Clinical trial NCT04452318
Conditions: Healthy Participants
Keywords: Asymptomatic Individuals at risk of exposure to SARS-CoV-2 Household Contacts of a Person Infected with SARS-CoV-2
Sponsor: Regeneron Pharmaceuticals
Start date: 2020-07-13; Completion date: 2021-10-04
Enrollment: 3303 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Primary Objectives:

Cohort A:

• To evaluate the efficacy of REGN10933+REGN10987 compared to placebo in preventing symptomatic SARS-CoV-2 infection (broad-term) confirmed by RT-qPCR

Cohort A and Cohort A1:

• To evaluate the safety and tolerability of REGN10933+REGN10987 following subcutaneous (SC) administration compared to placebo

Cohort B • To evaluate the efficacy of REGN10933+REGN10987 compared to placebo in preventing COVID-19 symptoms (broad-term)

Cohort B and Cohort B1

• To evaluate the safety and tolerability of REGN10933+REGN10987 following SC administration compared to placebo

Detailed description:
Cohort A: adult and adolescent subjects (≥12 years) who are SARS -CoV-2 RT-qPCR negative at baseline

Cohort A1: pediatric subjects (\<12 years) who are SARS-CoV-2 RT--qPCR negative at baseline

Cohort B: adult and adolescent subjects (≥12 years) who are SARS -CoV-2 RT-qPCR positive at baseline

Cohort B1: pediatric subjects (\<12 years) who are SARS-CoV-2 RT--qPCR positive at baseline

Arms: arm 1: None arm 2: None
Interventions: intervention 1: REGN10933 + REGN10987 intervention 2: Placebo
Intervention descriptions: intervention 1: Subcutaneous (SC) or Intramuscular (IM) injections intervention 2: SC or IM injections

Protocol documents:
ICF_000.pdf: 
 
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MAIN INFORMED CONSENT FORM (ICF) AND PARENTAL 
PERMISSION FORM FOR AGES 12 - 17 YEARS OLD 
 
TITLE: 
A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study 
Assessing the Efficacy and Safety of Anti-Spike SARS-CoV-2 
Monoclonal Antibodies in Preventing SARS-Cov-2 Infection in 
Household Contacts of Individuals Infected with SARS-CoV-2 
 
PROTOCOL NO.: 
R10933-10987-COV-2069 
WIRB® Protocol #20201773 
 
NCT No.: NCT04452318 
 
EudraCT No.: 2020-003654-71 
 
SPONSOR: 
Regeneron Pharmaceuticals, Inc. 
 
INVESTIGATOR: 
Name 
Address 
City, State  Zip 
Country 
 
STUDY-RELATED 
PHONE NUMBER(S): 
Phone Number 
Phone Number (24 hours) 
[24 hour number is required] 
 
 
Participant’s Printed Name: 
 
 
This research study involves both adults and children/adolescents (<18 years of age).  For 
purposes of this form, “you” refers to the person (adult or adolescent [ages 12 to 17]) participating 
in this study.  If you are the parent/caregivers reviewing this ICF on behalf of your child, “you” 
refers to your adolescent participating in this research study. 
 
Summary 
This research study is looking at experimental drugs to prevent the COVID-19 disease from occurring in 
people who have been exposed to the SARS-CoV-2 virus. The study drugs target the virus that causes 
COVID-19 and are designed to make it harder for the virus to infect you. The goals of the study include 
seeing REGN10933+REGN10987 lowers infection by the virus, whether they reduce the need for 
medical visits and the amount of time you spend away from your day-to-day activities (i.e., work, 
school, caring for others) due to COVID-19, and whether they can cause side effects.   
 
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If you agree to join, you will be in the study for about 32 weeks. You will be randomly assigned to 
receive 1 dose of either REGN10933+REGN10987 or a placebo.  This will be done subcutaneously 
(under the skin). During the study, you will have tests done at several times, including having 
nasopharyngeal swabs taken, as well as having blood drawn.   
 
Because this is a research study with experimental drugs, you may or may not benefit from being in the 
study. There is also only a limited amount of data about these REGN10933+REGN10987 in people. 
This is the first time that REGN10933+REGN10987 have been given to humans subcutaneously. There 
are other clinical trials by the sponsor with REGN10933+REGN10987 given intravenously (in a vein). 
Even though participants will be carefully watched, the risks of receiving the drug are unknown. Some 
of these risks may be serious or life-threatening.  
 
The choice to join is up to you. You will not be penalized in any way if you decide not to join or if you 
leave the study. Regardless of study participation, you can continue to receive any standard-of-care 
treatment. The rest of this form provides more information to help you decide if you want to join. 
 
What is the purpose of this form?  
You are being asked if you would like to join a research study (also called a clinical trial). This consent 
form explains why the study is being done, possible risks and benefits to you, your rights, and what you 
will have to do if you join. The choice is up to you, and you do not have to join the study if you do not 
want to. If you decide to join, you will be asked to sign and date this form, stating that you understand 
what was explained to you and that you agree to be in the study. This is called informed consent. 
 
The informed consent form may be delivered and signed in paper format. It may also be delivered and 
signed electronically (eConsent) if local laws, regulations, and study site policies allow this. 
 
Please read this form carefully. Ask the study doctor or staff any questions you have about the study. 
You can take an unsigned copy to review with your personal doctor, family, and friends. If you agree to 
join, you will be given a signed and dated copy. No tests will be done until this form is signed. 
 
If you decide not to join, you will not be penalized or lose any benefits that you would otherwise be 
entitled. 
 
Who is sponsoring this study? 
Regeneron Pharmaceuticals, Inc. (“Regeneron”) is the sponsor of the study. This means that Regeneron 
is paying for the study, and overseeing study conduct according to the requirements of the U.S. Food 
and Drug Administration (FDA) and other regulatory agencies, and the study doctor will be paid by 
Regeneron or its collaborators. 
 
Regeneron, its collaborators or those developing REGN10933+REGN10987, and their affiliates, 
representatives, agents, and contractors (the “Regeneron Parties”), are involved in the study. Some or all 
of these groups may use the information collected in the study to carry out the research described in this 
consent form. 
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This study is being reviewed by an independent group called an institutional review board (IRB) or 
ethics committee (EC). This group, which is not a part of Regeneron, looks out for the safety, welfare, 
and rights of people taking part in research studies. The IRB or EC reviewing this study has approved 
the study/given the study a favorable opinion. 
 
Why is this study being done? 
The study is researching an experimental drug combination casirivimab (REGN10933) and imdevimab 
(REGN10987), given as separate subcutaneous (SC, under the skin) injections.  REGN10933 and 
REGN10987 will sometimes be collectively referred to as the “REGN10933+REGN10987” in this 
consent form. 
 
The aim of the study is to see how safe, tolerable, and effective REGN10933+REGN10987 may be in 
preventing SARS-CoV-2 infection and/or COVID-19 in people who have been exposed to SARS CoV-2 
by someone with whom they live with and have tested negative or positive for SARS-CoV-2 virus but 
are not showing any signs of infection. 
The study is trying to answer several specific research questions. These include: 
• Whether REGN10933+REGN10987 can reduce the likelihood of a person getting the SARS-
CoV-2 infection who tested negative  
• Whether REGN10933+REGN10987 can prevent the SARS-CoV-2 infection from 
developing into COVID-19 disease for people who tested positive 
• Whether REGN10933+REGN10987 can help reduce the number days a person is away from 
work who tested positive or negative to the SARS-CoV-2 virus 
• Whether REGN10933+REGN10987 can help reduce the number of visits to the doctor’s 
office for people who tested positive or negative to the SARS-CoV-2 virus 
• Whether any side effects may happen from taking REGN10933+REGN10987  
• How much REGN10933+REGN10987 are in your blood at different times 
• Whether the body makes its own antibodies against REGN10933+REGN10987 (which could 
make them less effective or could lead to side effects) 
 
What is REGN10933+REGN10987? 
The study drug made of monoclonal antibodies, called REGN10933 and REGN10987. 
Antibodies are made by your immune system to fight infections.  A monoclonal antibody is made in a 
laboratory to fight specific types of infections, such as viruses. 
 
COVID-19 is caused by a coronavirus called SARS-CoV-2.  This virus uses “spike” to attach to the cells 
it infects. It is thought that the spike protein helps the virus infect cells in the nose, throat, lungs, and 
other tissues, leading to COVID-19 symptoms. 
 
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The antibodies in this study block the SARS-CoV-2 spike protein. When the spike protein is blocked, 
the virus may not be able to infect your cells. By making it harder to infect cells, the antibodies may stop 
COVID-19 symptoms from developing or getting worse.  The two antibodies are given together to block 
the spike protein in two different ways.  This may make it harder for the virus to mutate and escape the 
effects of REGN10933+REGN10987. 
 
It is very important to not participate in other clinical studies while you are in this study.  This includes 
not participating in other studies of investigational antibodies or vaccines. This is necessary for your 
safety and to avoid interference between study products in different studies.  Even if you leave the study 
early, you must not participate in other clinical studies for the length of this study, about 32 weeks.  
Please speak with the study doctor if you have any questions or concerns about this. 
 
The study drug is not approved by any public health agency to treat or prevent COVID-19. 
 
The United States Food and Drug Administration (FDA) has made the study drug available as a 
treatment for COVID-19 under an emergency access mechanism, called Emergency Use Authorization 
(EUA). The study drug has not undergone the same type of review as an FDA-approved or cleared 
product. The EUA only applies in the United States during the COVID-19 pandemic, and (like any 
EUA) can be revoked before the pandemic is over. 
 
If you decide to get the EUA COVID-19 vaccine, you must wait until after week 4 of the study before 
you should get the EUA COVID-19 vaccine. This is necessary for your safety and to avoid interference 
between the study drugs and the vaccine. 
 
If you want to learn more about this EUA and its conditions, talk to the study doctor. 
 
How big is the study? 
This study will include up to approximately 3750 participants in the United States and worldwide.  
 
How will I know if I can join this study? 
There are certain conditions you must meet to enter the study. The study doctor will go over these with 
you before you can join. There is a chance that you may not qualify or be able to join the study. 
 
How will I be given the study drugs?  
This is a randomized, double-blind, placebo-controlled study. “Randomized” means that which study 
drug you will receive will be by chance, similar to drawing numbers out of a hat or flipping a coin.  
“Double-blind” means that neither you nor the study doctor will know which study drug you have been 
given (i.e., if you are receiving study drugs or placebo). This is done to make sure the results of the 
study cannot be influenced by anyone. If there is an urgent need, the study doctor can find out quickly 
drug you received.  A placebo is an inactive substance, that looks like the medicine, but which contains 
no medicine. If you agree to take part in this study, you will receive REGN10933+REGN10987 or 
placebo.  
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You will have a 1 to 1 or 50/50 chance of getting either one dose of the REGN10933+REGN10987 or 
placebo.  The “one dose” is made up of 4 SC injections of either:  
• REGN10933 and REGN10987, 1200 mg (2 doses each of 300 mg of each REGN10933 and 
REGN10987)  
 
OR 
 
• Matching placebo 
 
The injections will rotate between different locations on your lower abdomen and upper legs.  The 
possible risks of being given the study drugs are described later in the form.  
 
What will happen in the study, and what will I have to do if I join? 
After you sign this document, testing will be done to determine if you are eligible to participate in this 
study. You must meet certain requirements to be able to participate in this study. The study doctor will 
review all of the restrictions and requirements of the study with you to determine if you qualify for the 
study.  This period, called the screening period, will last for about 1 day. During this time, you will be 
tested for SARS-CoV-2 infection.  You will be tested for SARS-CoV-2 infection at most visits to 
confirm your negative or positive status.  
 
The exact numbers of days or visits and study procedures that you will have in this study will vary upon 
when you join the study and if you test negative or positive for the SARS-CoV-2 infection during your 
participation.   
 
This study is divided into 3 groups.  In order to increase safety, the first 30 participants enrolled (Group 
1, participants 1 through 30) had a number of additional procedures done to collect safety data. If you 
were part of this first group, you were asked to stay longer in the clinic on the first day of dosing and 
asked to return to the clinic for extra site visits to complete blood draws.  
 
If you were enrolled into the second group (Group 2, participants 31 through 400), you also had 
additional visits and procedures done to collect safety data. 
 
Enrollment into Groups 1 and 2 have been completed. If you decide to join the study you will be placed 
in the third group (Group 3, participants 401 to 2000). 
 
Your participation will last about 32 weeks.  Participants in Group 1 are having about 14 clinic visits 
and at least 1 telephone visit.  Participants in the second group are having about 12 clinic visits and at 
least 1 scheduled telephone visits, while Group 3 will have about 12 clinic visits. The exact number of 
clinic visits may change if your SARS-CoV-2 status changes and you need to come in for additional 
SARS-CoV-2 testing and/or blood draws. It is possible that some of the clinic visits are replaced by a 
visit at your home or another location. In this case the site staff may also give you a phone call on those 
days.  
 
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The length of the study is based on the currently available information for how long the study drugs last 
in your body. The follow-up duration may change as more information becomes available from ongoing 
studies (e.g., clinical trials, laboratory and animal studies).  
• Screening period: 1 day (1 visit) – All groups 
− During this period, you will undergo a physical examination (including vital signs), a 
review of any medications you are taking, medical history, and any changes that occurred 
in your health recently. Nasopharyngeal swabs (NP) will be collected for SARS-CoV-2 
infection testing. The study staff may also collect an additional sample to perform a local 
test on-site to see if you have SARS-COV-2.  This sample may be either a NP, throat, or 
nasal swab or saliva sample. Blood and urine samples for safety assessments and research 
samples will also be collected. If you are a woman who can become pregnant, a urine 
pregnancy test will also be performed.  While participating in the study, you will be 
asked to keep a Participant Identification Card on you at all times.  This card has the 
clinic’s contact information and instructions on when to call the clinic when you are 
feeling unwell during the study. 
− You will also be given the study drugs at this time. 
− The amount of time that you will have to spend in the clinic will vary depending upon the 
assessments for that day and your SARS-CoV-2 test status (positive or negative).  The 
study staff will go over with you what the time commitment is for this visit.   
− You will be given a thermometer to take home.  It is recommended that you take your 
temperature daily until the end of the Assessment period and if you start to feel unwell. 
The study doctor or the study staff will go into more details about how and when to take 
your temperature at home. 
• Assessment period will last up to 4 weeks.  Participants in the first group had about 7 visits and 
at least 1 telephone visit.  Group 2 will have about 4 visits and 1 telephone visit, and Group 3 
will only have 4 visits and no scheduled telephone visits.  
− Group 1: The assessment  period starts as part of day 1 (screening) 
▪ Clinic visits (days 1, 2, and 4): You underwent physical examinations (including 
vital signs) at these clinic visits.  There was also a review of any medications you 
are taking and any changes that occurred to your health. Nasopharyngeal swab, 
nasal swab and/or saliva samples were collected for SARS-CoV-2 infection 
testing. The study staff also collected blood and urine samples for safety 
assessments and research samples on each of your clinic visits. 
▪ Telephone visit (day 3): There was a review of any medications you are taking 
and any changes that occurred to your health. 
▪ If you tested negative for SARS-CoV-2 infection and you start feeling unwell 
during the assessment period, you will need to call the study clinic as soon as 
possible. You may be asked to check your temperature. The study staff may ask 
you to come to the clinic to get tested for SARS-CoV-2 infection. Some blood 
maybe collected at this visit for research samples. 
− Group 2: The assessment period starts on day 4 with a telephone visit.  
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− Group 3: The assessment period starts on day 8. 
− All Groups: 
▪ You will undergo physical examinations (including vital signs) at day 29. A 
review of any medications you are taking and any changes that occurred to your 
health, and nasopharyngeal swabs (or nasal swab and saliva samples for some 
participants in Group 1) will be collected for SARS-CoV-2 infection testing at 
each visit (weekly). The study staff will also collect blood and urine samples for 
safety assessments and research samples on day 29. If you are a woman who can 
become pregnant, a urine pregnancy test will also be performed on day 29.  
▪ If you tested negative for SARS-CoV-2 infection and you start feeling unwell 
during the assessment period, you will need to call the study clinic as soon as 
possible. You may be asked to check your temperature. The study staff may ask 
you to come to the clinic to get tested for SARS-CoV-2 infection. Some blood 
maybe collected at this visit for research samples. 
▪ If you test positive for SARS-CoV-2 infection at any time during this period, you 
will be asked about any different symptoms related to the SARS-CoV-2 infection 
you are experiencing. The study staff will also ask you questions about how the 
COVID-19 disease is affecting your day-to-day activities, like if you are missing 
days from work or cannot complete routine activities because you are sick and if 
you had to make trips to the doctor’s office or urgent care. 
− If you start feeling unwell or your current symptoms are getting worse during the 
assessment period and you feel like this is a true medical emergency, please seek urgent 
care at a local hospital/emergency room first before contacting the study clinic. 
− The amount of time that you will have to spend in the clinic will vary depending upon the 
assessments for that day, the group you are in, and your SARS-CoV-2 test status (positive 
or negative).  The study staff will go over with you more on what procedures will take 
place and the time commitments are for each visit. 
• Follow-up period will last up to 28 weeks.  All groups will have about 7 visits. The follow-up 
period will start after day 29.  
− Everyone will undergo a physical examination (including vital signs) on the last day of 
the study. If you are a woman who can become pregnant, a urine pregnancy test will also 
be performed on the last study visit. 
− A review of any medications you are taking, and any changes that occurred to your health 
will occur at every visit. 
− If you are in the first or second groups, blood and urine samples for safety assessments 
and research samples will be collected monthly. If you are in the third group, you will 
only have blood taken on 3 visits.  
− If you tested negative during the study and you start feeling unwell during the follow-up 
period, you will need to call the study clinic as soon as possible. You may be asked to 
check your temperature. The study staff may ask you to come to the clinic to get tested 
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for SARS-CoV-2 infection. Some blood maybe collected at this visit for research 
samples. 
− If you test positive for SARS-CoV-2 infection before the end of the follow-up period, 
nasopharyngeal swabs (or nasal and saliva samples for some participants in Group 1) will 
be collected for SARS-CoV-2 infection testing until you have 2 negative tests in a row or 
until the end of the study, whichever is earlier. The study staff will continue to ask you 
questions about how the COVID-19 disease is affecting your day-to-day activities, like if 
you are missing days from work or cannot complete routine activities because you are 
sick.  
− If you start feeling unwell or your current symptoms are getting worse during the follow-
up period and you feel like this is a true medical emergency, please seek urgent care at a 
local hospital/emergency room first before contacting the study clinic. 
− The amount of time that you will have to spend in the clinic will vary depending upon the 
assessments for that day and your SARS-CoV-2 test status (positive or negative).  The 
study staff will go over with you what the time commitments are for each visit. 
 
Study Tests, Procedures, and What You Will be Expected to Do  
If you decide to participate, you will be asked to do the following things at different times.  Some of 
these may involve risks, which are described below. Because the study involves experimental research, 
there may be other risks that we cannot predict ahead of time. 
 
Nasopharyngeal swabs 
To measure infection by the virus, samples will be collected by taking what is called an NP swab. The 
study doctor or staff will take these samples. Each time a sample is collected, a swab will be gently 
inserted about 3 inches into one nostril until the swab reaches the back of your throat. The swab will be 
rotated a few times and removed. This will then be repeated in the other nostril using a fresh swab.  
 
Possible risks: Collecting nasopharyngeal swabs can be uncomfortable, but not painful. You may gag or 
feel the urge to sneeze or cough while the sample is being collected. You may also have a minor 
nosebleed after the sample is taken. 
 
Local on-site SARS-CoV-2 testing 
During the screening visit, there is a chance that an additional sample may be collected (nasal, throat 
swab, NP, saliva) based on the study clinic’s procedures for testing if you have SARS-CoV-2 infection 
before you are given the study drugs.  
 
This local test result may be available within hours of performing the test.  The test is for research 
purposes.  You may be told the result of this test based on local regulations and procedures.  However, 
further testing is needed to look for infection.  Another sample will be sent out to a contract lab which 
uses a standard clinical test, this may take a few days.  If you have any questions or concerns about these 
tests, please talk to your study doctor or staff. 
 
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Possible risks:  Risks related to nasal and throat swabs are similar to the NP swab risks, as mentioned 
above.  There are no expected risks associated with giving saliva samples.   
 
Providing Information About Your Health to the Study Doctor and Staff 
At the start of the study, the study doctor or staff will ask you questions about yourself, your health, and 
your medical history.  You will also be asked questions to determine your overall risk of SARS-CoV-2 
infection.  
 
Throughout the study, the doctor or staff will continue to collect information about any changes in your 
health. They may also ask about any medicine or supplements you are taking (prescribed and over-the-
counter).  
 
If you test positive during the study and require urgent care or have to go to the hospital/emergency 
room while you are in the study, please contact the study staff after any visit(s) to the 
hospital/emergency room.  The study staff will ask you questions about the trip and will ask you to 
provide documentation about any treatments you received.   
 
You will be provided a Participant Identification Card to keep on you, to help you contact your study 
doctor at any time during the study. On the Participant Identification Card will be a telephone number 
and guidance for when to call the study clinic if you are feeling unwell during the study. The study staff 
will give you more details at the first study visit.  
 
You will also be asked questions about any missing days of work or any impact on your daily activities 
(this includes things like not being able to go to school or take care of others because you are sick).  
 
Possible Risks: There are no expected physical risks to occur from answering questions. Information 
about privacy and confidentiality of your information is included later in this form. 
 
Limited Physical Exams 
A physical exam is an exam used to check your overall health.  Your weight and height will also be 
taken.  
 
Possible Risks: There are no expected risks to occur.  
 
Vital Signs 
The study staff will take your vital signs, which will include measuring your blood pressure, pulse rate, 
and breathing rate. 
 
Possible Risks: The inflation of the blood pressure cuff may cause discomfort.  
 
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Body Temperature 
Your temperature may be measured, or you may be asked to measure your own temperature from your 
mouth, ear, or forehead.  
 
Possible Risks: There may be slight discomfort when your temperature is measured in the ear. There is 
no discomfort expected when taking your temperature from under your arm or mouth.  
 
Urinalysis 
You will need to provide a urine sample for regular lab testing. 
 
Possible Risks: There are no expected risks or pain expected for taking urine samples.  
 
Pregnancy Test 
If you are a woman of childbearing potential, a urine pregnancy test will be required at screening and 
throughout the study.  If you have a positive pregnancy test, then a blood pregnancy test will be 
performed to confirm positive test. 
 
Possible Risks: There are no expected risks or pain expected for taking a pregnancy test. 
 
Having Medical Visits at Home 
In some cases, it may be possible to have a study visit at your home, rather than at the study site or other 
location. These home visits may be done by a third-party company (a company not affiliated with the 
study site or Regeneron).  The study doctor or staff will talk with you to see if you qualify for these 
visits. It is your choice whether to allow these kinds of visits or not. 
 
The third-party service may arrive by car or mobile medical unit. The third-party staff who performs the 
home visits may wear personal protective equipment as they enter and leave your home. 
 
Possible Risks: There could be a loss of privacy due to third-party being used to conduct the home 
health visits. If you are concerned about these risks, you can come into the study clinic for these visits.  
Information about privacy and confidentiality of your information is included later in this form. 
 
Having Medical Visits Electronically 
Some of your medical visits may be done by phone or by using an electronic app (on a smart phone, 
tablet, or computer). This type of visit is also called telemedicine. These visits will be done to check on 
your health, so that you can have fewer in-person visits during the study. The visits may involve video 
chats with the study doctor and/or staff. The study doctor or staff will talk to you about these types of 
visits.  
 
Possible Risks: There could be a loss of privacy due to third-party being used to conduct the electronic 
(telemedicine) visits. If you are concerned about these risks, you can come into the study clinic for these 
visits. Information about privacy and confidentiality of your information is included later in this form. 
 
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Automated Reminders 
As part of the study, you may receive automated reminders a few times a week between clinic visits to 
remind you to call the study clinic if you start to feel unwell during the study. 
 
Possible Risks: There are no expected physical risks to occur from receiving automated reminders. 
Information about privacy and confidentiality of your information is included later in this form. 
 
Subcutaneous injection risks 
Like any injection, this procedure may hurt for a brief moment when the study drugs are injected under 
the skin. In some cases, reactions such as redness, itchiness, swelling, warmth, pain, and 
tenderness/discomfort may occur at the injection site. Injection site reactions are generally mild to 
moderate in severity and generally go away without any treatment.  
 
In rare occasions, severe reactions could occur, such as the fat tissue around the injection site can 
become uneven (either too much fat tissue collects around the injection site or none) which is called 
lipodystrophy.  Tissue damage could occur around the injection site that could lead to lesions (sores) or 
skin discoloration (purple, deep red, or black) which could be signs of skin cell death (necrosis). 
 
What types of blood tests will be done during the study? 
Blood will be taken to check your health and carry out the research described in this consent form. The 
amount of blood taken during a visit will range from approximately 7 mL (half a tablespoon) to 53 mL 
(about 4 tablespoons). The exact amount of blood collected from you during the study will depend upon 
how long you are in the study and if you had any unscheduled visits. 
 
Possible risks: Blood draws may cause discomfort, bruising, or infection at the site where blood was 
taken. Some people become faint or dizzy when giving blood. 
 
The following will be tested: standard hematology, blood chemistries for safety testing, amount of drug 
in your blood and antibodies to the drug. 
 
What types of tests will be done on the nasopharyngeal swabs during this study? 
Nasopharyngeal swabs will be taken to test for the SARS-CoV-2 virus and to study the amount of virus 
you may have in your body. To do this, the samples collected from you will be used to measure levels of 
virus RNA. In addition, tests will be done on the virus RNA to look at its sequence (the genetic code of 
the virus). These tests will look at whether the viral sequence can affect whether or not the study drugs 
work.  
  
Possible risks: The samples that are collected will only be used to study virus RNA and not human 
RNA. Information about privacy and confidentiality of your information is included later in this form. 
 
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Will additional samples be collected?  
As described in this form, biological samples will be collected as part of this study. Your coded samples 
will be used by Regeneron Parties for the purposes of the study, including exploratory research, to 
identify new learnings, such as: 
• How REGN10933+REGN10987 work in the body; 
• What makes some people respond better to REGN10933+REGN10987 ; 
• Why some people develop side effects; 
• To study COVID-19 and the SARS-CoV-2 virus. 
 
These samples will be kept for up to 15 years after the study ends. During that time, the samples may be 
used for the research described in this form. The samples will be kept in a secure storage area at a 
Regeneron facility or at a storage facility designated by, and under the supervision of Regeneron in the 
United States. Unused samples will be destroyed.  
 
If you wish to withdraw your consent to use and store your samples, please notify the study doctor. If 
you withdraw from the trial, but do not withdraw your consent to use and store your samples, your 
samples will continue to be used as described in this form. If you withdraw your consent to use the 
sample and you wish to have the samples destroyed, your study doctor, Regeneron, and the laboratory 
responsible for processing the samples will make every reasonable effort to ensure your samples are 
destroyed. However, it is important that you understand that if your sample has already been processed 
and analyzed, the results and information obtained cannot be destroyed and will continue to be available 
to the Regeneron Parties.  
 
Will this study benefit me? 
The main purpose of this study is research. Because of this, you may or may not get any health benefit 
from being in the study.  
 
What are the possible risks and side effects of the study drug? 
The study drug is being tested in several different studies. The safety of all study participants is carefully 
watched, both by Regeneron and by an independent review board that is separate from Regeneron. You 
will be told about any important safety findings related to the study drug.  
 
Study Drug Risks 
The risks below are based on what is known about drugs that work in a similar way to the study drug or 
are given in the same way. Talk to the study doctor if you have any questions about these risks. 
 
Risk of allergic reaction 
You may have an allergic reaction. This can happen while you are getting the study drug or within a few 
minutes, hours or days after.  The symptoms can include rash, hives, itch, cough, chills, sweating, 
shortness of breath, nausea, abdominal (stomach) pain, or feeling flush. 
 
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Although rare, you could have a severe allergic reaction such as anaphylaxis. Symptoms can include the 
ones above but are usually more severe and can happen quickly (within minutes to hours after injection). 
Other symptoms include dizziness, paleness, loss of consciousness or death.  Get medical help right 
away if you think you are having severe symptoms of any kind.  Severe symptoms can result in 
permanent disability or death.  
 
Risk of unwanted immune response  
Your body could make its own antibodies against the study drug. Antibodies are the body’s normal 
defense against a foreign substance (like the study drug). If your body makes antibodies against the 
study drug, however, it could cause side effects or make the drug work less effectively. 
 
Possible risk of the study drug interfering with vaccines or your immune system’s memory 
It is possible that the study drug could interfere with your body's own ability to fight a future infection of 
COVID-19. It could also interfere with a vaccine for COVID-19. This has not been seen with any 
antibody treatment used against the virus that causes COVID-19. However, this risk cannot be ruled out 
with the study drug. 
 
Possible risk of virus infection getting worse 
Antibodies can sometimes make an infection worse. This has mostly been seen in studies of animals. 
This has not been seen with any antibody treatment used against the virus that causes COVID-19, but 
the risk cannot be ruled out with the study drug. It is possible that symptoms of COVID-19 could get 
worse weeks to months after receiving the study drug. Participants will be monitored throughout the 
study for any possible negative outcomes like this. 
 
Unknown Risks 
There may be other side effects related to the study drug that are unknown at this time. Some of these 
unknown side effects could be serious or life-threatening.  
 
For your safety, it is important that you promptly tell the study doctor or staff about any side effects that 
you are feeling or any changes in your health. You should also report any new medicine or supplements 
you start taking, including vitamins, herbal remedies, over-the-counter drugs, or prescription drugs.  
 
Pregnancy Risks  
The study drug has not been tested in women who are pregnant or breastfeeding. Studies in monkeys did 
not show any toxic effects on reproductive organs. However, antibodies like the ones in the study drug 
can sometimes cross the placental barrier (the lining around a fetus during pregnancy) or get into breast 
milk. Because of this, it is possible that the study drug could travel from a mother to a developing fetus 
or newborn baby.  
 
Laboratory tests have been done on human fetal tissue donated for research. These tests showed that the 
study drug did not react with fetal tissue. However, it is not known if the study drug can harm you or 
your baby if you become pregnant or breastfeed, or whether you could lose your pregnancy. 
 
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What happens if I get pregnant? 
If you become pregnant during the study, you must tell the study doctor right away. If you are pregnant 
at the start of the study or become pregnant while in the study the study doctor will follow-up with you 
on the outcome of your pregnancy.  
 
Because the study drug has not been tested in women who are pregnant, you may want to consider not 
becoming pregnant while in the study.  There may be unknown risks to the fetus. 
 
What other choices do I have if I do not join this study? 
Since this study is not intended to provide any therapeutic or other health-related benefit, you may 
choose to not participate in this study. If you decide not to take part in this study, you should follow 
advice from your doctor about minimizing your risk of SARS-CoV-2 infection. 
 
There are now vaccines available for COVID-19. If you have received or are planning to receive a 
vaccine for COVID-19, tell the study doctor. The doctor will explain whether you are eligible for this 
study and what this could mean while you are in the study. 
 
Your doctor may know of potential treatment plans that are available for you outside of research studies. 
You and the doctor can discuss what is best for you. 
 
Will I be paid to participate in this study? 
For your participation in the clinical study, you will receive a financial compensation of $[Amount]. If 
you are part of the first group, you will be compensated with an additional $[Amount]. 
 
If you are signing to allow your child to participate in this study, you will receive a financial 
compensation for your time, unfortunately, your child cannot be paid for their participation.  
 
The investigator and/or other site staff will discuss the payment schedule with you.  
 
Please note that if you withdraw from the clinical study for non-medical reasons or for reasons 
non-confirmed by the investigator, you may be paid pro-rata depending on our investigator’s decision.  
 
Will I have to spend money to be in this study? 
There will be no cost to you for the study drug, study doctor’s time or certain procedures and supplies 
required by this study. However, you are responsible for the cost of your standard medication, in 
addition to any costs related to procedures and supplies not required by the study.  
 
As part of the study, you may have travel arrangements made for you to travel to and from the study site 
or testing centers using a third-party company. You will not need to pay for these travel arrangements.  
 
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What happens if I get injured while I am in the study?  
If you think you have been injured as a result of participating in the study: 
• Promptly seek medical treatment, and  
• Call the emergency contact number on the first page of this form.  
 
If you have an injury that is directly caused by taking the study drugs or any properly performed study 
procedures included in the study (procedures you receive only because of your participation in the 
study) and you have followed the directions of your study doctor, Regeneron will provide 
reimbursement for reasonable and necessary medical costs to treat your injury that are not covered by 
your medical or hospital insurance, or from third party or other programs providing such coverage. 
 
Regeneron and its collaborator’s will not routinely provide monetary or financial compensation for:  
• Other injury- or illness-related costs (such as lost wages, disability or discomfort due to an 
injury),  
• Medical expenses that are paid for by a third party,  
• Medical expenses that happen due to a violation of the study or other misconduct or 
negligence, in each case by any agent or employee of the Institution conducting the study 
(including the study staff), or  
• Medical expenses for injury or illness unrelated to the study drugs and unrelated to the proper 
performance of any other procedure required by the study or Regeneron’s written instructions 
to the Institution conducting the study, including, without limitation, medical expenses 
associated with a pre-existing medical condition.  
 
This research is covered by the Public Readiness and Emergency Preparedness (PREP) Act. The PREP 
Act limits your ability to sue if you are injured by the study drugs or study procedures. However, you 
may be able to seek compensation from HRSA’s Countermeasure Injury Compensation Program for 
certain serious physical injuries. The declaration is available at:  
 
https://www.govinfo.gov/content/pkg/FR-2020-03-17/pdf/2020-05484.pdf 
 
No funds have been set aside to provide you with any further monetary or financial compensation in 
case of injury. By agreeing to participate in this study, you do not waive any of your legal rights.  
 
For more information, please contact the study doctor or a member of the study staff. 
 
Can I leave the study after I join? 
Yes. You can change your mind and leave the study at any time. You do not need to give a reason. If 
you leave the study, your medical care outside of the study will not be affected by your decision. You 
will not be penalized or lose any benefits that you would otherwise be entitled if you were not in the 
study.  
 
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If you decide to leave, it is important to let the study doctor know as soon as possible so you can stop 
safely. If you already received the study drug, you will be asked to come back for a follow-up visit so 
that tests can be done to check your health. You will also be asked to return all study-related items to the 
study site. If you do not return for a follow-up visit, the study doctor or study staff may want to contact 
you to check your health.  
 
You will be told of any important new information about the study or study drug, or any changes to the 
study, that may affect your decision to stay in the study. 
 
Is it possible that I might be asked to leave the study? 
Yes. You can be taken out of the study without your consent at any time by the investigator or the 
sponsor for reasons, including: if the study is no longer in the best interest of your health, if you 
experience unusual or serious side effects, or if you do not follow the study rules. The study may also be 
stopped by Regeneron, an IRB, or a health authority such as the U.S. FDA. 
 
DATA PROTECTION: YOUR RIGHTS AND CHOICES 
What information will the study staff collect from or about you in connection with 
this study? 
As part of this study, the study doctor and study staff (“Researchers”) will collect and review 
information about you that contains your name and other personal information. In addition, your treating 
physicians and other healthcare providers may disclose information from your medical records to the 
Researchers. The information collected from or about you (“Personal Information”) for this study may 
include: 
• Your medical information, including how you feel, medical and surgical history, your food 
intake, smoking and alcohol habits, menopausal history (women only), physical activity, 
sexual habits or behavior, contraception and previous and current medications 
• Other personally identifying information, including your name and other information (such 
as your age, race or ethnicity, gender and country location) 
• Results of examinations and laboratory tests 
• Biological samples  
 
Regeneron or its representatives may conduct site visits to monitor and ensure that the trial is executed 
according to the study protocol and applicable local laws and regulations.  
 
Who else will be able to look at my personal information? 
The Researchers will use and disclose your Personal Information to the following organizations:  
• Regeneron, its collaborators or those developing the study drug; and their affiliates, 
representatives, agents and contractors (the “Regeneron Parties”)  
• The FDA, other U.S. government agencies, and government authorities in other countries 
• IRB/EC, a group that looks out for the rights and welfare of research participants  
 
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Your personal data may also be shared with third-party companies that help run the study. This may 
include companies that provide travel services, home health services, as well as companies that develop 
systems for electronic consent and telemedicine. This data may include personally identifying 
information, such as your name, address, phone number, and email address. These companies are 
responsible for the confidentiality of your identifying information and will not share it with Regeneron. 
 
Access to your records may be provided to regulatory authorities, monitors, auditors, and representatives 
of Regeneron, in order to monitor, audit, and verify research procedures and/or study data. In some 
cases, this may involve having your records reviewed at the study site. In other cases, your records may 
be reviewed remotely over the internet, but only if the laws and regulations in your country allow this.  
 
Generally, your permission to use and/or share your Personal Information for the purposes described in 
this form does not have an expiration date, subject to applicable law, unless you withdraw your 
permission in writing to the study doctor at the address listed on page 1 of this form.  
 
What precautions will be taken to protect my privacy? 
Every effort will be taken to maintain your privacy. Your name will not be attached to records or 
samples released for research purposes. Instead, your records and samples will only be identified by a 
code. Only the study doctor and authorized personnel will be able to connect this code to your name. 
Your Personal Information will be protected by your study doctor and site in accordance with relevant 
data protection laws.  
 
All data will be stored in locked cabinet files and restricted-access computers. While these security 
measures reduce the risk of your personal information being misused or accessed by unauthorized 
individuals, such risks cannot be eliminated entirely. Although we believe that these risks are low, 
absolute confidentiality cannot be promised. However, all information will be collected and shared in 
accordance with applicable law and data sharing guidelines that the Sponsor must follow.  
 
Since identifiers are removed from the identifiable private information or identifiable samples, the 
information or samples could be used for future studies or be distributed to another investigator for 
future studies without additional informed consent. 
 
How will my personal information and results from this study be used? 
The Researchers and organizations listed above will use and disclose your Personal Information in 
connection with the study to assure quality control, analyze the data, and comply with regulatory duties. 
This includes the submission of the study results, regulatory approvals of the study drug, to report 
adverse events, and government reporting, if applicable. In addition, Regeneron Parties will use the 
study data to assess the safety and efficacy of the study drug.  
 
Your coded Personal Information will be added to a computerized database. This database will be part 
of the study results. Data and results from this study will be presented at meetings or published in 
journals. To fulfill regulatory requirements and industry guidelines, the results from this study will also 
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be provided to qualified researchers who request it for legitimate research purposes. While your coded 
information may be shared with these researchers or publications, your identity (such as your name, 
address and email) will not be shared with these researchers and will not be in any presentation or 
publication.  
 
Researchers may link your data with the data from other household members who volunteered for this 
study or other Regeneron COVID related studies to help us understand how COVID-19 infection is 
spread.  
 
As advancements in medical technology continue, Regeneron Parties may reanalyze the study data and 
the results in future research projects to find new scientific information about the study, 
REGN10933+REGN10987, COVID-19, or other related diseases.  
 
Once your personal information is disclosed to the Regeneron Parties and to the other organizations 
identified above, it may be subject to further disclosure and no longer protected by federal privacy law. 
 
Will I have access to my results? 
The results produced as part of this study are for research purposes only. The results are not reviewed 
for medical diagnosis of any disease. Because the results obtained during the course of the research have 
only clinical research value and are not for medical diagnosis, the Sponsor does not provide individual 
results to you. In some circumstances, the Sponsor may provide certain results to your study doctor. If, 
during the course of the study, the study doctor learns information related to your health from the study 
procedures, the study doctor may discuss this information and your options with you. 
 
What are my privacy rights? 
 
Your Right to Access and/or Correct Your Information  
You have the right to access, through your study doctor, all of the information collected about you in 
your medical record, and to ask for corrections, according to the rules of the study site. You have the 
right to request information on how the Personal Information reported to the Sponsor are being used and 
with whom the data have been shared. Please note that your right to access certain information in your 
medical records may be suspended during your participation in the study. Therefore, if you would like 
immediate access to your records, you may not be able to continue participating in the study.  
 
Your Right to Object/Withdraw 
In order to participate in this study, the Sponsor must collect and use your Personal Information. Your 
decision to allow the collection and use of your health information is completely voluntary but if you do 
not allow it, you may not participate in the study. If you change your mind about your Personal 
Information being used, you can voluntarily withdraw from the study at any time. If you choose to 
withdraw your permission, you will not be punished in any way or lose any right to access care, 
treatment, or services outside of the study. 
 
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If you withdraw your permission to use your Personal Information, the Personal Information collected 
prior to your withdrawal will still be processed along with other data collected as part of the study in 
order to preserve the integrity of the results and in accordance with regulatory requirements. The 
information collected about you up to the point when you discontinue from the study, or information 
obtained after you withdraw in connection with a safety issue related to the study, will continue to be 
used, including lab results, clinic notes, and any other information collected. However, no new 
information will be collected unless you specifically consent to that.  
 
Your Right to Request Deletion 
If you withdraw from the study, you may also request that the Personal Information already collected 
from you in connection with the study be deleted. However, your right to deletion is limited due to 
regulatory requirements and to preserve scientific integrity, as your Personal Information must be 
managed in specific ways in order for the research to be reliable and accurate. The study results and 
coded data will be kept as long as they are needed for research purposes, any regulatory requirements, 
and the Sponsor’s Data Retention Schedule.  
 
Please be aware that because the Sponsor only maintains coded study data, it generally cannot respond 
directly to individual requests regarding your privacy rights. Therefore, you should address any of these 
requests regarding these rights to the study site using the contact information on the first page of this 
consent form. If you have any questions, concerns, or complaints as to how your Personal Information 
has been handled, you can contact the Sponsor’s Data Protection Officer at 
DataProtection@Regeneron.com.  
 
Will my information be on the internet? 
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.  Some regulatory authorities 
and ethics committees may make information available on their websites.  
 
What if something is developed from this research? 
By participating in this study, you do not acquire any ownership rights in the samples you contribute or 
in any medical tests, drugs or other commercial products that may be developed through this research.  
 
Who do I call if I have questions?  
The people to contact for any questions, concerns, complaints, research related injury or problems in the 
study are listed on the first page of this consent. You may ask questions before you sign the consent, at 
any time during your participation in the study, and after you are finished with the study.  
 
This research is being overseen by an Institutional Review Board (“IRB”). An IRB is a group of people 
who perform independent review of research studies. You may talk to them at (800) 562-4789, 
help@wirb.com if:  
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• You have questions, concerns, or complaints that are not being answered by the research team. 
• You are not getting answers from the research team. 
• You cannot reach the research team. 
• You want to talk to someone else about the research. 
• You have questions about your rights as a research subject. 
 
Protocol Title: 
A Phase 3, Randomized, Double-Blind, Placebo-Controlled 
Study Assessing the Efficacy and Safety of Anti-Spike 
SARS-CoV-2 Monoclonal Antibodies in Preventing SARS-
Cov-2 Infection in Household Contacts of Individuals 
Infected with SARS-CoV-2 
Protocol Number: 
Sponsor: 
Research Site: 
R10933-10987-COV-2069 
Regeneron Pharmaceuticals Inc. 
[Site] 
 
Participant’s Agreement 
• I have read and understand this Informed Consent Form. This study has been explained to me 
in detail and all of my questions have been answered to my satisfaction. I have been given 
ample time to decide whether to participate. 
• I authorize the collection, use, disclosure and storage of my Personal Information and 
biological samples for the purposes of this study as described in this form. 
• I volunteer to participate in this research study.  
• I have been informed of my privacy rights related to the collection, use and disclosure of my 
Personal Information and consent to such collection, use and disclosure. 
• I am free to withdraw my consent to the collection, use, and disclosure of my Personal 
Information at any time without penalty and without affecting my medical treatment; 
however, I will not be able to continue my participation in the research study after I withdraw 
consent, and data already collected will continue to be included in study analyses, in 
accordance with regulatory requirements.  
• I agree that my GP/personal physician can be informed of my participation in this study. 
• By signing this form, I have not waived any of the legal rights that I otherwise would have as 
a participant in a research study. I understand that I will receive a signed copy of this form 
for my records. 
 
