (that is, live attenuated) 
within 4 weeks prior to screening. 
• History of chronic medical conditions, including chronic oxygen requirement and/or 
use of CPAP or BiPAP at home, prior to onset of COVID-19.  
• History of medication allergies. 
• Medications and therapies for this current COVID-19 illness and history of any 
medication listed in the exclusion criteria. Site should identify if the patient received 
any steroids in the 7 days prior to randomization.  
• Ask if the patient is participating in another clinical trial or plans to enroll in another 
clinical trial in the next 30 days. 
 
• Women of childbearing potential must agree to either abstinence or use at least one 
acceptable method of contraception from the time of screening through 5 months post study 
IP dosing.*  
*Note: Acceptable methods include barrier contraceptives (condoms or diaphragm) with spermicide, 
intrauterine devices (IUDs), hormonal contraceptives, oral contraceptive pills, and surgical sterilization. 
• 
Targeted physical examination (targeted exam details in MOP).  
• 
Height and weight (height can be self-reported). 
• 
Assess need for supplemental oxygen, mechanical ventilation, or ECMO. 
• 
Blood for screening laboratory evaluations, if not done as part of routine clinical care in the 
preceding 48 hours, should be collected to evaluate the following parameters: 


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 ALT 
 AST 
 Serum creatinine (and calculate eGFR)  
• Any automated calculation by the clinical laboratory or published formula for this 
calculation is acceptable. The site should select a formula to be used for all 
subjects enrolled at the site for the duration of the study. 
• 
Urine or serum pregnancy test (in women of childbearing potential).  
 
Clinical screening laboratory evaluations will be performed locally by the site laboratory. A 
screening lab (i.e., from the hematology and chemistry laboratory panels) may be repeated once 
if, in the opinion of the investigator, the laboratory abnormality is due to an intercurrent transient 
condition or it is an aberrant laboratory value. The overall eligibility of the subject to participate 
in the study will be assessed once all screening values are available. If performed just prior to 
randomization, data obtained from screening can also be a baseline assessment of severity and 
efficacy.  
 
Study subjects who qualify will be randomized in the interactive response technology (IRT) 
system, and all others will be registered as screen failures only in the EDC system. The ordinal 
scale should be done at the time of randomization; the site will need this data to randomize the 
subject. The study team has 24 hours to complete other Day 1 baseline assessments prior to the 
first study product administration including the collection of the OP swab and blood, assessment 
of the ordinal scale and NEWS, and completing or recording a baseline physical examination 
that was done. Clinical laboratory tests performed as part of routine clinical care in the 48 hours 
prior to enrollment will be accepted for determination of eligibility.  
8.1.2 
Efficacy Assessments 
For all baseline assessments and follow-up visits, refer to the Schedule of Assessments (SOA) 
for procedures to be completed, and details below for each assessment. 
 
Laboratory tests performed as part of routine clinical care in the 24 hours prior to first dose will 
be accepted for the baseline laboratory tests. Baseline may be the same as the screening 
laboratory tests if obtained in the 24 hours prior to first dose. 
8.1.2.1 
Measures of Clinical Support, Limitations, and Infection Control 
The subject’s clinical status will be captured on each study day while hospitalized up until and 
including Day 29. Once subjects are discharged from the hospital, they will have a study visit on 
Days 8, 15, 22, 29, and 60 visits (only the ordinal score will be obtained on Day 60) as an 
outpatient. The Day 8, Day 22 and Day 60 visits do not have laboratory tests or collection of 
samples and may be conducted by phone. Day 15 and 29 visits are preferred to be in person in 
order to collect safety laboratory testing, stored samples, and virologic assessments but may be 
performed. Clinical status is largely measured by the ordinal scale. The ordinal scale can also be 
evaluated over the phone if the discharged subject is unable to return for in-person visits on Day 
15 and 29.  
 


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The following measures are recorded for the ordinal scale. See MOP for more detailed description 
of ventilatory devices in each category: 
 
• Hospitalization. 
• Oxygen requirement. 
• Non-invasive mechanical ventilation (via mask) requirement. 
• High-flow oxygen requirement. 
• Invasive mechanical ventilation (via endotracheal tube or tracheostomy tube) 
requirement. 
• ECMO requirement. 
• Ongoing medical care preventing hospital discharge (COVID-19 related or other medical 
conditions). 
• Limitations of physical activity (self-assessed and reported as new or increased 
limitations as compared to status prior to the onset of COVID-19). 
• Isolated for infection control purposes. 
 
8.1.2.2 
Ordinal Scale 
The ordinal scale is the primary measure of clinical outcome per the Master protocol document 
(Section 8.1.1.1). 
8.1.3 
Exploratory Assessments 
See Section 8.1.2 of the Master protocol document. Additional exploratory assessments include: 
• Qualitative and quantitative polymerase chain reaction (PCR) for SARS-CoV-2 in OP 
swab on Day 1; Days 3, 5, 8, and 11 (while hospitalized); and Days 15 and 29 (if attends 
in-person visit or still hospitalized). 
• Qualitative and quantitative PCR for SARS-CoV-2 in blood on Day 1; Days 3, 5, 8, and 
11 (while hospitalized). 
• Plasma proteomic analysis of cytokines and markers of inflammation including IL-17A, 
IL-22, and IL-1b on Days 1, 3, 8, 15, and 29 (if attends in-person visit or still 
hospitalized). 
• Blood RNA transcriptome analysis on Days 1, 3, 8, 15, and 29 (if attends in-person visit 
or still hospitalized). 
• PBMC assessment for phenotype and functional reactivity on Days 1, 3, 8, 15, and 29 (if 
attends in-person visit or still hospitalized; collected only at sites capable of collecting 
and processing PBMC).  
• Serum samples for PK (at pre-dose, Day 5 (if hospitalized), Day 15, and Day 29) and 
serum samples for anti-drug antibodies and neutralizing antibodies at pre-dose and Day 
29. 


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8.2 
Safety and Other Assessments 
Safety procedures and assessments are described in Section 8.2 of the Master protocol document. 
The total volume of blood collected over the course of this study for safety and research 
evaluations (including samples for secondary research-defined in master protocol section 
10.1.1.2) is approximately 450 mL, with a maximum daily volume of approximately 73 mL. 
8.3 
Adverse Events and Serious Adverse Events 
AE reporting will occur as described in Section 8.3 of the Master protocol document. 
9. 
STATISTICAL CONSIDERATIONS 
See Section 9 of Master protocol document. 
10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
All supporting documentation and operational considerations are applicable to the entire 
platform trial and are not unique to the individual stages. These are therefore covered in the 
Master protocol document (Section 10). 
11. 
REFERENCES 
 
 
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