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CONSENT/ASSENT REQUIREMENTS 
• All subjects unable to consent are required to assent, unless the investigator determines that 
the capability of the subject is so limited that the subject cannot reasonably be consulted. 
• If assent is obtained, have the person obtaining assent document assent on the consent form. 
 
A copy of the information sheet and your signed consent form will be given to you to keep 
 
 
 
 
 
 
 
 
Name of Study Participant  
Signature 
Date (DDMMYYYY) 
(Print Name) 
 
Study Investigator or Person Obtaining Consent or Assent 
I have fully informed the participant about the study: 
 
 
 
 
 
 
 
 
Name of Study Investigator or Person 
Signature 
Date (DDMMYYYY) 
Obtaining Consent (Print Name) 
 
OR 
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❑ I have explained the study to the extent compatible with the subject’s capability, and the subject 
has agreed to be in the study. 
OR 
❑ The subject is not able to assent because the capability of the subject is so limited that the subject 
cannot reasonably be consulted. 
 
 
 
 
 
 
 
 
Name of Study Investigator or Person 
Signature 
Date (DDMMYYYY) 
Obtaining Consent (Print Name) 
 
Legally Authorized Representative  
The Legally Authorized Representative signature should be added if the participant is unable to sign for 
himself or herself. The relationship between the participant and the Legally Authorized Representative 
should be stated. 
 
 
 
 
 
 
 
 
Name of Legally Authorized 
Signature 
Date (DDMMYYYY) 
Representative (Print Name) 
 
 
 
 
Relationship to Study Participant 
 
Witness Signature 
 
[Site should decide whether witness section is required. This section is not mandatory.] 
 
☐ 
Not Applicable: witness agreement is not required. 
☐ 
Applicable: witness agreement and signature are provided below. 
 
As an impartial third party, I witnessed the entire consent discussion. I attest that the above-named 
participant received a verbal and written description of the study. This individual had sufficient time to 
consider this information, had an opportunity to ask questions, and voluntarily agreed to participate in 
this study. 
 
 
 
 
 
 
 
 
Name of Impartial Witness 
Signature 
Date (DDMMYYYY) 
(Print Name) 
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Parent or Legal Guardian (site: include this page only if parent is signing for a child 
[ages 12-17], if not remove) 
As a parent or legal guardian of the participant, I confirm that the participant is below the age of 
consent. I have read and agree with the parental permission agreement and provide permission on behalf 
of the participant. 
______________________________ 
Name (Print) 
 
 
______________________________ 
Signature 
_______________ 
Date 
______________________________ 
Relationship to Study Participant 
 
 
______________________________ 
Name (Print) 
 
 
______________________________ 
Signature 
_______________ 
Date 
______________________________ 
Relationship to Study Participant 
 
 
Permission should be provided by two parents. If permission cannot be provided by the second parent, 
provide the reason(s) below. 
 
The second parent: 
☐ 
Is deceased 
 
☐ 
Is unknown 
 
☐ 
Is not legally competent 
 
☐ 
Does not have legal custody 
 
☐ 
Is “not reasonably available” 
 
☐ 
Other reason: ______________________________ 
 
Study Investigator or Person Obtaining Permission 
 
I have fully informed the parent(s)/caregiver(s) of the participant about the study: 
______________________________ 
Name of Study Investigator or Person 
Obtaining Permission (Print Name) 
 
 
 
______________________________ 
Signature 
_______________ 
Date (DDMMMYYYY) 
 
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Legally Authorized Representative  
The Legally Authorized Representative signature should be added if the parent of the participant is 
unable to sign for himself or herself. The relationship between the parent of the participant, the 
participant and the Legally Authorized Representative should be stated. 
______________________________ 
Name of Legally Authorized 
Representative (Print Name) 
 
 
 
______________________________ 
Signature 
_______________ 
Date 
(MMDDYYYY) 
_____________/_________________ 
Relationship to the Parent of the Study 
Participant and the Study Participant 
 
 
Witness Signature 
Site should decide whether witness section is required. This section is not mandatory. 
☐ 
Not Applicable: witness agreement is not required. 
☐ 
Applicable: witness agreement and signature are provided below. 
As an impartial third party, I witnessed the entire discussion. I attest that the above-named participant 
received a verbal and written description of the study. This individual had sufficient time to consider this 
information, had an opportunity to ask questions, and voluntarily agreed to participate in this study. 
______________________________ 
Name of Impartial Witness 
(Print Name) 
 
 
 
______________________________ 
Signature 
_______________ 
Date (DDMMMYYYY) 
 
VV-TMF-1795887 - 1.0 - Approved


 
IRB Approved Template 
MUST BE APPROVED 
FOR SITES BEFORE USE 
AS MODIFIED 
Jan 22, 2021 
 
 
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Page 25 of 27 
**For Sites in California** 
AUTHORIZATION TO USE AND DISCLOSE INFORMATION FOR 
RESEARCH PURPOSES  
 
What information may be used and given to others? 
The study doctor will get your personal and medical information.  For example:  
• Past and present medical records 
• Research records 
• Records about phone calls made as part of this research 
• Records about your study visits. 
 
Who may use and give out information about you? 
The study doctor and the study staff.  [They may also share the research information with 
[enter SMO company name], an agent for the study doctor. delete if the site does not have 
an SMO] 
 
Who might get this information? 
The sponsor of this research.  “Sponsor” means any persons or companies that are: 
• working for or with the sponsor, or  
• owned by the sponsor. 
 
Your information may be given to:  
• The U.S. Food and Drug Administration (FDA), 
• Department of Health and Human Services (DHHS) agencies, 
• Governmental agencies in other countries,  
• The institution where the research is being done, 
• Governmental agencies to whom certain diseases (reportable diseases) must be 
reported, and 
• Institutional Review Board (IRB)  
 
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IRB Approved Template 
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Page 26 of 27 
Why will this information be used and/or given to others? 
• to do the research,  
• to study the results, and  
• to make sure that the research was done right.   
 
If the results of this study are made public, information that identifies you will not be 
used. 
 
What if I decide not to give permission to use and give out my health information? 
Then you will not be able to be in this research study. 
 
May I review or copy my information? 
Yes, but only after the research is over.  
 
May I withdraw or revoke (cancel) my permission? 
This permission will be good until December 31, 2070. 
 
You may withdraw or take away your permission to use and disclose your health 
information at any time.  You do this by sending written notice to the study doctor.  If 
you withdraw your permission, you will not be able to stay in this study. 
 
When you withdraw your permission, no new health information identifying you will be 
gathered after that date.  Information that has already been gathered may still be used and 
given to others.   
 
Is my health information protected after it has been given to others? 
There is a risk that your information will be given to others without your permission. 
 
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Authorization: 
I have been given the information about the use and disclosure of my health information for 
this research study.  My questions have been answered. 
 
I authorize the use and disclosure of my health information to the parties listed in the 
authorization section of this consent for the purposes described above. 
 
AUTHORIZATION SIGNATURE: 
 
 
 
 
 
 
Signature of Subject/LAR 
 
Date 
VV-TMF-1795887 - 1.0 - Approved

SAP_002.pdf: 
Clinical Development and Regulatory Affairs 
Biostatistics and Data Management 
CONFIDENTIAL 
Page 1 of 77 
Document’s type 
Document Reference 
Effective Date 
Standard 
BDM-STD-STA4-2.2 
March 1, 2015 
STATISTICAL ANALYSIS PLAN 
VERSION: FINAL 
Clinical Study Protocol Title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study 
Assessing the Efficacy and Safety of Anti-Spike SARS-CoV-2 Monoclonal Antibodies in 
Preventing SARS-Cov-2 Infection in Household Contacts of Individuals Infected with SARS-
CoV-2 
Compound: 
REGN10933+REGN10987 
Protocol Number: 
R10933-10987-COV-2069 
Clinical Phase:  
Phase 3 
Sponsor: 
Regeneron Pharmaceuticals, Inc. 
Study Biostatistician:  
Clinical Trial Manager: 
Study Medical Director: 
Version/Date:  
1.0/25MAR2021 
VV-RIM-00148558-1.0 Approved - 26 Mar 2021 GMT-5:00
NCT04452318


Regeneron Pharmaceuticals, Inc. 
 
Protocol: R10933-10987-COV-2069 
Statistical Analysis Plan 
 
Date: 25MAR2021 
 
CONFIDENTIAL 
Page 2 of 77 
The approval signatures below indicate that these individuals have reviewed the Statistical 
Analysis Plan (SAP) and agreed on the planned analysis defined in this document for 
reporting. 
 
 
See appended electronic signature page 
Study Biostatistician  
) 
 
 
See appended electronic signature page 
Study Pharmacokinetics 
(
) 
 
 
See appended electronic signature page 
Study Bioanalytical Sciences
 
 
 
See appended electronic signature page 
Study Medical Director 
 
 
 
See appended electronic signature page 
Project Biostatistician
 
 
 
See appended electronic signature page 
Head of BDM or designee 
 
 
                                        VV-RIM-00148558-1.0 Approved - 26 Mar 2021 GMT-5:00


Regeneron Pharmaceuticals, Inc. 
 
Protocol: R10933-10987-COV-2069 
Statistical Analysis Plan 
 
Date: 25MAR2021 
 
CONFIDENTIAL 
Page 3 of 77 
TABLE OF CONTENTS 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS ....................................................7 
1. 
OVERVIEW .................................................................................................................8 
1.1. 
Background/Rationale ..................................................................................................8 
1.2. 
Study Objectives ...........................................................................................................8 
1.2.1. 
Primary Objectives .......................................................................................................9 
1.2.2. 
Secondary Objectives ...................................................................................................9 
1.2.3. 
Exploratory Objectives ...............................................................................................11 
1.2.4. 
Modifications from the Statistical Section in the Final Protocol ................................13 
1.2.5. 
Revision History for SAP Amendments .....................................................................13 
2. 
INVESTIGATION PLAN ..........................................................................................14 
2.1. 
Study Design and Randomization ..............................................................................14 
2.2. 
Sample Size and Power Considerations .....................................................................15 
2.2.1. 
Cohort A .....................................................................................................................15 
2.2.2. 
Cohort B......................................................................................................................16 
3. 
ANALYSIS POPULATIONS ....................................................................................17 
3.1. 
The Efficacy Analysis Sets .........................................................................................17 
3.2. 
The Safety Analysis Set (SAF) ...................................................................................18 
3.3. 
Pharmacokinetic Analysis Set ....................................................................................18 
3.4. 
Immunogenicity Analysis Sets ...................................................................................18 
3.4.1. 
Anti-drug Antibodies Analysis Set .............................................................................18 
3.4.2. 
Neutralizing Antibody Analysis Set ...........................................................................18 
4. 
ANALYSIS VARIABLES .........................................................................................19 
4.1. 
Demographic and Baseline Characteristics ................................................................19 
4.2. 
Medical History ..........................................................................................................20 
4.3. 
Pre-Treatment / Concomitant Medication ..................................................................20 
4.4. 
Prohibited Medications ...............................................................................................21 
4.5. 
Efficacy Variable ........................................................................................................21 
4.5.1. 
Cohort A Primary Efficacy Variable ..........................................................................23 
4.5.2. 
Cohort A Key Secondary Efficacy Variables .............................................................23 
4.5.3. 
Cohort A and Cohort A1 Other Secondary Efficacy Variables ..................................24 
4.5.4. 
Cohort A and Cohort A1 Exploratory Efficacy Variables ..........................................26 
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Regeneron Pharmaceuticals, Inc. 
 
Protocol: R10933-10987-COV-2069 
Statistical Analysis Plan 
 
Date: 25MAR2021 
 
CONFIDENTIAL 
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4.5.5. 
Cohort B Primary Efficacy Variable ..........................................................................28 
4.5.6. 
Cohort B Key Secondary Efficacy Variables .............................................................28 
4.5.7. 
Cohort B and Cohort B1 Other Secondary Efficacy Variables ..................................28 
4.5.8. 
Cohort B and Cohort B1 Exploratory Variables .........................................................30 
4.6. 
Safety Variables ..........................................................................................................32 
4.6.1. 
Adverse Events and Serious Adverse Events .............................................................32 
4.6.2. 
Adverse Events of Special Interest .............................................................................33 
4.6.3. 
Events Causing Death .................................................................................................33 
4.6.4. 
Laboratory Safety Variables .......................................................................................33 
4.6.5. 
Physical Examination Variables .................................................................................34 
4.7. 
Pharmacokinetic Variables .........................................................................................34 
4.8. 
Immunogenicity Variables ..........................................................................................34 
5. 
STATISTICAL METHODS .......................................................................................35 
5.1. 
Demographics and Baseline Characteristics ...............................................................35 
5.2. 
Medical History ..........................................................................................................35 
5.3. 
Prior/concomitant Medications or Procedures............................................................35 
5.4. 
Prohibited Medications ...............................................................................................35 
5.5. 
Subject Disposition .....................................................................................................35 
5.6. 
Extent of Study Treatment Exposure and Compliance ...............................................36 
5.6.1. 
Measurement of Compliance ......................................................................................36 
5.6.2. 
Exposure to Investigational Product ...........................................................................36 
5.7. 
Analyses of Efficacy Variables ..................................................................................36 
5.7.1. 
Analysis of Primary Efficacy Variables .....................................................................36 
5.7.1.1. 
Sensitivity Analyses ....................................................................................................37 
5.7.1.2. 
Subgroup Analyses .....................................................................................................38 
5.7.2. 
Adjustment for Multiple Comparison .........................................................................38 
5.7.3. 
Analyses of Key Secondary Variables .......................................................................40 
5.7.4. 
Analyses of Other Secondary and Exploratory Efficacy Variables ............................41 
5.7.5. 
Interim Analysis ..........................................................................................................42 
5.8. 
Analysis of Safety Data ..............................................................................................42 
5.8.1. 
Adverse Events ...........................................................................................................43 
5.8.2. 
Clinical Laboratory Measurements.............................................................................44 
                                        VV-RIM-00148558-1.0 Approved - 26 Mar 2021 GMT-5:00


Regeneron Pharmaceuticals, Inc. 
 
Protocol: R10933-10987-COV-2069 
Statistical Analysis Plan 
 
Date: 25MAR2021 
 
CONFIDENTIAL 
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5.8.3. 
Analysis of Vital Signs ...............................................................................................44 
5.8.4. 
Analysis of Other Safety Variables - Abnormal Findings during SARS-CoV-
2 Infection-related Medically Attended Visits ...........................................................45 
5.9. 
Analysis of Pharmacokinetic Data ..............................................................................45 
5.9.1. 
Analysis of drug concentration data ...........................................................................45 
5.10. 
Analysis of Immunogenicity Data ..............................................................................46 
5.10.1. 
Analysis of Neutralizing Antibody (NAb) Data .........................................................47 
5.11. 
Association of Immunogenicity with Exposure, Safety and Efficacy ........................47 
5.11.1. 
Immunogenicity and Exposure ...................................................................................47 
5.11.2. 
Immunogenicity and Safety and Efficacy ...................................................................47 
6. 
DATA CONVENTIONS ............................................................................................49 
6.1. 
Definition of Baseline for Efficacy/Safety Variables .................................................49 
6.2. 
Data Handling Convention for Efficacy Variables .....................................................49 
6.3. 
Data Handling Convention for Missing Data .............................................................49 
6.4. 
Windows for Analysis Time Points ............................................................................50 
6.5. 
Pooling of Centers for Statistical Analyses ................................................................51 
6.6. 
Statistical Technical Issues .........................................................................................51 
7. 
TIMING OF STATISTICAL ANALYSES ................................................................54 
8. 
SOFTWARE ...............................................................................................................55 
9. 
REFERENCES ...........................................................................................................56 
10. 
APPENDIX.................................................................................................................57 
10.1. 
Summary of Statistical Analyses ................................................................................57 
10.2. 
Schedule of Events .....................................................................................................58 
10.2.1. 
Schedule of Events Table 6 (Cohorts A and B [Adult / Adolescent Subjects], 
RT-qPCR-Negative and Positive) Footnotes ..............................................................59 
10.2.2. 
Schedule of Events Table 4: All Cohorts A and B (Adult / Adolescent 
Subjects) for Drug Concentrations, Immunogenicity, and Laboratory Testing .........64 
10.2.3. 
Schedule of Events Table 5 Cohorts A1 and B1 (Pediatric Subjects [ <12 
years], RT-qPCR-Negative and Positive) Footnotes ..................................................66 
10.2.4. 
Schedule of Events Table 6: Cohorts A1 and B1 (Pediatric Subjects [<12 
years]) for Drug Concentration, Immunogenicity, and Laboratory Testing ...............70 
10.2.5. 
Early Termination Visit ..............................................................................................70 
10.2.6. 
Unscheduled Visits .....................................................................................................71 
10.3. 
Criteria for Potentially Clinically Significant Values (PCSV) ...................................72 
                                        VV-RIM-00148558-1.0 Approved - 26 Mar 2021 GMT-5:00


Regeneron Pharmaceuticals, Inc. 
 
Protocol: R10933-10987-COV-2069 
Statistical Analysis Plan 
 
Date: 25MAR2021 
 
CONFIDENTIAL 
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10.4. 
Example of SAS Procedures for Primary Analysis and Missing Data 
Imputations by FCS ....................................................................................................76 
 
LIST OF TABLES 
Table 1: 
Simulated Power for Household Design (1248 Subjects over 430 
Households) ................................................................................................................16 
Table 2: 
Hierarchy Testing Sequence of Key Secondary Efficacy Endpoints in 
Seronegative mFAS-A ................................................................................................39 
Table 3: 
Hierarchy Testing Sequence of Key Secondary Efficacy Endpoints in 
Seronegative mFAS-B ................................................................................................40 
Table 4: 
Efficacy Analysis Windows for Unscheduled Visits with RT-qPCR or Viral 
Load Results ...............................................................................................................50 
Table 5: 
Global Analysis Windows for Data Other Than RT-qPCR Test ................................51 
Table 6: 
Schedule of Events Cohorts A and B ([Adult / Adolescent Subjects], RT-
qPCR-Negative and Positive) .....................................................................................58 
Table 7: 
Schedule of Events: Cohorts A and B (Adult / Adolescent Subjects) for Drug 
Concentration, Immunogenicity, and Laboratory Testing ..........................................63 
Table 8: 
Schedule of Events: Cohorts A1 and B1 (Pediatric Subjects [<12 years], RT-
qPCR-Negative and Positive) .....................................................................................65 
Table 9: 
Schedule of Events: Cohorts A1 and B1 (Pediatric Subjects [<12 years]) for 
Drug Concentration, Immunogenicity, and Laboratory Testing ................................69 
 
LIST OF FIGURES 
Figure 1: 
Study Flow Diagram ...................................................................................................15 
 
                                        VV-RIM-00148558-1.0 Approved - 26 Mar 2021 GMT-5:00


Regeneron Pharmaceuticals, Inc. 
 
Protocol: R10933-10987-COV-2069 
Statistical Analysis Plan 
 
Date: 25MAR2021 
 
CONFIDENTIAL 
Page 7 of 77 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
ADA 
Anti-drug antibody 
AE 
Adverse event 
AESI 
Adverse event of special interest 
ALT 
Alanine aminotransferase 
AST 
Aspartate aminotransferase 
BUN 
Blood urea nitrogen 
COVID-19 
Coronavirus disease 2019 
CPK 
Creatine phosphokinase 
CRF 
Case report form (electronic or paper) 
EAP 
Efficacy assessment period 
EOS 
End of study 
FAS 
Full analysis set 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GEE 
Generalized estimation equation 
ICF 
Informed consent form 
ICH 
International Council for Harmonisation 
IWRS 
Interactive web response system 
mAb 
Monoclonal antibody 
NAb 
Neutralizing anti-drug antibody 
NCI-CTCAE 
National Cancer Institute-Common Terminology Criteria for Adverse Events 
PK 
Pharmacokinetic 
PCSV 
Potentially clinically significant value 
RBC 
Red blood cell 
RBD 
Receptor binding domain 
RT-qPCR 
Quantitative reverse transcription polymerase chain reaction (test; refers to the 
central lab testing in this protocol) 
SARS-CoV-2 
Severe acute respiratory syndrome coronavirus 2 
SAE 
Serious adverse event 
SAF 
Safety analysis set 
SAP 
Statistical analysis plan 
SAS 
Statistical Analysis System 
SC 
Subcutaneous 
SD 
Standard deviation 
SOC 
System organ class 
TEAE 
Treatment-emergent adverse event 
WBC 
White blood cell 
WHO 
World Health Organization 
WOCBP 
Women of childbearing potential 
 
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Regeneron Pharmaceuticals, Inc. 
 
Protocol: R10933-10987-COV-2069 
Statistical Analysis Plan 
 
Date: 25MAR2021 
 
CONFIDENTIAL 
Page 8 of 77 
1. 
OVERVIEW 
The purpose of the statistical analysis plan (SAP) is to ensure the credibility of the study results 
by pre-specifying the statistical approaches for the analysis of study data prior to database lock 
and unblinding. The SAP is intended to be a comprehensive and detailed description of the strategy 
and statistical methods to be used in the analysis of data for R10933-10987-COV-2069 study. The 
SAP includes multiple steps of analyses described in Section 7. 
This plan may be revised during the study to accommodate protocol amendments and/or to make 
changes to adapt to unexpected issues in study execution and/or data that affect planned analyses. 
These revisions will be based on blinded data review, and a final plan will be issued prior to the 
first step database lock and unblinding of the individual treatment assignment.  
1.1. 
Background/Rationale 
This study will assess the use of REGN10933+REGN10987 in preventing household transmission 
of SARS-CoV-2.  A household is defined as a group of people who live together at the same 
residence and share multiple living spaces (e.g., living room, bedroom, kitchen, bathroom).   
1.2. 
Study Objectives  
All subjects in the study will have household contact with the first household member known to 
be infected with SARS-CoV-2 infection (index case) but who are themselves either not infected 
or who are asymptomatic (having no active respiratory or non-respiratory symptoms consistent 
with COVID-19) at the time of screening. In this study, the household contact must share the same 
residence and have a close exposure to the first individual in the household with a known SARS-
CoV-2 infection (index case).  
For the analyses, there are four cohorts defined based on the subject's SARS-CoV-2 infection status 
at baseline, as measured by central lab SARS-CoV-2 RT-qPCR (quantitative reverse transcription 
polymerase chain reaction), and on the subject's age:  
• For subjects with SARS-CoV-2 RT-qPCR negative at baseline, they are assigned into 
two cohorts: 
− Cohort A (adult and adolescent subjects [≥12 years]) 
− Cohort A1 (pediatric subjects [<12 years])  
or  
• For subjects with SARS-CoV-2 RT-qPCR positive at baseline, they are assigned into 
two cohorts:  
− Cohort B (adult and adolescent subjects [≥12 years]) 
− Cohort B1 (pediatric subjects [<12 years]) 
 
                                        VV-RIM-00148558-1.0 Approved - 26 Mar 2021 GMT-5:00


Regeneron Pharmaceuticals, Inc. 
 
Protocol: R10933-10987-COV-2069 
Statistical Analysis Plan 
 
Date: 25MAR2021 
 
CONFIDENTIAL 
Page 9 of 77 
1.2.1. 
Primary Objectives  
The primary objectives are for subjects who are seronegative at baseline (based on central lab 
test) unless stated otherwise. 
Efficacy – Cohort A (Adult and adolescent subjects (≥12 years) who are SARS-CoV-2 RT-qPCR 
negative at baseline)  
• To evaluate the efficacy of REGN10933+REGN10987 compared to placebo in 
preventing symptomatic SARS-CoV-2 infection (broad-term) confirmed by RT-qPCR 
Efficacy – Cohort B (Adult and adolescent subjects (≥12 years) who are SARS-CoV-2 RT-qPCR 
positive at baseline)  
• To evaluate the efficacy of REGN109333+REGN10987 compared to placebo in 
preventing COVID-19 symptoms (broad-term) 
Safety – Cohort A and Cohort A1, Cohort B and B1  
To evaluate the safety and tolerability of REGN10933+REGN10987 following subcutaneous (SC) 
administration compared to placebo 
1.2.2. 
Secondary Objectives 
Cohort A and Cohort A1 
The following secondary objectives are for subjects who are seronegative at baseline (based on 
central lab test) unless stated otherwise. 
• To evaluate the efficacy of REGN10933+REGN10987 compared to placebo in 
preventing a SARS-CoV-2 infection with a high viral load (i.e. viral load >4 (log10 
copies/mL))  
• To evaluate the impact of REGN10933+REGN10987 compared to placebo on the 
duration of signs and symptoms in subjects with symptomatic SARS-CoV-2 infection 
(broad-term) confirmed by RT-qPCR 
• To evaluate the impact of REGN10933+REGN10987 compared to placebo on the 
duration of SARS-CoV-2 infection with a high viral load (i.e. viral load >4 (log10 
copies/mL))  
• To evaluate the impact of REGN10933+REGN10987 compared to placebo on the 
duration of SARS-CoV-2 infection  
• To evaluate the efficacy of REGN10933+REGN10987 compared to placebo in 
preventing asymptomatic or symptomatic SARS-CoV-2 infection confirmed by RT-
qPCR 
• To evaluate the impact of treating the index case with REGN10933+REGN10987 on 
the incidence of SARS-CoV-2 infection among their household contacts in placebo 
group (note: This is a cross-study analysis based on only subjects in  placebo group of  
R10933-10987-COV-2069 whose index cases participated in  R10933-10987-COV-
2067) 
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Statistical Analysis Plan 
 
Date: 25MAR2021 
 
CONFIDENTIAL 
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• To evaluate the efficacy of REGN10933+REGN10987 compared to placebo in 
preventing symptomatic SARS-CoV-2 infection (Centers for Disease Control and 
Prevention (CDC) definition) confirmed by RT-qPCR 
• To evaluate the efficacy of REGN10933+REGN10987 compared to placebo in 
preventing symptomatic SARS-CoV-2 infection (strict-term) confirmed by RT-qPCR 
• To evaluate the impact of REGN10933+REGN10987 compared to placebo on SARS-
CoV-2 RT-qPCR viral load   
• To evaluate the impact of REGN10933+REGN10987 compared to placebo on SARS-
CoV-2 infection:  
− On health care utilization 
− On absenteeism from daily responsibilities (where applicable) 
• To evaluate the impact of treating any SARS-CoV-2 RT-qPCR positive household 
member with REGN10933+REGN10987 on the incidence of SARS-CoV-2 infection 
among their household contacts in placebo group (note: This is a cross-study analysis 
based on only subjects in placebo group of R10933-10987-COV-2069 whose  index or 
other household member participated in R10933-10987-COV-2067 or in cohort B )  
• To characterize the drug concentration-time profiles of REGN10933 and REGN10987 
in serum and selected PK parameters 
• To assess the immunogenicity of REGN10933 and REGN10987  
• To evaluate the safety and tolerability of REGN10933+REGN10987 following SC 
administration in seropositive subjects  
• To estimate the incidence and severity of symptomatic SARS-CoV-2 infection over 
time, 
including 
the 
period 
following 
study 
drug 
treatment, 
in 
REGN10933+REGN10987-treated seronegative and seropositive subjects compared 
with placebo-treated subjects 
• To evaluate the efficacy of REGN10933+REGN10987 compared to placebo in 
preventing symptomatic SARS-CoV-2 infection (broad-term) confirmed by RT-qPCR 
(cohort A1) 
Cohort B and Cohort B1  
Secondary objectives for Cohort B and Cohort B1 are for all seronegative subjects at baseline (by 
central lab test) unless stated otherwise. 
• To evaluate the efficacy of REGN10933+REGN10987 compared to placebo in 
preventing development of:  
− Symptomatic SARS-CoV-2 infection (strict-term) 
− Symptomatic SARS-CoV-2 infection (broad-term; cohort B1) 
− Symptomatic SARS-CoV-2 infection (CDC definition) 
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Statistical Analysis Plan 
 
Date: 25MAR2021 
 
CONFIDENTIAL 
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• To evaluate the impact of REGN10933+REGN10987 compared to placebo on the 
duration of signs and symptoms in subjects with symptomatic SARS‑CoV-2 infection 
confirmed by RT-qPCR 
• To evaluate the impact of REGN10933+REGN10987 compared to placebo on the 
duration of SARS-CoV-2 infection with a high viral load  
• To evaluate the impact of REGN10933+REGN10987 compared to placebo on 
SARS-CoV-2 viral load  
• To evaluate the impact of REGN10933+REGN10987 compared to placebo in 
SARS-CoV-2 infection:  
• On health care utilization  
• On absenteeism from daily responsibilities (where applicable) 
• To characterize the drug concentration-time profiles of REGN10933 and REGN10987 
in serum and selected PK parameters  
• To assess the immunogenicity of REGN10933 and REGN10987  
• To evaluate the safety and tolerability of REGN10933+REGN10987 following SC 
administration  
• To estimate the incidence and severity of symptomatic SARS-CoV-2 infection over 
time, 
including 
the 
period 
following 
study 
drug 
treatment, 
in 
REGN10933+REGN10987-treated subjects compared with placebo-treated subjects 
1.2.3. 
Exploratory Objectives 
Cohort A and Cohort A1 
• To evaluate the efficacy of REGN10933+REGN10987 compared to placebo in 
preventing SARS-CoV-2 infection assessed by seroconversion in baseline seronegative 
subjects  
• To explore the impact of REGN10987+REGN10933 compared to placebo:  
− On humoral immune response to SARS-CoV-2 infection  
− On measures of infectivity of SARS-CoV-2 as assessed in experimental laboratory 
assays  
• To evaluate the impact of REGN10933+REGN10987 compared to placebo in 
SARS-CoV-2 infection in subjects who are seropositive at baseline:  
− Prevention of symptomatic infection (strict-term)  
− Prevention of symptomatic infection (broad-term)  
− Prevention of symptomatic infection (CDC definition) 
− Prevention of asymptomatic infection or symptomatic re-infection (strict-term, 
CDC definition, or broad-term)  
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Statistical Analysis Plan 
 
Date: 25MAR2021 
 
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• To explore the relationships between REGN10933+REGN10987 exposure and 
selected clinical efficacy and safety endpoints and/or biomarkers in seropositive and 
seronegative subjects  
• To assess viral genetic variation in SARS-CoV-2 in subjects with a positive 
SARS-CoV-2 RT-qPCR  
• To explore biomarkers (including host genome variants) associated with safety and 
efficacy of REGN10933+REGN10987 and to study SARS-CoV-2 (cohort A only)  
• To evaluate the impact of treating any household member with anti-SARS CoV-2 
monoclonal antibody on the incidence of SARS-CoV-2 infection among their 
household contacts. The monoclonal antibody treatment considered for this analysis 
are any EUA approved antibody including REGN10933+REGN10987 (within or 
outside of the study R10933-R10987-COV-2067) 
 
Cohort B and Cohort B1 
• To evaluate the impact of REGN10933+REGN10987 compared to placebo in 
seropositive subjects in preventing:  
− Symptomatic SARS-CoV-2 infection (strict-term)  
− Symptomatic SARS-CoV-2 infection (broad-term) 
− Symptomatic SARS-CoV-2 infection (CDC definition) 
• To evaluate the impact of REGN10933+REGN10987 compared to placebo on the 
duration of signs and symptoms in seropositive subjects with symptomatic SARS‑CoV-
2 infection confirmed by RT-qPCR 
• To evaluate the impact of REGN10933+REGN10987 compared to placebo in 
seropositive subjects on SARS-CoV-2 RT-qPCR viral load  
• To evaluate the impact of REGN10933+REGN10987 compared to placebo in 
seropositive subjects on SARS-CoV-2 infection:  
− On health care utilization  
− On absenteeism from daily responsibilities (where applicable) 
• To explore the impact of REGN10987+REGN10933 compared to placebo in subjects, 
by their baseline serology test status (e.g., seropositive or seronegative, based on central 
lab test) on SARS-CoV-2 infection:  
− On humoral immune response  
− On measures of infectivity of SARS-CoV-2 as assessed in experimental laboratory 
assays  
• To explore the relationships between REGN10933+REGN10987 exposure and 
selected clinical efficacy and safety endpoints and/or biomarkers in seropositive and 
seronegative subjects  
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• To assess viral genetic variation in SARS-CoV-2 in subjects with a positive 
SARS-CoV-2 RT-qPCR.  
• To explore biomarkers (including host genome variants) associated with safety and 
efficacy of REGN10933+REGN10987 and to study SARS-CoV-2 
1.2.4. 
Modifications from the Statistical Section in the Final Protocol 
There are no modifications compared to protocol amendment 6. 
1.2.5. 
Revision History for SAP Amendments 
This is the first version of SAP. 
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2. 
INVESTIGATION PLAN 
2.1. 
Study Design and Randomization 
This is a phase 3 randomized, double-blind, placebo-controlled study in adults/adolescent subjects 
( ≥12 years) and pediatric subjects (<12 years of age) who are household contacts of the first known 
household member infected with SARS-CoV-2 (index case). All subjects in the study are 
asymptomatic (having no active respiratory or non-respiratory symptoms consistent with COVID-
19) at the time of screening.  The index case will have a diagnosis of SARS-CoV-2 infection using 
a diagnostic test, e.g., RT-PCR, antigen test, or other test format (approved or with Emergency 
Use Authorization issued by the US FDA or by local health authority). Randomization will be 
performed by individual study subjects, not by households.  Some of the index cases of household 
contacts in this study may be participating in a separate treatment study (R10933-10987-COV-
2067).      
Randomization will be performed by site and stratified for assigning subjects in a 1:1 allocation 
ratio to placebo or REGN10933+REGN10987 [1200 mg (600 mg of each mAb SC). 
Randomization stratifications are test results (positive, negative, or unavailable) of a local 
diagnostic assay for SARS-CoV-2 (e.g., molecular assay such as RT-PCR assay for SARS-CoV-2 
or a SARS-CoV-2 antigen test) from appropriate samples, e.g., nasopharyngeal (NP), 
oropharyngeal (OP), nasal, or saliva, and age group ( <12 years, ≥12 to <18 years, ≥18 to <50 
years, or ≥50 years).  For pediatric subjects (<12 years), the weight group (≥20 kg, ≥10 to <20 kg, 
and <10 kg) will be used as an additional stratification factor.  
The study was originally planned to enroll 2000 adult and adolescent subjects. A blinded analysis 
of approximately 25% of enrolled subjects in this study was performed, demonstrating that higher 
than expected seropositivity was observed in cohort A. In addition, an unblinded administrative 
analyses was performed on the data based on 554 subjects to verify assumptions and adequacy of 
sample size.  The subjects who were included in the administrative assessment will not be included 
in the final efficacy analysis. Thus, sample size was increased to accommodate higher 
seropositivity rate and the unblinded administrative assessment. The total study population was 
planned to be approximately 3500 adult and adolescent subjects (~3150 subjects in cohort A and 
~350 subjects in cohort B) including 554 cohort A subjects in the administrative assessment and 
approximately 250 pediatric subjects <12 years old (~225 subjects in cohort A1 and 25 subjects in 
cohort B1), with household contact exposure to individual with a confirmed SARS-CoV-2 
infection.   
Statistical analyses will be conducted separately in each cohort.  For the purpose of the study 
analysis, cohorts A, A1, B, and B1 are independent.  As specified earlier, the 554 subjects in the 
administrative assessment will not be included in the final efficacy analyses (first step analysis) 
however, these subjects will be included in the safety analyses. Also, the final efficacy analysis 
(first step analysis) will include only subjects randomized on or before January 28, 2021. The total 
number of subjects to be included in the first step analysis is approximately 2459. The subjects 
randomized after January 28, 2021 will remain blinded until the final analysis but will not be part 
of any formal statistical testing.   
For each subject, the study comprises 3 periods: a 1-day screening/baseline period, a 1-month 
EAP, and a 7-month follow-up period (See Figure 1 ). 
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Figure 1: 
Study Flow Diagram 
 
The schedule of events tables for this study can be found in the Appendix 10.2. 
2.2. 
Sample Size and Power Considerations 
2.2.1. 
Cohort A  
The primary hypothesis is the reduction in the proportion of symptomatic RT-qPCR (broad-term) 
confirmed SARS-CoV-2 infections in seronegative subjects.  To calculate the sample size to 
achieve at least 90% power for seronegative subjects in cohort A, it is assumed that the statistical 
hypothesis will be tested in a 2-sided test. Based on the administrative assessment results among 
409 seronegative subjects in cohort A, an approximately 50% reduction of infection (symptomatic 
or asymptomatic) compared to placebo group and a 100% reduction of symptomatic infection 
compared to placebo group was observed. Due to the small sample size in the administrative 
assessment, it was assumed, for the purpose of assessing study power, that an approximately 50% 
reduction or greater in symptomatic infections compared to the placebo group will be expected for 
the final primary efficacy analysis.  
In this household study design, the number of subjects per household, the correlation between 
subjects and symptomatic infection rates within a household are unknown.  To detect a relative 
risk of 0.5 (i.e., 50% reduction of the assumed 10% attack rate in the placebo arm), equivalent to 
an odds ratio of 0.47, power was calculated compared to the p-value of 0.05 based on 2000 
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simulations in 1248 subjects from 430 households (i.e., assuming an average household size of 
2.9 seronegative subjects).  Table 1 provides power calculations by varying degrees of correlation 
within household.  In all cases, the power of the study is >90% using a generalized linear model 
with the generalized estimation equation (GEE) approach assuming a compound symmetry 
covariance matrix. 
Table 1: 
Simulated Power for Household Design (1248 Subjects over 430 Households)  
Placebo  
Attack Rate 
REGN10933+ 
REGN10987 
Attack Rate 
Correlation 
within Household 
Average Odds Ratio 
REGN10933+REGN10987 
versus Placebo 
Power 
10% 
5% 
0.1 
0.485 
0.914 
10% 
5% 
0.2 
0.485 
0.934 
10% 
5% 
0.3 
0.480 
0.956 
10% 
5% 
0.4 
0.481 
0.972 
10% 
5% 
0.5 
0.476 
0.983 
10% 
5% 
0.6 
0.478 
0.999 
 
At least 1980 subjects will need to be enrolled in cohort A to have a minimum of 1248 seronegative 
subjects, assuming that 10% of subjects drop out, and 30% of subjects are seropositive at baseline. 
The correlation among subjects within each household, the rates for seronegativity, and the rates 
for seropositivity will be monitored in a blinded fashion.  The 2 assumptions, that 90% of 
randomized subjects will have a baseline negative RT-qPCR and be assigned to cohort A and that 
70% of these subjects in cohort A are seronegative, will be monitored periodically to ensure that 
there will be a sufficient number of seronegative subjects (~1248) enrolled in Cohort A to be 
included in the primary analysis.  This will maintain the planned statistical power. 
2.2.2. 
Cohort B  
The primary endpoint in asymptomatic seronegative subjects in cohort B is the proportions of 
subjects who subsequently develop signs and symptoms (broad term) within 14 days of a positive 
RT-qPCR test result at baseline or during the EAP. 
The sample size of Cohort B is based on the frequency of finding positive subjects while enrolling 
Cohort A and assumes that approximately 10% of subjects in a household are already positive for 
SARS-CoV-2 by RT-qPCR at baseline.  Among approximately 3500 adult and adolescent subjects 
that will be enrolled in cohort A or cohort B, the number of subjects expected in Cohort B is 
approximately 220 or higher, including 200 seronegative subjects. Assuming that 50% of infected 
placebo subjects at baseline will develop symptoms, 200 seronegative subjects in cohort B will 
provide >90% power to detect a relative risk of 0.5, using a 2-sided Fisher’s exact test at an alpha 
level of 0.05.  
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3. 
ANALYSIS POPULATIONS 
In accordance with guidance from the International Conference of Harmonization of Technical 
Requirements for Registration of Pharmaceuticals for Human Use (ICH) guideline ICH E9 
Statistical Principles for Clinical Trials (ICH, 1998), the following population of analysis will be 
used for all statistical analysis. 
3.1. 
The Efficacy Analysis Sets 
Seronegative Modified Full Analysis Set (Seronegative mFAS-A) – Cohort A 
The seronegative modified full analysis set for Cohort A (Seronegative mFAS-A) includes all 
randomized subjects aged 12 years and older who are laboratory confirmed negative for SARS-
CoV-2 (per central lab PCR test) and who test negative for antibodies for SARS-CoV-2 (per central 
lab serology testing) at baseline.   
Subjects included in the administrative assessment analysis are excluded from the Seronegative 
mFAS-A population. 
Subjects will be analyzed based on the randomized treatment assignment. The seronegative mFAS-
A population is the primary analysis population for the primary and secondary endpoints for 
Cohort A of this study unless specified otherwise.  
Note: There are three antibody assays used for serology test: EuroImmun anti-S IgA, EuroImmun 
anti-S IgG, and Abbott anti-N IgG (Architect). Seronegative is defined as all available test results 
are negative. Seropositive is defined as 1 or more available test results are positive. 
Seronegative Modified Full Analysis Set (Seronegative mFAS-A1) – Cohort A1 
The seronegative modified full analysis set for Cohort A1 (seronegative mFAS-A1) includes all 
randomized subjects aged less than 12 years who are laboratory confirmed negative for SARS-
CoV-2 (per central lab PCR test) and who test negative for antibodies for SARS-CoV-2 (per central 
lab serology testing) at baseline.   
Subjects will be analyzed based on the randomized treatment assignment. The efficacy endpoints 
for Cohort A1 will be analyzed using the seronegative mFAS-A1 unless specified otherwise.  
Seronegative Modified Full Analysis Set (Seronegative mFAS-B) – Cohort B 
The seronegative modified full analysis set for Cohort B (seronegative mFAS-B) includes all 
randomized subjects aged 12  years and older who have laboratory confirmed positive tests at 
baseline for SARS-CoV-2 RT-qPCR and negative SARS-CoV-2 serology (both based on central 
lab testing) at baseline and are asymptomatic.  Subjects will be analyzed based on the randomized 
treatment assignment. The primary and secondary efficacy endpoints for cohort B will be analyzed 
using the seronegative mFAS-B unless specified otherwise.  
Seronegative Modified Full Analysis Set (Seronegative mFAS-B1) – Cohort B1 
The seronegative modified full analysis set for Cohort B1 (seronegative mFAS-B1) includes all 
randomized subjects aged less than 12 years who have laboratory confirmed positive tests at 
baseline for SARS-CoV-2 RT-qPCR and negative SARS-CoV-2 serology (both based on central 
lab testing) at baseline and are asymptomatic. Subjects will be analyzed based on the randomized 
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treatment assignment. The efficacy endpoints for Cohort B1 will be analyzed using the 
seronegative mFAS-B1 unless specified otherwise. 
3.2. 
The Safety Analysis Set (SAF) 
The safety analysis set (SAF) includes all randomized subjects who received at least 1 dose or part 
of a dose of study drug. Subjects in the SAF will be analyzed based on the treatment received (as 
treated). In general, safety will be evaluated by study cohort: SAF-A (Cohort A), SAF-B (Cohort 
B), SAF-A1(Cohort A1), and SAF-B1 (Cohort B1). However, injection site reactions will also be 
based on all cohorts combined.  
3.3. 
Pharmacokinetic Analysis Set 
The PK analysis set includes all subjects who received any study drug and who had at least 1 non-
missing drug concentration measurement following study drug administration. Subjects will be 
analyzed based on actual treatment received. 
3.4. 
Immunogenicity Analysis Sets 
3.4.1. 
 Anti-drug Antibodies Analysis Set 
The ADA analysis set (AAS) includes all subjects who received study drug and had at least 1 
non-missing ADA result after study drug administration. Subjects will be analyzed based on the 
actual treatment received 
3.4.2. 
Neutralizing Antibody Analysis Set 
The NAb analysis set (NAS) includes all subjects who received any study drug and who are either 
negative in the ADA assay or positive for ADA with at least one non-missing result in the NAb 
assay after first dose of the study drug. Subjects who are ADA negative are set to negative in the 
NAb analysis set.  Subjects will be analyzed according to the treatment actually received. 
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4. 
ANALYSIS VARIABLES 
For each subject, demographic and baseline characteristics will be obtained from the last 
available value up to the date of the first study treatment administration (i.e., baseline definition). 
For subjects randomized but not treated, the baseline value is defined as the last available value 
prior to or on the date of randomization. If a subject was randomized over once, the latest 
randomization record will be used for analysis. 
4.1. 
Demographic and Baseline Characteristics 
The following demographic variables will be summarized:  
• Age in years (continuous and categorical variable for subjects≥12 years will be 
categorized as follows: ≥12 to <18, ≥18 to <50, ≥50 to <65, ≥65 to <80, ≥80 years) 
• Sex (Male, Female) 
• Race (American Indian or Alaskan Native, Asian, Black or African American, Native 
Hawaiian or Other Pacific Islander, White and Other, where “Other” may include, for 
example, not reported, unknown, and multiracial, etc.) 
• Ethnicity (Hispanic or Latino with further subgroups [ Black Hispanic or Latino and 
White Hispanic or Latino], not Hispanic or Latino with further subgroups [Black not 
Hispanic or Latino and White not Hispanic or Latino], not reported, and unknown) 
Baseline characteristic variables include: 
• Weight (kg) (quantitative and qualitative variable for pediatric subjects: <10, ≥10 to 
<20, and ≥20)  
• Height (cm) 
• Body mass index (BMI) (kg/m2) (quantitative and qualitative variable for subjects 
≥12 years: <30 and ≥30)  
• Randomization strata: local RT-qPCR status and age  
• Region (US vs ex-US) and country 
• Total household size including the house member(s) not participating this study 
• Number of study subjects within household and cohort   
• Index case interaction and household risk factors (e.g., share a bedroom, share a 
common room, no one wears a mask in home, etc.) per eCRF 
• Status of index case participating R10933-10987-COV-2067  
• Total household members, including index case, who participate the R10933-10987-
COV-2067  
• Infection risks (e.g.  healthcare worker (Yes/ No), received influenza vaccine in last 
14 days (Yes/No), first responder (Yes/No), Need to contact strangers on a regular basis 
(Yes/No), etc.) per exposure risk factors eCRFs 
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• Baseline overall serology status and observed combinations of three serology antibody 
assays 
• Viral load (log10 copies/mL) at baseline for subject in cohort B 
• Days between baseline central RT-qPCR test and study drug administration 
• Baseline high risk subjects with at least one of the following criteria: 
−  ≥65 years of age 
− BMI ≥35  
− Chronic kidney disease 
− Diabetes  
− Immunosuppressive disease 
− Are currently receiving immunosuppressive treatment 
Are ≥55 years of age AND have cardiovascular disease OR hypertension OR chronic obstructive 
pulmonary disease 
4.2. 
Medical History 
Medical history will be coded to a Preferred Term (PT) and associated primary System Organ 
Class (SOC) according to the latest available version of Medical Dictionary for Regulatory 
Activities (MedDRA®). 
4.3. 
Pre-Treatment / Concomitant Medication 
Medications/Procedures will be recorded from the day of informed consent until the end-of-study 
(EOS) visit. Medications will be coded to the ATC level 2 (therapeutic main group) and ATC level 
4 (chemical/therapeutic subgroup), according to the latest available version of WHO Drug 
Dictionary (WHODD, Drug Global version SEP2020 B3). Subjects will be counted once in all 
ATC categories linked to the medication.  
Prior medications/procedures: medications taken, or procedures performed prior to administration 
of the first study drug. 
Concomitant medications/procedures during treatment-emergent EAP: medications taken or 
procedures performed in the period from the day of the first dose of study drug to 28 days after the 
last dose of study drug or to the last visit if a subject discontinue from the study, whichever is 
earlier. This includes medications that were started before the initiation of study treatment and are 
ongoing during the treatment-emergent EAP. 
Concomitant medications/procedures during the treatment-emergent follow-up period: 
medications taken, or procedures performed from the day after the end of treatment-emergent EAP 
to the final study visit or started during the treatment-emergent EAP and are ongoing after 
treatment-emergent EAP. 
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4.4. 
Prohibited Medications 
The definition of prohibited medications is described in the section 8.9 of the protocol. They will 
be reviewed and identified by the study clinician and reported in protocol deviations. 
4.5. 
Efficacy Variable 
Unless otherwise specified, the baseline assessment is the last available measurement prior to the 
date of the study treatment administration. For subjects randomized but not treated, the baseline 
value is defined as the last available value prior to the date of randomization. 
Unless otherwise specified, all efficacy endpoints will be analyzed based on seronegative subjects 
in the corresponding cohort. 
The definitions of broad-term, strict-term, and CDC definition symptoms are as follows: 
Strict term:  
• Fever (≥38°C) PLUS ≥1 respiratory symptom (sore throat, cough, shortness of 
breath) 
OR 
• 2 respiratory symptoms (sore throat, cough, shortness of breath) 
OR 
• 1 respiratory symptom (sore throat, cough, shortness of breath) PLUS ≥2 non-
respiratory symptoms (chills, nausea, vomiting, diarrhea, headache, conjunctivitis, 
myalgia, arthralgia, loss of taste or smell, fatigue or general malaise) 
Broad term:  
ANY of the following: 
1. Fever ≥38°C 
2. Feverish 
3. Sore throat 
4. Cough 
5. Shortness of breath/difficulty breathing (nasal flaring*) 
6. Chills 
7. Nausea 
8. Vomiting 
9. Diarrhea 
10. Headache 
11. Red or watery eyes (conjunctivitis) 
12. Body aches such as muscle pain or joint pain (myalgia, arthralgia) 
13. Loss of taste/smell 
14. Fatigue (fatigue or general malaise or lethargy*) 
15. Loss of appetite or poor eating/feeding 
16. Confusion 
17. Dizziness 
18. Pressure/tightness in chest 
19. Chest pain 
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20. Stomachache (Abdominal pain*) 
21. Rash 
22. Sneezing 
23. Runny nose 
24. Sputum/phlegm 
25. Other 
*Signs and symptoms observed in pediatric subjects (age<12 years) 
 
CDC definition 
At least two of the following symptoms: fever (measured, i.e., fever ≥38°C, or subjective, i.e., 
feverish), chills, rigors, myalgia, headache, sore throat, nausea or vomiting, diarrhea, fatigue, 
congestion or runny nose 
OR 
Any one of the following symptoms: cough, shortness of breath, difficulty breathing, new olfactory 
disorder, new taste disorder 
OR 
Severe respiratory illness with at least one of the following, clinical or radiographic evidence of 
pneumonia, acute respiratory distress syndrome (ARDS)  
Note: Fever information will be collected from the fever assessment eCRF, and signs and 
symptoms will be collected from COVID-19 symptoms eCRF.  
The following general rules will be used for efficacy variables and all SARS-CoV-2 RT-qPCR test 
results are based on the central lab testing: 
• For cohort determination, qualitative PCR results from swabs taken prior to or within 
2 hours of study drug administration will be used if there are no available test results 
prior to study drug administration.   
• Quantitative values of viral load will be determined based on NP swabs only.  For 
baseline viral load, only RT-qPCR results from swabs taken prior to dosing will be 
used. 
• A positive infection will be defined based on any available RT-qPCR result (either NP, 
nasal or saliva) which is reported as “detected”. A negative infection will be defined 
based on all available RT-qPCR results (either NP, nasal or saliva) which are reported 
as “not detected”. 
• Symptomatic SARS-CoV-2 infection (broad-term) is defined as a positive central lab 
SARS-CoV-2 RT-qPCR result (either NP, nasal or saliva) associated with signs and 
symptoms with the onset date occurring within 14 days of a positive RT-qPCR during 
the EAP. 
• For subjects in Cohort B, symptomatic SARS-CoV-2 infection (broad-term) is defined 
as having at least one signs and symptoms with the onset date occurring within 14 days 
of a positive RT-qPCR (either NP, nasal or saliva)  at baseline or during the EAP.  
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• Viral loads less than the lower limit of quantification of the PCR assay but with positive 
qualitative results will be set to half of the lower limit of quantification of the PCR 
assay; values with nondetectable RNA will be set to 0 log10 copies/mL Viral load values 
above the upper limit of quantification will be re-tested using the reflex test and the 
corresponding quantitative value will be used in the analysis.  
4.5.1. 
Cohort A Primary Efficacy Variable 
The primary efficacy variable in Cohort A is:  
• Proportion of subjects who have a symptomatic RT-qPCR confirmed SARS-CoV-2 
infection (broad-term) during the EAP 
A symptomatic RT-qPCR confirmed SARS-CoV-2 infection during the EAP will be any positive 
post-baseline RT-qPCR obtained during the EAP in which the subject experiences COVID-19 
related signs or symptoms within 14 days of a positive test.  
4.5.2. 
Cohort A Key Secondary Efficacy Variables 
The key secondary efficacy variables listed below include two types of variables: binary (B) and 
continuous (C) variables.  
Key Secondary Efficacy Variables 
Type 
Cohort A 
Proportion of subjects with viral load >4 (log10 copies/mL) in NP swab 
samples during the EAP 
B 
X 
Number of weeks of symptomatic RT-qPCR confirmed SARS-CoV-2 
infection (broad-term) during the EAP  
C 
X 
Number of weeks of high viral load >4 (log10 copies/mL) in NP swab 
samples during the EAP  
C 
X 
Number of weeks of RT-qPCR confirmed SARS-CoV-2 infection 
(regardless of symptoms) during the EAP 
C 
X 
Proportion of subjects who have a RT-qPCR confirmed SARS-CoV-2 
infection (regardless of symptoms) during the EAP 
B 
X 
Proportion of subjects in placebo group with a RT-qPCR confirmed 
SARS-CoV-2 infection during the EAP with an index case participating 
in Study R10933-10987-COV-2067 (comparison of those whose index 
cases receive REGN10933+REGN10987 vs placebo in Study R1033-
10987-COV-2067)  
C 
X 
Duration of symptomatic infection (weeks) is defined as (the end date of all symptoms minus the 
date of the first symptom+1)/7, where a symptom is defined in Section 4.5. If the symptom is 
ongoing at the time of the first step analysis, the end date of the symptom will be set as the cutoff 
date for the first step analysis.   
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4.5.3. 
Cohort A and Cohort A1 Other Secondary Efficacy Variables 
The secondary efficacy variables listed below include two types of variables: binary (B) and 
continuous (C) variables and marked for the corresponding cohort. 
Other Secondary Efficacy Variables 
Type 
Cohort 
A 
A1 
Proportion of subjects who have a symptomatic RT-qPCR 
confirmed SARS-CoV-2 infection (CDC definition) during the EAP 
B 
X 
X 
Number of weeks of symptomatic RT-qPCR-confirmed SARS-
CoV-2 infection (CDC definition) during the EAP  
C 
X 
X 
Proportion of subjects who have a symptomatic RT-qPCR 
confirmed SARS-CoV-2 infection (strict-term) during the EAP  
B 
X 
X 
Number of weeks of symptomatic RT-qPCR-confirmed SARS-
CoV-2 infection (strict-term) during the EAP  
C 
X 
X 
Proportion of subjects who have a RT-qPCR confirmed SARS-
CoV-2 infection at each week in the EAP 
B 
X 
X 
Proportion of subjects who have a symptomatic RT-qPCR 
confirmed SARS-CoV-2 infection (broad term) at each week in the 
EAP 
B 
X 
X 
Time-weighted average of viral load (log10 copies/mL) from the 
first positive SARS-CoV-2 RT-qPCR in NP swab samples (that has 
an onset during the EAP) until the third weekly visit after the first 
positive test during the EAP  
 
Note: Only for RT-qPCR positive subjects during the EAP in the 
Seronegative mFAS-A set 
C 
X 
X 
Time-weighted average of viral load (log10 copies/mL) from the 
first positive SARS-CoV-2 RT-qPCR in NP swab samples (that has 
an onset during the EAP) until the second weekly visit after the first 
positive test during the EAP 
 
Note: Only for RT-qPCR positive subjects during the EAP in the 
Seronegative mFAS-A set 
C 
X 
X 
Maximum SARS-CoV-2 RT-qPCR viral load (log10 viral 
copies/mL) in NP swab samples among individuals with ≥1 RT-
qPCR positive that has an onset during the EAP 
C 
X 
X 
SARS-CoV-2 RT-qPCR viral load (log10 viral copies/mL) in NP 
swab samples corresponding to the onset of first positive RT-qPCR 
during the EAP  
C 
X 
X 
Area under the curve (AUC) in viral load (log10 copies/mL) from 
the first positive SARS-CoV-2 RT-qPCR NP swab samples detected 
during the EAP until the first confirmed negative test (testing that 
occurs after the EAP will be included if necessary to achieve a 
negative test result). 
 
C 
X 
X 
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Note: Only for RT-qPCR positive subjects during the EAP in the 
Seronegative mFAS-A set 
Number of medically attended visits in emergency rooms or urgent 
care centers related to a RT-qPCR confirmed SARS-CoV-2 
infection that has an onset during the EAP 
C 
X 
X 
Proportion of subjects with at least one COVID-19 related 
hospitalization or emergency room visit associated with a positive 
RT-qPCR during the EAP, or all-cause death 
B 
X 
X 
Proportion of subjects requiring medically attended visits in 
emergency rooms or urgent care centers related to a RT-qPCR 
confirmed SARS-CoV-2 infection that has an onset during the EAP 
B 
X 
X 
Proportion of subjects hospitalized related to a RT-qPCR confirmed 
SARS-CoV-2 infection that has an onset during the EAP 
B 
X 
X 
Number of days of hospital and intensive care unit (ICU) stay in 
subjects hospitalized for a RT-qPCR confirmed SARS-CoV-2 
infection that has an onset during the EAP 
C 
X 
X 
Number of days missed for daily responsibilities (where applicable), 
including work (employed adults) or school (students), daycare or 
family obligations/responsibilities (childcare or eldercare) due to a 
RT-qPCR confirmed SARS-CoV-2 infection that has an onset 
during the EAP 
C 
X 
X 
Proportion of subjects in placebo group with a RT-qPCR confirmed 
SARS-CoV-2 infection during the EAP with at least one household 
member participating either in R10933-10987-COV-2067 or in 
cohort B (comparison of those whose households members receive 
REGN10933+REGN10987 vs placebo in R1033-10987-COV-2067 
or in Cohort B)  
B 
X 
X 
Proportion of subjects who have a symptomatic RT-qPCR 
confirmed SARS-CoV-2 infection (broad-term) during the EAP 
B 
 
X 
Proportion of subjects with viral load >4 (log10 copies/mL) in NP 
swab samples during the EAP 
B 
 
X 
Number of weeks of symptomatic RT-qPCR-confirmed SARS-
CoV-2 infection (broad-term) during the EAP   
C 
 
X 
Number of weeks of high-viral load >4 (log10 copies/mL) in NP 
swab samples during the EAP  
C 
 
X 
Number of weeks of RT-qPCR confirmed SARS-CoV-2 infection 
(regardless of symptoms) during the EAP 
C 
 
X 
Proportion of subjects who have a RT-qPCR confirmed SARS-
CoV-2 infection (regardless of symptoms) during the EAP 
B 
 
X 
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Proportion of subjects in placebo group with a RT-qPCR confirmed 
SARS-CoV-2 infection during the EAP with an index case 
participating in R10933-10987-COV-2067 (comparison of those 
whose index cases receive REGN10933+REGN10987 vs placebo in 
R1033-10987-COV-2067) 
C 
 
X 
 
Time-weighted average (TWA) of viral load (log10 copies/mL) in NP swab samples from the 
day of the first positive SARS-CoV-2 RT-qPCR (central lab) to the third weekly visit after the 
first positive test visit: all observed viral load data from the first positive visit to the third weekly 
visit will be calculated using the trapezoidal rule as the area under the curve divided by this 
observational period as follows: 
𝑇𝑊𝐴= 𝐴𝑈𝐶/(𝑡𝑘−𝑡1) = [∑(𝑡𝑖
𝑘=3
𝑖=2
−𝑡𝑖−1) ∗(𝑉𝑖+ 𝑉𝑖−1)/2]/(𝑡𝑘−𝑡1) 
where  𝑉𝑖 is the result of viral load (log10 copies/mL) at time point 𝑡𝑖. 𝑉1 is the result of the viral 
load (log10 copies/mL) for the first positive SARS-CoV-2 RT-qPCR at timepoint 𝑡1.  If the 𝑉𝑖 is 
not available at the scheduled time point 𝑡𝑖 or missing due to failed test or other reasons, only the 
time points with non-missing values will be included for TWA calculation. If there are duplicate 
samples at a time point, the highest viral result will be used for analysis. 
Note: For TWA of viral from the first positive to the second weekly visit  after the first positive 
test visit endpoint, all observed viral load data from the first positive visit to the second weekly 
visits will be calculated using the same formula described above.  
4.5.4. 
Cohort A and Cohort A1 Exploratory Efficacy Variables 
The following exploratory variables are for both Cohort A and Cohort A1. Some of the endpoints 
will mature and be assessed after all subjects complete the study. For continuous variables the 
analysis only applies to subjects who have a positive central lab SARS-CoV-2 RT-qPCR test 
(based on observed data) during the EAP. 
Exploratory Variables 
Type 
Proportion of baseline-seronegative subjects who have a first RT-qPCR confirmed SARS-
CoV-2 infection in the follow-up period (i.e. after Day 29 visit) 
B 
Proportion of baseline-seronegative subjects who become seropositive (based on central lab 
test) up to day 57  
(Note: For post-treatment serology, only antibody assay(s) that do not bind to REGN10933 or 
REGN10987 will be used to define the endpoint) 
B 
Proportion of baseline-seropositive subjects (based on central lab test) who subsequently have 
a positive SARS-CoV-2 RT-qPCR and symptomatic (strict-term) SARS-CoV-2 infection 
during the EAP 
B 
Proportion of subjects with negative RT-qPCR (based on central lab test) regardless of the 
serology status at baseline who subsequently have a positive SARS-CoV-2 RT-qPCR and 
symptomatic (strict-term) SARS-CoV-2 infection during the EAP 
B 
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Proportion of baseline-seronegative or baseline-seropositive subjects with negative RT-qPCR 
(based on central lab test) who subsequently have a positive SARS-CoV-2 RT-qPCR and 
symptomatic (strict-term) SARS-CoV-2 infection during the EAP 
B 
Proportion of baseline-seropositive subjects (based on central lab test) who subsequently have 
a positive SARS-CoV-2 RT-qPCR and symptomatic (broad-term) SARS-CoV-2 infection 
during the EAP 
B 
Proportion of subjects with negative RT-qPCR (based on central lab test) regardless of 
serology status at baseline who subsequently have a positive SARS-CoV-2 RT-qPCR and 
symptomatic (broad-term) SARS-CoV-2 infection during the EAP 
B 
Proportion of baseline-seronegative or baseline-seropositive subjects with negative RT-qPCR 
(based on central lab test) who subsequently have a positive SARS-CoV-2 RT-qPCR and 
symptomatic (broad-term) SARS-CoV-2 infection during the EAP 
B 
Proportion of baseline-seropositive subjects (based on central lab test) who subsequently have 
a positive SARS-CoV-2 RT-qPCR and symptomatic (CDC definition) SARS-CoV-2 infection 
during the EAP 
B 
Proportion of subjects with negative RT-qPCR (based on central lab test) regardless of 
serology status at baseline who subsequently have a positive SARS-CoV-2 RT-qPCR and 
symptomatic (CDC definition) SARS-CoV-2 infection during the EAP 
B 
Proportion of baseline-seronegative or baseline-seropositive subjects with negative RT-qPCR 
(based on central lab test) who subsequently have a positive SARS-CoV-2 RT-qPCR and 
symptomatic (CDC definition) SARS-CoV-2 infection during the EAP 
B 
Proportion of baseline-seropositive subjects (based on central lab test) who subsequently have 
a positive SARS-CoV-2 RT-qPCR during the EAP 
B 
Time-weighted average of viral load (log10 copies/mL) from the first positive SARS-CoV-2 
RT-qPCR in NP swab sample (that has an onset during the EAP) until third weekly visit after 
the first positive test in seropositive subjects (based on central lab test) during the EAP 
C 
Time-weighted average of viral load (log10 copies/mL) from the first positive SARS-CoV-2 
RT-qPCR in NP swab sample (that has an onset during the EAP) until the second weekly visit 
after the first positive test in seropositive subjects (based on central lab test) during the EAP 
C 
Area under the curve (AUC) in viral load (log10 copies/mL) in NP swab samples from the 
first positive SARS-CoV-2 RT-qPCR NP swab sample until the first confirmed negative test, 
in seropositive subjects (based on central lab test) that has an onset during the EAP 
 
Note: Only for RT-qPCR positive subjects during the EAP with confirmed negative tests in the 
seronegative mFAS 
C 
Proportion of subjects in placebo group who have a RT-qPCR confirmed SARS-CoV-2 
infection (regardless of symptoms) during the EAP by the status of household members 
participating in study R10933-10987-COV-2067 and receiving REGN10933+REGN10987 or 
whose household member did not receive treatment with REGN10933+REGN10987 
B 
Proportion of subjects who have a RT-qPCR confirmed SARS-CoV-2 infection (regardless of 
symptoms) during the EAP by the status of household members participating in study 
R10933-10987-COV-2067 and receiving REGN10933+REGN10987 
B 
Proportion of subjects who have a RT-qPCR confirmed SARS-CoV-2 infection (regardless of 
symptoms) during the EAP by the status of household members receiving an approved 
monoclonal antibody treatment for COVID-19 
B 
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Proportion of subjects who have a RT-qPCR confirmed SARS-CoV-2 infection (regardless of 
symptoms) during the EAP by the status of household members receiving an approved 
monoclonal antibody treatment for COVID-19 or REGN10933+REGN10987 in study 
R10933-R10987-COV-2067   
B 
Maximum RT-qPCR viral load (log10 copies/mL) in NP swab samples during the EAP in 
subjects who have asymptomatic infection during the EAP 
C  
Maximum RT-qPCR viral load (log10 copies/mL) in NP swab samples during the EAP in 
subjects who have symptomatic infection during the EAP  
C 
Maximum RT-qPCR viral load (log10 copies/mL) in NP swab samples during the EAP in 
subjects who have a medically attended visit 
C 
4.5.5. 
Cohort B Primary Efficacy Variable 
The primary efficacy variable for Cohort B is: 
• Proportion of subjects who subsequently develop signs and symptoms (broad-term) 
within 14 days of a positive RT-qPCR at baseline or during the EAP 
4.5.6. 
Cohort B Key Secondary Efficacy Variables 
The key secondary efficacy variables listed below are continuous (C) variables.  
Key Secondary Efficacy Variables 
Type 
Number of weeks of symptomatic SARS-CoV-2 infection (broad-term) within 14 days of a 
positive RT-qPCR at baseline or during the EAP 
C 
Number of weeks of high viral load >4 (log10 copies/mL) in NP swab samples during the EAP C 
4.5.7. 
Cohort B and Cohort B1 Other Secondary Efficacy Variables 
The secondary efficacy variables listed below include two types of variables: binary (B) and 
continuous (C) variables and marked for the corresponding cohort. 
Other Secondary Efficacy Variables 
Type 
Cohort 
B 
B1 
Proportion of subjects who subsequently develop signs and 
symptoms (CDC definition) within 14 days of a positive RT-
qPCR at baseline or during the EAP  
B 
X 
X 
Proportion of subjects who subsequently develop signs and 
symptoms (strict-term) within 14 days of a positive RT-qPCR 
at baseline or during the EAP  
B 
X 
X 
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Number of weeks of symptomatic SARS-CoV-2 infection 
(CDC definition) within 14 days of a positive RT-qPCR at 
baseline or during the EAP 
C 
X 
X 
Number of weeks of symptomatic SARS-CoV-2 infection 
(strict-term) within 14 days of a positive RT-qPCR at baseline 
or during the EAP 
C 
X 
X 
Proportion of subjects with viral load >4 (log10 copies/mL) in 
NP swab samples during the EAP 
B 
X 
X 
Change in viral load (log10 copies/mL) from baseline to Day 
8 visit in NP swab samples 
C 
X 
X 
Change in viral load (log10 copies/mL) from baseline to Day 
15 visit in NP swab samples 
C 
X 
X 
Time-weighted average change from baseline in viral load 
(log10 copies/mL) in NP swab samples until the Day 22 visit  
C 
X 
X 
Area under the curve (AUC) in viral load (log10 copies/mL) 
in NP swab samples from baseline to the first confirmed 
negative test 
C 
X 
X 
Maximum SARS-CoV-2 RT-qPCR viral load (log10 
copies/mL) in NP swab samples during the EAP 
C 
X 
X 
Number of medically attended visits in emergency rooms or 
urgent care centers related to RT-qPCR confirmed SARS-
CoV-2 infection that has an onset at baseline or during the EAP 
C 
X 
X 
Proportion of subjects requiring medically attended visits in 
emergency rooms or urgent care centers related to a RT-qPCR 
confirmed SARS-CoV-2 infection that has an onset at baseline 
or during the EAP 
B 
X 
X 
Proportion of subjects hospitalized related to a RT-qPCR 
confirmed SARS-CoV-2 infection that has an onset at baseline 
or during the EAP 
B 
X 
X 
Number of days of hospital and ICU stay in subjects 
hospitalized for a RT-qPCR confirmed SARS-CoV-2 infection 
that has an onset at baseline or during the EAP 
C 
X 
X 
Number of days missed for daily responsibilities (where 
applicable), including work (employed adults) or school 
C 
X 
X 
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(students), or family obligations/responsibilities (childcare or 
eldercare) due to a RT-qPCR confirmed SARS-CoV-2 
infection that has an onset at baseline or during the EAP 
Proportion of subjects with at least one COVID-19 related 
hospitalization or emergency room visit associated with a 
positive RT-qPCR at baseline or during the EAP, or all-cause 
death 
B 
X 
X 
Proportion of subjects who subsequently develop signs and 
symptoms (broad-term) within 14 days of a positive RT-qPCR 
at baseline or during the EAP  
B 
 
X 
Number of weeks of symptomatic SARS-CoV-2 infection 
(broad-term) within 14 days of a positive RT-qPCR at baseline 
or during the EAP 
C  
 
X 
Number of weeks of high viral load >4 (log10 copies/mL) in 
NP swab samples during the EAP 
C 
 
X 
 
Time-weighted average (TWA) of change from baseline in viral load until the Day 22 visit: All 
observed viral load data from baseline to Day 22 visit will be calculated for each subject using the 
trapezoidal rule as the AUC for change from baseline at each time point divided by the time 
interval of this observational period as follows: 
𝑇𝑊𝐴= 𝐴𝑈𝐶/(𝑡𝑘−𝑡1) = [∑(𝑡𝑖
𝑘=4
𝑖=2
−𝑡𝑖−1) ∗(𝐷𝑖+ 𝐷𝑖−1)/2]/(𝑡𝑘−𝑡1) 
Where Di is the change from baseline (t1) in viral load (log10 copies/mL) obtained at time ti and 
D1 =0. If the Di is not available or missing due to failed test or other reasons, only the time points 
with non-missing values will be included for TWA calculation. If there are duplicate samples at a 
time point, the highest viral result (log10 copies/ml) will be used for analysis. 
For TWA of percent change from baseline, variable Pi will be applied to the formula above 
instead of Di, where Pi=Di/baseline. 
4.5.8. 
Cohort B and Cohort B1 Exploratory Variables 
The following exploratory variables are for both Cohort B and Cohort B1.  
Exploratory Variables 
Type 
Proportion of subjects who subsequently have symptomatic (strict-term) SARS-CoV-2 infection 
confirmed by RT-qPCR within the EAP according to their baseline serology test status (i.e., 
seropositive or other, based on central lab test) 
B 
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Proportion of subjects who subsequently have symptomatic (broad-term) SARS-CoV-2 
infection confirmed by RT-qPCR within the EAP according to their baseline serology test status 
(i.e., seropositive or other, based on central lab test) 
B 
Proportion of subjects who subsequently have symptomatic (CDC definition) SARS-CoV-2 
infection confirmed by RT-qPCR within the EAP according to baseline serology test status (i.e., 
seropositive or other, based on central lab test) 
B 
Number of weeks of symptomatic SARS-CoV-2 infection (strict-term) within 14 days of a 
positive RT-qPCR at baseline or during the EAP, according to baseline serology test status (i.e., 
seropositive or other, based on central lab test) 
C 
Number of weeks of symptomatic SARS-CoV-2 infection (broad-term) within 14 days of a 
positive RT-qPCR at baseline or during the EAP, according to baseline serology test status (i.e., 
seropositive or other, based on central lab test) 
C 
Number of weeks of symptomatic SARS-CoV-2 infection (CDC definition) within 14 days of a 
positive RT-qPCR at baseline or during the EAP, according to baseline serology test status (i.e., 
seropositive or other, based on central lab test) 
C 
Time-weighted average change and percent change from baseline viral load (log10 copies/mL) 
in NP swab samples until the Day 22 visit according to baseline serology test status (i.e., 
seropositive or other, based on central lab test) 
C 
Area under the curve (AUC) in viral load (log10 copies/mL) in NP swab samples from baseline 
to the first confirmed negative test according to baseline serology test status (i.e., seropositive 
or other, based on central lab test) 
C 
Maximum SARS-CoV-2 RT-qPCR (log10 viral copies/mL) in NP swab samples during the 
EAP according to baseline serology test status (i.e., seropositive or other, based on central lab 
test) 
C 
Number of medically attended visits in emergency rooms or urgent care centers related to RT-
qPCR confirmed SARS-CoV-2 infection at baseline or during the EAP, according to baseline 
serology test status (i.e., seropositive or other, based on central lab test) 
C 
Proportion of subjects requiring medically attended visits in emergency rooms or urgent care 
centers related to a RT-qPCR confirmed SARS-CoV-2 infection at baseline or during the EAP, 
according to baseline serology test status (i.e., seropositive or other, based on central lab test) 
B 
Proportion of subjects hospitalized related to a RT-qPCR confirmed SARS-CoV-2 infection at 
baseline or during the EAP, according to baseline serology test status (i.e., seropositive or other, 
based on central lab test) 
B 
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Number of days of hospital and ICU stay in subjects hospitalized for a RT-qPCR confirmed 
SARS-CoV-2 infection at baseline or during the EAP, according to baseline serology test status 
(i.e., seropositive or other, based on central lab test) 
C 
Number of days missed for daily responsibilities (where applicable), including work (employed 
adults) or school (matriculating students), or family obligations/responsibilities (childcare or 
eldercare) due to a RT-qPCR confirmed SARS-CoV-2 infection at baseline or during the EAP, 
according to baseline serology test status (i.e., seropositive or other, based on central lab test) 
C 
Maximum RT-qPCR viral load (log10 copies/mL) in NP swab samples during the EAP in 
subjects who have asymptomatic infection during the EAP 
C 
Maximum RT-qPCR viral load (log10 copies/mL) in NP swab samples during the EAP in 
subjects who have symptomatic infection during the EAP  
C 
Maximum RT-qPCR viral load (log10 copies/mL) in NP swab samples during the EAP in 
subjects who have a medically attended visit related to a RT-qPCR confirmed SARS-CoV-2 
infection at baseline or during the EAP 
C 
4.6. 
Safety Variables 
4.6.1. 
Adverse Events and Serious Adverse Events 
Adverse events and serious adverse events will be collected from the time of informed consent 
signature and then at each visit until the end of the study. All adverse events are to be coded to a 
“Preferred Term (PT)” and associated primary “System Organ Class (SOC)” according to the 
Medical Dictionary for Regulatory Activities (MedDRA version 23.1). The severity of AEs 
(including test findings classified as AEs) and injection-site -related reactions will be graded by 
the investigator using the current version of the NCI–CTCAE v5.0 0. The NCI-CTCAE severity 
grading systems for anaphylaxis, allergic reaction, and injection site reaction are specifically in 
section 10.2.4 of the protocol. 
An adverse event is any untoward medical occurrence in a subject or clinical investigation subject 
administered a pharmaceutical product and which does not necessarily have to have a causal 
relationship with this treatment. 
A serious adverse event is an adverse event (AE) that is classified as serious according to the 
criteria specified in the protocol. 
For safety variables, the following observation periods are defined: 
• The pre-treatment period is defined as the time from signing the ICF to before the first 
dose of study drug.   
• The treatment-emergent EAP (TEEAP) is defined as the day from first dose of study 
drug to 28 days after the last dose of study drug (Note: There is only one planned dose.) 
• The treatment-emergent follow-up period (TEFUP) is defined from the day after the 
end of the TEEAP to the end of the Follow-up Period (i.e., last study visit). 
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Treatment-emergent adverse events (TEAEs) are defined as those that are not present at baseline 
or represent the exacerbation of a pre-existing condition. 
Treatment-emergent adverse events (TEAEs) will be summarized for each of the following 
periods: treatment-emergent EAP, treatment-emergent follow-up period, and the study period (i.e. 
combination of the treatment-emergent EAP and follow-up periods).  Adverse events that occur 
prior to treatment will be listed. 
Laboratory results, physical examination, and vital signs are to be recorded as AEs if they are 
medically relevant: symptomatic, requiring corrective therapy, leading to study discontinuation 
and/or fulfilling a seriousness criterion. 
4.6.2. 
Adverse Events of Special Interest 
Adverse events of special interest (AESI) are AEs (serious or non-serious) required to be 
monitored, documented, and managed in a pre-specified manner as described in the protocol. In 
this study, AESI are listed below (as provided in the protocol), along with each AESI detailed 
definition: 
• Grade 3 or greater injection site reactions or hypersensitivity reactions including but 
not limited to anaphylaxis, laryngeal/pharyngeal edema, severe bronchospasm, chest 
pain, seizure, or severe hypotension (eCRF specific tick box on the AE page) 
4.6.3. 
Events Causing Death 
Subject deaths are per the observation periods will be summarized as follows.  
• Deaths during the TEEAP 
• Deaths during the TEFUP 
• Deaths during the overall study period 
4.6.4. 
Laboratory Safety Variables 
Samples for laboratory testing will be collected at visits according to the schedule of events tables 
in the protocol. Samples will be analyzed by a central laboratory. The clinical laboratory data 
consists of serum chemistry, hematology, urinalysis and other specified in section 9.2.3.2 of the 
protocol. 
Clinical laboratory values will be converted and analyzed in both standard international (SI) units 
and US conventional units provided by the central laboratory. Both actual test values and “change 
from baseline” values (defined as the post-baseline value minus the baseline value) over time will 
be summarized, where the post-baseline visits will be assigned to the Global Analysis Windows 
(See Section 6.4).  
Potentially clinically significant values (PCSV) ranges will be applied to the laboratory test values 
as applicable (see PCSV criteria in Appendix 10.3  ). 
Vital Signs 
Both actual test values and “change from baseline” (defined as the post-baseline value minus the 
baseline value) over time in vital signs parameters (e.g., weight (kg), height (cm), BMI (kg/m2), 
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temperature (0C or 0F), pulse rate (beats/min), and systolic and diastolic blood pressure (mmHg)) 
will be summarized as laboratory safety variables. Potentially clinically significant values (PCSV) 
ranges will be applied to the vital sign parameter values as applicable (see Appendix 10.3 for 
PCSV criteria). 
4.6.5. 
Physical Examination Variables 
Physical examination will be conducted as the protocol scheduled visits. If any abnormal findings 
during the screening period, they will be recorded in medical history eCRF form and AE eCRF 
form for any findings during post-screening period.   
4.7. 
Pharmacokinetic Variables   
The pharmacokinetic variables are the concentrations of REGN10933 and REGN10987 in serum 
and time when a sample was collected.  The sampling time points for dense and sparse collection 
schedules are specified in the schedule of events tables in the protocol. 
4.8. 
Immunogenicity Variables 
The immunogenicity variables are ADA status, titer, NAb status, and time-point/visit. Serum 
samples for Immunogenicity will be collected at the clinic visits specified in the schedule of events 
tables in the protocol. 
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5. 
STATISTICAL METHODS 
For continuous variables, descriptive statistics will include the following: the number of subjects 
reflected in the calculation (n), mean, median, standard deviation, minimum, and maximum. For 
categorical or ordinal data, frequencies and percentages will be displayed for each category. 
Baseline is defined as the last assessment obtained before the first dose of study drug.  
Statistical hypotheses will be performed in seronegative subjects in Cohort A and Cohort B 
independently with separate type I error controls.  
5.1. 
Demographics and Baseline Characteristics 
Demographic and baseline characteristics will be summarized descriptively by treatment group 
and overall, for the study. These will be analyzed by cohort for both seronegative mFAS and SAF 
populations. 
5.2. 
Medical History 
Medical history will be summarized by SOC and PT and by treatment group and all groups 
combined for the seronegative mFAS populations defined in Section 3.1. 
5.3. 
Prior/concomitant Medications or Procedures  
All prior medications will be descriptively summarized by treatment group and overall, for the 
study, for subjects in SAF population.  
Summaries will present subject counts (and percentages) for all prior medications, by decreasing 
frequency of the overall group incidence of ATC followed by ATC level 2, ATC level 4 and 
preferred term. For prior procedure, summaries will be by SOC and PT, sorted by decreasing 
frequency of SOC and PT based on the incidence in the overall group incidence. Subjects will be 
counted only once for each SOC and PT linked to the procedure. 
All concomitant medications/procedures will be descriptively summarized by treatment group and 
observation period defined in Section 4.6.1, for subjects in SAF. 
5.4. 
Prohibited Medications 
Listing of prohibited medications described in Section 4.4  will be provided for subjects in SAF. 
5.5. 
Subject Disposition 
Subject study status will be summarized by treatment group and overall for the study. 
The following will be provided: 
• Number of screened subjects, defined as signed the ICF 
• Number of randomized subjects 
• Number of subjects randomized but who did not receive study treatment 
• Number of subjects who discontinued the study, and the reasons for discontinuation 
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• A listing of subjects treated but not randomized, subjects randomized but not treated, 
and subjects randomized but not treated as randomized 
• A listing of subjects prematurely discontinued from the study, along with reasons for 
discontinuation 
• A summary of analysis sets including randomized subjects and randomized subjects by 
cohort, mFAS sets, SAF, PK, immunogenicity (ADA). 
5.6. 
Extent of Study Treatment Exposure and Compliance 
5.6.1. 
Measurement of Compliance 
Subject treatment compliance is not applicable for this study, since the study drug is 
administered once at the site and will be the same as treatment exposure. 
5.6.2. 
Exposure to Investigational Product 
The duration of study treatment will be defined as 28 days after the last dose for a subject in 
SAF. 
5.7. 
Analyses of Efficacy Variables 
The following null and alternate hypotheses will be tested for the primary and secondary endpoints 
unless otherwise specified: 
H0: There is no treatment difference between REGN10933+REGN10987 and placebo 
H1: There is a treatment difference between REGN10933+REGN10987 and placebo  
5.7.1. 
Analysis of Primary Efficacy Variables 
Cohort A 
The Cohort A primary efficacy endpoint described in Section 4.5.1 will be analyzed in the 
seronegative mFAS-A population. All post-baseline efficacy assessments obtained in the EAP will 
be included for the primary analysis.  
In order to account for the correlation among subjects within a household and control the 
associated type 1 error inflation, a generalized linear model will be used to estimate the odds ratio 
between the treatment groups by using the GEE approach (See Appendix 10.4 for an example of 
SAS procedure). This model estimates a single within-household correlation coefficient. The 
model will include the fixed category effects of treatment group (placebo versus 
REGN10933+REGN10987), region (US versus ex-US), and age (≥12 to <50, ≥50 years). The 
model will use a compound symmetry covariance matrix and estimate the odds ratio between the 
treatment groups and corresponding 95% CI and p-value. 
If the GEE model fails to converge due to most households containing only a single study subject 
in seronegative mFAS-A or the percentage of households in Cohort A with only a single study 
subject is 70% or more, then a logistic regression model will be used with treatment, region, and 
age group as fixed effects. The threshold of 70% was based on simulations of within-household 
correlation which show the type I error rate is inflated and the power is decreased when the 
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proportion of single-subject households is high (details provided in Section 6.6). If the logistic 
regression model does not converge, an exact logistic regression will be used. The estimates of 
odds ratio, the corresponding 95% CI and p-value will be provided from logistic regression (or 
exact logistic regression) for comparison of REGN10933+REGN10987 against placebo group.  
In Cohort A, a subject will be considered having a symptomatic RT-qPCR confirmed SARS-CoV-
2 infection (broad-term) during the EAP if any of the post-baseline RT-qPCR results during the 
EAP are positive with at least one symptom within 14 days of a positive RT-qPCR result 
(Section 4.5 ).  
Cohort B 
The Cohort B primary efficacy endpoint described in Section 4.5.5 will be analyzed in the 
seronegative mFAS-B population. The same statistical methods as described for Cohort A will be 
used to obtain the estimate of odds ratio and p-value for comparison between the treatment groups.  
In Cohort B, a subject will be considered having a symptomatic RT-qPCR confirmed SARS-CoV-
2 infection (broad-term) during the EAP if subjects have at least one symptom within 14 days of a 
positive RT-qPCR result at baseline or during the EAP.  
Handling of Missing Central Lab SAR-CoV-2 RT-qPCR Data for Both Cohort A and Cohort 
B  
Subjects with COVID-19 symptoms that are missing a central lab determined RT-qPCR test during 
the EAP (eg. are too sick to go to the study site) but have a positive SARS-COV-2 test from a local 
lab (eg. in the hospital) will be considered as having a symptomatic infection if any of the 
symptoms occurred within 14 days of the positive SARS-COV-2 test that was observed during the 
EAP. 
The graphical display using Kaplan-Meier curve for the time to first symptom will also be 
provided.  
5.7.1.1. 
Sensitivity Analyses  
Robustness of the primary analyses results in Cohort A and Cohort B will be assessed through 
sensitivity analyses as follows: 
Sensitivity analysis by excluding subjects who develop asymptomatic or symptomatic 
SARS-CoV-2 infection within 72 hours of the study drug administration 
This analysis assesses for the sensitivity of the results to subjects who may have had undetected 
infections prior to dosing. That is, a subject had any onset of a positive RT-qPCR within 72 
hours of the study drug administration will be excluded for this sensitivity analysis.  
This sensitivity analysis will only be performed for Cohort A primary endpoint.  
Sensitivity analysis by excluding subjects from non-good clinical practice (GCP) Compliant 
Site(s) 
To access the impact of sites that had non-GCP compliance issues on the primary efficacy points, 
the primary analyses will be performed by excluding non-GCP compliant site(s).  
This sensitivity analysis will be performed for both Cohort A and Cohort B primary endpoints.  
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5.7.1.2. 
Subgroup Analyses 
To assess the homogeneity of the treatment effect across various subgroups, the primary analysis 
model with GEE approach will be applied to each subgroup if applicable; otherwise, the logistic 
regression model will be used. Odds ratio between the treatment groups and corresponding 95% 
CI will be provided, as well as the within-household correlation coefficient from GEE approach, 
within each subgroup.  
The following subgroups of interest for Cohort A and Cohort B primary endpoints will be 
evaluated: 
• Stratification age (years) group (≥12 to <18, ≥18 to <50, ≥50), and the additional age 
group: ≥12 to <18, and ≥18 years 
• Sex  
• Race (American Indian or Alaskan Native, Asian, Black or African American, Native 
Hawaiian or Other Pacific Islander, White and Other, where “Other” may include, for 
example, not reported, unknown, and multiracial, etc.) and an additional race group 
(White Hispanic or Latino, White not Hispanic or Latino, Black Hispanic or Latino, 
Back not Hispanic or Latino, and Other) 
• Ethnicity (Hispanic or Latino, not Hispanic or Latino, and not reported or unknown) 
• BMI (<30, ≥30)  
• Number of study subjects in cohort B within a household (0, ≥1) (Cohort A only) 
• Total household size including the household member(s) not participating this study 
(2, and >2)  
• Region (US, ex-US)  
• Baseline high risk factor (Yes versus No) (as defined in Section 4.1)  
• Healthcare worker (Yes/No)  per exposure risk factor eCRF 
• High viral load (> 4 log 10 copies/ml) at baseline (Yes/No) (Cohort B only) 
5.7.2. 
Adjustment for Multiple Comparison 
The overall type I error will be controlled in each of seronegative mFAS-A and seronegative 
mFAS-B independently at 2-sided 5% significance level.  
Seronegative mFAS-A Subjects 
The overall type I error will be controlled for the primary hypothesis in Cohort A based on a 
2-sided test at an alpha level of 0.05 as follows: 
H0: There is no treatment difference between REGN10933+REGN10987 and placebo in 
the proportion of subjects with a symptomatic RT-qPCR confirmed SARS-CoV-2 infection 
during the EAP. 
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H1: There is a treatment difference between REGN10933+REGN10987 and placebo in the 
proportion of subjects with a symptomatic RT-qPCR confirmed SARS-CoV-2 infection 
during the EAP 
If the primary efficacy endpoint in Cohort A is statistically significant, the alpha level of 0.05 will 
be released for the key secondary endpoints in Cohort A. The hierarchy testing sequence of key 
secondary endpoints is presented in the following table. 
Table 2: 
Hierarchy Testing Sequence of Key Secondary Efficacy Endpoints in 
Seronegative mFAS-A 
Key Secondary Efficacy Variables 
Proportion of subjects with viral load >4 (log10 copies/mL) in NP swab samples during the EAP 
Number of weeks of symptomatic RT-qPCR confirmed SARS-CoV-2 infection (broad-term) 
during the EAP  
Number of weeks of high-viral load >4 (log10 copies/mL) in NP swab samples during the EAP  
Number of weeks of RT-qPCR confirmed SARS-CoV-2 infection (regardless of symptoms) 
during the EAP 
Proportion of subjects who have a RT-qPCR confirmed SARS-CoV-2 infection (regardless of 
symptoms) during the EAP 
Proportion of subjects in placebo group with a RT-qPCR confirmed SARS-CoV-2 infection 
during the EAP with an index case participating in study R10933-10987-COV-2067 
(comparison of those whose index cases receive REGN10933+REGN10987 vs placebo in 
R1033-10987-COV-2067) 
Seronegative mFAS-B Subjects 
The overall type I error will be controlled for the primary hypothesis in Cohort B based on a 2-
sided test at an alpha level of 0.05 as follows:  
H0: There is no treatment difference between REGN10933+REGN10987 and placebo in 
the proportion of subjects who subsequently develop signs and symptoms (broad-term) 
within 14 days of a positive RT-qPCR at baseline or during the EAP 
H1: There is a treatment difference between REGN10933+REGN10987 and placebo in the 
proportion of subjects who subsequently develop signs and symptoms (broad-term) within 
14 days of a positive RT-qPCR at baseline or during the EAP 
If statistical significance is established for the primary efficacy endpoint in cohort B, a hierarchical 
testing procedure will be applied to the key secondary endpoints in Cohort B at a 2-sided 0.05 
significance level. The order of testing sequence for key secondary endpoints is presented in the 
following table.  
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Table 3: 
Hierarchy Testing Sequence of Key Secondary Efficacy Endpoints in 
Seronegative mFAS-B 
Key Secondary Efficacy Variables 
Number of weeks of symptomatic SARS-CoV-2 infection (broad-term) within 14 days of a 
positive RT-qPCR at baseline or during the EAP 
Number of weeks of high viral load (log10 copies/mL) >4 in NP swab samples during the EAP 
5.7.3. 
Analyses of Key Secondary Variables 
For Cohort A, the key binary endpoint of the proportion of subjects who have a RT-qPCR 
confirmed SARS-CoV-2 infection (regardless of symptoms) during the EAP, the same statistical 
method used in the primary analysis will be applied. If a subject’s overall infection status during 
the EAP cannot be determined due to missing RT-qPCR results, the following rules will be applied 
to impute the missing RT-qPCR data. 
1. For subjects satisfying the criteria specified in the handling missing central lab SARS-
CoV-2 RT-qPCR data of the analysis of primary efficacy variables, the corresponding 
visit(s) will be considered as having a positive RT-qPCR test.  
2. After the first step above, each planned visit with missing RT-qPCR data will be imputed 
100 times to generate 100 complete datasets based on the predicted probability using the 
fully conditional specification (FCS) (Van Buuren, S, 2005)[7] through the logistic 
regression. The logistic regression model includes the fixed effect factors of treatment 
group, region, age group, and RT-qPCR testing status at other analysis visits during the 
EAP. This imputation will repeat by iterating for each analysis visit with missing RT-qPCR 
testing status.  Appendix 10.4 provides details on the use of FCS from the SAS MI 
procedure. These 100 complete datasets will be analyzed using the model specified above 
for the primary analysis. Results from 100 analyses will be combined using Rubin’s 
formulae to obtain the final estimate of log(odds ratio), 95% CI and the associated p-value. 
The odds ratio and 95% CI will be derived by taking the exponential of these estimates. 
For the key binary endpoint of the proportion of subjects with viral load >4 (log10 copies/mL), if 
NP swab viral load data is missing for a visit, it will not be imputed regardless of symptoms. Only 
non-missing available NP swab viral load data will be used for the analysis of this endpoint. Only 
subjects with at least one post-baseline viral load (log10 copies/mL) data in NP swab samples will 
be included in the analysis. 
For Cohort A the key binary endpoint regarding the index case linkage to R10933-10987-COV-
2067, the Fisher's exact test will be used.  
For continuous  key secondary endpoints in Cohort A and Cohort B (e.g., number of weeks of high 
viral load >4 (log10 copies/mL) in NP swab samples and number of weeks of symptomatic RT-
qPCR-confirmed SARS-CoV-2 infection (broad-term) during the EAP, etc.), visits with missing 
viral load regardless of symptoms and visits with missing RT-qPCR that do not have any broad-
term symptoms within 14 days will not be considered as meeting these endpoint criteria, 
respectively. For endpoints regarding viral load, only subjects with at least one post-baseline data 
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will be included in the analysis. These endpoints will be analyzed by the non-parametric method, 
a stratified Wilcoxon rank sum test (Van Elteren Test) with the region and age group. Descriptive 
statistics will be provided for number (%) of subjects with each interval of duration in weeks (i.e., 
0 week, > 0 to ≤ 1 week, > 1 to ≤2 weeks, etc.) within each treatment group. The total weeks of 
infection and normalized duration (e.g., average duration infection per 1000 subjects) per treatment 
group will also be reported. 
5.7.4. 
Analyses of Other Secondary and Exploratory Efficacy Variables 
Other secondary efficacy endpoints will be analyzed by type of endpoint defined in Sections 4.5.2 
to 4.5.8 for all cohorts. The analysis methods for key secondary efficacy endpoints in both cohort 
A and cohort B will also be applied to exploratory endpoints in both cohort A and cohort B if 
appropriate. Otherwise, the primary approach to the data will be descriptive statistics. For the 
comprehensive evaluation of efficacy, nominal p-values may be reported. Raw data descriptive 
statistics will also be presented.  
Other secondary efficacy and exploratory endpoints for cohort A1 and cohort B1 may also be 
analyzed by type of endpoint.  If the sample size is sufficient, continuous variables will be 
summarized by the descriptive statistics (e.g., n, mean, SD, Q1, median, Q3, minimum and 
maximum, etc.). Binary variables will be summarized using the number and percentage of subjects 
in each treatment group. No statistical hypothesis testing will be performed for cohort A1 and 
cohort B1. This approach may also be applied to adolescent subjects. 
Binary Endpoints 
Binary endpoints in cohort A and cohort B will be analyzed by applying the same approach used 
for the primary efficacy endpoints.  
For endpoints regarding viral loads, visits with missing viral load (log10 copies/mL) in NP swab 
samples will not be included in the analyses. For binary endpoints regarding the index case or 
household members linkage to R10933-10987-COV-2067 or subjects in cohort B, and endpoints 
regarding the medically attended visits, Fisher’s exact test will be used. KM curves will be used 
to assess the exploratory endpoint of proportion of baseline-seronegative subjects who have a first 
RT-qPCR confirmed SARS-CoV-2 infection in the follow-up period. 
Continuous Endpoints  
The secondary and exploratory continuous efficacy endpoints such as TWA, AUC, and maximum 
viral load (log10 copies/mL) will be analyzed using the ANOVA including treatment group, 
region, and age group as fixed effects in the model. The continuous endpoints regarding change 
from baseline in cohort B (e.g., TWA of change/percent change from baseline) will be analyzed 
using the ANCOVA model with treatment group, region, and age group as fixed effects, and the 
relevant baseline values as covariate as well as treatment-by-covariate interaction. The 
REGN10933+REGN10987 group will be compared to the placebo group and corresponding least 
square of mean difference, standard error (SE) and 95% confidence interval will be provided. For 
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other endpoints with non-normal/skewed distribution (e.g. number of days of symptoms (strict-
term, and CDC definition, etc.)), Van Elteren test will be used. 
5.7.5. 
Interim Analysis 
No interim analysis will be conducted for this study. 
5.8. 
Analysis of Safety Data 
The analysis of safety and tolerability will be performed in SAF, as defined in Section 3.2. For 
each cohort, the safety analysis will also be performed by subject baseline serology status and age 
group (≥12 to <18 years and ≥18), respectively. 
The safety analysis will be based on the reported AEs and other safety information (clinical 
laboratory evaluations, and vital signs).  
Thresholds for PCSV in laboratory variables, and vital signs are defined in Appendix 10.3.  
The summary of AE results will be presented for each treatment group for each of three TEAE 
periods: treatment-emergent EAP (TEEAP), treatment-emergent follow-up period (TEFUP), and 
overall study period (i.e., combined across the TEEAP and TEFUP), and by study cohort. For 
laboratory and vital sign results they will be presented for each treatment group for each of three 
periods: EAP, follow-up, and overall study period.  
General common rules 
All safety analyses will be performed, unless otherwise specified, using the following common 
rules: 
• Safety data in subjects who do not belong to the safety analysis set (i.e., exposed but 
not randomized) will be listed separately. 
• PCSV values are thosevalues considered medically important by the Sponsor according 
to predefined criteria/thresholds based on literature review and defined by the Sponsor 
for clinical laboratory tests and vital signs (PCSV criteria described in Appendix 10.3 
). Considering that the threshold defined in the PCSV list for monocytes and basophils 
can be below the ULN, the following PCSV criterion will be used for the PCSV 
analysis of monocytes and basophils:  
− PCSV criterion for monocytes: >0.7 Giga/L or >ULN (if ULN ≥0.7 Giga/L). 
− PCSV criterion for basophils: >0.1 Giga/L or >ULN (if ULN ≥0.1 Giga/L). 
• PCSV criteria will determine which subjects had at least 1 PCSV during the respective 
TEAE periods, taking into account all evaluations including unscheduled or repeated 
evaluations. 
• The treatment-emergent PCSV denominator by treatment group for a given parameter 
will be based on the number of subjects assessed for that given parameter at least once 
during the respective TEAE periods. 
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• All unscheduled measurements will be assigned to Global Analysis Windows defined 
in Table 5 of Section 6.4 in order to provide an assessment for the screening/baseline 
visit through follow-up visit time points. 
• For quantitative safety parameters including central laboratory measurements and vital 
sign scores, descriptive statistics will be used to summarize observed values and change 
from baseline values by visit.  
5.8.1. 
Adverse Events  
All AEs reported in this study will be coded using the currently available version of the Medical 
Dictionary for Regulatory Activities (MedDRA®).  The preferred term (PT), and the primary 
system organ class (SOC) will be listed. 
The number and percentage of subjects with TEAEs will be summarized by treatment group.  
Summaries will include: 
• Overview of TEAEs, i.e., overall number (%) of subjects with any TEAE, Serious 
TEAE, TEAE leading to death, TEAE leading to study drug withdrawn, or subjects 
with any COVID-19 TEAE or asymptomatic COVID-19 TEAE  
• Overview of non-COVID TEAEs (excluding COVID-19 and asymptomatic COVID-
19), i.e., overall number (%) of subjects with any TEAE, Serious TEAE, TEAE leading 
to death, or TEAE leading to study drug withdrawn 
• Overview of AESI, i.e., overall number (%) of subjects with any AESI, grade 3 or 
greater injection site reactions, grade 3 or greater hypersensitivity reactions, AESI 
leading to death, or AESI leading to study drug withdrawn) 
• TEAEs by primary SOC and PT  
• Number of subjects experiencing common TEAE(s) by primary SOC and PT (PT 
incidence≥5% in any treatment group) 
• TEAEs by severity (according to the grading scale outlined in section 10.2.4 of the 
protocol), presented by primary SOC and PT 
• TEAEs by relationship to treatment (related, not related), presented by primary SOC 
and PT 
• Treatment-emergent SAEs by primary SOC and PT  
• Treatment-emergent AESIs by primary SOC and PT  
• TEAEs leading to study drug withdrawn by primary SOC and PT  
• Treatment-emergent AESIs leading to study drug withdrawn by primary SOC and PT  
• Treatment-emergent AESIs by severity, presented by primary SOC and PT 
• Number of subjects who died during TEEAP, TEFUP, and the study period, 
respectively, and reason for death 
• TEAEs leading to death (death as an outcome on the AE CRF page, as reported by 
the Investigator) by SOC and PT  
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• AESIs leading to death (death as an outcome on the AE CRF page, as reported by the 
Investigator) by SOC and PT. 
In addition, the number (%) of subjects with any post-baseline fever reported from the fever 
assessment eCRF, any subject self-recorded symptoms assessment collected in the COVID-19 
symptoms assessment eCRF will be summarized by treatment group. The descriptive statistics of 
the duration (days) of each COVID-19 symptom will also be presented. Subject listing of 
COVID-19 symptoms including the details such as the start date, end date, and duration of each 
symptom will be provided. In addition, subject listing of SAEs, AESI, TEAEs related to study 
drug, and TEAEs leading to study drug withdrawn will also be presented. 
5.8.2. 
Clinical Laboratory Measurements  
For the respective EAP, FUP, and overall study period, clinical laboratory parameter actual values 
(quantitative) and change from baseline values will be descriptively summarized at baseline and 
each post-baseline visit by treatment group.   
Individual subject laboratory parameter measurements will be additionally evaluated by PCSV 
criteria (See Appendix 10.3), specifically identifying subjects with at least one post-baseline 
measurement that meets the PCSV criteria. These laboratory parameters will be presented by the 
biological functions. The incidence of PCSVs at any time during the respective treatment-emergent 
periods (EAP and FUP) will be summarized regardless of the baseline level, and again according 
to the following baseline categories: 
• Normal (according to PCSV criterion/criteria)/missing 
• Abnormal according to PCSV criterion or criteria 
Shift tables based on baseline normal/abnormal and other tabular and graphical methods may be 
used to present the results for laboratory tests of interest. 
Subject listings of laboratory measurements that meet PCSV criteria will be provided for the report 
appendix.  
A listing of all women of childbearing potential with a confirmed serum pregnancy test during the 
study will be provided. 
5.8.3. 
Analysis of Vital Signs 
For the respective EAP, FUP, and overall study period, the vital sign actual values (quantitative) 
and change from baseline values will be descriptively summarized at baseline and each post-
baseline visit will be summarized by treatment group.   
Individual subject laboratory parameter measurements will be additionally evaluated by PCSV 
criteria (See Appendix 10.3 ), specifically identifying subjects with at least one post-baseline 
measurement that meets the PCSV criteria.  
Subject listings of vital sign measurements that meet PCSV criteria will be provided for the report 
appendix. 
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5.8.4. 
Analysis of Other Safety Variables - Abnormal Findings during SARS-CoV-2 
Infection-related Medically Attended Visits  
For subjects who become SARS-CoV-2 positive and require medically attended visits to the 
emergency department (ED), urgent care center (UCC), or hospitalization starting from the 
timepoint of SARS-CoV-2 RT-qPCR positive and through the end of the study, will have the 
following parameters or occurrences (worst or most abnormal finding) during the medically 
attended visit/stay collected (eCRF).  
• Nature of visit (ED, UCC, hospital stay) 
• Abnormal vital signs: respiratory rate ≥30 per minute, heart rate ≥125 per minute, 
peripheral capillary oxygen saturation (SpO2) ≤93% on room air at sea level, or 
oxygen partial pressure (PaO2)/fractional inspired oxygen (FiO2) <300 mm Hg) 
• Respiratory failure: needing high-flow oxygen, noninvasive ventilation, mechanical 
ventilation, extracorporeal membrane oxygenation (ECMO) 
• Evidence of shock: systolic blood pressure (SBP) <90 mm Hg, diastolic blood 
pressure (DBP) <60 mm Hg or requiring vasopressors (Note:  these limits for 
abnormal vital signs are for adult and adolescent subjects.) 
• Multiorgan dysfunction: Significant acute renal, hepatic, or neurologic dysfunction 
• Multisystem inflammatory syndrome in children (MIS-C). (Note:  for pediatric 
subjects <12 years only.)  
• Admission to an ICU 
Number and percentage of subjects who presented at least one of abnormal findings and then by 
each of these 5 abnormal findings will be provided by treatment group and TEAE period (TEEAP, 
TEFUP, and overall study period). Within each abnormal findings, number and percentages of 
subjects will also be reported for each observed criterion.  
A listing of subjects who have any of these abnormal findings with any SARS-CoV-2 
infection-related medically-attended visit will be provided including the corresponding study 
period information.   
5.9. 
Analysis of Pharmacokinetic Data  
5.9.1. 
Analysis of drug concentration data 
Concentrations of REGN10933 and REGN10987 over time will be summarized by descriptive 
statistics for each cohort. No formal statistical hypothesis testing will be performed. 
Dense PK sentinel cohort 
The PK parameters to be determined after the first dose for REGN10933 and REGN10987 may 
include, but are not limited to: 
• Cmax 
• Cmax/Dose 
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• tmax 
• tlast 
• Clast 
• AUCinf 
• AUCinf/Dose 
• t1/2 
• C28 (concentration in serum 28 days after dosing)    
Selected PK parameters will be summarized by descriptive statistics for each cohort. Results from 
two different cohorts may be combined if appropriate.  
Sparse PK 
Concentrations of REGN10933 and REGN10987 in serum over time will be summarized by 
descriptive statistics for each cohort. No formal statistical hypothesis testing will be performed. 
5.10. 
Analysis of Immunogenicity Data  
The immunogenicity variables described in Section 4.8 will be summarized using descriptive 
statistics.  
Immunogenicity will be characterized by ADA responses and titers observed in subjects in the 
ADA analysis set. ADA response categories and titer categories are defined as follows: 
ADA response categories: 
• ADA Negative, defined as ADA negative response in the ADA assay at all time points, 
regardless of any missing samples. 
• Pre-existing immunoreactivity, defined as either an ADA positive response in the ADA 
assay at baseline with all post first dose ADA results negative, OR a positive response 
at baseline with all post first dose ADA responses less than 9-fold over baseline titer 
levels. 
• Treatment-emergent response, defined as an ADA positive response in the ADA assay 
post first dose when baseline results are negative or missing. The treatment-emergent 
responses will be further characterized as Persistent, Indeterminate or Transient.   
− Persistent Response – Treatment-emergent ADA positive response with two or 
more consecutive ADA positive sampling time points, separated by at least 16-
week period (based on nominal sampling time), with no ADA negative samples in 
between, regardless of any missing samples. 
− Indeterminate Response –Treatment-emergent ADA positive response with only 
the last collected sample positive in the ADA assay, regardless of any missing 
samples. 
− Transient Response –Treatment-emergent ADA positive response that is not 
considered persistent or indeterminate, regardless of any missing samples. 
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• Treatment-boosted response, defined as a positive response in the ADA assay post first 
dose that is greater than or equal to 9-fold over baseline titer levels, when baseline 
results are positive 
Titer categories (Maximum titer values) 
− Low (titer <1,000) 
− Moderate (1,000 ≤ titer ≤ 10,000) 
− High (titer >10,000) 
The following analysis will be provided: 
• Number (n) and percent (%) of ADA-negative subjects (pre-existing immunoreactivity 
or negative in the ADA assay at all time points) by treatment groups  
• Number (n) and percent (%) of treatment-emergent ADA positive subjects by treatment 
groups and ADA titer categories and at the 
− Number (n) and percent (%) of persistent treatment-emergent ADA positive 
subjects 
− Number (n) and percent (%) of indeterminate treatment-emergent ADA positive 
subjects 
− Number (n) and percent (%) of transient treatment-emergent ADA positive subjects 
• Number (n) and percent (%) of treatment-boosted ADA positive subjects by treatment 
groups and ADA titer categories  
Listing of all ADA titer levels will be provided for subjects with pre-existing, treatment-emergent 
and treatment-boosted ADA response. 
5.10.1. 
Analysis of Neutralizing Antibody (NAb) Data 
The absolute occurrence (n) and percent of subjects (%) with NAb status in the NAb analysis set 
will be provided by treatment groups. 
5.11. 
Association of Immunogenicity with Exposure, Safety and Efficacy  
5.11.1. 
Immunogenicity and Exposure 
Potential association between immunogenicity variables and systemic exposure to will be explored 
by treatment groups. Plots of drug concentration time profiles may be provided to examine the 
potential impact of ADA response status, titer, and NAb on these profiles.  
5.11.2. 
Immunogenicity and Safety and Efficacy 
Potential association between immunogenicity variables and safety may be explored with a 
primary focus on the following safety events during the TEAE period:  
• Injection site reaction (serious or severe and lasting 24 hours or longer) 
• Hypersensitivity (SMQ: Hypersensitivity [Narrow]) 
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• Anaphylaxis reaction (SMQ: Anaphylaxis [Narrow]) 
Potential association between immunogenicity variables and efficacy endpoints may be explored 
(e.g., scatter plot or spaghetti plot).  
The safety and efficacy analyses mentioned above will be conducted using the following 
categories: 
• ADA positive subjects: subjects with treatment-emergent or treatment-boosted 
response. 
• ADA negative subjects: subjects with pre-existing immunoreactivity or negative in the 
ADA assay at all time points. 
• Subjects with persistent treatment-emergent ADA response 
• NAb positive subjects: ADA positive subjects who were positive in the NAb assay at 
any time point analyzed.  
• Maximum post-baseline titer in treatment-emergent or treatment-boosted ADA 
positive subjects:  
− Low (titer <1,000) 
− Moderate (1,000 ≤ titer ≤10,000) 
− High (titer >10,000) 
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6. 
DATA CONVENTIONS 
The following analysis conventions will be used in the statistical analysis.  
6.1. 
Definition of Baseline for Efficacy/Safety Variables 
Unless otherwise specified, the Baseline assessment for all measurements will be the latest 
available measurement taken prior to the administration of study drug.  
6.2. 
Data Handling Convention for Efficacy Variables  
Rules for handling missing RT-qPCR test results for primary and secondary efficacy variables are 
described in Section 5.7.1. 
6.3. 
Data Handling Convention for Missing Data 
Missing data will not be imputed in listings.  This section includes the methods for missing data 
imputation for some summary analyses, if necessary. 
Date and Time of Study Treatment Injection 
Since the study drug is administered at the site, the date and time of study drug administration are 
filled in eCRF. No missing data is expected. The information is filled in eCRF. 
Adverse Event 
If the severity of a TEAE is missing, it will be classified as “severe” or “Grade 3” in the frequency 
tables by intensity of TEAEs. If the assessment of relationship of a TEAE to the investigational 
product is missing, it will be classified as related to study drug. 
When the partial AE date/time information does not indicate that the AE started prior to study 
treatment or after the TEAE period, the AE will be classified as treatment-emergent. 
Medication/Procedure 
If a medication date or time is missing or partially missing and it cannot be determined whether it 
was taken prior or concomitantly or stopped prior to the first study treatment administration, it will 
be considered as concomitant medication/procedure by imputing the start date on the date of first 
study treatment administration. 
Potentially Clinically Significant Value (PCSV) 
If a subject has a missing baseline value, this subject will be grouped in the category 
“normal/missing at baseline.” 
For PCSVs with 2 conditions, one based on a change from baseline value and the other on a 
threshold value or a normal range, with the first condition being missing, the PCSV will be based 
only on the second condition. 
For a PCSV defined on a threshold and/or a normal range, this PCSV will be derived using this 
threshold if the normal range is missing; e.g., for eosinophils the PCSV is >0.5 giga/L or >ULN if 
ULN ≥0.5 giga/L.  When ULN is missing, the value 0.5 should be used. 
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Measurements flagged as invalid by the laboratory will not be summarized or taken into account 
in the computation of PCSVs. 
6.4. 
Windows for Analysis Time Points 
Data analyzed by-visit-analysis will be summarized by the scheduled visit described in protocol 
section 9.1 Schedule of Events. Below are the definitions for the visit windows programmatically 
imposed on all available measures from unscheduled visits collected over the course of the study 
including early termination visit and end of study visit.  No analysis visit windows will be applied 
for the study scheduled visits nor for drug concentration and immunogenicity data. 
The visit windows are constructed using ranges applied to the number of days in study (study days) 
when the measure is collected. Below are the relevant definitions for the analysis visit windows: 
1. The first study treatment occurs on Study Day 1.  
2. Study day is defined as the number of days since the first study treatment administration+1. 
3. Since the protocol specifies that measurements be collected before study treatment is 
administered on a given day, it is appropriate that baseline include Day 1. 
4. For randomized but not treated subjects, Day 1 is the day of randomization. 
Table 4: 
Efficacy Analysis Windows for Unscheduled Visits with RT-qPCR or Viral 
Load Results 
Visit Label 
Targeted Study Day 
Analysis Window in Study Day 
Baseline 
1 
≤ 1 
Week 1 
8 
[2, 11] 
Week 2 
15 
[12, 18] 
Week 3 
22 
[19, 25] 
Week 4 
29 
[26, 32] 
Week 5 
36 
[33, 39]  
Week 6 
43 
[40, 46] 
… 
… 
… 
Week x 
29+7x 
[26+7(x-4), 32+7(x-4)] 
If a subject has multiple efficacy assessment visits within an analysis visit window, the one with 
worst result (e.g., the positive test result will be used for analysis if one record is positive and the 
other one is negative; the highest viral load result will be used if multiple viral load results are in 
the same analysis window.) will be selected. If the test results are all negative, the value of the 
latter visit will be used. If there are multiple positive RT-qPCR results within an analysis window, 
the record with the highest quantitative result will be used.  
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Table 5: 
Global Analysis Windows for Data Other Than RT-qPCR Test 
Visit Label 
Targeted Study Day 
Analysis Window in Study Day 
Baseline 
1 
≤ 1 
Day 2 
2 
[2, 2] 
Day 4 
4 
[3, 4] 
Week 1 
8 
[5, 11] 
Week 2 
15 
[12, 18] 
Week 3 
22 
[19, 25] 
Week 4 
29 
[26, 42] 
Week 8 
57 
[43, 70] 
Week 12 
85 
[71, 98] 
Week 16 
113 
[99, 126] 
Week 20 
141 
[127, 154] 
Week 24 
169 
[155, 182] 
Week 28 
197 
[183, 210] 
Week 32 
225 
>=211 
Unscheduled Assessments 
For efficacy, safety laboratory data, and vital signs, unscheduled visit measurements may be used 
to provide a measurement for a time point, including baseline, if appropriate according to their 
definitions. The measurements may also be used to determine abnormal values, AESIs, and 
PCSVs. 
6.5. 
Pooling of Centers for Statistical Analyses 
Currently, the randomization is stratified by site. Since a potential differential treatment effect 
among countries may exist, region variable as a fixed effect factor will be included in the statistical 
analysis model. A subgroup analysis regarding region will also be performed for the primary 
efficacy endpoint.   Results will also be summarized descriptively by country. 
6.6. 
Statistical Technical Issues 
To consider the potential impact that not all of study subjects come from a household with more 
than one member participating this trial, a simulation has been conducted to explore the potential 
impact to the type I error rate and power by the percent of households with a single study subject 
only.  
This simulation is based on the same sample size of 1248 (See Table 1 in Section 2.2.1) assuming 
the attack rates are 10% and 5% in placebo and REGN10933+REGN10987 treatment group, 
respectively. The correlated Bernoulli response data (e.g. 1=infected vs 0=not infected) within a 
household was generated by using Gaussian multivariate cumulative distribution function 
proposed by Emrich and Piedmonte (1991). For example, the table below exhibits the correlation 
between the bivariate normal data with correlation 𝜌 used to generate the Bernoulli correlated data 
and the corresponding Bernoulli correlation 𝛾 in the cases where the attack rates are both 10% 
(e.g., 𝑝1 = 𝑝2 = 0.1 under the null hypothesis), and 10% and 5% (e.g., 𝑝1 = 0.1, 𝑝2 =0.05 under 
the alternative hypothesis). 
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𝑝1 = 𝑝2 = 0.1 
  𝑝1 = 0.1, 𝑝2 =0.05 
ρ Normal γ Bernoulli   ρ Normal γ Bernoulli 
0.1 
0.03706 
  
0.1 
0.03065 
0.2 
0.07996 
  
0.2 
0.06748 
0.3 
0.12907 
  
0.3 
0.11089 
0.4 
0.18504 
  
0.4 
0.16150 
0.5 
0.24891 
  
0.5 
0.22020 
0.6 
0.32242 
  
0.6 
0.28834 
0.7 
0.40866 
  
0.7 
0.36813 
0.8 
0.51381 
  
0.8 
0.46328 
0.9 
0.65405 
  
0.9 
0.58016 
 
Given the percent of subjects from households with single study subject (HHS), the rest of 
household size was randomly generated by using a truncated Poisson (𝑙= 4) (i.e., resampling if 
≤1). The simulation is repeatedly 2000 times by different HHS to compare the power between 
GEE model and logistic regression model based on boundary p-value=0.044 after 2 planned 
interim analyses. 
Summary of power and type I error rate between the GEE model and logistic regression model by 
different HHS, considering the extreme high correlated data. The power is based on the testing p-
value compared to the boundary p-value of 0.044 after 2 interim analyses at 50% and 75% 
information fraction for the final analysis. 
Comparisons of Power                                              Comparisons of Type I Error  
𝛾= 0.58 (𝑝1 = 0.1, 𝑝2 = 0.05) 
 
 
𝛾= 0.65 (𝑝1 = 0.1, 𝑝2 = 0.1) 
HHS(%) power-GEE 
power-Logistic 
 
 HHS(%) 
𝛼-GEE 
𝛼 -Logistic 
10 
0.9920 
0.9035 
 
 
10 
0.0480 
0.0435 
20 
0.9905 
0.9040 
 
 
20 
0.0490 
0.0440 
30 
0.9855 
0.9140 
 
 
30 
0.0495 
0.0475 
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40 
0.9590 
0.8980 
 
 
40 
0.0510 
0.0445 
50 
0.9245 
0.9075 
 
 
50 
0.0410 
0.0360 
60 
0.9035 
0.9085 
 
 
60 
0.0600 
0.0490 
70 
0.8640 
0.9175 
 
 
70 
0.0575 
0.0390 
80 
0.8460 
0.9155 
 
 
80 
0.0735 
0.0370 
 
Based on the potential inflation of type I error (𝛼) and decreasing power as HHS over 50%, 
conservatively the percent of households with a single study subject could be higher than 70%. 
Thus, if this situation occurs, the logistic regression will be used instead of using GEE approach. 
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7. 
TIMING OF STATISTICAL ANALYSES 
There are multiple steps of analyses planned for this study. 
• An administrative descriptive analysis based on approximately first 554 randomized 
Cohort A subjects has been conducted. No formal statistical hypothesis testing will be 
performed. The individuals who have the subject treatment information will be 
described in the communication plan. 
• The first step analysis: The database lock will occur when all Cohort A and Cohort B 
subjects complete the EAP and all their data during the EAP have been collected and 
validated. The individual treatment codes will be unblinded and final analyses of the 
primary and some secondary efficacy endpoints of cohort A and Cohort B will be 
conducted. The subjects who are included in the administrative analysis will not be 
included in the first step efficacy analysis. Also, subjects who are randomized after 
January 28th (approximately 269) will not be included in this analysis.  
Note: The results of primary and some secondary efficacy endpoints in the first step 
analysis maybe used for a submission dossier to health authorities.    
• The second step analysis (final analysis): The database lock will occur after the last 
subject completes the study. All treated subjects including 554 subjects in the 
administrative assessment, subjects in the first step analysis, and those subjects (~269) 
who were randomized after 28 January, 2021, will be included in the safety analysis. 
The second-step analysis for efficacy will include all subjects except those subjects 
who were included in the administrative assessment. 
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8. 
SOFTWARE 
All analyses will be done using SAS Version 9.4 or higher, and R 3.5.3 or higher.  
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9. 
REFERENCES 
1. ICH. (1996, July 30). ICH Harmonized tripartite guideline: Structure and content of clinical 
study reports (E3). International Conference on Harmonization of Technical Requirements 
for Registration of Pharmaceuticals for Human Use. 
2. ICH. (1997, July 17). ICH Harmonized tripartite guideline: General considerations for 
clinical trials (E8). International Conference on Harmonization of Technical Requirements 
for Registration of Pharmaceuticals for Human Use. 
3. ICH. (1998, February 5). ICH Harmonized tripartite guideline: Statistical principles for 
clinical trials (E9). International Conference on Harmonization of Technical Requirements 
for Registration of Pharmaceuticals for Human Use. 
4. Michael A. Proschan, Robert P. McMahon, Joanna H. Shih, Sally A. Hunsberger, Nancy 
L. Geller, Genell Knatterud, Janet Wittes (2001). Sensitivity analysis using an imputation 
method for missing binary data in clinical trials. Journal of Statistical Planning and 
Inference, 96 155-165 
5. Halle/Saale. How to Use SAS® for Logistic regression with Correlated Data, Proceedings 
of the 27th Annual SAS® Users Group International Conference (SUGI 27), 261-27  
6. Patricia A. Berglund Multiple Imputation Using the Fully Conditional Specification 
Method: A comparison of SAS®, Stata, IVEware, and R, SAS Support Paper 2081-2015 
7. Van Buuren, S., J. P. L. Brand, C. G. M. Groothuis-Oudshoorn, and D. B. Rubin. 2006. 
“Fully Conditional Specification in Multivariate Imputation.” Journal of Statistical 
Computation and Simulation 76 (12): 1049–64 
8. Hwang IK, Shih WJ and DeCani JS 1990. Group sequential designs using a family of type 
I error probability spending functions. Statistics in Medicine, 9, 1439-1445 
9. Novel 
Coronavirus 
(2019-nCoV) 
Situation 
Report 
– 
22. 
https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports/. 
Published 2020b.  [Accessed] 24 Apr. 
10. Zou L, Ruan F, Huang M, Liang L, Huang H, Hong Z, et al. SARS-CoV-2 Viral Load in 
Upper Respiratory Specimens of Infected Patients. N Engl J Med 2020; 382(12):1177-9. 
11. Lai CC, Ko WC, Lee PI, Jean SS, Hsueh PR. Extra-respiratory manifestations of COVID-
19. Int J Antimicrob Agents 2020:106024. 
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10. 
APPENDIX 
10.1. 
Summary of Statistical Analyses 
Primary Efficacy Analysis: 
Endpoint 
Analysis 
Population 
Estimand 
Statistical 
Method 
Supportive 
Analysis 
Subgroup 
Analysis 
Other 
Analyses 
Proportion of 
subjects who 
have a 
symptomatic 
RT-qPCR 
confirmed 
SARS-CoV-2 
infection 
(broad-term) 
during the 
EAP 
Seronegative 
mFAS-A  
A broad-term 
symptom 
occurring within 
a 14-days 
window of any 
positive RT-
qPCR during the 
EAP regardless 
of adherence to 
study treatment 
will be included 
for the primary 
analysis.  
 
A generalized 
linear model with 
the generalized 
estimation 
equation (GEE) 
approach or 
logistic 
regression If 
percent of 
households with 
single study 
subject greater 
than or equal to 
70%. Missing 
RT-qPCR will be 
imputed as 
positive RT-
qPCR if a subject 
with COVID-19 
signs and 
symptoms 
(broad-term) 
occurring within 
a 14-day window 
of a visit with 
missing RT-
qPCR data.  
Yes 
 
Yes  
1. Excluding 
those subjects 
who develop 
asymptomatic 
or 
symptomatic 
SARS-CoV-2 
infection 
within 72 
hours of the 
study drug 
administration 
2. Exclude 
subjects from 
non-GCP 
compliance 
sites 
 
Proportion of 
subjects who 
have a 
symptomatic 
RT-qPCR 
confirmed 
SARS-CoV-2 
infection 
(broad-term) 
at baseline or 
during the 
EAP 
Seronegative 
mFAS-B 
Same as above 
including a 
positive RT-
qPCR at baseline 
Same as above 
including a 
positive RT-
qPCR at baseline 
Yes 
No 
1. Exclude 
subjects from 
non-GCP 
compliance 
sites 
 
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10.2. 
Schedule of Events 
Table 6: 
Schedule of Events Cohorts A and B ([Adult / Adolescent Subjects], RT-qPCR-Negative and Positive) 
Visit 
Screening / 
Baseline1 
Additional Safety 
(Sentinel Only)2 
Efficacy Assessment 
Period (EAP)3 
Follow-up Period 
ET Unsche
dVisit4 
Visit Location Site (S), Phone (P)5 
S 
S 
S 
P 
S 
S 
S 
S 
S 
S 
S 
S 
S 
S 
S 
S 
Visit Number 
1 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 EOS 
 
 
Day 
1 
1 
2 
3 
4 
8 
15 
22 
29 
57 
85 
113 141 169 197 225 
 
 
Week 
0 
0 
0 
0 
0 
1 
2 
3 
4 
8 
12 
16 
20 
24 
28 
32 
 
 
Window (day) 
 
 
 
 
 
±1 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Screening/Baseline: 
Inclusion/exclusion 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Informed consent (adult subject or parent/guardian)/pediatric 
assent (adolescent subject) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Informed consent (adults or parent/guardian)/pediatric assent 
for PGx sub-study(optional)6 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics and risk factors for SARS-CoV-2 infection 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Household assessment 
X16 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
Appropriate sample, diagnostic assay for SARS-CoV-2 (local 
lab)  
X7 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Randomization 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Treatment: 
Study drug administration 
X8 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Efficacy (Virology): 
NP swab, SARS-CoV-2 RT-qPCR (central lab)7,17 
X8 
 
 
 
 
X 
X 
X 
X 
X3,4,9 X3,4,9 X3,4,9 X3,4,9 X3,4,9 X3,4,9 X3,4,9 X 
X 
Efficacy (Subject-Reported) only for RT-qPCR positive subjects: 
Assessment of ED, UCC, hospital visits18 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Absenteeism assessment18 
 
 
 
 
 
X 
X 
X 
X 
 
 
 
 
 
 
X 
 
 
Safety: 
 
 
 
 
Vital signs 
X2,11 
X2 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
 
X 
Targeted PE11 
X 
 
X 
 
X 
 
 
 
X 
 
 
 
 
 
 
X 
 
X 
Adverse events15,19 
X 
X2 X2 X2 X2,10 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Con Meds, Procedures 
X 
X X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urine pregnancy test for WOCBP (dipstick, local lab)12 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
X 
Laboratory Testing13: 
Clinical Laboratory, Hematology, Blood Chemistry, 
Urinalysis  
Refer to Table 7  
Pharmacokinetics and Immunogencity13: 
Drug concentration  
Refer to Table 7  
Anti-drug antibodies (ADA) 
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10.2.1. 
Schedule of Events Table 6 (Cohorts A and B [Adult / Adolescent Subjects], RT-qPCR-Negative and Positive) 
Footnotes 
1. The screening visit and baseline visit should both occur on the same day.  If needed, a remote visit may occur to sign the ICF 
and collect medical history and concomitant medication use, on the day prior to, but within 24 hours of study drug administration, 
so that the in-person screening and randomization visit may be abbreviated, due to COVID-19 considerations. Study drug 
administration must occur within 96 hours of collection of the index cases’ positive SARS-CoV-2 diagnostic test sample. 
2. The sentinel group (see Section 6.1.1 of the protocol) had additional safety monitoring on day 1 and through day 4. 
Vital signs: On day 1, vital signs (blood pressure, pulse rate, body temperature, and respiratory rate) will be measured at predose, 
approximately every 30 minutes during the first 2 hours after dose, at hour 3, and at hour 4 before dismissal. 
Adverse Events (injection site reactions and hypersensitivity): after the administration of the first dose of study drug, subjects 
will be monitored on site for a minimum of 4 hours and then by daily visits to the study site or phone calls for the first 4 days 
(96 hours), particularly focusing on the assessment of injection site reactions and hypersensitivity after study drug administration. 
3. Subjects who have a positive RT-PCR result during screening, or who have a positive RT-qPCR result any time after screening, 
will have the additional assessments done as indicated (RT-qPCR positive subjects only). A PK sample and an ADA sample 
will be collected (1) as soon as possible or within 7 days of receiving first positive SARS-CoV-2 RT-qPCR result for cohort A 
subjects and (2) as soon as possible or within 7 days of first new positive SARS-CoV-2 RT-qPCR result after achieving 2 
consecutive negative results for all subjects. 
For subjects who become RT-qPCR positive after screening, the visit schedule will proceed as follows: (a) If the positive RT-
qPCR result is from a scheduled visit for sample collection, the next weekly visit will occur as planned.  (b) If the positive 
RT-qPCR result is from an unscheduled sample collection (eg, between scheduled visits) but within the window (±3 days) of the 
next weekly visit, this visit will be recorded as the scheduled next weekly visit.  (c) If the positive RT-qPCR result is from an 
Biomarkers: 
Serum for serology (central lab)14 
X 
 
 
 
 
 
 
 
X 
X 
 
 
 
 
 
X 
 
 
Research plasma 
X 
 
 
 
 
 
 
 
X20 
X20 
 
 
 
 
 
X20 
 
 
Research serum 
X 
 
 
 
 
 
 
 
X20 
X20 
 
 
 
 
 
X20 
 
 
Pharmacogenomics Sub-Study: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Whole Blood for RNA (Optional)6 
X 
 
 
 
 
 
 
 
X20 
X20 
 
 
 
 
 
X20 
 
 
Whole Blood for DNA (Optional)6  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
EAP, Efficacy assessment period; EOS, end of study; ED, emergency departments; ET, Early termination; UCC, urgent care centers; PE, physical exam; PGx, pharmacogenomics; 
RT-PCR, reverse transcription polymerase chain reaction; RT-qPCR, quantitative reverse transcription polymerase chain reaction; SARS-CoV-2, severe acute respiratory 
syndrome coronavirus 2; WOCBP, women of childbearing potential. 
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unscheduled sample collection (eg, between scheduled visits) and not within the window (±3 days) of the next weekly visit, this 
visit will be recorded as an unscheduled visit, and the next weekly visit will occur as planned. 
4. Unscheduled visits: If, at any time after randomization until end of study, a subject develops fever, an acute respiratory illness 
or other symptoms they may feel could be related to COVID-19 or is hospitalized for suspected COVID-19, the subject or 
parent/guardian (adolescent pediatric subject) should alert the investigator or designee immediately who will assess the subject’s 
symptoms and condition (can be performed by phone contact, telemedicine, online meeting, home health care, etc) to decide if 
the subject should have an unscheduled visit for collection of NP swab sample for RT-qPCR testing.  The subject or 
parent/guardian (adolescent pediatric subject) may also be asked to provide blood samples if it corresponds to a scheduled visit, 
according to the Schedule of Events (specified in Section 9.1 of the protocol).  The investigator or designee should query the 
subject about AEs in general and AEs consistent of COVID-19 and record the information on CRF (see detailed description of 
the procedure in Section 9.2.2.2 of the protocol). 
(a) If the positive RT-qPCR result is from a scheduled visit for sample collection, the next weekly visit will occur as planned.  
(b) If the positive RT-qPCR result is from an unscheduled sample collection (eg, between scheduled visits) but within the window 
(±3 days) of the next weekly visit, this visit will be recorded as the scheduled next weekly visit.  (c) If the positive RT-qPCR 
result is from an unscheduled sample collection (eg, between scheduled visits) and not within the window (±3 days) of the next 
weekly visit, this visit will be recorded as an unscheduled visit, and the next weekly visit will occur as planned. 
5. Visit may occur by phone or electronic means 
6. Separate consent (adult subject or parent/guardian of adolescent pediatric subject)/pediatric assent is required for participation 
in the optional genomic sub-study and collection of blood samples for DNA and RNA. The sample for RNA, should be collected 
on day 1/baseline (pre-dose). Genomic DNA should be collected on day 1/baseline. If not collected at baseline, the sample for 
genomic DNA may be collected at any visit. 
7. Sample for diagnostic assay for SARS-CoV-2 (local lab) (see Section 9.1.2 of the protocol) and RT-qPCR (NP swab; central 
lab) should be collected before administration of study drug.  Samples for RT-qPCR (NP swab) will be collected by swabbing 
through both nostrils (see Section 9.2.2.1 of the protocol). The remnant samples may additionally be used for exploratory viral 
RNA sequencing and viral infectivity analyses.  The requirement for a local diagnostic assay for SARS-CoV-2 may be waived 
if the results are not expected to be available in a timely manner for randomization. 
8. Study drug should be administered after all biological samples at screening/baseline have been collected. 
9. Subjects who are RT-qPCR positive at the end of the EAP will continue to have samples collected weekly (NP swab; central 
lab) for RT-qPCR.  Subjects will continue assessments/sample collections until 2 negative RT-qPCR test results have been 
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obtained ≥24 hours apart (all samples must be negative).  Subjects who are RT-qPCR negative at the end of the EAP will have 
samples collected only if they become symptomatic with COVID-19 in the follow-up period. 
10. For subjects who are not in the sentinel group (subset 1; completed), vital signs will be monitored on site as follows: Safety 
group (subset 2; completed): at baseline predose and then every hour for 2 hours after study drug administration and a phone call 
on day 4 to assess AEs, specifically injection site reactions and hypersensitivity; all other subjects (subset 3): at baseline and 
1 hour after study drug administration.  All subjects will be advised to call the site if signs/symptoms of injection site or 
hypersensitivity reactions occur.  If the subject experiences a true medical emergency, they should visit their local hospital ED 
and contact the site personnel later. 
11. The investigator may perform a targeted physical exam, request an exam and/or vital signs at any time.  These assessments can 
be performed using a clinic visit or a remote visit with the investigator or sub-investigator, or designee (ie, nurse practitioner in 
countries where allowed by local law). 
12. For all women of childbearing potential (WOCBP) and girls at or beyond menarche, except subjects with a confirmed pregnancy.  
If the local urine pregnancy test is positive, the site must perform a serum pregnancy test for confirmation.  
13. Samples for drug concentration and, immunogenicity, and laboratory testing will be collected based on the subject subset 
designation as indicated in Table 7.  
14. The serology test results will not be communicated to the sites. The sponsor’s blinded study team will not have access to post-
baseline results associated with subject identification until after the database is locked. 
15. During each scheduled or unscheduled visit/contact, the investigator or designee will query subject about AEs in general (see 
Section 10.1.1 of the protocol) and evaluate if the AEs are associated with SARS-CoV-2 infection, including fever (see Section 
9.2.2.2 of the protocol).  The investigator should recommend that subjects (themselves or by their parent/guardian) measure their 
temperature daily during EAP, approximately at the same time, and also every time when the subject feels feverish, chills, or 
sick.  Subjects with symptomatic SARS-CoV-2 infection should be queried on their symptoms weekly until symptoms resolve, 
even during follow-up period, then follow the regular schedule.  
16. The information for the household assessment, including household members who receive an EUA approved monoclonal 
antibody treatment for COVID-19 or household members participating in the R10933-10987-COV-2067 study, should 
preferably be collected at the baseline visit. There will be a follow-up assessment at day 29.  
17. All subjects will have a weekly NP swab sample collected during the EAP.  Only subjects who are RT-qPCR positive will 
continue to have weekly NP swab samples collected during the follow-up period until 2 consecutive negative (≥24 hr) RT-qPCR 
results or the end of study visit.  
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18. Only for RT-qPCR positive subjects (cohort A and cohort B): Complete assessments from the time the subject first becomes RT-
qPCR positive or from the time they develop symptoms suspected to be COVID-19 (later confirmed by RT-qPCR positive 
results) until the subject has had 2 negative tests or COVID-19 related symptoms have resolved (whichever lasts longer), or until 
the end of study visit.  
19. All subjects or parent/guardians of adolescent pediatric subjects will complete the TEAE assessment weekly during the EAP.  
Subjects who are RT-qPCR negative will complete the TEAE assessment monthly during the follow-up period.  Subjects who 
have symptomatic SARS-CoV-2 infection will complete the TEAE assessment weekly during the follow-up period until the 
COVID-19 related symptoms resolve after which the subject will complete the TEAE assessment monthly until the end of study 
visit. 
20. Samples will be collected only from RT-qPCR positive subjects (cohort A and cohort B) from the time the subject first becomes 
RT-qPCR positive until the end of study. Note: this includes subjects who have returned to RT-qPCR negative by this visit.   
 
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Table 7: 
Schedule of Events: Cohorts A and B (Adult / Adolescent Subjects) for Drug Concentration, Immunogenicity, 
and Laboratory Testing 
Samples for drug concentration (dense PK, sparse PK), immunogenicity assessment (ADA), and clinical laboratory testing (hematology, blood 
chemistry, and urinalysis) will be collected based on subset designation using subject number (assigned by IWRS): 
• Sentinel group (Subset 1; completed): First 30 subjects 
• Safety group (Subset 2; completed): 31st to 400th subject 
All other subjects (Subset 3): 401st to last subject 
Visit 
Screening / 
Baseline1 
Sentinel 
Group Only  
Efficacy Assessment 
Period (EAP) 
Follow-up Period 
ET 
Visit5 
Unscheduled 
Visit 
Site (S) 
S 
S 
S 
S 
S 
S 
S 
S 
S 
S 
S 
S 
S 
 
Visit Number 
1 
2 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
EOS 15 
 
 
Day 
1 
2 
4 
8 
15 
22 
29 
57 
85 
113 
141 
169 
197 
225 
 
 
Week 
0 
0 
0 
1 
2 
3 
4 
8 
12 
16 
20 
24 
28 
32 
 
 
Window (day) 
 
 
±1 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
 
 
 
Sentinel Group (Subset 1) 
Dense PK2 
X1 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X6,7 
ADA2,3 
X1 
 
 
 
 
 
X 
 
 
X 
 
 
 
X 
X 
X6,7 
Hematology4 
X1 
X 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Blood chemistry4 
X1 
X 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Urinalysis4 
X1 
X 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Safety group (Subset 2) 
Sparse PK2 
X1 
 
 
 
 
 
X 
X 
 
X 
 
X 
 
X 
X 
X6,7 
ADA2,3 
X1 
 
 
 
 
 
X 
 
 
X 
 
 
 
X 
X 
X6,7 
Hematology4 
X1 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Blood chemistry4 
X1 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Urinalysis4 
X1 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
All other subjects (Subset 3) 
PK2 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X6,7 
ADA2,3 
X1 
 
 
 
 
 
X 
 
 
X 
 
 
 
X 
X 
X6,7 
Hematology4 
X1 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
Blood chemistry4 
X1 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
Urinalysis4 
X1 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
ADA, anti-drug antibodies; EAP, Efficacy assessment period; EOS, end of study; ET, Early termination; PK, Pharmacokinetics 
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10.2.2. 
Schedule of Events Table 4: All Cohorts A and B (Adult / Adolescent Subjects) for Drug Concentrations, 
Immunogenicity, and Laboratory Testing  
1. Samples should be collected before the administration of study drug. Administration of study drug must be performed on the on 
same day as sample collection.  
2. Actual dosing time and dense PK, sparse PK, and ADA sample collection times will be recorded.  
3. At the screening/baseline visit, the window for baseline pre-dose ADA sample collection is as close to administration of study 
drug as is reasonable. Actual dosing times and ADA sample collection times will be recorded. 
4. Whole blood samples for hematology and blood chemistry and urine samples for urinalysis will be analyzed at central lab. 
5. Subjects who prematurely discontinue the study should have sample collection listed in the ET visit before exiting the study. 
6. A PK serum sample and an ADA serum sample will be collected as soon as possible or within 7 days of receiving the first 
positive SARS-CoV-2 RT-qPCR result for cohort A subjects.  The ADA serum samples may be analyzed for ADA and NAb, if 
feasible. 
7. A PK serum sample and an ADA serum sample will be collected as soon as possible or within 7 days of first new positive SARS-
CoV-2 RT-qPCR result after achieving 2 consecutive negative results for all subjects. 
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Table 8: 
Schedule of Events: Cohorts A1 and B1 (Pediatric Subjects [<12 years], RT-qPCR-Negative and Positive) 
Visit 
Screening / 
Baseline1 
Additional Safety 
(Sentinel Only)2 
Efficacy Assessment 
Period (EAP)3 
Follow-up Period 
ET Unsche
dVisit4 
Visit Location Site (S), Phone (P)5 
S 
S 
S 
P5 
S 
S 
S 
S 
S 
S 
S 
S 
S 
S 
S 
S 
Visit Number 
1 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
EOS 
 
 
Day 
1 
1 
2 
3 
4 
8 
15 22 29 
57 
85 
113 141 169 197 
225 
 
 
Week 
0 
0 
0 
0 
0 
1 
2 
3 
4 
8 
12 
16 
20 
24 
28 
32 
 
 
Window (day) 
 
 
 
 
 
±1 
±3 ±3 ±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Screening/Baseline: 
Inclusion/exclusion 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Informed consent (parent/guardian)/pediatric assent (subject) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Informed consent(adults or parent/guardian)/pediatric assent for 
PGx sub-study(optional)19 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics and risk factors for SARS-CoV-2 infection 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Household assessment 
X15 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
Appropriate sample, diagnostic assay for SARS-CoV-2 (local lab)  
X6 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Randomization 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Treatment: 
Study drug administration 
X7 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Efficacy (Virology): 
NP swab, SARS-CoV-2 RT-qPCR (central lab)6,16 
X7 
 
 
 
 
X 
X 
X 
X X3,4,8 X3,4,8 X3,4,8 X3,4,8 X3,4,8 X3,4,8 X3,4,8 X 
X 
Efficacy (Subject-Reported) only for RT-qPCR positive subjects: 
Assessment of ED, UCC, hospital visits17 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Absenteeism assessment17 
 
 
 
 
 
X 
X 
X 
X 
 
 
 
 
 
 
X 
 
 
Safety: 
 
 
 
 
Vital signs 
X2,10 
X2 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
 
X 
Targeted PE10 
X 
 
X 
 
X 
 
 
 
X 
 
 
 
 
 
 
X 
 
X 
Adverse events14,18 
X9 
X2 X2 X2 X2 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Con Meds, Procedures 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urine pregnancy test for WOCBP (dipstick, local lab)11 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
 
Laboratory Testing12: 
Clinical Laboratory, Hematology, Blood Chemistry 
Refer to Table 9 
Pharmacokinetics and Immunogencity12: 
Drug concentration / Anti-drug antibodies (ADA) 
Refer to Table 9 
Biomarkers: 
Serum for serology (central lab)12,13 
Refer to Table 9 
Pharmacogenomics Sub-Study: 
 
Whole Blood for RNA (Optional)12,19 
Refer to Table 9 
Whole Blood for DNA (Optional)12,19  
Refer to Table 9 
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10.2.3. 
Schedule of Events Table 5 Cohorts A1 and B1 (Pediatric Subjects [ <12 years], RT-qPCR-Negative and Positive) 
Footnotes  
1. The screening visit and baseline visit should both occur on the same day.  If needed, a remote visit may occur to sign the ICF 
and collect medical history and concomitant medication use, on the day prior to, but within 24 hours of study drug administration, 
so that the in-person screening and randomization visit may be abbreviated, due to COVID-19 considerations. Study drug 
administration must occur within 96 hours of collection of the index cases’ positive SARS-CoV-2 diagnostic test sample. 
2. The pediatric sentinel group (subset 4) (see Section 6.1.2 of the protocol) will have additional safety monitoring on day 1 and 
through day 4. 
Vital signs: On day 1, vital signs (pulse rate, respiratory rate, body temperature and blood pressure [if feasible, according to the 
child’s age]) will be measured at predose, approximately every 30 minutes during the first 2 hours after dose before dismissal. 
Adverse Events (injection site reactions and hypersensitivity): after the administration of the first dose of study drug, subjects 
will be monitored on site for a minimum of 2 hours and then by daily visits to the study site or phone calls for the first 4 days 
(96 hours), particularly focusing on the assessment of injection site reactions and hypersensitivity after study drug administration. 
3. Pediatric subjects who have a positive RT-PCR result during screening, or who have a positive RT-qPCR result any time after 
screening, will have the additional assessments done as indicated (RT-qPCR positive pediatric subjects only).  A PK sample 
and an ADA sample will be collected (1) as soon as possible or within 7 days of receiving first positive SARS-CoV-2 RT-qPCR 
result for cohort A1 pediatric subjects and (2) as soon as possible or within 7 days of first new positive SARS-CoV-2 RT-qPCR 
result after achieving 2 consecutive negative results for all pediatric subjects. 
For pediatric subjects who become RT-qPCR positive after screening, the visit schedule will proceed as follows: (a) If the 
positive RT-qPCR result is from a scheduled visit for sample collection, the next weekly visit will occur as planned.  (b) If the 
positive RT-qPCR result is from an unscheduled sample collection (eg, between scheduled visits) but within the window (±3 
days) of the next weekly visit, this visit will be recorded as the scheduled next weekly visit.  (c) If the positive RT-qPCR result 
is from an unscheduled sample collection (eg, between scheduled visits) and not within the window (±3 days) of the next weekly 
visit, this visit will be recorded as an unscheduled visit, and the next weekly visit will occur as planned. 
4. Unscheduled visits: If, at any time after randomization until end of study, a pediatric subject develops fever, an acute respiratory 
illness or other symptoms they may feel could be related to COVID-19 or is hospitalized for suspected COVID-19, the pediatric 
EAP, Efficacy assessment period; EOS, end of study; ED, emergency departments; ET, Early termination; UCC, urgent care centers; PE, physical exam; RT-PCR, reverse 
transcription polymerase chain reaction; RT-qPCR, quantitative reverse transcription polymerase chain reaction; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2;  
WOCBP, women of childbearing potential.  
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subject and/or parent/guardian should alert the investigator or designee immediately who will assess the subject’s symptoms and 
condition (can be performed by phone contact, telemedicine, online meeting, home health care, etc) to decide if the pediatric 
subject should have an unscheduled visit for collection of NP swab sample for RT-qPCR testing.  The pediatric subject and/or 
parent/guardian may also be asked to provide blood samples if it corresponds to a scheduled visit, according to the Schedule of 
Events (specified in Section 9.1 of the protocol).  The investigator or designee should query the subject and/or parents/guardians 
about AEs in general and AEs consistent of COVID-19 and record the information on CRF (see detailed description of the 
procedure in Section 9.2.2.2 of the protocol). 
(a) If the positive RT-qPCR result is from a scheduled visit for sample collection, the next weekly visit will occur as planned.  
(b) If the positive RT-qPCR result is from an unscheduled sample collection (eg, between scheduled visits) but within the window 
(±3 days) of the next weekly visit, this visit will be recorded as the scheduled next weekly visit.  (c) If the positive RT-qPCR 
result is from an unscheduled sample collection (eg, between scheduled visits) and not within the window (±3 days) of the next 
weekly visit, this visit will be recorded as an unscheduled visit, and the next weekly visit will occur as planned. 
5. Visit may occur by phone or electronic means 
6. Sample for diagnostic assay for SARS-CoV-2 (local lab) (see Section 9.2.1.2 of the protocol) and RT-qPCR (NP swab; central 
lab) should be collected before administration of study drug.  Samples for RT-qPCR (NP swab) will be collected by swabbing a 
single nostril (see Section 9.2.2.1 of the protocol). The remnant samples may additionally be used for exploratory viral RNA 
sequencing and viral infectivity analyses.  The requirement for a local diagnostic assay for SARS-CoV-2 may be waived if the 
results are not expected to be available in a timely manner for randomization. 
7. Study drug should be administered after all biological samples at screening/baseline have been collected. 
8. Pediatric subjects who are RT-qPCR positive at the end of the EAP will continue to have samples collected weekly (NP swab; 
central lab) for RT-qPCR.  Pediatric subjects will continue assessments/sample collections until 2 negative RT-qPCR test results 
have been obtained ≥24 hours apart (all samples must be negative).  Subjects who are RT-qPCR negative at the end of the EAP 
will have samples collected only if they become symptomatic with COVID-19 in the follow-up period. 
9. All other pediatric subjects (subset 5) will have additional safety monitoring on day 1 at baseline and 1 hour after study drug 
administration.  All pediatric subjects or their parent/guardian will be advised to call the site if signs/symptoms of injection site 
or hypersensitivity reactions occur.  If the pediatric subject experiences a true medical emergency, they and their parent/guardian 
should visit their local hospital ED and contact the site personnel later. 
10. The investigator may perform a targeted physical exam, request an exam and/or vital signs at any time.  These assessments can 
be performed using a clinic visit or a remote visit with the investigator or sub-investigator, or designee (ie, nurse practitioner in 
countries where allowed by local law). 
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11.  For all girls at or beyond menarche.  If the local urine pregnancy test is positive, the site must perform a serum pregnancy test 
for confirmation. 
12. Samples for drug concentration, immunogenicity, laboratory testing, serology, and pharmacogenomics sub-study will be 
collected based on the pediatric subject subset designation as indicated in Table 9 . 
13. The serology test results will not be communicated to the sites. The sponsor’s blinded study team will not have access to post-
baseline results associated with pediatric subject identification until after the database is locked. 
14. During each scheduled or unscheduled visit/contact, the investigator or designee will query the pediatric subject and/or 
parent/guardian about AEs in general (see Section 10 of the protocol) and evaluate if the AEs are associated with SARS-CoV-2 
infection (see Section 9.2.2.2. of the protocol).  Pediatric subjects and/or parent/guardian with symptomatic SARS-CoV-2 
infection should be queried on their symptoms weekly until symptoms resolve, even during follow-up period, then follow the 
regular schedule.  
15. The information for the household assessment, including household members who received EUA approved monoclonal antibody 
treatment for COVID-19 or household members participating in the R10933-10987-COV-2067 study should preferably be 
collected at the baseline visit. There will be a follow-up assessment at day 29.  
16. All pediatric subjects will have a weekly NP swab sample collected during the EAP.  Only pediatric subjects who are RT-qPCR 
positive will continue to have weekly NP swab samples collected during the follow-up period until 2 consecutive negative (≥24 
hr) RT-qPCR results or the end of study visit.  
17. Only for RT-qPCR positive subjects (cohort A1 and cohort B1): Complete assessments from the time the subject first becomes 
RT-qPCR positive or from the time they develop symptoms suspected to be COVID-19 (later confirmed by RT-qPCR positive 
results) until the subject has had 2 negative tests or COVID-19 related symptoms have resolved (whichever lasts longer), or until 
the end of study visit.  
18. All pediatric subjects and/or parent/guardian will complete the TEAE assessment weekly during the EAP.  Subjects who are RT-
qPCR negative will complete the TEAE assessment monthly during the follow-up period.  Pediatric subjects and/or 
parent/guardian who have symptomatic SARS-CoV-2 infection will complete the TEAE assessment weekly during the follow-
up period until the COVID-19 related symptoms resolve after which the pediatric subject and/or parent/guardian will complete 
the TEAE assessment monthly until the end of study visit. 
19. Separate consent (parent/guardian of pediatric subject)/pediatric assent is required for participation of pediatric subjects who 
weigh ≥10 kg in the optional genomic sub-study and collection of blood samples for DNA and RNA.  
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Table 9: 
Schedule of Events: Cohorts A1 and B1 (Pediatric Subjects [<12 years]) for Drug Concentration, 
Immunogenicity, and Laboratory Testing  
Samples for drug concentration (PK), immunogenicity assessment (ADA), and clinical laboratory testing (hematology, blood chemistry, and 
serology) will be collected based on subset designation and sample schedule (A, B, C, D) using subject number (assigned by IWRS): 
• Pediatric sentinel group (Subset 4): First 12 pediatric subjects (4 subjects per weight group (≥20 kg; 10 kg to <20 kg; 
<10 kg)  
• All other pediatric subjects (Subset 5): All other pediatric subjects  
Visit 
Screening / 
Baseline1 
Sentinel 
Group Only  
Efficacy Assessment 
Period (EAP) 
Follow-up Period 
ET 
Visit5 
Unscheduled 
Visit 
Site (S) 
S 
S 
S 
S 
S 
S 
S 
S 
S 
S 
S 
 
Visit Number 
1 
2 
5 
6 
8 
9 
10 
11 
12 
13 
14 
EOS 15 
 
 
Day 
1 
2 
8 
15 
29 
57 
85 
113 
141 
169 
197 
225 
 
 
Week 
0 
0 
1 
2 
4 
8 
12 
16 
20 
24 
28 
32 
 
 
Window (day) 
+2 
±1 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
 
 
 
Sentinel Group (Subset 4) 
PK-ADA2,3,9; Hematology4; Blood Chemistry4, Serology4,8 
Schedule A 
X1,8 
X 
 
 
X8 
 
 
 
 
 
 
 
X 
X6,7 
All other subjects (Subset 5) 
PK-ADA2,3,9; Hematology4, Blood Chemistry4, Serology8 
Schedule A 
X1,8 
X 
 
 
X8 
 
 
 
 
 
 
 
X 
X6,7 
Schedule B 
X1,8 
 
X 
 
X8 
 
 
 
 
 
 
 
X 
X6,7 
Schedule C 
X1,8 
 
 
X 
X8 
 
 
 
 
 
 
 
X 
X6,7 
Schedule D 
X1,8 
 
 
 
X8 
 
 
X8 
 
 
 
 
X 
X6,7 
Pharmacogenomics Sub-Study (only subjects ≥10 kg) 
Whole Blood for RNA 
(Optional) 
X10 
 
 
 
 
 
 
 
 
 
 
 
 
 
Whole Blood for DNA 
(Optional)  
X10 
 
 
 
 
 
 
 
 
 
 
 
 
 
ADA, anti-drug antibodies; EAP, Efficacy assessment period; EOS, end of study; ET, Early termination; PK, Pharmacokinetics 
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10.2.4. 
Schedule of Events Table 6: Cohorts A1 and B1 (Pediatric Subjects [<12 years]) for Drug Concentration, 
Immunogenicity, and Laboratory Testing 
1. Samples should be collected before the administration of study drug. Administration of study drug must be performed on the on 
same day as sample collection.  
2. Actual dosing time and sample collection times will be recorded for PK-ADA samples.   
3. At the screening/baseline visit, the window for baseline pre-dose PK-ADA sample collection is as close to administration of 
study drug as is reasonable. 
4. Whole blood samples for hematology and blood chemistry will be analyzed at central lab. 
5. Pediatric subjects who prematurely discontinue the study should have sample collection listed in the ET visit before exiting the 
study. 
6. A PK-ADA serum sample will be collected as soon as possible or within 7 days of receiving the first positive SARS-CoV-2 
RT-qPCR result for cohort A pediatric subjects. 
7. A PK-ADA serum sample will be collected as soon as possible or within 7 days of first new positive SARS-CoV-2 RT-qPCR 
result after achieving 2 consecutive negative results for all pediatric subjects. 
8. Serum samples for serology will be collected at baseline and day 29.  For pediatric subjects <10 kg, the serum sample for serology 
on the day 29 visit will not be collected due to restrictions in total blood volumes collection.  For pediatric subjects <3 kg, the 
serum sample for serology on the baseline and day 29 visit will not be collected due to restrictions in total blood volumes 
collection.  
9. The PK-ADA serum samples may be analyzed for ADA and NAb, if feasible. 
10. Only for pediatric subjects who weigh ≥10 kg:  The whole blood sample for RNA, should be collected on day 1/baseline (pre-
dose).  The whole blood for genomic DNA should be collected on day 1/baseline. If not collected at baseline, the sample for 
genomic DNA may be collected at any visit. 
10.2.5. 
Early Termination Visit 
Subjects who are withdrawn from the study will be asked to provide final blood samples for drug concentration and immunogenicity 
analysis. 
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10.2.6. 
Unscheduled Visits 
All attempts should be made to keep subjects on the study schedule.  Unscheduled visits may be necessary to repeat testing following 
abnormal laboratory results, for follow-up of AEs, for SARS-CoV-2 RT-qPCR and serology testing when subjects experience symptoms 
consistent with SARS-CoV-2 infection (per the broad-term list specified in Section 9.2.2.2 of the protocol), or for any other reason, as 
warranted. 
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Regeneron Pharmaceuticals, Inc. 
 
Protocol: R10933-10987-COV-2069 
Statistical Analysis Plan 
 
Date: 25MAR2021 
 
CONFIDENTIAL 
Page 72 of 77 
10.3. 
Criteria for Potentially Clinically Significant Values (PCSV) 
Parameter 
PCSV 
For Studies in healthy subjects only 
Comments 
Clinical chemistry 
ALT 
>3 and ≤5 ULN and baseline ≤3 ULN 
>5 and ≤10 ULN and baseline ≤5 ULN 
>10 and ≤20 ULN and baseline ≤10 ULN 
>20 ULN and baseline ≤20 ULN 
Enzymes activities must be 
expressed in ULN, not in IU/L.  
Each category is calculated 
independently. 
AST 
>3 and ≤5 ULN and baseline ≤3 ULN 
>5 and ≤10 ULN and baseline ≤5 ULN 
>10 and ≤20 ULN and baseline ≤10 ULN 
>20 ULN and baseline ≤20 ULN 
Enzymes activities must be 
expressed in ULN, not in IU/L.  
Each category is calculated 
independently. 
Alkaline 
Phosphatase 
>1.5 ULN and baseline ≤1.5 ULN 
Enzymes activities must be expressed 
in ULN, not in IU/L. 
 
Total Bilirubin 
>1.5 and ≤2 ULN and baseline ≤1.5 ULN 
>2 ULN and baseline ≤2.0 ULN 
Must be expressed in ULN, not in 
µmol/L or mg/L.  
Conjugated bilirubin >35% Total Bilirubin and TBILI >1.5 ULN, 
and baseline Total Bilirubin ≤35% or TBILI 
≤1.5 ULN 
Conjugated bilirubin dosed on a case-
by-case basis 
ALT and Total 
Bilirubin 
ALT>3 ULN and TBILI >2 ULN, and 
baseline ALT ≤3 ULN or TBILI ≤2ULN 
 
CPK 
>3 and ≤10 ULN and baseline ≤3ULN 
>10 ULN and baseline ≤10ULN 
 
Creatinine 
≥150 μmol/L (Adults) or ≥ULN (if ULN ≥150 
μmol/L) and baseline <150 μmol/L or <ULN 
(if ULN ≥150 μmol/L)   
≥30% change from baseline 
≥100% change from baseline 
3 independent criteria 
Creatinine 
Clearance 
(Cockcroft's 
formula) 
<15 ml/min and baseline ≥15 ml/min (end 
stage renal impairment) 
≥15 to <30 ml/min and baseline ≥30 ml/min 
(severe renal impairment) 
≥30 to < 60 ml/min and baseline ≥60 ml/min 
(moderate renal impairment) 
≥60 to < 90 ml/min and baseline ≥90 ml/min 
(mild renal impairment) 
Four independent criteria 
                                        VV-RIM-00148558-1.0 Approved - 26 Mar 2021 GMT-5:00


Regeneron Pharmaceuticals, Inc. 
 
Protocol: R10933-10987-COV-2069 
Statistical Analysis Plan 
 
Date: 25MAR2021 
 
CONFIDENTIAL 
Page 73 of 77 
Parameter 
PCSV 
For Studies in healthy subjects only 
Comments 
Uric Acid 
Hyperuricemia: 
 
     
    Hypouricemia: 
 
>408 μmol/L or >ULN (if ULN ≥408 
μmol/L) and baseline ≤408 μmol/L or ≤ULN 
(if ULN ≥408 μmol/L)   
<120 μmol/L or <LLN (if LLN ≤120 μmol/L) 
and baseline ≥120 μmol/L or ≥LLN (if LLN 
≤120 μmol/L)   
Two independent criteria 
Blood Urea 
Nitrogen 
≥17 mmol/L or ≥ULN (if ULN ≥17 mmol/L) 
and baseline <17 mmol/L or <ULN (if 
ULN≥17 mmol/L)   
Two independent criteria 
Chloride                   
   Hypochloremia: 
 
   Hyperchloremia: 
 
<80 mmol/L or <LLN (if LLN ≤80 mmol/L) 
and baseline ≥80 mmol/L or ≥LLN (if LLN 
≤80 mmol/L)   
>115 mmol/L or >ULN (if ULN ≥115 
mmol/L) and baseline ≤115 mmol/L or ≤ULN 
(if ULN ≥115 mmol/L)   
Two independent criteria  
Sodium 
   Hyponatremia: 
 
 
  Hypernatremia: 
 
≤129 mmol/L  or ≤LLN (if LLN ≤129 
mmol/L) and baseline >129 mmol/L  or 
>LLN (if LLN ≤129 mmol/L)   
≥160 mmol/L  or ≥ULN (if ULN ≥160 
mmol/L )  and baseline <160 mmol/L  or 
<ULN (if ULN ≥160 mmol/L )   
Two independent criteria 
Potassium 
   Hypokalemia 
 
 
   Hyperkalemia 
 
<3 mmol/L or <LLN (if LLN ≤3 mmol/L) and 
baseline ≥3 mmol/L or ≥LLN (if LLN ≤3 
mmol/L)   
≥5.5 mmol/L or ≥ULN (if ULN ≥5.5 mmol/L) 
and baseline <5.5 mmol/L or <ULN (if ULN 
≥5.5 mmol/L) 
Two independent criteria 
Total Cholesterol 
≥7.74 mmol/L or ≥ULN (if ULN ≥7.74 
mmol/L) and baseline <7.74 mmol/L or 
<ULN (if ULN ≥7.74 mmol/L) 
Threshold for therapeutic 
intervention. 
Triglycerides 
≥4.6 mmol/L or ≥ULN (if ULN ≥4.6 mmol/L) 
and baseline <4.6 mmol/L or <ULN (if ULN 
≥4.6 mmol/L) 
Threshold for therapeutic intervention 
                                        VV-RIM-00148558-1.0 Approved - 26 Mar 2021 GMT-5:00


Regeneron Pharmaceuticals, Inc. 
 
Protocol: R10933-10987-COV-2069 
Statistical Analysis Plan 
 
Date: 25MAR2021 
 
CONFIDENTIAL 
Page 74 of 77 
Parameter 
PCSV 
For Studies in healthy subjects only 
Comments 
Glucose 
 Hypoglycemia 
 
 Hyperglycemia 
 
≤3.9 mmol/L and <LLN and baseline >3.9 
mmol/L or ≥ LLN  
≥11.1 mmol/L (unfasted); ≥7 mmol/L (fasted) 
and baseline <11.1 mmol/L (unfasted); <7 
mmol/L (fasted)  
 
 
HbA1c 
>8%  and baseline  ≤ 8%  
 
Albumin 
≤25 g/L or ≤LLN (if LLN≤25 g/L) and 
baseline >25 g/L or >LLN (if LLN ≤25 g/L)   
 
CRP 
>2 ULN or >10 mg/L (if ULN not provided) 
and 
baseline ≤2 ULN or ≤10 mg/L (if ULN not 
provided) 
 
Hematology 
WBC 
<3.0 Giga/L or <LLN (if LLN ≤3.0 Giga/L) 
and baseline ≥3.0 Giga/L or ≥LLN (if 
LLN≤3.0 Giga/L) (Non-Black);  
<2.0 Giga/L or <LLN (if LLN ≤2.0 Giga/L) 
and baseline ≥2.0 Giga/L or ≥LLN (if 
LLN≤2.0 Giga/L) (Black) 
 
≥16.0 Giga/L or ≥ULN (if ULN ≥16.0 
Giga/L) and baseline < 16 Giga/L or <ULN 
(if ULN ≥16.0 Giga/L) 
 
Lymphocytes 
>4.0 Giga/L or >ULN (if ULN ≥4.0 Giga/L) 
and baseline ≤4.0 Giga/L or ≤ULN (if ULN 
≥4.0 Giga/L) 
 
Neutrophils 
<1.5 Giga/L or <LLN (if LLN ≤1.5 Giga/L)  
and baseline ≥1.5 Giga/L or ≥LLN (if LLN 
≤1.5 Giga/L) (Non-Black);  
 
<1.0 Giga/L or <LLN (if LLN ≤1.0 Giga/L)  
and baseline ≥1.0 Giga/L or ≥LLN (if LLN 
≤1.0 Giga/L)  (Black) 
 
Monocytes 
>0.7 Giga/L or >ULN (if ULN ≥0.7 Giga/L) 
and baseline ≤0.7 Giga/L or ≤ULN (if ULN 
≥0.7 Giga/L)   
 
                                        VV-RIM-00148558-1.0 Approved - 26 Mar 2021 GMT-5:00


Regeneron Pharmaceuticals, Inc. 
 
Protocol: R10933-10987-COV-2069 
Statistical Analysis Plan 
 
Date: 25MAR2021 
 
CONFIDENTIAL 
Page 75 of 77 
Parameter 
PCSV 
For Studies in healthy subjects only 
Comments 
Basophils 
>0.1 Giga/L or >ULN (if ULN ≥0.1 Giga/L) 
and baseline ≤0.1 Giga/L or ≤ULN (if ULN 
≥0.1 Giga/L)   
 
Eosinophils 
>0.5 Giga/L or >ULN (if ULN ≥0.5 Giga/L) 
and baseline ≤0.5 Giga/L or ≤ULN (if ULN 
≥0.5 Giga/L) 
 
Hemoglobin 
≤115 g/L or ≤LLN (if LLN ≤115 g/L) and 
baseline >115 g/L or >LLN (if LLN ≤115 
g/L) for male; ≤95 g/L or ≤LLN (if LLN ≤95 
g/L) and baseline >95 g/L or >LLN (if LLN 
≤95 g/L) for Female. 
 
≥185 g/L or ≥ULN (if ULN ≥185 g/L) and 
baseline <185 g/L or <ULN (if ULN ≥185 
g/L) for Male; ≥165 g/L or ≥ULN (if ULN 
≥165 g/L) and baseline <165 g/L or <ULN (if 
ULN ≥165 g/L) for Female 
 
Decrease from Baseline ≥20 g/L 
Three criteria are independent. 
Hematocrit 
≤0.37 v/v or ≤LLN (if LLN ≤0.37 v/v) and 
baseline >0.37 v/v or >LLN (if LLN ≤0.37 
v/v) for Male; ≤0.32 v/v or ≤LLN (if LLN 
≤0.32 v/v) and baseline > 0.32 v/v or >LLN 
(if LLN ≤0.32 v/v) for Female 
 
≥0.55 v/v or ≥ULN (if ULN ≥0.55 v/v) and 
baseline <0.55 v/v or <ULN (if ULN ≥0.55 
v/v) for Male; ≥0.5 v/v or ≥ULN (if ULN 
≥0.5 v/v) and baseline < 0.5 v/v or <ULN (if 
ULN ≥0.5 v/v) for Female 
Two Criteria are independent 
 
RBC 
≥6 Tera/L or ≥ULN (if ULN ≥6 Tera/L) and 
baseline < 6 Tera/L or <ULN (if ULN ≥6 
Tera/L) 
 
Platelets 
<100 Giga/L or <LLN (if LLN ≤100 Giga/L) 
and baseline ≥100 Giga/L or ≥LLN (if 
LLN≤100 Giga/L) 
 
≥700 Giga/L or ≥ULN (if ULN ≥700 Giga/L) 
and baseline <700 Giga/L or <ULN (if ULN 
≥700 Giga/L)   
Two independent criteria 
                                        VV-RIM-00148558-1.0 Approved - 26 Mar 2021 GMT-5:00


Regeneron Pharmaceuticals, Inc. 
 
Protocol: R10933-10987-COV-2069 
Statistical Analysis Plan 
 
Date: 25MAR2021 
 
CONFIDENTIAL 
Page 76 of 77 
Parameter 
PCSV 
For Studies in healthy subjects only 
Comments 
Vital signs 
HR 
<45 bpm and decrease from baseline ≥20 bpm 
≥120 bpm and increase from baseline ≥20 
bpm 
To be applied for all positions 
except STANDING 
SBP 
≤95 mmHg and decrease from baseline 
≥20 mmHg 
≥160 mmHg and increase from baseline 
≥20 mmHg 
To be applied for all positions 
except STANDING 
DBP 
≤45 mmHg and decrease from baseline 
≥10 mmHg 
≥110 mmHg and increase from baseline 
≥10 mmHg 
To be applied for all positions 
except STANDING 
 
10.4. 
Example of SAS Procedures for Primary Analysis and Missing Data 
Imputations by FCS   
 
Primary Analysis - GEE Model 
 
Below is an example of SAS code using a generalized linear model to estimate the odds ratio 
between the treatment groups with the generalized estimation equation (GEE) approach after 100 
imputations.  
 
proc genmod data=DATA_IN; 
class treatment(ref='0') Age_group region;/*eg.treatment= 0:placebo */ 
by _imputation_; 
model response(event='1’) =treatment region age_group/dist=bin link=logit; 
repeat subject=household_id/type=cs; 
lsmeans treatment/diff om cl ilink; 
ods output diffs=logOR geeexchcorr=icc; 
run; 
 
Primary Analysis - Logistic Regression Model 
 
Below is an example of SAS code using a logistic regression model instead of using GEE approach 
when the percentage of households with a single study subject is 70% or more to estimate the odds 
ratio between the treatment groups after 100 imputations. 
 
proc genmod data=DATA_IN descending; 
class treatment(ref='0') Age_group region; 
by _imputation_; 
model response(event='1’) =treatment region age_group/dist=bin link=logit; 
lsmeans treatment/diff om cl ilink; 
ods output diffs=logOR ParameterEstimates=parameterestimates; 
                                        VV-RIM-00148558-1.0 Approved - 26 Mar 2021 GMT-5:00


Regeneron Pharmaceuticals, Inc. 
 
Protocol: R10933-10987-COV-2069 
Statistical Analysis Plan 
 
Date: 25MAR2021 
 
CONFIDENTIAL 
Page 77 of 77 
run; 
 
 
Missing Data Imputations – FCS 
 
Assume the missing RT-qPCR test results occurred across Visit 5 (Day 8) to Visit 8 (Day 29) (e.g. 
1=positive vs 0=negative). An example of SAS code for FCS MI with the random seed=2069 is 
presented below. 
 
proc mi data=DATAIN out=DATAOUT seed=2069 nimpute=100; 
class treatment age_group   region v5 v6 v7 v8;  
var treatment age_group region v5 v6 v7 v8; 
fcs logistic(v5/LIKELIHOOD=AUGMENT); 
fcs logistic(v6/LIKELIHOOD=AUGMENT); 
fcs logistic(v7/LIKELIHOOD=AUGMENT); 
fcs logistic(v8/LIKELIHOOD=AUGMENT); 
run;  
 
After FCS MI to generate 100 complete datasets, each subject’s overall RT-qPCR test status during 
the EAP can be determined by any of imputed value V5 to V8 is equal to 1. The same model using 
GEE approach or logistic regression for the primary analysis will be applied.   
 
The results from the 100 analyses will be combined using Rubin’s formulae through PROC 
MIANALYZE procedure shown below.  
 
proc mianalyze data=logOR; 
ods output parameterestimates=final_logor; 
modeleffects estimate; 
stderr stderr; 
run; 
 
The estimates of log(odds ratio) and the corresponding 95% confidence interval (CI) will be 
provided in the FINAL_LOGOR dataset. The results of odds ratio and 95% CI will be derived by 
taking the exponential of these estimates.   
 
 
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Prot_001.pdf: 
EudraCT 2020‐003654‐71 
Regeneron Pharmaceuticals, Inc 
IND: 148069 
Clinical Study Protocol 
A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Assessing 
the Efficacy and Safety of Anti-Spike SARS-CoV-2 Monoclonal Antibodies in 
Preventing SARS-CoV-2 Infection in Household Contacts of Individuals 
Infected with SARS-CoV-2 
Compound: 
REGN10933+REGN10987 
Clinical Phase: 
3 
Protocol Number: 
R10933-10987-COV-2069 
Protocol Version: 
R10933-10987-COV-2069 Amendment 6 
Amendment 6 Date of Issue: 
See appended electronic signature page
Amendment 5 Date of Issue: 
19 Jan 2021 
Amendment 4 Date of Issue: 
24 Nov 2020 
Amendment 3 Date of Issue: 
07 Oct 2020 
Amendment 2 Date of Issue: 
26 Aug 2020 
Amendment 1 Date of Issue: 
17 Jul 2020 
Original Date of Issue 
16 Jun 2020 
Medical/Study Director: 
r, Early Clinical 
Development and Experimental Sciences 
, Early Clinical 
Development and Experimental Sciences  
, Early Clinical 
Development and Experimental Sciences 
Regeneron Pharmaceuticals, Inc. 
777 Old Saw Mill River Road 
Tarrytown, NY 10591 
VV-RIM-00142963-1.0 Approved - 25 Mar 2021 GMT-5:00
NCT04452318


Clinical Study Protocol 
 
R10933-10987-COV-2069 Amendment 6 
 
Regeneron Pharmaceuticals, Inc. 
 
Page 2 
 
CONFIDENTIAL 
AMENDMENT HISTORY 
Amendment 6 
The primary purpose of this amendment is to revise and add objectives and endpoints, as well as 
to define the statistical testing hierarchy for the primary and key secondary endpoints.    
Description of Change 
Brief Rationale 
Section(s) Changed 
Objectives, Endpoints, and Planned Statistical Analysis  
The 
following 
modifications 
were made to the planned 
statistical analysis: 
 
• Revised the primary objective 
and endpoint for cohort A  
The revision of the primary objective and 
endpoint for cohort A is informed by the 
administrative assessment of 409 cohort A 
seronegative subjects, where there was a 100% 
reduction in symptomatic events (broad-term) 
in 
the 
REGN10933+REGN10987 
treated 
subjects as compared to the placebo treated 
subjects with 8/223 (3.6%) placebo treated 
subjects developing symptomatic infection 
versus 0/186 (0%) REGN10933+REGN10987 
treated subjects; OR 0.00 (0.00, 0.69) p<0.01. 
The single primary objective is now to evaluate 
the efficacy of REGN10933+REGN10987 
compared 
to 
placebo 
in 
preventing 
symptomatic SARS-CoV-2 infection (broad-
term) confirmed by RT-qPCR 
Clinical Study Protocol 
Synopsis: Objectives, Endpoints, 
Statistical Plan 
Section 2 Study Objectives 
Section 2.1.1.1 Cohort A Primary 
Efficacy Objective 
Section 4 Endpoints 
Section 4.1.1 Cohort A Primary 
Endpoints 
Section 6.1.6 Description of 
Study Cohorts 
Section 9.2.2.2 COVID-19 
Symptomology (Strict Terms, 
Broad Terms, and CDC 
Definition) 
• Added a primary objective 
and endpoint for cohort B 
 
Because cohort B is a separate population from 
cohort A, where cohort B subjects are infected 
at baseline (SARS-CoV-2 RT-qPCR positive), 
a new primary objective and endpoint was 
added 
to 
evaluate 
whether 
REGN10933+REGN10987 may be efficacious 
as preemptive therapy to prevent symptoms in 
those who are already infected, therefore the 
objective is to evaluate the efficacy of 
REGN10933+REGN10987 
compared 
to 
placebo in preventing COVID-19 symptoms 
(broad-term) in asymptomatic subjects that are 
SARS-CoV-2 
RT-qPCR 
positive 
and 
seronegative at baseline 
Section 2.2 Cohort B and Cohort 
B1: SARS-CoV-2 RT-qPCR 
Positive at Baseline 
Section 2.2.1 Cohort B Primary 
Efficacy  Objective 
Section 2.2.2 Cohort B and 
Cohort B1 Primary Safety 
Objective 
Section 4.2.1 Cohort B Primary 
Efficacy Endpoint 
Defined 
key 
secondary 
endpoints for all cohorts  
The revision of the key secondary objectives 
and endpoints is informed by the  administrative 
assessment  of 409 cohort A seronegative 
subjects, such that revised key secondary 
endpoints now include the evaluation of 
REGN10933+REGN10987 as compared to 
placebo to reduce high viral load, defined as 
viral load >4 (log10 copies/mL), duration of 
symptomatic infection, duration of high viral 
load infection, duration of any infection, 
development of  infection (regardless of 
symptoms), all during the 28 day efficacy 
Section 4.1.2 Cohort A Key 
Secondary Endpoints 
Section 4.2.2 Cohort B Key 
Secondary Endpoints 
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Clinical Study Protocol 
 
R10933-10987-COV-2069 Amendment 6 
 
Regeneron Pharmaceuticals, Inc. 
 
Page 3 
 
CONFIDENTIAL 
assessment period.  An additional key 
secondary endpoint links the Regeneron 
R10933-10987-COV-2067 
outpatient 
treatment study with the R10933-10987-COV-
2069 prevention study, where households who 
enrolled 
symptomatic 
infected 
household 
members into 2067 and their asymptomatic 
uninfected members into 2069.  These data may 
inform whether treatment of symptomatic 
infected 
household 
members 
with 
REGN10933+REGN10987 
may 
prevent 
infection in uninfected household members.  
• Revised the secondary and 
exploratory objectives and 
endpoints for all cohorts  
 
Objectives and endpoints that were determined 
not to be key are listed as other secondary and 
exploratory. 
Section 2.1.3 Cohort A and 
Cohort A1 Secondary Objectives  
Section 2.1.4  Cohort A and 
Cohort A1 Exploratory 
Objectives 
Section 4.1.3 Cohort A and 
Cohort A1 Other Secondary 
Endpoints 
Section 4.1.4 Cohort A and 
Cohort A1 Exploratory 
Endpoints 
Section 2.2.3 Cohort B and 
Cohort B1 Secondary Objectives 
Section 2.2.4 Cohort B and 
Cohort B1 Exploratory 
Objectives 
Section 4.2.3 Cohort B and 
Cohort B1 Other Secondary 
Efficacy Endpoints 
Section 4.2.4 Cohort B and 
Cohort B1 Exploratory 
Endpoints  
• Updated 
the 
statistical 
hypotheses and the planned 
analyses for efficacy and 
safety 
 
Statistical hypothesis and planned analyses 
were updated in accordance with the revised 
primary(s) and key secondary objectives and 
endpoints 
Section 11.1 Statistical 
Hypothesis 
Section 11.4 Statistical Methods 
Section 11.4.3.1 Primary 
Efficacy Analysis  
Section 11.4.3.1.1. Sensitivity 
Analyses 
Section 11.4.3.1.2. Subgroup 
Analyses 
Section 11.4.3.2. Key Secondary 
Efficacy Analyses 
Section 11.4.3.3. Other 
Secondary Efficacy Analyses   
Section 11.4.1 Subject 
Disposition 
Section 11.4.5.1. Adverse Events  
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Clinical Study Protocol 
 
R10933-10987-COV-2069 Amendment 6 
 
Regeneron Pharmaceuticals, Inc. 
 
Page 4 
 
CONFIDENTIAL 
• The scope of analyses for 
first-step 
and 
second-step 
analyses were specified.   
• The data-cutoff for the first 
step analysis was specified 
The rationale for scope of analyses and the first-
step analysis data cut off are based on the results 
of the  administrative assessment and the 
sample size justification.  
Section 11.4.9. Timing of 
Statistical Analysis 
• Defined the statistical testing 
hierarchy for the primary 
endpoint and key secondary 
endpoints for cohort A and 
cohort B 
The statistical testing hierarchy was determined 
by considering which endpoints would be most 
relevant and important to understand the 
efficacy of  REGN10933+REGN10987  to 
prevent 
symptomatic 
infection 
and 
transmission potential, including the prevention 
of infections with high viral loads, longer 
duration of high viral loads, and whether 
REGN10933+REGN10987 can be considered 
for treatment of the symptomatic infected 
household member to prevent infection of the 
uninfected household member. 
Section 11.4.4. Control of 
Multiplicity  
Table 10 Hierarchy Testing 
Sequence of Key Secondary 
Efficacy Endpoints in 
Seronegative mFAS-A 
Table 11 Hierarchy Testing 
Sequence of Key Secondary 
Efficacy Endpoints in 
Seronegative mFAS-B 
• Updated the sample size 
justification 
 
 
 
Based on the decision not to conduct any 
interim analysis, the full alpha will be used for 
the first-step analysis.  
Section 11.2 Justification of 
Sample Size 
Table 9 Simulated Power for 
Household Design (1248 
Subjects over 430 Households 
Section 11.2.1 Cohort A: Adult 
and Adolescent Subjects (≥12 
years) Who Are SARS-CoV-2 
RT-qPCR Negative at Baseline 
Section 11.2.2 Cohort B: Adult 
and Adolescent Subjects (≥12 
years) Who Are SARS-CoV-2 
RT-qPCR Positive at Baseline 
• Updated the analysis set 
definitions 
The definitions were revised to specify that only 
seronegative subjects are eligible for the 
efficacy analysis sets.  
Section 11.3.1 Efficacy Analysis 
Sets 
Section 11.3.2 Safety Analysis 
Set 
Section 11.3.4 Immunogenicity 
Analysis Set 
Section 11.3.5 Neutralizing 
Antibody Analysis Set 
• Added statement that no 
interim 
analysis 
will 
be 
conducted for this study 
No interim analyses will be conducted for this 
study. 
Section 8.5 Blinding 
Section 11.5 Interim Analysis 
• Updated 
the 
variable 
definition for SARS-CoV-2 
infection  
The definition for positive and negative 
infection results was revised for consistency 
with the statistical analyses specified. 
Section 5.2 Efficacy Variables 
Clinical Rationales for the Changes to Objectives and Endpoints 
• Provided the rationales for 
the changes to the objectives 
and endpoints 
The rationales for the primary and secondary 
objectives and endpoints were revised based on 
the results of the  administrative assessment .  
Section 3.2.1 Study Design 
Section 3.2.3 Enrollment by 
Baseline SARS-CoV-2 Infection 
Section 3.2.5 Primary Objective 
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Clinical Study Protocol 
 
R10933-10987-COV-2069 Amendment 6 
 
Regeneron Pharmaceuticals, Inc. 
 
Page 5 
 
CONFIDENTIAL 
 
Section 3.2.6 Secondary 
Objectives 
Study Design 
• Added collection of external 
SARS-CoV-2 test results for 
subjects with COVID-19 
symptoms 
Collection of local SARS-CoV-2 test results 
will support confirmation of infection in 
subjects with COVID-19 symptoms 
Section 6.1.4 Efficacy 
Assessment Period 
Section 6.1.5 Follow-up Period 
Section 8.8 Concomitant 
Medications and Procedures 
Section 9.1.1 Schedule of Events 
Table 3 (Cohorts A and B [Adult 
/Adolescent Subjects], RT 
qPCR-Negative and Positive) 
Footnotes), footnote #9 
Section 11.4.3.1 Primary 
Efficacy Analysis  
Other changes 
• Updated confidentiality 
statement 
Revised per current corporate version    
Title Page 
• Minor editorial updates 
-changed verb tense 
-fixed numbered list 
formatting  
Corrected minor issues. 
Throughout the document 
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Clinical Study Protocol 
 
R10933-10987-COV-2069 Amendment 6 
 
Regeneron Pharmaceuticals, Inc. 
 
Page 6 
 
CONFIDENTIAL 
Amendment 5 
The primary purpose of this amendment is to describe the verification of the sample size 
assumptions used to design the study.   
Description of Change 
Brief Rationale 
Section(s) Changed 
• Added an administrative 
assessment for assumption 
verification and sample size 
estimation for the study 
• Sample size increased to 
3500 subjects to ensure that 
the formal analysis of the 
phase 3 study has an 
adequate sample size. 
The initial sample size assumptions used for 
the study design were based on COVID-19 
household contact infection rates observed 
in the literature available during study 
planning.  Currently, the range of reported 
infection rates, including onset of infection 
and symptomatic infection, is more variable 
in the literature than originally understood. 
Some early study data will be used, 
therefore, to verify the assumptions and 
estimated sample size by assessing infection 
rates in the population in this study. 
Clinical Study Protocol Synopsis: 
Study Design, Population, Statistical 
Plan 
Section 3.2.2 Subject Population 
Section 6.1 Study Description and 
Duration 
Section 7.1  Number of Subject Planned 
Section 11.2 Justification of Sample 
Size 
Section 11.2.1 Cohort A- SARS-CoV-2 
RT-qPCR Negative 
Section 8.5 Blinding 
Section 11.3.1 Full Analysis Sets 
Section 11.4.9 Timing of Statistical 
Analysis 
• Consolidated 
the 
dose 
information into a single 
section of the protocol 
The dose information is presented in one 
section.  
Section 
8.1 
Investigational 
and 
Reference Treatments 
Section 8.4 Method of Treatment 
Assignment 
• Added guidance related to 
the use of an EUA approved 
COVID-19 
vaccine 
by 
subjects in the study 
Specified that an EUA approved COVID-19 
vaccine is prohibited during the EAP and 
permitted in the Follow-up period.  The 
unblinding performed for the purpose of 
COVID-19 vaccine decision making does 
not need to be discussed with the medical 
director. 
Section 8.6 Emergency Unblinding 
Section 8.9 Prohibited Medications 
Section 8.10 Permitted Medications 
• Added 
collection 
of 
information 
for 
the 
household members related 
to 
an 
EUA 
approved 
monoclonal 
antibody 
treatment for COVID-19 or 
participation 
in 
 
the 
R10933-10987-COV-2067 
study 
Collection of this information is needed to 
understand the COVID-19 transmission in 
the household setting.   
Section 9.1.1 Schedule of Events Table 
3 (Cohorts A and B [Adult / Adolescent 
Subjects], 
RT-qPCR-Negative 
and 
Positive) Footnotes, #16  
Section 9.1.3 f Schedule of Events 
Table 5 Cohorts A1 and B1 (Pediatric 
Subjects [ <12 years], RT-qPCR-
Negative and Positive) Footnotes, # 15  
Section 9.2.1 Procedures Performed 
Only at the Screening/Baseline Visit 
• Updated 
the 
title 
for 
medical/study directors 
The medical/study director title were 
updated 
Title page 
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Page 7 
 
CONFIDENTIAL 
Amendment 4 
The primary purposes of this amendment are 1) to change from 2 primary endpoints to 1 primary 
endpoint, 2) to increase the sample size, 3) to allow for the inclusion of pediatric subjects aged 
<12 years, 4) to allow for the inclusion of women who are pregnant or breastfeeding, and 5) to add 
an exploratory objective and endpoint to assess whether the treatment of index cases with 
REGN10933+REGN10987 in the R10933-10987-COV-2067 study has an impact on rates of 
infectivity in household contacts in this study.  The endpoint and sample size changes are based 
on blinded review of the data with regard to SARS-CoV-2 infection events and baseline 
seropositivity prevalence in cohort A. The inclusion of pediatric subjects younger than 12 years 
and pregnant or breastfeeding women is considered relevant to the populations at risk for infection 
with SARS-CoV-2. 
Description of Change 
Brief Rationale 
Section(s) Changed 
• Study now has 1 primary 
efficacy endpoint: 
proportion of SARS-CoV-
2 infection during the 
efficacy assessment period 
(EAP). The proportion of  
“strict-term” symptomatic 
SARS-CoV-2 infection 
during the EAP has been 
moved to a secondary 
endpoint.  
A blinded analysis of approximately 25% of 
enrolled subjects was performed, 
demonstrating that lower than expected 
symptomatic infection events were 
observed in Cohort A: adult and adolescent 
Subjects (≥12 years) who are SARS-CoV-2 
RT-qPCR Negative at Baseline.  If 
2 primary endpoints were to be retained, the 
study is considered infeasible as the sample 
size would need to increase several fold to 
have enough symptomatic events in cohort 
A to be powered sufficiently.  The single 
primary endpoint of the prevention of 
laboratory confirmed SARS-CoV-2 
infection is considered highly clinically 
important because infection is the necessary 
antecedent event for illness. 
Clinical Study Protocol Synopsis: 
Primary 
Endpoints, 
Secondary 
Endpoints, Statistical Plan 
Section 3.2.5 Primary Objectives 
Section 3.2.6 Secondary Objectives 
Section 4.1.1 Cohort A Primary 
Endpoints 
Section 4.1.2 Cohort A and Cohort A1 
Secondary Endpoints 
Section 11.4.3.1 Primary Efficacy 
Analysis 
Section 11.4.4.1 Cohort A 
• Increased the sample size 
for the study 
A blinded analysis of approximately 25% of 
enrolled subjects was performed, 
demonstrating a higher than expected 
seropositivity rate at baseline in Cohort A.  
The sample size of cohort A is therefore 
being revised upwards to account for this 
seropositivity rate because only 
seronegative individuals are included in the 
primary analysis population. 
Section 7.1 Number of Subjects 
Planned 
Section 11.2 Justification of Sample 
Size 
Section 11.2.1 Cohort A- SARS-CoV-
2 RT-qPCR Negative 
Section 11.2.2 Cohort B - SARS-CoV-
2 RT-qPCR Positive 
• Pediatric subjects aged <12 
years are added to the 
study. 
• Added description of the 
informed consent for the 
parent/guardian and assent 
for pediatric subjects 
 
 
Pediatric subjects <12 years of age are 
added to the study because they are a 
population at risk of SARS-COV-2 
infection in a household and may contribute 
to the infection of others in the household. 
 
 
 
Pregnant women who are household 
contacts of an index case are at risk of 
SARS-CoV-2 infection and are at higher 
Clinical Study Protocol Synopsis: 
Objectives, Study Design, Sample 
Size, Target Population, Treatments, 
Primary 
Endpoints, 
Secondary 
Endpoints, 
Procedures 
and 
Assessments, Statistical Plan 
Section 1.2 Populations at Increased 
Risk of SARS-CoV-2 Infection Among 
Household Contacts of a Person 
Infected with SARS-CoV-2 
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CONFIDENTIAL 
•  Pregnant women and 
breastfeeding women are 
added to the study. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
• The requirement for 
contraception use by 
women of childbearing 
potential (WOCBP) was 
removed 
 
 
 
 
 
 
 
 
 
 
 
• The requirement for 
contraception use by men 
enrolled in the study was 
removed. 
 
 
 
 
 
• The stratification for 
pediatric subjects in 
randomization will take 
weight group into account 
(ie, ≥20 kg, ≥10 kg to 
<20 kg, and <10 kg ).  
risk of severe COVID-19 than non-pregnant 
women.  Inclusion of pediatric subjects, 
pregnant women, and breastfeeding women 
is supported by ongoing blinded review of 
the safety profile in adult and adolescent 
subjects, which is demonstrating that 
REGN10933+REGN10987 treatment is 
sufficiently well-tolerated.  In addition, 
there is no human fetal tissue cross-
reactivity of REGN10933 and REGN10987 
to suggest a risk to the fetus. The safety 
profile in pediatric subjects less than 12 
years and pregnant and breastfeeding 
women is expected to be similar to that 
observed in adults and adolescents. 
 
Because pregnant women are allowed in the 
study, contraception for women of 
childbearing potential (WOCBP) is no 
longer required as an exclusion criterion.  
However, WOCBP will undergo pregnancy 
testing prior to dosing and at the end of 
study.  Women who are pregnant or who 
become pregnant during the study will be 
followed for the outcome of their 
pregnancy.  The inclusion of pregnant 
women who are identified at study entry as 
well as women who become pregnant 
during the study will provide important 
safety and efficacy data in this population at 
increased risk of severe COVID-19. 
 
Because pregnant women are allowed in the 
study, contraception for men enrolled in the 
study is no longer required as an exclusion 
criterion.   Information regarding 
pregnancies occurring in the female 
partners of male study subjects will not be 
solicited as the risk of exposure is 
negligible in this scenario 
 
The stratification is to ensure relative 
balance in treatment allocation among 
different pediatric weight groups for PK 
analysis. 
Section 1.5 A Randomized, Placebo-
Controlled Study of Anti- Spike 
Protein Monoclonal Antibodies as 
Post-Exposure Prophylaxis and Pre-
emptive 
Therapy 
in 
Household 
Contacts 
Section 3.2.1 Study Design 
Section 3.2.2 Subject Population  
Section 3.2.4 Sentinel Safety Group 
and Subsequent Safety Reviews 
Section 3.3 Risk-Benefit 
Section 6.1 Study Description and 
Duration 
Figure 1 Study Flow Diagram 
Section 6.1.2 Pediatric Subjects (<12 
years) 
Section 6.1.3 Screening/Baseline 
Section 7.1 Number of Subjects 
Planned 
Section 7.2 Study Population 
Section 
7.2.1 
Inclusion 
Criteria, 
criterion #1 
Section 7.2.2 Exclusion Criteria, #14, 
#15, #16 
Section 8.6 Emergency Unblinding 
Section 13.2 Informed Consent 
 
• Specified doses for 
subjects <12 years of age 
using weight-tiered dosing 
groups 
Based on population pharmacokinetics 
modeling and simulation, lower doses were 
selected for children using a weight-tiered 
approach in order to achieve approximately 
Section 3.2.7 Rationale for Dose 
Selection 
Figure 1 Study Flow Diagram 
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CONFIDENTIAL 
similar exposures as those observed in 
adults.  Weight is the primary variable 
influencing drug exposure. 
 
Section 
8.1 
Investigational 
and 
Reference Treatments 
Section 8.4 Method of Treatment 
Assignment 
Section 9.2.4 Drug Concentration and 
Measurements 
Table 6 Schedule of Events: Cohorts 
A1 and B1 (Pediatric Subjects [<12 
years]) 
for 
Drug 
Concentration, 
Immunogenicity, 
and 
Laboratory 
Testing 
Section 9.1.4 Schedule of Events 
Table 6 Schedule of Events: Cohorts 
A1 and B1 (Pediatric Subjects [<12 
years]) for Drug Concentration, 
Immunogenicity, and Laboratory 
Testing 
•  Subjects <12 years of age 
will be divided into 2 
independent study cohorts, 
cohort A1 (SARS-CoV-2 
RT-PCR negative at 
baseline) or cohort B1 
(SARS-CoV-2 RT-PCR 
positive at baseline) using 
the same parameters used 
to define cohort A and B 
for the adult and 
adolescent subjects. 
 
• Study objectives and 
endpoints were specified 
for cohort A1 and cohort 
B1 
 
• Cohort A1 and cohort B1 
will be analyzed separately 
from the adult and 
adolescent subjects. 
The pediatric subjects <12 years are 
proposed to be analyzed separately from the 
adults and adolescents because 1) drug 
concentrations and exposures need to be 
evaluated and may change during the study, 
2) nasopharyngeal (NP) sampling for 
RT-qPCR is not identical to that used for 
adult and adolescent subjects, 3) subjects 
<12 years may have milder disease, 4) 
COVID-19 signs and symptoms/AE 
reporting may be different in subjects <12 
years  
Clinical Study Protocol Synopsis: 
Objectives, 
Sample 
Size, 
Target 
Population, 
Treatments, 
Primary 
Endpoints, 
Secondary 
Endpoints, 
Statistical Plan 
Section 2 Study Objectives 
Section 2.1 Cohort A: SARS-CoV-2 
RT qPCR Negative at Baseline 
Section 2.1.2 Cohort A and Cohort A1 
Primary Safety Objective 
Section 2.1.3 Cohort A and Cohort A1 
Secondary Objectives 
Section 2.1.4 Additional Cohort A1 
Secondary Efficacy Objective 
Section 2.1.5 Cohort A and Cohort A1 
Exploratory Objectives 
Section 2.2 Cohort B and Cohort B1: 
SARS-CoV-2 RT qPCR Positive at 
Baseline 
Section 2.2.1 Cohort B and Cohort B1 
Secondary Objectives 
Section 2.2.2 Cohort B and Cohort B1 
Exploratory Objectives 
Section 3.2.1 Study Design 
Section 3.2.3 Enrollment by Baseline 
SARS-CoV-2 Infection 
Section 4.1 Cohort A and Cohort A1: 
SARS-CoV-2 RT-qPCR Negative at 
Baseline 
Section 4.1.1 Cohort A Primary 
Endpoints 
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CONFIDENTIAL 
Section 4.1.2 Cohort A and Cohort A1 
Secondary Endpoints 
Section 4.1.3 Cohort A and Cohort A1 
Exploratory Endpoints 
Section 4.2 Cohort B: SARS-CoV-2 
RT-qPCR Positive at Baseline 
Section 4.2.1 Cohort B and Cohort B1 
Secondary Efficacy Endpoints 
Section 4.2.2 Cohort B and Cohort B1 
Exploratory Endpoints 
Section 6.1.6 Description of Study 
Cohorts 
Section 11.3.1 Full Analysis Sets 
Section 11.4.3.2 Secondary Efficacy 
Analyses 
Section 11.4.5.1 Adverse Events 
• Specified assessments for 
cohort A1 and cohort B1 
(subjects <12 years of age) 
The assessments were modified for 
pediatric subjects younger than 12 years to 
minimize blood draws and procedures.  
Clinical Study Protocol Synopsis: 
Procedures and Assessments 
Table 3 Schedule of Events (Cohorts A 
and B [Adult / Adolescent Subjects], 
RT-qPCR-Negative and Positive)  
Section 9.1.1 Schedule of Events Table 
2 (Cohorts A and B [Adult / Adolescent 
Subjects], 
RT-qPCR-Negative 
and 
Positive) Footnotes #2, #4, #6, #12, 
#18, #19, #20 
Table 4  Schedule of Events: Cohorts A 
and B (Adult / Adolescent Subjects) for 
Drug Concentration, Immunogenicity, 
and Laboratory Testing 
Section 9.1.2 Schedule of Events Table 
3:  Cohorts A and B (Adult / 
Adolescent 
Subjects) 
for 
Drug 
Concentrations, Immunogenicity, and 
Laboratory Testing 
Table 5 Schedule of Events: Cohorts 
A1 and B1 (Pediatric Subjects [<12 
years], 
RT-qPCR-Negative 
and 
Positive) 
Section 9.1.3 Schedule of Events Table 
4 Cohorts A1 and B1 (Pediatric 
Subjects 
[<12 
years], 
RT-qPCR-
Negative and Positive) Footnotes 
Table 6 Schedule of Events:  Cohorts 
A1 and B1 (Pediatric Subjects [<12 
years]) 
for 
Drug 
Concentration, 
Immunogenicity, 
and 
Laboratory 
Testing 
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Regeneron Pharmaceuticals, Inc. 
 
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CONFIDENTIAL 
Section 9.1.4  Schedule of Events 
Table 5: Cohorts A1 and B1 (Pediatric 
Subjects 
[<12 
years]) 
for 
Drug 
Concentration, Immunogenicity, and 
Laboratory Testing 
Section 9.2.2.1 Nasopharyngeal Swab 
SARS-CoV-2 RT-qPCR Test (Central 
Lab) 
Section 
9.2.2.2 
COVID-19 
Symptomology (Strict Terms, Broad 
Terms, and CDC Definition) 
Section 
9.2.2.3 
Assessment 
of 
Medically Attended Visits 
Section 
9.2.2.4 
Absenteeism 
Assessment 
Section 
9.2.3.1Targeted 
Physical 
Examination and Vital Signs 
Section 9.2.3.2 Laboratory Testing 
Section 
9.2.6 
Exploratory 
Pharmacodynamic/Biomarker 
Procedures 
Section 
9.2.7 
Pharmacogenomic 
Analysis (Optional) 
Section 10.1.3 Events that Require 
Expedited Reporting to Sponsor 
• Added exploratory 
objective to assess the 
impact of the treatment of 
index cases receiving  
REGN10933+REGN10987 
in study R10933-10987-
COV-2067 on rates of 
infectivity in household 
contacts 
Included to study the infection dynamics 
within a household and assess if the  
treatment of the index case with 
REGN10933+REGN10987 in study 
R10933-10987-COV-2067 affects 
secondary infection rates in study 
R10933-10987-COV-2069. 
Section 2.1.5Cohort A and Cohort A1 
Exploratory Objectives 
Section 4.1.3Cohort A and Cohort A1 
Exploratory Endpoints 
Section 9.1.1Schedule of Events Table 
2 (Cohorts A and B [Adult / 
Adolescent Subjects], RT-qPCR-
Negative and Positive) Footnote #16 
• Added a secondary 
objective and an endpoint 
based on the CDC 
definition of COVID-19 
symptoms  
The use of the CDC definition for a 
secondary objective and an endpoint 
support comparability of results across 
clinical studies in the field. 
Clinical Study Protocol Synopsis:  
Objectives, Endpoints, Secondary 
Endpoints, Procedures and 
Assessments, Statistical Plan 
Section 2.1.3 Cohort A and Cohort A1 
Secondary Objectives 
Section 2.2.1 Cohort B and Cohort B1 
Secondary Objectives 
Section 3.2.6 Secondary Objectives  
Section 4.1.2 Cohort A and Cohort A1 
Secondary Endpoints 
 Section 4.1.3 Cohort A and Cohort 
A1 Exploratory Endpoints 
Section 4.2.1 Cohort B and Cohort B1 
Secondary Efficacy Endpoints 
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CONFIDENTIAL 
Section 4.2.2 Cohort B and Cohort B1 
Exploratory Endpoints 
Section 5.2 Efficacy Variables 
Section 9.2.2.2  COVID-19 
Symptomology (Strict Terms, Broad 
Terms, and CDC Definition) 
Table 7 Strict-Terms ,and Broad-
Terms, and CDC Definition COVID-
19 Signs and Symptoms 
• Changed the definition of 
the index case such that the 
index case must be the first  
household member known 
to be infected with SARS-
CoV-2 
Adding the requirement that the index case 
be the first known infected household 
member in the house may increase the 
number of household members who have 
not yet been exposed to SARS-CoV-2 and 
may therefore still be susceptible to 
infection. 
Clinical Study Protocol Synopsis: 
Study Design, Target Population 
Section 2 Study Objectives 
Section 3.2.1 Study Design 
Section 3.2.2 Subject Population 
Section 6.1 Study Description and 
Duration 
Section 6.1.6 Description of Study 
Cohorts 
Section 7.2 Study Population 
Section 7.2.2 Exclusion Criteria, #2 
• Revised the description of 
the screening and baseline 
visit to allow a remote visit 
to occur on the day prior to 
randomization and study 
drug administration to sign 
the informed consent form 
and collect medical history 
and concomitant 
medication use. 
Provide flexibility for subjects to complete 
the screening remotely so that in-person 
screening may be abbreviated due to 
COVID-19 considerations 
Section 6.1 Study Description and 
Duration 
Section 9.1.1 Schedule of Events  
Table 2 (Cohorts A and B [Adult / 
Adolescent Subjects], RT-qPCR-
Negative and Positive) Footnotes #1 
• Added assessment of 
neutralizing antibodies, if 
feasible 
Provide information about the assessment 
of NAbs in the study 
Clinical Study Protocol Synopsis:  
Secondary Endpoints 
Section 3.2.1 Study Design 
Section 4.1.2 Cohort A and Cohort A1 
Secondary Endpoints 
Section 4.2.2 Cohort B and Cohort B1 
Exploratory Endpoints 
Section 5.5 Immunogenicity Variables 
Section 9.1.2 Schedule of Events 
Table 3:  Cohorts A and B (Adult / 
Adolescent Subjects) for Drug 
Concentrations, Immunogenicity, and 
Laboratory Testing 
Section 9.1.4  Schedule of Events 
Table 5: Cohorts A1 and B1 (Pediatric 
Subjects [<12 years]) for Drug 
Concentration, Immunogenicity, and 
Laboratory Testing 
Section 9.2.5 Immunogenicity 
Measurements and Samples 
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CONFIDENTIAL 
Amendment 3 
The primary purpose of this amendment is to include adolescent subjects aged 12 years to less than 
18 years in the study. The inclusion of adolescent subjects is considered relevant to the populations 
at risk for infection with SARS-CoV-2.   
Section 11.3.4 Immunogenicity 
Analysis Sets 
Section 11.4.8 Analysis of 
Immunogenicity Data 
• Added a description of 
current approved treatment 
and therapies for COVID-
19  
Provide information about current 
treatments  and therapies for COVID-19 
Section 1.5  A Randomized, Placebo-
Controlled Study of Anti- Spike 
Protein Monoclonal Antibodies as 
Post-Exposure Prophylaxis and Pre-
emptive Therapy in Household 
Contacts   
• Clarified the exclusion of 
drugs used to treat 
COVID-19 
Specified that prohibited drugs (eg, 
hydroxychloroquine)  can be used to treat a 
non-COVID-19 disease (eg, autoimmune 
disease). 
Section 7.2.2 Exclusion Criteria, #2, 
#12 
Section 8.9 Prohibited Medications 
• Minor editorial updates 
-added abbreviations  
-changed verb tense 
- added and deleted 
references 
Updated the abbreviation and reference 
lists. 
Throughout the document 
Description of Change 
Brief Rationale 
Section(s) Changed 
• Adolescent subjects aged 
12 years to less than 18 
years are added to the 
study  
 
 
• Provided a rationale for 
dose selection for 
adolescent subjects (≥40 
kg) 
 
 
 
 
• Revised the description of 
women of childbearing 
potential (WOCBP) to 
include ‘girls at or beyond 
menarche (≥12 to <18 
years of age)’ 
 
• Added description of the 
informed consent process 
Adolescent subjects ≥12 to <18 years of 
age (weight ≥40 kg) are added to the 
study because they are a population at 
risk of SARS-CoV-2 infection in a 
household.   
 
Inclusion of adolescent subjects is 
supported by ongoing blinded review of 
the safety profile, which is 
demonstrating that 
REGN10933+REGN10987 treatment is 
well-tolerated in more than 1000 adult 
subjects who have received drug.  
 
Defined the age range for adolescent 
female subjects to be considered 
WOCBP. 
 
 
 
 
Clinical Study Protocol Synopsis: Study 
Design, Population, Treatments, 
Procedures and Assessments, Statistical 
Plan 
Section 1.2 Populations at Increased Risk 
of SARS-CoV-2 Infection Among 
Household Contacts of a Person Infected 
with SARS-CoV-2 
Section 2 Study Objectives 
Section 3.2.1 Study Design 
Section 3.2.2 Subject Population  
Section 3.2.3 Enrollment by Baseline 
SARS-CoV-2 Infection 
Section 3.2.4 Sentinel Safety Group and 
Subsequent Safety Reviews 
Section 3.2.5 Primary Objectives 
Section 3.2.6 Rationale for Dose Selection 
Section 3.3 Risk-Benefit 
Section 6.1 Study Description and 
Duration 
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CONFIDENTIAL 
for adolescent subjects and 
their parent/guardian 
 
• The stratification for age 
group in randomization 
will take adolescents into 
account (ie, ≥12 to <18, 
≥18 to <50, ≥50). 
 
• Specify the sample size re-
estimation will be 
conducted periodically, 
starting when 
approximately 25% of 
subjects in cohort A have 
completed the efficacy 
assessment period (EAP).   
 
 
 
 
• Summaries of treatment-
emergent adverse events 
(TEAEs) for adolescent 
subjects will also be 
provided. 
Provided instruction for documenting 
consent of the adolescent subject and 
their parent/guardian 
 
 
The stratification is to ensure relative 
balance in treatment allocation in 
adolescents. 
 
 
 
The rate of symptomatic SARS-CoV-2 
infections among adolescent subjects 
may differ from adults. Since adolescent 
subjects are being added after the start 
of the study, greater flexibility in the 
timing of the sample size re-estimations 
is needed to ensure that the attack rate 
can be estimated for adolescent 
subjects.  
 
 
 
To evaluate the safety data among 
adolescent subjects. 
Section 6.1.1 Sentinel Subjects and 
Staggered Enrollment/Dosing 
Section 6.1.2 Screening/Baseline 
Section 6.1.3 Efficacy Assessment Period 
Section 6.1.4 Follow-up Period 
Section 6.1.5 . Description of Study 
Cohorts 
Section 6.3.2 Safety Review Committee 
for REGN 2069/CoVPN3502 
Section 7.1 Number of Subjects Planned 
Section 7.2 Study Population 
Section 7.2.1 Inclusion Criteria, criterion 
#1 
Section 7.2.2 Exclusion Criteria, #16 
Section 7.3 Premature Withdrawal from 
the Study 
Table 1 Schedule of Events (All Cohorts, 
RT-qPCR-Negative and Positive)  
Section 9.1.1 Schedule of Events Table 1 
(All Cohorts[Adult / Adolescent 
Subjects], RT-qPCR-Negative and 
Positive) Footnotes #2, #4, #6, #12, #19 
Section 9.2.1.1 Informed Consent 
Section 9.2.2.2 COVID-19 
Symptomology (Strict Terms and Broad 
Terms) 
Section 9.2.3.1 Targeted Physical 
Examination and Vital Signs 
Section 9.2.4 Drug Concentration and 
Measurements 
Section 10.1.1 General Guidelines 
Section 11.2.1 Cohort A- Justification of 
Sample Size 
Section 11.4.5.1 Adverse Events 
Section 13.2 Informed Consent 
• Added description that the 
investigator will 
recommend that subjects 
measure their body 
temperature daily and 
when they feel unwell.  
 
 
 
 
 
• Revised the description of 
subject subset 1 and subset 
2 to indicate these are 
completed. 
 
Per protocol, fever is 1 of the signs that 
define 1 of the primary endpoints of the 
study (ie, symptomatic SARS-CoV-2 
infection).  In order to reduce the 
possibility that study subjects forget to 
measure their temperature, wording was 
added to the protocol for investigators 
to recommend that temperature be 
measured daily and when subjects feel 
unwell 
 
These subject subsets are completed 
 
 
 
 
Clinical Study Protocol Synopsis: Study 
Design,  Statistical Plan 
Section 6.1.3 Efficacy Assessment Period 
Section 6.1.4 Follow-up Period 
Table 2 Schedule of Events for Drug 
Concentration, Immunogenicity, and 
Laboratory Testing 
Section 10.1.1 General Guidelines 
Section 11.4.3.1.1 Primary Efficacy 
Analysis (Cohort A) 
Section 11.4.3.1.3 Secondary Efficacy 
Analyses 
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CONFIDENTIAL 
Amendment 2 
The primary purpose of this amendment is to remove the requirement for subjects to have at least 
48 hours of sustained exposure to the index case. The 48-hour exposure requirement is considered 
to be too restrictive and not necessary since the subject is expected to be living in the same 
household with the index case. Additionally, the definition of ‘household’ was updated to clarify 
the specific characteristics of a household; the guidance for the conduct of the local diagnostic 
assay testing at baseline was revised; and the analysis of cohort B was revised to include all 
subjects at baseline (ie, subjects who are seropositive or seronegative). 
 
• Revised the description of 
the automated reminders to 
being optional if not 
technically feasible 
(language barriers, no 
mobile phone, etc)  
 
 
 
• Modify the analysis for 
continuous endpoints from 
GEE model to 
ANOVA/ANCOVA 
model. 
 
The use of automated reminders was 
made optional in case of 
technical/operational difficulties/delays 
in implementation. 
 
 
 
 
 
For continuous endpoints the analysis 
population consists of those subjects 
who have at least 1 positive RT-qPCR 
during EAP instead of all subjects in 
full analysis set (FAS) (ie, smaller 
sample size). Thus, the ANOVA model 
will be used and for change and percent 
change from baseline endpoints the 
relevant baseline values will be 
included as covariate in the model (ie, 
ANCOVA model). 
• Minor editorial updates 
-added a statement about 
anti-drug antibody (ADA) 
assessment to the synopsis  
- deleted ‘post-baseline’   
-added and deleted 
references 
 
Added for consistency with the protocol 
body  
 
Corrected an error 
Updated the reference list 
 Clinical Study Protocol Synopsis:  
Procedures and Assessments  
Section 3.2.3 Enrollment by Baseline 
SARS-CoV-2 Infection 
Section 19 References 
Description of Change 
Brief Rationale 
Section(s) Changed 
• Removed requirement for 
subjects to have sustained 
exposure to the index case for 
‘at least 48 hours’  
The 48-hour exposure requirement 
is considered to be too restrictive 
and not necessary since the subject 
is expected to be living in the same 
household with the index case.   
These changes were made to 
address feasibility issues. 
Clinical Study Protocol Synopsis: 
Study Design  
Section 6.1 Study Description and Duration 
Section 7.2.1 Inclusion Criteria, criterion 
#2 
• Updated the definition of 
‘household’ with specific 
characteristics. 
This change was made to specify 
the characteristics of a ‘household 
‘that are compatible with the 
Section 3.2.2 Subject Population 
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assumptions used for the sample 
size calculation. 
• Revised the description of 
local diagnostic assay to 
include SARS-CoV-2 antigen 
or RT-PCR using an 
appropriate sample such as 
nasopharyngeal (NP), nasal, 
oropharyngeal (OP), or saliva. 
• Added the option to not 
perform the local diagnostic 
assay for SARS-CoV-2 if the 
results are not anticipated to 
be available in a timely 
manner for randomization. 
• Revised the description of the 
automated reminders to be 
‘implemented as soon as 
technologically feasible’ 
• Revised the Schedule of 
Events and footnotes to clarify 
the procedures for subjects 
who are RT-qPCR negative 
and the procedures for 
subjects who are RT-qPCR 
positive 
These changes were made to 
address feasibility and operational 
constraints for clinical sites. 
Clinical Study Protocol Synopsis, Study 
Design, Procedures and Assessments 
Section 3.2.1 Study Design 
Section 3.2.3 Enrollment by Baseline 
SARS-CoV-2 Infection 
Section 5.1 Demographic and Baseline 
Characteristics 
Figure 1 Study Flow Diagram 
Section 6.1 Study Description and Duration 
Section 6.1.2 Screening/Baseline 
Section 6.1.3 Efficacy Assessment Period 
Section 8.4 Method of Treatment 
Assignment 
Table 1 Schedule of Events (All Cohorts, 
RT-qPCR-Negative and Positive) 
Section 9.1.1 Schedule of Events Table 1 
(All Cohorts, RT-qPCR-Negative and 
Positive) Footnotes - #7, #9, #17, #18, #19, 
#20 
Section 9.2.1 Procedures Performed Only 
at the Screening/Baseline Visit 
Section 9.2.1.2 Local Diagnostic Assay for 
SARS-CoV-2 
• Revised the planned analysis 
for cohort B to also include 
subjects who are seropositive 
at baseline 
• Updated the cohort B 
exploratory endpoints 
• Updated the primary efficacy 
analysis (cohort A) and 
secondary efficacy analyses  
This change was made since many 
of the subjects enrolled in cohort B 
(RT-qPCR positive at baseline) are 
seropositive at baseline, using 
semi-quantitative assays, and the 
presence of antibodies in subjects 
with an active infection is of 
unknown clinical relevance. 
Clinical Study Protocol Synopsis:  
Objectives, Endpoints, Statistical Plan 
Section 2 Study Objectives 
Section 2.1 Cohort A: SARS-CoV-2 RT 
qPCR Negative at Baseline 
Section 2.2 Cohort B: SARS-CoV-2 RT 
qPCR Positive at Baseline 
Section 2.2.1 Cohort B Secondary 
Objectives 
Section 2.2.2 Cohort B Exploratory 
Objectives 
Section 4.1 Cohort A: SARS-CoV-2 RT 
qPCR Negative at Baseline 
Section 4.2 SARS-CoV-2 RT-qPCR 
Positive at Baseline 
Section 4.2.1 Cohort B Secondary Efficacy 
Endpoints 
Section 4.2.2 Cohort B Exploratory 
Endpoints Section 11.3.1 Full Analysis 
Sets 
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Section 11.4.3.1.1 Primary Efficacy 
Analysis (Cohort A) 
Section 11.4.3.1.1 Primary Efficacy 
Analysis (Cohort A) 
Section 11.4.3.1.2 Events that Require 
Expedited Reporting to Sponsor 
Section 11.4.3.1.3 Secondary Efficacy 
Analyses 
• Added the caveat that the use 
of automated reminders for 
subjects would be 
implemented if systems allow, 
as soon as or if feasible. 
This change was made to clarify 
the use of automated reminders in 
the study. 
Section 6.1.3 Efficacy Assessment Period 
• Added a summary of safety 
results from the sentinel safety 
group of this study 
This summary was added to present 
the safety results.  
Section 3.2.1 Study Design 
• Revised the description of the 
Safety Review Committee  
Clarified the composition of the 
Safety Review Committee 
Section 6.3.2 Safety Review Committee for 
REGN 2069/CoVPN3502 
• Removed ‘electrocardiogram’ 
from the description of results 
of the sentinel safety group 
data from earlier studies in the 
REGN10933+REGN10987 
clinical development program 
This change is a correction of an 
error in the description of the 
assessments for the sentinel safety 
group. 
List of Abbreviations 
Section 3.2.4 Sentinel Safety Group and 
Subsequent Safety Reviews 
Section 3.3 Risk-Benefit 
• Revised text describing the 
measurement and analysis of 
drug or anti-drug antibodies 
(ADA) 
• Updated the footnotes 
describing the collection of 
PK and ADA samples  
These changes clarify the 
descriptions related to PK or ADA 
assessments. 
Clinical Study Protocol Synopsis:  
Endpoints 
Section 4.1.2 Cohort A Secondary 
Endpoints 
Section 5.4 Pharmacokinetic Variables 
Table 2 Schedule of Events for Drug 
Concentration, Immunogenicity, and 
Laboratory Testing 
Section 9.1.2 Schedule of Events Table 2: 
Drug Concentrations, Immunogenicity, and 
Laboratory Testing, Footnotes #6, #7 
Section 11.3.3 Pharmacokinetic Analysis 
Set 
Section 11.3.4 Immunogenicity Analysis 
Set 
• Added the statement 
highlighting that for this study 
only severity grade 3 or above 
for anaphylaxis, allergic 
reaction (hypersensitivity 
reaction), and injection site 
reaction are reportable as 
This change was made to clarify 
the reporting of AESIs. 
Table 4 NCI-CTCAE Severity Grading 
System for Adverse Events for 
Anaphylaxis, Allergic Reaction, and 
Injection Site Reaction 
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adverse events of special 
interest (AESIs)  
• Minor editorial update  
- addition of EudraCT number 
to the title page 
- corrected a sentence in the 
Introduction 
- minor edits for clarity 
- study monitoring section 
updated to match the current 
protocol template 
- Risk Management Lead 
updated to Global Safety Lead 
to match current nomenclature 
for role 
Throughout 
Title Page 
Section 1.3 The Role of Spike Protein in 
SARS-CoV-2 Pathogenesis 
Section 5.2 Efficacy Variables 
Section 3.2.1 Study Design 
Section 3.2.3 Enrollment by Baseline 
SARS0CoV-2 Infection 
Section 6.1.1 Sentinel Subjects and 
Staggered Enrollment/Dosing 
Section 6.3.2 Safety Review Committee for 
REGN 2069/CoVPN3502 
Section 12.2.1 Monitoring of Study Sites 
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Amendment 1 
The purpose of this amendment is to change the collection of respiratory samples for SARS-CoV-2 
reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR) from nasal swabs and 
saliva samples to nasopharyngeal (NP) swab samples due to analysis of data from baseline samples 
from the REGN10933+REGN10987 treatment studies, where study patients were sampled by NP 
swabs, nasal swabs, and saliva for side-by-side comparison.  NP swabs had markedly better 
sensitivity to detect SARS-CoV-2 than nasal swabs and saliva samples.  Additionally, the 
requirement for local serology testing at baseline was removed because it is anticipated that most 
subjects will be negative and local serology testing is not feasible at many sites. In addition, this 
amendment includes updates to address health authority feedback and collaborator comments.  
Description of Change 
Brief Rationale 
Section(s) Changed 
• Changed collection from nasal 
swabs and saliva samples to 
nasopharyngeal (NP) swabs for 
SARS-CoV-2 RT-qPCR test 
• Removed collection of nasal 
swab and saliva samples for 
SARS-CoV-2 RT-qPCR test 
• Removed endpoints based on 
analysis of saliva samples for 
SARS-CoV-2 RT-qPCR test 
• Clarified that molecular 
diagnostic RT-PCR tests, 
qualitative and quantitative, 
will be unblinded to site 
personnel and the Sponsor 
Based on review of blinded 
RT-PCR data from 
REGN10933-10987 treatment 
studies, use of NP swab 
samples had better sensitivity 
to detect RT-PCR positivity 
than nasal swab and saliva 
samples. 
 
 
 
This change is to ensure proper 
medical care and isolation of 
positive subjects and to ensure 
appropriate quality control of 
NP samples. 
Clinical Study Protocol Synopsis: Study 
Design, 
Endpoints, 
Procedures 
and 
Assessments, Statistical Plan 
Section 3.2.3 Enrollment by Baseline SARS-
CoV-2 Infection 
Section 3.2.5 Primary Objectives 
Section 4.1.2 Cohort A Secondary Endpoints 
Section 4.1.3 Cohort A Exploratory Endpoints 
Section 4.2.1 Cohort B Secondary Endpoints  
Section 4.2.2 Cohort B Exploratory Endpoints  
Section 5.2 Efficacy Variables 
Figure 1 Study Flow Diagram 
Section 6.1.3 Screening/Baseline 
Section 6.1.4 Efficacy Assessment Period 
Section 6.1.5 Follow-up Period 
Table 3 Schedule of Events (All Cohorts, RT-
qPCR-Negative and Positive) 
Section 9.1.1 Schedule of Events Table 1 (All 
Cohorts, RT-qPCR-Negative and Positive) 
Footnotes - #4, #7, #9 
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Section 9.2.2.1 Nasopharyngeal Swab SARS-
CoV-2 RT-qPCR Test (Central Lab) 
Section 9.2.2.2 COVID-19 Symptomology 
(Strict Terms and Broad Terms) 
Section 9.2.6.1.1 Viral Sequencing 
Section 
9.2.6.2 
Serological 
Assays 
for 
Endogenous Anti-SARS-CoV-2 Antibodies 
Section 11.4.1 Subject Disposition 
Section 11.4.3.1.1 Primary Efficacy Analysis 
(Cohort A) 
Section 11.4.3.2 Secondary Efficacy Analyses 
Section 11.4.4.1 Cohort A 
Section 11.4.4.2 Cohort B 
Section 11.4.5.1 Adverse Events 
Section 11.4.5.2 Other Safety (Vital Signs and 
Laboratory Tests 
Section 
11.4.6.1 
Analysis 
of 
Drug 
Concentration Data 
Section 
11.4.7 
Pharmacokinetics 
and 
Pharmacokinetics /Pharmacodynamics 
Section 11.5 Interim Analysis 
• Removed collection of local 
serology (onsite) at baseline 
The purpose of including local 
serology testing as a 
stratification factor for 
randomization was to improve 
the relative balance of 
enrollment of seronegative and 
seropositive subjects in each of 
the study arms.  However, due 
to clinical laboratory 
restrictions, local testing using 
the lateral flow immunoassay 
is not feasible at most sites. 
Additionally, the majority of 
subjects are expected to be 
seronegative. Because serology 
testing will be performed by 
the central lab, subgroup 
analyses will be performed 
using baseline central lab 
serology data and this analysis 
will not be affected by the 
elimination of local serology 
testing.  
 Clinical Study Protocol Synopsis: Study 
Design  
Section 2 Objectives 
Section 3.2.1 Study Design 
Section 3.2.3 Enrollment by Baseline SARS-
CoV-2 Infection 
Section 
5.1 
Demographic 
and 
Baseline 
Characteristics 
Section 6.1 Study Description and Duration 
Figure 1 Study Flow Diagram 
Section 6.1.3 Screening/Baseline 
Section 8.4 Method of Treatment Assignment 
Section 8.5 Blinding 
Table 3 Schedule of Events (All Cohorts, RT 
qPCR-Negative and Positive) 
Section 9.1.1 Schedule of Events Table 1 (All 
Cohorts, RT-qPCR-Negative and Positive) 
Footnotes - Footnote #8 (removed) 
Section 9.2.1 Procedures Performed Only at 
the Screening/Baseline Visit 
• Removed mention of the 
sentinel group from the study 
REGN10933-10987-COV-2068 
The REGN10933-10987-
COV-2068 study was not 
initiated in parallel with 2069; 
Figure 1 Study Flow Diagram 
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therefore, the sentinel group is 
based on REGN10933-10987-
COV-2069 study only. 
Section 6.1.1 Sentinel Subjects and Staggered 
Enrollment/Dosing 
• Specify that index case test 
results can be from SARS-
CoV-2 diagnostic test formats 
that are approved or have 
Emergency Use Authorization 
issued by the US FDA or by 
local health authority. 
To improve the feasibility of 
enrolling household contacts 
due to the short window 
(96 hours) between the 
collection of the index cases’ 
positive SARS-COV-2 RTPCR 
diagnostic test sample. 
Clinical Study Protocol Synopsis: Study 
Design, Population  
Section 3.2.1 Study Design 
Section 3.2.2 Subject Population  
Section 6.1 Study Description and Duration 
Section 7.2 Study Population 
Section 7.2.1 Inclusion Criteria, criterion #2 
• Revised the description of the 
use of any unused or leftover 
biological samples collected 
during the study for exploratory 
research to indicate that the 
maximum time period of 
allowable storage (for both 
exploratory research samples 
and pharmacogenomic 
samples) may be shorter per 
regional laws and regulations 
To clarify the intended use and 
storage of biological samples 
collected. 
Section 
9.2.4 
Drug 
Concentration 
and 
Measurements 
Section 9.2.5 Immunogenicity Measurements 
and Samples 
Section 
9.2.6 
Exploratory 
Pharmacodynamic/Biomarker Procedures 
Section 
9.2.6.2 
Serological 
Assays 
for 
Endogenous Anti-SARS-CoV-2 Antibodies 
Section 9.2.7 Pharmacogenomic Analysis 
(Optional) 
• Clarify the imputation method 
for missing RT-qPCR results 
revised the rules for imputing 
results 
 Clinical Study Protocol Synopsis: Statistical 
Plan  
Section 11.4.3.1.1 Primary Efficacy Analysis 
(Cohort A) 
• Added country as a fixed factor 
in the statistical model 
• Added a description of the 
timing of statistical analysis 
To address health authority 
requests. 
Clinical Study Protocol Synopsis: Study Design 
Section 6.2 Planned Interim Analysis 
Section 11.4.9 Timing of Statistical Analysis 
• Clarified the justification of 
sample size for cohort A 
Rationale was strengthened to 
enhance readability based on 
collaborator feedback. 
Section 11.2.1 Cohort A- Justification of 
Sample Size 
• Added a summary of clinical 
data from the pooled sentinel 
cohorts from treatment studies 
(R10933-10987-COV-2066 and 
R10933 10987-COV-2067) 
• Clarified that ‘healthy subjects’ 
include the elderly or those 
with stable chronic illness who 
are considered fit for the study  
• Clarified the follow-up period 
for contraception use 
• Increased frequency of site 
and/or investigator contact with 
To address collaborator 
comments. 
Section 3.2.4 Sentinel Safety Group and 
Subsequent Safety Reviews 
Section 3.3 Risk-Benefit 
Section 5.3 Safety Variables 
Section 6.1.3 Screening/Baseline 
Section 6.1.4 Efficacy Assessment Period 
Section 6.1.5 Follow-up Period 
Section 6.3.1 Independent Data Monitoring 
Committee/Data and Safety Monitoring Board 
Section 6.3.2 Safety Review Committee for 
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subjects who have confirmed 
SARS-CoV-2 infection  
• Increased monitoring time after 
dosing to assess for 
hypersensitivity and injection 
site reactions in all subjects 
who are not in the sentinel 
group (which has a 4-hour 
monitoring window) 
• Clarified that subjects should 
contact their local emergency 
department if they experience a 
true medical emergency  
• Removed assessment for 
absenteeism at the 
screening/baseline visit 
• Clarified that pregnant subjects 
are not withdrawn but are 
followed for safety  
• Described the specific data to 
be collected for subjects with a 
positive RT-PCR result who 
have medically attended visits 
(ED, UCC, hospitalization) 
• Added a household assessment 
to collect general information 
about household members 
• Clarified who can review study 
records 
Section 7.2.1 Inclusion Criteria, #4 
Section 7.2.2 Exclusion Criteria, #8, #12, #14 
Section 8.9 Prohibited Medications 
Table 3 Schedule of Events (All Cohorts, RT-
qPCR-Negative and Positive)  
Section 9.1.1 Schedule of Events Table 1 (All 
Cohorts, RT-qPCR-Negative and Positive) 
Footnotes #11, #13, #16 
Section 9.2.1 Procedures Performed Only at the 
Screening/Baseline Visit 
Section 9.2.1.2 Local Molecular Diagnostic 
Assay for SARS-CoV-2 
Section 9.2.2.3 Assessment of Medically 
Attended Visits  
Section 9.2.2.4 Absenteeism Assessment 
Section 9.2.3.1 Targeted Physical Examination 
and Vital Signs 
Section 9.2.3.2 Laboratory Testing 
• Clarified the Sponsor access to 
study results 
The Sponsor will not have 
access to post-baseline patient 
level study results  
Section 8.5 Blinding 
Section 9.1.1 Schedule of Events Table 1 (All 
Cohorts, RT-qPCR-Negative and Positive) 
Footnote #14 
• Added ethics committee text 
relevant sections 
The study may include sites in 
other countries  
Section 10.4 Notifying Health Authorities, 
Institutional Review Board/Ethics Committee 
and Investigators 
Section 12.3 Audits and Inspections 
Section 13.2 Informed Consent 
Section 13.4 Institutional Review Board/Ethics 
Committee 
Section 15.2 Close-out of a Site 
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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
ACE2 
Angiotensin-converting enzyme 2 
ADA 
Anti-drug antibody 
ADE 
Antibody-dependent enhancement 
AE 
Adverse event 
AESI 
Adverse event of special interest 
ALT 
Alanine aminotransferase 
AST 
Aspartate aminotransferase 
ARDS 
Acute respiratory distress syndrome 
BUN 
Blood urea nitrogen 
CDC 
Center for Disease Control 
COVID-19 
Coronavirus disease 2019 
CoVPN 
COVID-19 Prevention Network 
CPK 
Creatine phosphokinase 
CRF 
Case report form (electronic or paper) 
CRO 
Contract research organization 
CTCAE 
Common Terminology Criteria for Adverse Events 
DSMB 
Data and Safety Monitoring Board  
E (protein) 
Envelope protein 
EAP 
Efficacy assessment period 
EC 
Ethics Committee 
ED 
Emergency department 
EDC 
Electronic data capture 
ELF 
Epithelial lining fluid 
EOS 
End of study 
EUA 
Emergency Use Authorization 
FAS 
Full analysis set 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GEE 
Generalized estimation equation 
GLP 
Good Laboratory Practice 
IB 
Investigator’s Brochure 
ICF 
Informed consent form 
ICH 
International Council for Harmonisation 
IDMC 
Independent Data Monitoring Committee 
IRB 
Institutional Review Board 
IM 
Intramuscular 
IV 
Intravenous 
IWRS 
Interactive web response system 
LDH 
Lactate dehydrogenase 
LDL 
Low-density lipoprotein 
M (protein) 
Membrane protein 
mAb 
Monoclonal antibody 
MERS-CoV 
Middle East respiratory syndrome coronavirus 
NAb 
Neutralizing anti-drug antibody 
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NCI-CTCAE 
National Cancer Institute-Common Terminology Criteria for Adverse 
Events 
NIAID 
National Institute of Allergy and Infectious Diseases 
NIH 
National Institutes of Health 
NP 
Nasopharyngeal 
OP 
Oropharyngeal 
PK 
Pharmacokinetic 
PCSV 
Potentially clinically significant value 
RBC 
Red blood cell 
RBD 
Receptor binding domain 
RBQM 
Risk-Based Quality Monitoring 
Regeneron 
Regeneron Pharmaceuticals, Inc. 
RT-PCR 
Reverse transcription polymerase chain reaction (test) 
RT-qPCR 
Quantitative reverse transcription polymerase chain reaction (test; refers to 
the central lab testing in this protocol) 
S 
Spike protein of the SARS-CoV-2 virus 
SARS-CoV 
Severe acute respiratory syndrome coronavirus 
SARS-CoV-2 
Severe acute respiratory syndrome coronavirus 2 
SAE 
Serious adverse event 
SAF 
Safety analysis set 
SAP 
Statistical analysis plan 
SAS 
Statistical Analysis System 
SC 
Subcutaneous 
SD 
Standard deviation 
SDR 
Source data review  
SDV 
Source data verification  
SOC 
System organ class 
SRC 
Safety Review Committee 
SUSAR 
Suspected unexpected serious adverse reaction 
TEAE 
Treatment-emergent adverse event 
UCC 
Urgent care centers 
WBC 
White blood cell 
WHO 
World Health Organization 
WOCBP 
Women of childbearing potential 
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TABLE OF CONTENTS 
AMENDMENT HISTORY .............................................................................................................2 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ................................................23 
CLINICAL STUDY PROTOCOL SYNOPSIS.............................................................................32 
1. 
INTRODUCTION ......................................................................................................52 
1.1. 
Emergence of SARS-CoV-2 and COVID-19 .............................................................52 
1.2. 
Populations at Increased Risk of SARS-CoV-2 Infection Among Household 
Contacts of a Person Infected with SARS-CoV-2 ......................................................52 
1.3. 
The Role of Spike Protein in SARS-CoV-2 Pathogenesis .........................................53 
1.4. 
REGN10933+REGN10987: Fully Human Monoclonal Antibodies that 
Target SARS-CoV-2 S Protein ...................................................................................53 
1.5. 
A Randomized, Placebo-Controlled Study of Anti-Spike Protein Monoclonal 
Antibodies as Post-Exposure Prophylaxis and Pre-emptive Therapy in 
Household Contacts ....................................................................................................54 
2. 
STUDY OBJECTIVES ..............................................................................................55 
2.1. 
Cohort A and Cohort A1:  SARS-CoV-2 RT-qPCR Negative at Baseline ................55 
2.1.1. 
Primary Objectives .....................................................................................................55 
2.1.1.1. 
Cohort A Primary Efficacy Objective ........................................................................55 
2.1.2. 
Cohort A and Cohort A1 Primary Safety Objective ...................................................55 
2.1.3. 
Cohort A and Cohort A1 Secondary Objectives .........................................................56 
2.1.4. 
Cohort A and Cohort A1 Exploratory Objectives ......................................................57 
2.2. 
Cohort B and Cohort B1: SARS-CoV-2 RT-qPCR Positive at Baseline ...................58 
2.2.1. 
Cohort B Primary Efficacy Objective .........................................................................58 
2.2.2. 
Cohort B and Cohort B1 Primary Safety Objective ...................................................58 
2.2.3. 
Cohort B and Cohort B1 Secondary Objectives .........................................................58 
2.2.4. 
Cohort B and Cohort B1 Exploratory Objectives .......................................................59 
3. 
HYPOTHESIS AND RATIONALE ..........................................................................59 
3.1. 
Hypotheses ..................................................................................................................59 
3.2. 
Rationale .....................................................................................................................60 
3.2.1. 
Study Design ...............................................................................................................60 
3.2.2. 
Subject Population ......................................................................................................63 
3.2.3. 
Enrollment by Baseline SARS-CoV-2 Infection ........................................................64 
3.2.4. 
Sentinel Safety Group and Subsequent Safety Reviews .............................................65 
3.2.5. 
Primary Objective .......................................................................................................66 
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3.2.6. 
Secondary Objectives .................................................................................................66 
3.2.7. 
Rationale for Dose Selection ......................................................................................67 
3.3. 
Risk-Benefit ................................................................................................................69 
4. 
ENDPOINTS ..............................................................................................................71 
4.1. 
Cohort A and Cohort A1: SARS-CoV-2 RT-qPCR Negative at Baseline .................72 
4.1.1. 
Cohort A Primary Endpoints ......................................................................................72 
4.1.2. 
Cohort A Key Secondary Endpoints...........................................................................72 
4.1.3. 
Cohort A and Cohort A1 Other Secondary Endpoints ...............................................72 
4.1.4. 
Cohort A and Cohort A1 Exploratory Endpoints .......................................................74 
4.2. 
Cohort B and Cohort B1: SARS-CoV-2 RT-qPCR Positive at Baseline ...................76 
4.2.1. 
Cohort B Primary Efficacy Endpoint .........................................................................76 
4.2.2. 
Cohort B Key Secondary Efficacy Endpoints ............................................................76 
4.2.3. 
Cohort B and Cohort B1 Other Secondary Efficacy Endpoints .................................77 
4.2.4. 
Cohort B and Cohort B1 Exploratory Endpoints ........................................................78 
5. 
STUDY VARIABLES................................................................................................80 
5.1. 
Demographic and Baseline Characteristics ................................................................80 
5.2. 
Efficacy Variables ......................................................................................................80 
5.3. 
Safety Variables ..........................................................................................................81 
5.4. 
Pharmacokinetic Variables .........................................................................................81 
5.5. 
Immunogenicity Variables ..........................................................................................81 
6. 
STUDY DESIGN .......................................................................................................81 
6.1. 
Study Description and Duration .................................................................................81 
6.1.1. 
Sentinel Subjects and Staggered Enrollment/Dosing: ................................................83 
6.1.2. 
Pediatric Subjects (<12 years) ....................................................................................84 
6.1.3. 
Screening/Baseline .....................................................................................................85 
6.1.4. 
Efficacy Assessment Period .......................................................................................86 
6.1.5. 
Follow-up Period ........................................................................................................87 
6.1.6. 
Description of Study Cohorts .....................................................................................88 
6.1.7. 
Study Stopping Rules .................................................................................................89 
6.1.7.1. 
Study Stopping Criteria ..............................................................................................89 
6.1.8. 
End of Study Definition ..............................................................................................89 
6.2. 
Planned Interim Analysis ............................................................................................90 
6.3. 
Study Committees .......................................................................................................90 
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6.3.1. 
Independent Data Monitoring Committee/Data and Safety Monitoring Board .........90 
6.3.2. 
Safety Review Committee for REGN 2069/ CoVPN 3502 ........................................90 
7. 
SELECTION, WITHDRAWAL, AND REPLACEMENT OF SUBJECTS ..............90 
7.1. 
Number of Subjects Planned ......................................................................................90 
7.2. 
Study Population .........................................................................................................91 
7.2.1. 
Inclusion Criteria ........................................................................................................91 
7.2.2. 
Exclusion Criteria .......................................................................................................91 
7.3. 
Premature Withdrawal from the Study .......................................................................93 
7.4. 
Replacement of Subjects .............................................................................................93 
8. 
STUDY TREATMENTS............................................................................................93 
8.1. 
Investigational and Reference Treatments ..................................................................93 
8.2. 
Dose Modification and Study Treatment Discontinuation Rules ...............................94 
8.2.1. 
Dose Modification ......................................................................................................94 
8.2.2. 
Study Drug Discontinuation .......................................................................................94 
8.3. 
Management of Acute Reactions ................................................................................95 
8.3.1. 
Acute Injection Reactions ...........................................................................................95 
8.3.1.1. 
Systemic Injection Reactions ......................................................................................95 
8.3.1.2. 
Local Injection Site Reactions ....................................................................................95 
8.4. 
Method of Treatment Assignment ..............................................................................95 
8.5. 
Blinding ......................................................................................................................96 
8.6. 
Emergency Unblinding ...............................................................................................96 
8.7. 
Treatment Logistics and Accountability .....................................................................97 
8.7.1. 
Packaging, Labeling, and Storage ..............................................................................97 
8.7.2. 
Supply and Disposition of Treatments .......................................................................97 
8.7.3. 
Treatment Accountability ...........................................................................................97 
8.7.4. 
Treatment Compliance ................................................................................................97 
8.8. 
Concomitant Medications and Procedures .................................................................97 
8.9. 
Prohibited Medications ...............................................................................................98 
8.10. 
Permitted Medications ................................................................................................98 
9. 
STUDY SCHEDULE OF EVENTS AND PROCEDURES ......................................99 
9.1. 
Schedule of Events .....................................................................................................99 
9.1.1. 
Schedule of Events Table 3 (Cohorts A and B [Adult / Adolescent Subjects], 
RT-qPCR-Negative and Positive) Footnotes ............................................................102 
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9.1.2. 
Schedule of Events Table 4: All Cohorts A and B (Adult / Adolescent 
Subjects) for Drug Concentrations, Immunogenicity, and Laboratory Testing .......107 
9.1.3. 
Schedule of Events Table 5 Cohorts A1 and B1 (Pediatric Subjects [ <12 
years], RT-qPCR-Negative and Positive) Footnotes ................................................110 
9.1.4. 
Schedule of Events Table 6: Cohorts A1 and B1 (Pediatric Subjects [<12 
years]) for Drug Concentration, Immunogenicity, and Laboratory Testing .............114 
9.1.5. 
Early Termination Visit ............................................................................................114 
9.1.6. 
Unscheduled Visits ...................................................................................................114 
9.2. 
Study Procedures ......................................................................................................115 
9.2.1. 
Procedures Performed Only at the Screening/Baseline Visit ...................................115 
9.2.1.1. 
Informed Consent .....................................................................................................115 
9.2.1.2. 
Local Diagnostic Assay for SARS-CoV-2 ...............................................................115 
9.2.2. 
Efficacy Procedures ..................................................................................................115 
9.2.2.1. 
Nasopharyngeal Swab SARS-CoV-2 RT-qPCR Test (Central Lab) ........................115 
9.2.2.2. 
COVID-19 Symptomology (Strict Terms, Broad Terms, and CDC 
Definition) .................................................................................................................116 
9.2.2.3. 
Assessment of Medically Attended Visits ................................................................118 
9.2.2.4. 
Absenteeism Assessment ..........................................................................................118 
9.2.3. 
Safety Procedures .....................................................................................................119 
9.2.3.1. 
Targeted Physical Examination and Vital Signs ......................................................119 
9.2.3.2. 
Laboratory Testing ....................................................................................................119 
9.2.4. 
Drug Concentration and Measurements ...................................................................120 
9.2.5. 
Immunogenicity Measurements and Samples ..........................................................121 
9.2.6. 
Exploratory Pharmacodynamic/Biomarker Procedures ...........................................121 
9.2.6.1. 
Virology ....................................................................................................................121 
9.2.6.2. 
Serological Assays for Endogenous Anti-SARS-CoV-2 Antibodies .......................122 
9.2.6.3. 
Serum and Plasma for Research ...............................................................................122 
9.2.7. 
Pharmacogenomic Analysis (Optional) ....................................................................122 
10. 
SAFETY EVALUATION AND REPORTING .......................................................124 
10.1. 
Recording and Reporting Adverse Events ................................................................124 
10.1.1. 
General Guidelines ...................................................................................................124 
10.1.2. 
Reporting Procedure .................................................................................................125 
10.1.3. 
Events that Require Expedited Reporting to Sponsor ..............................................125 
10.2. 
Definitions ................................................................................................................126 
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10.2.1. 
Adverse Event ...........................................................................................................126 
10.2.2. 
Serious Adverse Event ..............................................................................................126 
10.2.3. 
Adverse Events of Special Interest ...........................................................................126 
10.2.4. 
Severity .....................................................................................................................127 
10.2.5. 
Causality ...................................................................................................................127 
10.3. 
Safety Monitoring .....................................................................................................129 
10.4. 
Notifying Health Authorities, Institutional Review Board/Ethics Committee 
and Investigators .......................................................................................................129 
11. 
STATISTICAL PLAN..............................................................................................130 
11.1. 
Statistical Hypothesis ................................................................................................130 
11.2. 
Justification of Sample Size......................................................................................130 
11.2.1. 
Cohort A: Adult and Adolescent Subjects (≥12 years) Who Are SARS-CoV-
2 RT-qPCR Negative at Baseline .............................................................................130 
11.2.1.1. 
Cohort A1: Pediatric Subjects (<12 years) Who Are SARS-CoV-2 RT-qPCR 
Negative at Baseline .................................................................................................131 
11.2.2. 
Cohort B: Adult and Adolescent Subjects (≥12 years) Who Are SARS-CoV-
2 RT-qPCR Positive at Baseline ...............................................................................131 
11.2.2.1. 
Cohort B1: Pediatric Subjects (<12 years) Who Are SARS-CoV-2 RT-qPCR 
Positive at Baseline ...................................................................................................132 
11.3. 
Analysis Sets .............................................................................................................132 
11.3.1. 
Efficacy Analysis Sets ..............................................................................................132 
11.3.2. 
Safety Analysis Set ...................................................................................................133 
11.3.3. 
Pharmacokinetic Analysis Set ..................................................................................133 
11.3.4. 
Immunogenicity Analysis Sets .................................................................................133 
11.3.5. 
Neutralizing Antibody Analysis Set .........................................................................133 
11.4. 
Statistical Methods ....................................................................................................133 
11.4.1. 
Subject Disposition ...................................................................................................134 
11.4.2. 
Demography and Baseline Characteristics ...............................................................134 
11.4.3. 
Efficacy Analyses .....................................................................................................134 
11.4.3.1. 
Primary Efficacy Analysis ........................................................................................134 
11.4.3.2. 
Key Secondary Efficacy Analyses ............................................................................136 
11.4.3.3. 
Other Secondary Efficacy Analyses .........................................................................137 
11.4.4. 
Control of Multiplicity ..............................................................................................138 
11.4.5. 
Safety Analysis .........................................................................................................139 
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11.4.5.1. 
Adverse Events .........................................................................................................139 
11.4.5.2. 
Other Safety (Vital Signs and Laboratory Tests) .....................................................140 
11.4.5.3. 
Treatment Exposure ..................................................................................................141 
11.4.5.4. 
Treatment Compliance ..............................................................................................141 
11.4.6. 
Pharmacokinetics ......................................................................................................141 
11.4.6.1. 
Analysis of Drug Concentration Data .......................................................................141 
11.4.7. 
Pharmacokinetics and Pharmacokinetics/Pharmacodynamics Analyses ..................141 
11.4.8. 
Analysis of Immunogenicity Data ............................................................................142 
11.4.9. 
Timing of Statistical Analysis ..................................................................................142 
11.5. 
Interim Analysis ........................................................................................................143 
11.6. 
Statistical Considerations Surrounding the Premature Termination of a Study .......143 
12. 
QUALITY CONTROL AND QUALITY ASSURANCE .......................................144 
12.1. 
Data Management and Electronic Systems ..............................................................144 
12.1.1. 
Data Management .....................................................................................................144 
12.1.2. 
Electronic Systems ....................................................................................................144 
12.2. 
Study Monitoring ......................................................................................................144 
12.2.1. 
Monitoring of Study Sites .........................................................................................144 
12.2.2. 
Source Document Requirements ..............................................................................145 
12.2.3. 
Case Report Form Requirements ..............................................................................145 
12.3. 
Audits and Inspections ..............................................................................................145 
12.4. 
Study Documentation ...............................................................................................146 
12.4.1. 
Certification of Accuracy of Data .............................................................................146 
12.4.2. 
Retention of Records ................................................................................................146 
13. 
ETHICAL AND REGULATORY CONSIDERATIONS ........................................146 
13.1. 
Good Clinical Practice Statement .............................................................................146 
13.2. 
Informed Consent .....................................................................................................146 
13.3. 
Subjects Confidentiality and Data Protection ...........................................................147 
13.4. 
Institutional Review Board/Ethics Committee .........................................................148 
13.5. 
Clinical Study Data Transparency ............................................................................148 
14. 
PROTOCOL AMENDMENTS ................................................................................148 
15. 
PREMATURE TERMINATION OF THE STUDY OR CLOSE-OUT OF A 
SITE ..........................................................................................................................149 
15.1. 
Premature Termination of the Study .........................................................................149 
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15.2. 
Close-out of a Site ....................................................................................................149 
16. 
CONFIDENTIALITY ..............................................................................................149 
17. 
FINANCING AND INSURANCE ...........................................................................149 
18. 
PUBLICATION POLICY ........................................................................................149 
19. 
REFERENCES .........................................................................................................150 
20. 
INVESTIGATOR’S AGREEMENT ........................................................................154 
SIGNATURE OF SPONSOR’S RESPONSIBLE OFFICERS ...................................................155 
 
LIST OF TABLES 
Table 1: 
REGN10933+REGN10987 Doses for Each Pediatric Weight-Tiered Groups ..........68 
Table 2: 
Weight-Tiered Dose Groups for Pediatric Subjects <12 Years of Age ......................94 
Table 3: 
Schedule of Events Cohorts A and B ([Adult / Adolescent Subjects], RT-
qPCR-Negative and Positive) ...................................................................................100 
Table 4: 
Schedule of Events: Cohorts A and B (Adult / Adolescent Subjects) for Drug 
Concentration, Immunogenicity, and Laboratory Testing ........................................106 
Table 5: 
Schedule of Events: Cohorts A1 and B1 (Pediatric Subjects [<12 years], RT-
qPCR-Negative and Positive) ...................................................................................108 
Table 6: 
Schedule of Events: Cohorts A1 and B1 (Pediatric Subjects [<12 years]) for 
Drug Concentration, Immunogenicity, and Laboratory Testing ..............................113 
Table 7: 
Strict-Terms, Broad-Terms, and CDC Definition COVID-19 Signs and 
Symptoms .................................................................................................................117 
Table 8: 
NCI-CTCAE Severity Grading System for Adverse Events for Anaphylaxis, 
Allergic Reaction, and Injection Site Reaction .........................................................127 
Table 9: 
Simulated Power for Household Design (1248 Subjects over 430 
Households) ..............................................................................................................131 
Table 10: Hierarchy Testing Sequence of Key Secondary Efficacy Endpoints in 
Seronegative mFAS-A ..............................................................................................138 
Table 11: Hierarchy Testing Sequence of Key Secondary Efficacy Endpoints in 
Seronegative mFAS-B ..............................................................................................139 
 
LIST OF FIGURES 
Figure 1: 
Study Flow Diagram ...................................................................................................83 
 
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CLINICAL STUDY PROTOCOL SYNOPSIS 
Title 
A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Assessing 
the Efficacy and Safety of Anti-Spike SARS-CoV-2 Monoclonal Antibodies in 
Preventing SARS-CoV-2 Infection in Household Contacts of Individuals 
Infected with SARS-CoV-2 
Site Location(s) 
 
Principal Investigator 
Multiple sites in the United States (US) and other countries 
TBD 
Objectives 
The primary efficacy objective for cohort A (subjects who are negative for 
SARS-CoV-2 infection at baseline) is to evaluate the efficacy of 
REGN10933+REGN10987 (also referred to as casirivimab+imdevimab) 
compared to placebo in preventing symptomatic SARS-CoV-2 infection 
(broad-term) that is confirmed by quantitative reverse transcription polymerase 
chain reaction (RT-qPCR, the central laboratory testing in this study).   
The primary efficacy objective for cohort B (subjects who are positive for 
SARS-CoV-2 infection but asymptomatic at baseline) is to evaluate the efficacy 
of REGN10933+REGN10987 compared to placebo in preventing COVID-19 
symptoms (broad-term).  
Symptomatic SARS-CoV-2 infections will be defined by strict and broad 
definitions, as well as by the Center for Disease Control (CDC) case definition.  
A strict definition includes: fever PLUS ≥1 respiratory symptoms (sore throat, 
cough, shortness of breath), OR 2 respiratory symptoms, OR 1 respiratory 
symptom PLUS ≥2 non-respiratory symptoms (chills, nausea, vomiting, 
diarrhea, headache, conjunctivitis, myalgia, arthralgia, loss of taste or smell, 
fatigue or general malaise).   
A broad definition includes: the signs/symptoms in the strict definition and 
additional symptoms (23 terms: Feverish, Sore throat, Cough, Shortness of 
breath/difficulty breathing [nasal flaring*], Chills, Nausea, Vomiting, Diarrhea, 
Headache, Red or watery eyes, Body aches such as muscle pain or joint pain, 
Loss of taste/smell, Fatigue [fatigue or general malaise or lethargy*], Loss of 
appetite or poor eating/feeding, Confusion, Dizziness, Pressure/tightness in 
chest, Chest pain, Stomach ache (abdominal pain*), Rash, Sneezing, Runny 
nose, Sputum/phlegm [*Signs and symptoms observed in pediatric subjects]).  
The CDC definition is: at least 2 of the following symptoms: fever (measured 
or subjective), chills, rigors, myalgia, headache, sore throat, nausea or vomiting, 
diarrhea, fatigue, congestion or runny nose OR Any 1 of the following 
symptoms: cough, shortness of breath, difficulty breathing, new olfactory 
disorder, new taste disorder OR Severe respiratory illness with at least 1 of the 
following, clinical or radiographic evidence of pneumonia, acute respiratory 
distress syndrome (ARDS).  
There are 4 defined cohorts in this study based on the subjects’ age and 
SARS-CoV-2 infection status at baseline, as measured by central lab 
SARS -CoV-2 RT-qPCR:  
1. Cohort A: adult and adolescent subjects (≥12 years) who are 
SARS-CoV-2 RT-qPCR negative at baseline 
2. Cohort A1: pediatric subjects (<12 years) who are SARS-CoV-2 
RT--qPCR negative at baseline 
3. Cohort B: adult and adolescent subjects (≥12 years) who are 
SARS-CoV-2 RT-qPCR positive at baseline 
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4. Cohort B1: pediatric subjects (<12 years) who are SARS-CoV-2 
RT--qPCR positive at baseline 
Cohort A and Cohort A1: SARS-CoV-2 RT-qPCR Negative at Baseline 
Objectives for cohort A and cohort A1 are for subjects who are seronegative at 
baseline (by central lab test) unless stated otherwise.  
Cohort A Primary Efficacy Objective  
• 
To evaluate the efficacy of REGN10933+REGN10987 compared to 
placebo in preventing symptomatic SARS-CoV-2 infection (broad-term) 
confirmed by RT-qPCR  
Cohort A and Cohort A1 Primary Safety Objective  
• 
To evaluate the safety and tolerability of REGN10933+REGN10987 
following subcutaneous (SC) administration compared to placebo 
Cohort A and Cohort A1 Secondary Objectives  
• 
To evaluate the efficacy of REGN10933+REGN10987 compared to 
placebo in preventing a SARS-CoV-2 infection with a high viral load 
(ie, viral load >4 (log10 copies/mL) 
• 
To evaluate the impact of REGN10933+REGN10987 compared to 
placebo on the duration of signs and symptoms in subjects with 
symptomatic SARS-CoV-2 infection (broad-term) confirmed by RT-
qPCR 
• 
To evaluate the impact of REGN10933+REGN10987 compared to 
placebo on the duration of SARS-CoV-2 infection with a high viral load 
(ie, viral load >4 (log10 copies/mL)   
• 
To evaluate the impact of REGN10933+REGN10987 compared to 
placebo on the duration of SARS-CoV-2 infection 
• 
To evaluate the efficacy of REGN10933+REGN10987 compared to 
placebo in preventing asymptomatic or symptomatic SARS-CoV-2 
infection confirmed by RT-qPCR 
• 
To 
evaluate 
the 
impact 
of 
treating 
the 
index 
case 
with 
REGN10933+REGN10987 on the incidence of SARS-CoV-2 infection 
among household contacts in the placebo group (note: This is a cross-
study analysis based on only subjects in the placebo group of study 
R10933-10987-COV-2069 whose index cases participated in study 
R10933-10987-COV-2067) 
• 
To evaluate the efficacy of REGN10933+REGN10987 compared to 
placebo in preventing symptomatic SARS-CoV-2 infection (Centers for 
Disease Control [CDC] definition) confirmed by RT-qPCR 
• 
To evaluate the efficacy of REGN10933+REGN10987 compared to 
placebo in preventing symptomatic SARS-CoV-2 infection (strict-term) 
confirmed by RT-qPCR  
• 
To evaluate the impact of REGN10933+REGN10987 compared to 
placebo on SARS-CoV-2 RT-qPCR viral load 
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• 
To evaluate the impact of REGN10933+REGN10987 compared to 
placebo on SARS-CoV-2 infection: 
− 
On health care utilization  
− 
On 
absenteeism 
from 
daily 
responsibilities 
(where 
applicable) 
• 
To evaluate the impact of treating any SARS-CoV-2 RT-qPCR positive 
household member with REGN10933+REGN10987 on the incidence of 
SARS-CoV-2 infection among their household contacts in placebo 
group (note: This is a cross-study analysis based on only subjects in 
placebo group of study R10933-10987-COV-2069 whose  index or other 
household member participated in study R10933-10987-COV-2067 or 
in cohort B) 
• 
To characterize the drug concentration-time profiles of REGN10933 and 
REGN10987 in serum and selected pharmacokinetic (PK) parameters.  
• 
To assess the immunogenicity of REGN10933 and REGN10987  
• 
To evaluate the safety and tolerability of REGN10933+REGN10987 
following SC administration in seropositive subjects 
To estimate the incidence and severity of symptomatic SARS-CoV-2 
infection over time, including the period following study drug treatment, 
in REGN10933+REGN10987-treated seronegative and seropositive 
subjects compared with placebo-treated subjects 
• 
To evaluate the efficacy of REGN10933+REGN10987 compared to 
placebo in preventing symptomatic SARS-CoV-2 infection (broad-term) 
confirmed by RT-qPCR (cohort A1)  
Cohort B and Cohort B1: SARS-CoV-2 RT-qPCR Positive at Baseline 
Objectives for cohort B and cohort B1 are for subjects who are seronegative at 
baseline (by central lab test) unless stated otherwise.  
Cohort B and Cohort B1 Primary Efficacy Objective  
• 
To evaluate the efficacy of REGN10933+REGN10987 compared to 
placebo in preventing COVID-19 symptoms (broad-term)  
Cohort B and Cohort B1 Primary Safety Objective  
• 
To evaluate the safety and tolerability of REGN10933+REGN10987 
following SC administration compared to placebo 
Cohort B and Cohort B1 Secondary Objectives  
• 
To evaluate the efficacy of REGN10933+REGN10987 compared to 
placebo in preventing development of: 
− 
Symptomatic SARS-CoV-2 infection (strict-term) 
− 
Symptomatic SARS-CoV-2 infection (broad-term; cohort 
B1) 
− 
Symptomatic SARS-CoV-2 infection (CDC definition) 
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• 
To evaluate the impact of REGN10933+REGN10987 compared to 
placebo on the duration of signs and symptoms in subjects with 
symptomatic SARS-CoV-2 infection confirmed by RT-qPCR 
• 
To evaluate the impact of REGN10933+REGN10987 compared to 
placebo on the duration of SARS-CoV-2 infection with a high viral load 
• 
To evaluate the impact of REGN10933+REGN10987 compared to 
placebo on SARS-CoV-2 RT-qPCR viral load   
• 
To evaluate the impact of REGN10933+REGN10987 compared to 
placebo on SARS-CoV-2 infection:  
− 
On health care utilization  
− 
On 
absenteeism 
from 
daily 
responsibilities 
(where 
applicable) 
• 
To characterize the drug concentration-time profiles of REGN10933 and 
REGN10987 in serum and selected PK parameters  
• 
To assess the immunogenicity of REGN10933 and REGN10987  
• 
To evaluate the safety and tolerability of REGN10933+REGN10987 
following SC administration  
• 
To estimate the incidence and severity of symptomatic SARS-CoV-2 
infection over time, including the period following study drug treatment, 
in REGN10933+REGN10987-treated subjects compared with placebo-
treated subjects 
Study Design 
This is a phase 3 randomized, double-blind, placebo-controlled study in adults, 
adolescents, and children with household contact exposure to individuals with 
SARS-CoV-2 infection. 
All subjects in the study will be household contacts with close exposure to the 
first household member known to be infected with SARS-CoV-2 (index case) 
but who are themselves asymptomatic (having no active respiratory or 
non-respiratory symptoms consistent with COVID-19) but may be either 
positive or negative for SARS-CoV-2 during screening, as assessed by central 
laboratory RT-qPCR performed at baseline. The index case will have a 
diagnosis of SARS-CoV-2 infection using a diagnostic test, eg, RT-PCR, 
antigen test, or other test format (approved or with Emergency Use 
Authorization [EUA] issued by the US Food and Drug Administration [FDA] 
or by the equivalent local health authority).  
Randomization will be performed by individual study subjects, not by 
households. 
Approximately 3500 adult and adolescent (≥12 years) + 250 pediatric subjects 
(<12 years) will be enrolled. 
Screening/Baseline (day 1) 
After subjects provide informed consent, they will be assessed for study 
eligibility.  The screening visit and randomization visit should occur on the 
same day.  If needed, a remote visit may occur to sign the ICF and collect 
medical history and concomitant medication use, on the day prior to, but within 
24 hours of study drug administration, so that the in-person screening and 
randomization visit may be abbreviated, due to COVID-19 considerations. 
Study drug administration must occur within 96 hours of collection of the index 
cases’ positive SARS-CoV-2 diagnostic test sample.  On day 1, prior to 
randomization, a local diagnostic assay for SARS-CoV-2 from appropriate 
samples will be performed. The results of this assay will be used as a 
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stratification factor for randomization to treatment groups (placebo or 
REGN10933+REGN10987).  The requirement for a local diagnostic assay for 
SARS-CoV-2 is waived when the results are not expected to be available in a 
timely manner for randomization.  Nasopharyngeal (NP) swab sample 
(swabbing through both nostrils in adults/adolescents and through one nostril in 
pediatrics <12 years) for central lab testing of SARS-CoV-2 RT-qPCR and 
blood sample for central lab serology will also be collected and sent to central 
lab. On day 1, after completing baseline assessments, sample collection, and 
randomization, all subjects will receive a single dose of study drug.  
Randomization will be performed on an individual subject basis. In addition to 
a randomization number, all subjects randomized will be given a household 
identification number in the case that multiple members of the same household 
are enrolled and receive study drug.  This ensures that correlation among 
subjects within the same household may be considered in the statistical analysis. 
Randomization will be performed by site and stratified for assignment of 
treatment group by test results (positive, negative, or undetermined) of a local 
diagnostic assay for SARS-CoV-2 (eg, molecular assay such as RT-PCR assay 
for SARS-CoV-2 or a SARS-CoV-2 antigen test) from appropriate samples, eg, 
nasopharyngeal (NP), oropharyngeal (OP), nasal, or saliva, and age group 
(≥12 to <18 years, ≥18 to <50 years, or ≥50 years).  For pediatric subjects 
(<12 years), the weight group (≥20 kg, ≥10 to <20 kg, and <10 kg) will be used 
as an additional stratification factor. The local diagnostic assay for 
SARS-CoV-2 must be considered acceptable for clinical use by local standards. 
If the test has not been approved or received EUA issued by the US FDA or by 
the equivalent local health authority, then the Sponsor should be consulted. 
Cohort allocation will be based on central lab baseline SARS-CoV-2 RT-qPCR 
results for data analysis: cohort A or cohort A1 (negative) and cohort B or 
cohort B1 (positive). Statistical analyses will be conducted separately in each 
cohort which will be based on central lab determination of viral positivity and 
serological status. 
Subjects will be randomized in a 1:1 allocation ratio to 1 of 2 treatment groups 
(placebo or REGN10933+REGN10987 [1200 mg (600 mg of each mAb SC)]). 
This study was preceded by safety review of data from other studies:  a safety 
sentinel 
group 
of 
30 
patients 
with 
COVID-19 
dosed 
with 
REGN10933+REGN10987 2400 mg IV, REGN10933+REGN10987 8000 mg 
IV or placebo in the leading phase 1 studies of REGN10933+REGN10987 in 
the treatment of COVID-19 patients. Randomization in this study did not begin 
until the Independent Data Monitoring Committee (IDMC) for the treatment 
studies provided a "study may proceed" conclusion from the IV dosing sentinel 
group. 
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Sentinel Group (day 1 to day 4) 
Enrollment in this study was carried out in 2 phases: 
Sentinel group of approximately 30 adult subjects, irrespective of allocation to 
cohort A or cohort B.  
1. Subjects were monitored for safety on-site for a minimum of 4 hours after 
administration of the first dose of study drug and then daily via visits to the 
study site or phone calls for the first 4 days (96 hours).  Because 
REGN10933+REGN10987 had already cleared an adult safety sentinel 
cohort at higher doses administered IV in previous studies, the sentinel 
group in this study focused on safety evaluation for injection site reactions 
and hypersensitivity reactions, and data were reviewed before progressing 
with enrollment of additional study subjects. The blinded safety data review 
was led by a designated member of the Regeneron clinical team (generally 
either the medical monitor or the clinical trial manager) and at a minimum 
the data review team included the Regeneron Medical Monitor, Study 
Biostatistician, Global Safety Lead or designee, and the Senior Vice 
President of Early Clinical Development & Experimental Sciences.  
2. Following a conclusion of the blinded safety data review that the study 
could proceed, the study resumed enrollment. 
Pediatric Sentinel Subjects and Staggered Enrollment/Dosing: 
Approximately 250 pediatric subjects across all weight-tiered dose ranges will 
be enrolled.  However, since the enrollment of pediatric subjects (<12 years) 
will end once enrollment of adult and adolescent subjects is complete, the 
number of pediatric subjects may be adjusted.    
Enrollment of pediatric subjects in this study will be carried out in 2 phases each 
for safety assessment and for confirmation of appropriate level of drug exposure 
for each weight group. 
Pediatric Subjects Safety Sentinel Group 
1. Sentinel group will comprise 12 pediatric subjects (by subject number 
assigned by IWRS; irrespective of allocation to cohort A1 or cohort 
B1) in 3 weight groups (≥20 kg; 10 kg to <20 kg; <10 kg).  Each weight 
group will have 4 subjects randomized 1:1 to 1 of 2 treatment groups 
(placebo or REGN10933+REGN10987) and study drug administered 
first.  After all 4 subjects in a weight group complete the sentinel 
review, enrollment of additional subjects in that weight group will 
proceed.  Pediatric subjects will be monitored for safety on-site for a 
minimum of 2 hours after administration of study drug and then daily 
via visits to the study site or phone calls for the first 4 days (96 hours). 
Because REGN10933+REGN10987 has already cleared an adult 
safety sentinel cohort at higher doses administered IV in previous 
studies and the adult safety sentinel in this study, the pediatric sentinel 
group in this study is focused on safety evaluation for injection site 
reactions and hypersensitivity reactions.  Data will be reviewed before 
progressing with enrollment of additional pediatric subjects. The 
blinded safety data review will be led by a designated member of the 
Regeneron clinical team (generally either the medical monitor or the 
clinical trial manager) and at a minimum the data review team will 
include the Regeneron Medical Monitor, Study Biostatistician, Global 
Safety Lead or designee, and the Senior Vice President of Early 
Clinical Development & Experimental Sciences. 
2. Following a conclusion of the blinded safety data review that the study 
may proceed for a weight group, the enrollment of pediatric subjects 
in that weight group will resume.  However, close monitoring by the 
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Safety Review Committee will continue on a periodic cumulative 
aggregate basis, including stratification to facilitate early and periodic 
review of data for adolescent subjects (≥12 years to <18 years)  and 
pediatric subjects (<12 years) in each of the weight groups.   
Confirmation of Drug Exposure for Pediatric Subjects Weight Groups 
1. All pediatric subjects (subset 4 and subset 5) will have samples 
collected (Schedules A, B, C, and D) in the EAP and Follow-Up 
periods for drug concentration measurement as well as ADA 
assessment and clinical laboratory tests (hematology, blood 
chemistry).  The drug concentration data  from approximately the first 
20 subjects per weight group (<10 kg, 10 to 20 kg, ≥20 kg) will be 
evaluated to confirm that the REGN10933 and REGN10987 dose for 
the weight group is providing the expected exposure.   
2. Based on simulations using a population PK model using data from 
adult patients with COVID-19, the proposed doses for the pediatric 
subjects (see Table below) is expected to match the exposure in adult 
subjects at SC dose of 1200 mg (600 mg per mAb) in this study.  Once 
the exposure for a dose is confirmed in a weight group, enrollment 
beyond 25 subjects for this weight group can continue.  Based on the 
results of the drug concentration analyses from up to 20 pediatric 
subjects receiving active drug in the weight groups, the dose for 
participating pediatric subjects may be adjusted in 1 or more of the 
weight-tiered group(s) to ensure drug exposure comparable to adult 
subjects in this study.  If the dose for a particular weight group needs 
to be adjusted, the new dose for that weight group will used for 
approximately a subsequent 20 subjects for that weight group.  These 
subjects who received the new dose will have drug concentrations 
analyzed to confirm that it is providing the expected exposure.  When 
the new dose is started, the subjects will resume dosing according to 
the next sample collection schedule since the last subject received 
study drug. 
Efficacy Assessment Period (day 1 to day 29)  
Efficacy, safety, sample collections, and other study assessments will be 
performed at specified time points throughout the efficacy assessment period 
(EAP).  If subjects are able to travel and can do so while maintaining social 
distancing guidelines, subsequent site visits will be conducted; alternatively, 
telemedicine visits, phone calls, mobile units or home health nurses may be 
utilized.  Throughout the study, biological samples will be obtained by 
adequately trained and delegated study personnel at study locations where 
appropriate personal protective equipment (PPE) are available to be used.  
Subjects will be instructed to contact the study site staff for any new or changing 
symptoms or signs possibly related to COVID-19, including fever. The 
investigator should recommend that subjects (themselves or by their 
parent/guardian) measure their temperature daily during the EAP, 
approximately at the same time, and also every time when the subject feels 
feverish, chills, or sick.  Adult subjects may receive automated reminders (eg, 
text messages to mobile phones; implemented as soon as technologically 
feasible and when subjects confirm to opt in) in between the weekly visits to 
prompt them to contact the study site staff as needed. 
At each weekly visit, NP swab sample will be collected for SARS-CoV-2 
RT-qPCR to be tested at a central lab.  The investigator or designee will contact 
each subject weekly (site visit or telemedicine) to assess the subject’s general 
health, and to document all AEs in general, and any signs and symptoms 
associated with SARS-CoV-2 infection since the last contact. 
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Any subject who develops fever, an acute respiratory illness, symptoms related 
to multisystem inflammatory syndrome in children ([MIS-C] [pediatric subjects 
<18 years only]), or other symptoms that they feel could be related to COVID-
19 should alert the study staff immediately.  If the subject experiences a true 
medical emergency, they should visit their local hospital ED or call the local 
emergency telephone number (eg, 911 in North America) and contact the 
clinical site personnel later.  Subjects’ symptoms must be evaluated by the 
investigator or designee, which can occur through site visit, mobile unit, home 
visit, telemedicine, etc. If the investigator or designee suspects SARS-CoV-2 
infection, a NP swab sample should be collected and sent for central lab testing. 
The subject may also be asked to provide a blood sample if it corresponds to a 
scheduled visit (according to the Schedule of Events). 
Subjects with laboratory confirmed SARS-CoV-2 infection during the EAP 
should be informed as soon as possible and should undergo medical isolation to 
prevent contact with others to reduce the risk of further transmission. Since 
these subjects will likely be isolated, the study visits, assessments and sample 
collections may occur through a variety of methods. 
All subjects who have a confirmed SARS-CoV-2 infection will continue to be 
tested (sample collection weekly) until 2 consecutive confirmed negative 
SARS-CoV-2 RT-qPCR test results are achieved ≥24 hours apart.  This testing 
may continue through the EAP and into the Follow-up period.  For subjects who 
have a confirmed SARS-CoV-2 infection, the investigator will assess AEs 
weekly or more frequently than weekly, depending on the clinical status of the 
subject, as assessed by the investigator or designee (these more frequent AE 
assessments will be reported as unscheduled visits).  The investigator will also 
collect information for any SARS-CoV-2 infection-related medically attended 
visits to the ED, UCC, or hospitalization starting from the timepoint of SARS-
CoV-2 RT-qPCR positive result. 
Subjects presenting with acute illness should be medically managed according 
to local standard of care as per the discretion of the treating physician. 
If a subject is hospitalized for suspected SARS-CoV-2 infection, every effort 
should be made by the site personnel to collect, as soon as possible, an NP swab 
sample for central lab SARS-CoV-2 RT-qPCR testing.  In subjects where it is 
not possible to have samples collected for assessment in the central laboratory, 
study site personnel will attempt to obtain and record information about any 
positive SARS-CoV-2 assays conducted in local laboratories associated with 
other medical facilities. 
Follow-up Period (day 30 to day 225) 
Subjects who remain SARS-CoV-2 RT-qPCR negative throughout the EAP 
will complete the end of the EAP and enter the Follow-up Period to be followed 
for 7 months. 
Subjects who become SARS-CoV-2 RT-qPCR positive during the EAP will 
continue to have weekly NP swab samples for SARS-CoV-2 RT-qPCR testing 
until 2 confirmed negative SARS-CoV-2 RT-qPCR test results are achieved at 
least 24 hours apart, even after they complete the EAP and enter the study 
Follow-up Period to be followed for 7 months.  In such situations, these visits 
for sample collection should be characterized as unscheduled visits. 
At each scheduled visit, the investigator or designee will contact each subject 
(site visit or telemedicine) to assess and document the subject’s general health, 
AEs in general and signs and symptoms associated with SARS-CoV-2 infection 
since the last contact, as described for the EAP. 
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Study Duration 
For each subject, there are 3 study periods: a 1- to 2-day screening/baseline 
period, a 1-month EAP, and a 7-month follow-up period after the end of the 
EAP. 
End of Study Definition 
The end of study is defined as the date the last subject completes the last study 
visit, withdraws from the study, or is lost to follow-up. 
Population 
 
 
Sample Size: 
Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline: Approximately 
3150 adult and adolescent subjects will be enrolled.  Cohort A is expected to 
include the majority of study subjects. 
Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline: Approximately 
350 adult and adolescent subjects will be enrolled. 
Cohort A1: SARS-CoV-2 RT-qPCR Negative at Baseline: Approximately 
225 pediatric subjects (<12 years) will be enrolled. 
Cohort B1: SARS-CoV-2 RT-qPCR Positive at Baseline: Approximately 
25 pediatric subjects (<12 years) will be enrolled. 
 
Target Population: 
Asymptomatic, healthy adults (≥18 years), adolescents (≥12 years to 
<18 years), and children (<12 years) who are household contacts to the first 
known household member with a diagnosis of SARS-CoV-2 infection (index 
case) 
Treatments 
 
 
Study Drug 
 
Dose/Route/Schedule: 
REGN10987 and REGN10933 
Adult and adolescent subjects (≥12 years): 
• 
1200 mg (600 mg of each mAb) / SC / single dose on day 1 
Weight-Tiered Dose Groups for Pediatric Subjects <12 Years of Age 
Weight-
Tiered Dose 
Group 
Total Dose 
(mg) 
Route of 
Administration 
Total 
Number 
of 
Injections 
Total Volume 
(mL) of 
Injection 
≥40 kg 
1200  
(600 per mAb) 
SC1 
4 
10  
(5 per mAb) 
≥20 to <40 kg 
792  
(396 per mAb) 
SC1 
4 
6.6  
(3.3 per mAb) 
≥10 to <20 kg 
408  
(204 per mAb) 
SC1 
2 or 4 
3.42  
(1.7 per mAb) 
≥5 to <10 kg3 
144  
(72 per mAb) 
IM 
1 or 2 
1.24  
(0.6 per mAb) 
≥2.5 to <5 kg3 
96  
(48 per mAb) 
IM 
1 
0.8  
(0.4 per mAb) 
<2.5 kg3 
48  
(24 per mAb) 
IM 
1 
0.4  
(0.2 per mAb) 
1.  Investigators have the option to use an infusion pump for SC administration of study drug containing the combined 
volume with both mAbs. 
2.  If the Investigator prefers not to exceed 1 mL per syringe, then study drug may be administered using 2 syringes 
for each mAb (ie, 4 injections), one with 0.8 mL and another with 0.9 mL for each mAb. If the Investigator prefers 
to use only 2 syringes (ie, 2 injections), the 1.7 mL administered in each syringe will contain a different mAb.   
3.  Investigators have the option to administer the dose in a single syringe containing the combined volume with both 
mAbs. 
4.  If the Investigator prefers not to exceed 1 mL per syringe, then study drug may be administered using 1 syringe for 
each mAb.  If the Investigator prefers to use 1 syringe, the1.2 mL administered in 1 syringe should be combined 
volume of 0.6 mL of each mAb. 
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Placebo 
 
Route/Schedule: 
Matching solution  
SC / single dose on day 1 
IM / single dose on day 1 for pediatric subjects <10 kg 
Endpoint 
Endpoints are specified for study cohorts.  
Symptomatic SARS-CoV-2 infection is determined by a positive central lab 
SARS-CoV-2 RT-qPCR result during the EAP with signs/symptoms occurring 
within ±14 days of a positive RT-qPCR. 
The “strict-term”, “broad-term”, and CDC definitions for signs/symptoms of 
SARS-CoV-2 infection are presented earlier in Objectives. 
Primary Endpoints: 
Cohort A and Cohort A1: SARS-CoV-2 RT-qPCR Negative at Baseline 
The endpoints are for subjects who are seronegative at baseline (based on 
central lab test) unless stated otherwise.  
Cohort A Primary Efficacy Endpoint  
• 
Proportion of subjects who have a symptomatic RT-qPCR confirmed 
SARS-CoV-2 infection (broad-term) during the EAP 
Cohort A and Cohort A1 Primary Safety Endpoint 
• 
Proportion of subjects with treatment-emergent adverse events 
(TEAEs) and severity of TEAEs  
Secondary Endpoints: 
Cohort A and Cohort A1: SARS-CoV-2 RT-qPCR Negative at Baseline 
Cohort A Key Secondary Endpoints  
• 
Proportion of subjects with viral load >4 (log10 copies/mL) in 
nasopharyngeal (NP) swab samples during the EAP 
• 
Number of weeks of symptomatic RT-qPCR confirmed SARS-CoV-2 
infection (broad-term) during the EAP 
• 
Number of weeks of high-viral load >4 (log10 copies/mL) in NP swab 
samples during the EAP 
• 
Number of weeks of RT-qPCR confirmed SARS-CoV-2 infection 
(regardless of symptoms) during the EAP 
• 
Proportion of subjects who have a RT-qPCR confirmed SARS-CoV-2 
infection (regardless of symptoms) during the EAP 
• 
Proportion of subjects in placebo group with a RT-qPCR confirmed 
SARS-CoV-2 infection during the EAP with an index case participating 
in study R10933-10987-COV-2067 (comparison of those whose index 
cases receive REGN10933+REGN10987 versus placebo in study 
R1033-10987-COV-2067) 
Cohort A and Cohort A1 Other Secondary Endpoints  
• 
Proportion of subjects who have a symptomatic RT-qPCR confirmed 
SARS-CoV-2 infection (CDC definition) during the EAP 
• 
Number of weeks of symptomatic RT-qPCR confirmed SARS-CoV-2 
infection (CDC definition) during EAP 
• 
Proportion of subjects who have a symptomatic RT-qPCR confirmed 
SARS-CoV-2 infection (strict-term) during the EAP 
• 
Number of weeks of symptomatic RT-qPCR-confirmed SARS-CoV-2 
infection (strict-term) during the EAP  
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• 
Proportion of subjects who have a RT-qPCR confirmed SARS-CoV-2 
infection at each week in the EAP 
• 
Proportion of subjects who have a symptomatic RT-qPCR confirmed 
SARS-CoV-2 infection (broad term) at each week in the EAP 
• 
Time-weighted average of viral load (log10 copies/mL) from the first 
positive SARS-CoV-2 RT-qPCR in NP swab sample (that has an onset 
during the EAP) until the third weekly visit after the first positive test 
during the EAP 
Note: Only for RT-qPCR positive subjects during the EAP in the 
seronegative modified full analysis set for cohort A (seronegative 
mFAS-A) 
• 
Time-weighted average of viral load (log10 copies/mL) from the first 
positive SARS-CoV-2 RT-qPCR in NP swab sample (that has an onset 
during the EAP) until the second weekly visit after the first positive test 
during the EAP 
Note: Only for RT-qPCR positive subjects during the EAP in the 
seronegative mFAS-A 
• 
Maximum SARS-CoV-2 RT-qPCR viral load (log10 copies/mL) in NP 
swab samples among individuals with ≥1 RT-qPCR positive that has an 
onset during the EAP 
• 
SARS-CoV-2 RT-qPCR viral load (log10 copies/mL) in NP swab 
samples corresponding to the onset of first positive RT-qPCR during the 
EAP 
• 
Area under the curve (AUC) in viral load (log10 copies/mL) from the 
first positive SARS-CoV-2 RT-qPCR NP swab sample detected during 
the EAP until the first confirmed negative test (testing that occurs after 
the EAP will be included if necessary to achieve a negative test result) 
Note: Only for RT-qPCR positive subjects during the EAP in the 
seronegative mFAS-A 
• 
Number of medically attended visits in emergency rooms or urgent care 
centers related to a RT-qPCR confirmed SARS-CoV-2 infection that has 
an onset during the EAP 
• 
Proportion of subjects with at least 1 COVID-19-related hospitalization 
or emergency room visit associated a positive RT-qPCR during the EAP, 
or all-caused death 
• 
Proportion of subjects requiring medically attended visits in emergency 
rooms or urgent care centers related to a RT-qPCR confirmed 
SARS-CoV-2 infection that has an onset during the EAP 
• 
Proportion of subjects hospitalized related to a RT-qPCR confirmed 
SARS-CoV-2 infection that has an onset during the EAP 
• 
Number of days of hospital and intensive care unit (ICU) stay in subjects 
hospitalized for a RT-qPCR confirmed SARS-CoV-2 infection that has 
an onset during the EAP 
• 
Number of days missed for daily responsibilities (where applicable), 
including work (employed adults) or school (students), daycare or 
family obligations/responsibilities (childcare or eldercare) due to a RT-
qPCR confirmed SARS-CoV-2 infection that has an onset during the 
EAP 
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• 
Proportion of subjects in the placebo group with a RT-qPCR confirmed 
SARS-CoV-2 infection during the EAP with at least 1 household 
member participating either in study R10933-10987-COV-2067 or in 
cohort B (comparison of those whose households members receive 
REGN10933+REGN10987 versus placebo in study R1033-10987-
COV-2067 or in cohort B) 
Additional Cohort A1 Secondary Efficacy Endpoint  
• 
Proportion of subjects who have a symptomatic RT-qPCR confirmed 
SARS-CoV-2 infection (broad-term) during the EAP 
• 
Proportion of subjects with viral load >4 (log10 copies/mL) in 
nasopharyngeal (NP) swab samples during the EAP 
• 
Number of weeks of symptomatic RT-qPCR confirmed SARS-CoV-2 
infection (broad-term) during the EAP 
• 
Number of weeks of high-viral load >4 (log10 copies/mL) in NP swab 
samples during the EAP 
• 
Number of weeks of RT-qPCR confirmed SARS-CoV-2 infection 
(regardless of symptoms) during the EAP 
• 
Proportion of subjects who have a RT-qPCR confirmed SARS-CoV-2 
infection (regardless of symptoms) during the EAP 
• 
Proportion of subjects in placebo group with a RT-qPCR confirmed 
SARS-CoV-2 infection during the EAP with an index case participating 
in study R10933-10987-COV-2067 (comparison of those whose index 
cases receive REGN10933+REGN10987 versus placebo in study 
R1033-10987-COV-2067) 
Cohort A and Cohort A1 Secondary Safety Endpoints 
• 
Proportion of baseline seropositive subjects (based on central lab test) 
with TEAEs and severity of TEAEs 
• 
Incidence and severity of symptomatic SARS-CoV-2 infection in 
seronegative and seropositive subjects (based on central lab test) in both 
the EAP and follow-up periods 
Cohort A and Cohort A1 Pharmacokinetic and Immunogenicity Endpoints 
• 
Concentrations of REGN10933and REGN10987 in serum over time and 
selected PK parameters in both seronegative and seropositive subjects 
(based on baseline central lab test) 
• 
Immunogenicity as measured by anti-drug antibodies (ADA) and 
neutralizing antibodies (NAbs) to REGN10933 and REGN10987 over 
time in both seronegative and seropositive subjects (based on baseline 
central lab test) 
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Cohort B and Cohort B1: SARS-CoV-2 RT-qPCR Positive at Baseline 
The endpoints are for all subjects who are seronegative at baseline (based on 
central lab test), unless stated otherwise.  
Cohort B Primary Efficacy Endpoint  
• 
Proportion of subjects who subsequently develop signs and symptoms 
(broad-term) within 14 days of a positive RT-qPCR at baseline or during 
the EAP 
Cohort B Key Secondary Efficacy Endpoints  
• 
Number of weeks of symptomatic SARS-CoV-2 infection (broad-term) 
within 14 days of a positive RT-qPCR at baseline or during the EAP  
• 
Number of weeks of high viral load >4 (log10 copies/mL) in NP swab 
samples during the EAP 
Cohort B and Cohort B1 Other Secondary Efficacy Endpoints 
• 
Proportion of subjects who subsequently develop signs and symptoms 
(CDC definition) within 14 days of a positive RT-qPCR at baseline or 
during the EAP 
• 
Proportion of subjects who subsequently develop signs and symptoms 
(strict-term) within 14 days of a positive RT-qPCR at baseline or during 
the EAP 
• 
Number of weeks of symptomatic SARS-CoV-2 infection (CDC 
definition) within 14 days of a positive RT-qPCR at baseline or during 
the EAP 
• 
Number of weeks of symptomatic SARS-CoV-2 infection (strict-term) 
within 14 days of a positive RT-qPCR at baseline or during the EAP 
• 
Proportion of subjects with viral load >4 (log10 copies/mL) in NP swab 
samples during the EAP 
• 
Change in viral load (log10 copies/mL) from baseline to day 8 visit in 
NP swab samples 
• 
Change in viral load (log10 copies/mL) from baseline to day 15 visit in 
NP swab samples 
• 
Time-weighted average change from baseline in viral load (log10 
copies/mL) in NP swab samples until the day 22 visit. 
• 
Area under the curve (AUC) in viral load (log10 copies/mL) in NP swab 
samples from baseline to the first confirmed negative test 
• 
Maximum SARS-CoV-2 RT-qPCR viral load (log10 copies/mL) in NP 
swab samples during the EAP 
• 
Number of medically attended visits in emergency rooms or urgent care 
centers related to RT-qPCR confirmed SARS-CoV-2 infection that has 
an onset at baseline or during the EAP 
• 
Proportion of subjects requiring medically attended visits in emergency 
rooms or urgent care centers related to a RT-qPCR confirmed 
SARS-CoV-2 infection that has an onset at baseline or during the EAP 
• 
Proportion of subjects hospitalized related to a RT-qPCR confirmed 
SARS-CoV-2 infection that has an onset at baseline or during the EAP 
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• 
Number of days of hospital and ICU stay in subjects hospitalized for a 
RT-qPCR confirmed SARS-CoV-2 infection that has an onset at 
baseline or during the EAP 
• 
Number of days missed for daily responsibilities (where applicable), 
including work (employed adults) or school (students), or family 
obligations/responsibilities (childcare or eldercare) due to a RT-qPCR 
confirmed SARS-CoV-2 infection that has an onset at baseline or during 
the EAP 
• 
Proportion of subjects with at least 1 COVID-19 related hospitalization 
or emergency room visit associated with a positive RT-qPCR at baseline 
or during the EAP, or all-cause death 
Additional Cohort B1 Secondary Efficacy Endpoints 
• 
Proportion of subjects who subsequently develop signs and symptoms 
(broad-term) within 14 days of a positive RT-qPCR at baseline or during 
the EAP 
• 
Number of weeks of symptomatic SARS-CoV-2 infection (broad-term) 
within 14 days of a positive RT-qPCR at baseline or during the EAP 
• 
Number of weeks with high viral load >4 (log10 copies/mL) in NP swab 
samples at during the EAP 
Cohort B and Cohort B1 Secondary Safety Endpoints 
• 
Proportion of subjects with TEAEs and severity of TEAEs  
• 
Incidence and severity of symptomatic SARS-CoV-2 infection in both 
the EAP and follow-up periods 
Cohort B and Cohort B1 Pharmacokinetic and Immunogenicity Endpoints 
• 
Concentrations of REGN10933 and REGN10987 in serum over time 
and selected PK parameters in both seronegative and seropositive 
subjects (based on baseline central lab test) 
• 
Immunogenicity as measured by ADAs and NAbs to REGN10933 and 
REGN10987 over time in both seronegative and seropositive subjects 
(based on baseline central lab test) 
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Procedures and Assessments 
Screening/Baseline Procedures:  
The following procedures will be performed for the purpose of determining 
study eligibility or characterizing the baseline population: demographics (eg, 
age, sex, race, weight, height, etc), medical history, local diagnostic assay for 
SARS-CoV-2, query for risk for SARS-CoV-2 infection, and household 
assessment in which subjects will be asked to provide general information about 
the household members. 
The investigator or sub-investigator will verify that the subject tests negative or 
positive by a local diagnostic assay for SARS-CoV-2 (eg, molecular assay such 
as RT-PCR assay for SARS-CoV-2 or a SARS-CoV-2 antigen test using an 
appropriate sample such as NP, nasal, OP, or saliva). The local diagnostic assay 
for SARS-CoV-2 must be considered acceptable for clinical use by local 
standards. If the test has not been approved or received EUA issued by the US 
FDA or by the equivalent local health authority, then the Sponsor should be 
consulted.  The use of a RT-PCR assay is highly recommended.  
The local diagnostic test result, specimen type (eg, nasal swab), assay type, and 
date of test will be recorded in the eCRF.  The sample type collected is 
dependent on local lab requirements. 
Efficacy Procedures: 
Nasopharyngeal Swab SARS-CoV-2 RT-qPCR Test (Central Lab):  
Nasopharyngeal swab sample will be collected from subjects to determine 
presence or absence of SARS-CoV-2 virus and to determine the relative 
quantification in viral load. 
COVID-19 Symptomology (Broad Term, Strict Term, CDC definition):  
During each scheduled or unscheduled visit/contact, the investigator or sub-
investigator, or designee (ie, nurse practitioner in countries where allowed by 
local law) will query the subject and/or subject’s parent or guardian about 
adverse events the subject is experiencing or has experienced since the last 
visit/contact (eg, within the prior week if it is a weekly scheduled visit) and ask 
about all of the signs and symptoms associated with these adverse events 
including the start date, end date and severity of each. The investigator should 
avoid querying the subject and/or subject’s parent or guardian by running a 
check-list of signs and symptoms, but rather allow the subject and/or subject’s 
parent or guardian to spontaneously report everything that they presented.  
All signs and symptoms related to the AEs, along with the corresponding start 
date, end date and severity should be documented in the subject’s medical 
records (source document). As signs and symptoms may appear and resolve on 
different days and may precede or occur after the collection of NP swab sample 
for the SARS-CoV-2 RT-qPCR test, it is important that this detailed 
information be captured in the source document. 
Independent of the results (positive or negative) of the SARS-CoV-2 RT-qPCR 
tests performed on samples collected from study subjects during the weekly or 
unscheduled visits, all adverse events must be documented in the AE CRF. 
Signs and symptoms related to the adverse events reported in the AE CRF and 
confirmed to be temporally related to a positive SARS-CoV-2 RT-qPCR test 
collected from the subject’s NP swab sample will be reported on a separate CRF 
(individual sign or symptom with start date and end date, and associated 
severity). 
 
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Strict-term COVID-19 signs and symptoms, defined as: 
o 
fever (≥38°C) PLUS ≥1 respiratory symptom (sore throat, cough, 
shortness of breath);  
OR  
o 
2 respiratory symptoms (sore throat, cough, shortness of breath);  
OR  
o 
1 respiratory symptom (sore throat, cough, shortness of breath) PLUS 
≥2 non-respiratory symptoms (chills, nausea, vomiting, diarrhea, 
headache, conjunctivitis, myalgia, arthralgia, loss of taste or smell, 
fatigue or general malaise). 
• Broad-term COVID-19 signs and symptoms:  defined as any of the 
23 symptoms (listed earlier in the Objectives) or fever (≥38°C). 
• The CDC definition:  defined as at least 2 of the following symptoms: fever 
(measured or subjective), chills, rigors, myalgia, headache, sore throat, 
nausea or vomiting, diarrhea, fatigue, congestion or runny nose OR Any 1 
of the following symptoms: cough, shortness of breath, difficulty breathing, 
new olfactory disorder, new taste disorder OR Severe respiratory illness 
with at least 1 of the following, clinical or radiographic evidence of 
pneumonia, ARDS.  
Medically Attended Visits:  Subjects and/or their parent/guardian (as 
appropriate) who become SARS-CoV-2 RT-qPCR positive will be queried on 
any SARS-CoV-2 infection-related medically attended visits to the ED, UCC, 
or hospitalization.  The assessment of medically attended visits to ED, UCC or 
hospitalization will be performed from the time  the subject first becomes 
SARS-CoV-2 RT-qPCR positive or from the time they develop symptoms 
suspected to be COVID-19 (later confirmed by RT-qPCR positive results) until 
the subject has had 2 negative tests or COVID-19 related symptoms have 
resolved (whichever lasts longer), or of until the end of study visit. 
Absenteeism Assessment:  Subjects and/or their parent/guardian who are or 
become SARS-CoV-2 RT-PCR positive during the EAP will be queried on any 
SARS-CoV-2 infection-related absenteeism. Data include absenteeism (where 
applicable) defined as number of days missed for daily responsibilities, 
including work (employed adults) or school (students), daycare, or family 
obligations/responsibilities (childcare or eldercare) due to COVID-19. 
Safety Procedures: 
Targeted Physical Examination and Vital Signs:  The targeted physical 
examination and vital signs include measurements of body temperature, blood 
pressure (measured after the subject has been resting quietly for at least 
5 minutes and may be obtained from a seated or supine position), pulse rate, 
and respiratory rate, and examination of the oropharynx, skin, heart, lungs and 
any other system(s) depending on any complaints or concerns expressed by the 
subjects. 
Laboratory Testing:  samples for blood chemistry, hematology, and urinalysis 
(only for adolescent/adult subjects) will be collected and analyzed.  For all 
women of childbearing potential, a urine pregnancy test will be performed 
onsite and any positive urine pregnancy test will be confirmed with a serum 
pregnancy test at the central laboratory.  
 
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Other Procedures: 
Drug Concentration and Immunogenicity measurements: Dense sample and 
sparse sample collection for drug concentration measurement will be performed 
in subsets of subjects.  Samples for ADA and NAb assessment will be collected 
at various times throughout the study. Any unused serum samples may be used 
for exploratory research. 
Serological Assays for Endogenous Anti-SARS-CoV-2 Antibodies:  In order to 
assess the impact of baseline humoral immunity/antibody response to 
SARS-CoV-2 on REGN10933+REGN10987 efficacy to prevent SARS-CoV-2 
infection, serum anti-SARS-CoV-2 will be measured at baseline, including but 
not limited to those which detect antibodies against the S protein and/or the 
N protein and/or neutralization assays. Samples will be collected from adult and 
pediatric subjects (<18 years). 
Exploratory Pharmacodynamic/Biomarker and Serum/Plasma Samples for 
Research:  Samples for assessment of pharmacodynamic and exploratory 
research will be collected from adult and adolescent subjects.  
Pharmacogenomic Analysis (Optional):  Adult and pediatric subjects (<18 years 
and >10 kg) subjects may participate in an optional genomics sub-study 
(separate informed consent required).  Blood sample for RNA and DNA will be 
collected for this substudy. 
Statistical Plan 
Justification of Sample Size 
An administrative assessment for assumption verification and sample size 
estimation for cohort A will be conducted using unblinded descriptive analyses 
without performing any formal statistical hypothesis testing.  Analyses will be 
conducted in the group of cohort A subjects randomized from study initiation 
through the date of randomization that are associated with 30 RT-PCR events 
amongst cohort A seronegative subjects during the EAP (approximately 600 
subjects overall regardless of baseline serology status[eg, seronegative, 
seropositive, or other (eg, borderline or undetermined, etc)]).  The subjects 
evaluated in this descriptive analysis will not be included for the final efficacy 
analyses, however, these subjects will be included in the safety analyses.  To 
maintain operational efficiencies and because of the progressive rollout of 
SARS-CoV-2 vaccination which may change the dynamics of virus 
transmission/infection in the near future, enrollment into the study will not be 
paused while the administrative assessment is performed and it is estimated that 
the total enrollment may reach approximately 3500 subjects.  The following 
justification of sample size in cohort A with the assumption of reduction of 
symptomatic infection is based on the results from the administrative 
assessment described below. For the purpose of the study analysis, cohort A 
and cohort B are independent with separate type I error control for each cohort. 
Cohort A: Adult and Adolescent Subjects (≥12years) Who Are SARS-CoV-2 
RT-qPCR Negative 
In cohort A, subjects are randomized in a 1:1 allocation ratio to 
REGN10933+REGN10987 or placebo.  The primary hypothesis is the reduction 
in the proportion of symptomatic RT-qPCR (broad-term) confirmed SARS-
CoV-2 infections in seronegative subjects.  To calculate the sample size 
required to achieve at least 90% power for seronegative subjects in cohort A, it 
is assumed that the statistical hypothesis will be tested in a 2-sided test. Based 
on the administrative assessment results among 409 seronegative subjects in 
cohort A, a 50% reduction of infections (symptomatic or asymptomatic) 
compared to the placebo group and a 100% reduction of symptomatic infections 
compared to placebo group were observed. Due to the small sample size in the 
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administrative assessment, it was assumed, for the purpose of assessing study 
power, that an approximately 50% reduction or greater in symptomatic 
infections compared to the placebo group will be expected for the final primary 
efficacy analysis. 
In this household study design, the number of subjects per household, the 
correlation between subjects and symptomatic infection rates within a 
household are unknown.  To detect a relative risk of 0.5 (ie, 50% reduction of 
the assumed 10% attack rate in the placebo arm), equivalent to an odds ratio of 
0.47, power was also calculated compared to the boundary p-value of 0.05 based 
on 2000 simulations in 1248 subjects from 430 households (ie, assuming an 
average household size of 2.9 seronegative subjects by varying degrees of 
correlation within household.  In all cases, the power of the study is >90% using 
a generalized linear model with the generalized estimation equation (GEE) 
approach and assuming a compound symmetry covariance matrix.  
At least 1980 subjects will need to be enrolled in cohort A to have a minimum 
of 1248 seronegative subjects, assuming that 10% of subjects drop out, 30% of 
subjects are seropositive at baseline. 
Cohort A1: Pediatric Subjects (<12 years) with SARS-CoV-2 RT-qPCR 
Negative 
Approximately up to a total of 250 pediatric subjects (<12 years) will be 
enrolled in this study. Of the 250 subjects, 90% (225/250) are expected to be 
enrolled in this cohort (ie, central lab RT-qPCR negative at baseline) for 
evaluating the drug concentration and exposure, and safety. The actual number 
of subjects in this cohort will depend on the actual percentage of subjects with 
a baseline negative RT-qPCR enrolled. No statistical hypothesis tests will be 
performed. 
Cohort B: SARS-CoV-2 RT-qPCR Positive 
The primary endpoint in asymptomatic, seronegative subjects in cohort B is the 
proportion of subjects who subsequently develop signs and symptoms (broad 
term) within 14 days of a positive RT-qPCR test result at baseline or during the 
EAP. 
The sample size of cohort B is based on the frequency of finding positive 
subjects while enrolling cohort A and assumes that approximately 10% of 
subjects in a household are already positive for SARS-CoV-2 by RT-qPCR at 
baseline.  Among approximately 3500 adult and adolescent subjects that are 
anticipated to be enrolled in cohort A or cohort B, the number of subjects 
expected in cohort B is approximately 220 or greater, including 200 
seronegative subjects. Assuming that 50% of infected placebo subjects at 
baseline will develop symptoms, 200 seronegative subjects in cohort B will 
provide >90% power to detect a relative risk of 0.5, using a 2-sided Fisher’s 
exact test at an alpha level of 0.05.  
Cohort B1: Pediatric Subjects (<12 years) with SARS-CoV-2 RT-qPCR 
Positive 
Approximately up to a total of 250 pediatric subjects (<12 years) will be 
enrolled in this study.  Of 250 subjects, 10% (25/250) are expected to be 
enrolled in this cohort (ie, central lab RT-qPCR positive at baseline) for 
evaluating the drug concentration and exposure, and safety. The actual number 
of subjects in this cohort will depend on the actual percentage of subjects with 
a baseline positive RT-qPCR enrolled. No statistical hypothesis tests will be 
performed. 
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Efficacy Analysis Sets 
Seronegative Modified Full Analysis Set (Seronegative mFAS-A) – Cohort A 
The seronegative modified full analysis set for cohort A (seronegative mFAS-
A) includes all randomized subjects aged 12 years and older who are laboratory 
confirmed negative for SARS-CoV-2 (per central lab PCR test) and who test 
negative for antibodies for SARS-CoV-2 (per central lab serology testing) at 
baseline.   
Subjects included in the administrative assessment analysis are excluded from 
the seronegative mFAS-A population. 
Subjects will be analyzed based on the randomized treatment assignment. The 
seronegative mFAS-A population is the primary analysis population for the 
primary and secondary endpoints for cohort A of this study unless specified 
otherwise.  
Seronegative Modified Full Analysis Set (Seronegative mFAS-A1) – 
Cohort A1 
The seronegative modified full analysis set for cohort A1 (seronegative 
mFAS-A1) includes all randomized subjects aged less than 12 years who are 
laboratory confirmed negative for SARS-CoV-2 (per central lab PCR test) and 
who test negative for antibodies for SARS-CoV-2 (per central lab serology 
testing) at baseline.   
Subjects will be analyzed based on the randomized treatment assignment. The 
efficacy endpoints for cohort A1 will be analyzed using the seronegative 
mFAS-A1 unless specified otherwise.  
Seronegative Modified Full Analysis Set (Seronegative mFAS-B) – Cohort B 
The seronegative modified full analysis set for cohort B (seronegative mFAS-B) 
includes all randomized subjects aged 12 years and older who have laboratory 
confirmed positive tests at baseline for SARS-CoV-2 RT-qPCR and negative 
SARS-CoV-2 serology (both based on central lab testing) and are asymptomatic 
at baseline.  Subjects will be analyzed based on the randomized treatment 
assignment. The primary and secondary efficacy endpoints for cohort B will be 
analyzed using the seronegative mFAS-B unless specified otherwise.  
Seronegative Modified Full Analysis Set (Seronegative mFAS-B1) – 
Cohort B1 
The seronegative modified full analysis set for cohort B1 (seronegative 
mFAS-B1)  includes all randomized subjects aged less than 12 years who have 
laboratory confirmed positive tests at baseline for SARS-CoV-2 RT-qPCR and 
negative SARS-CoV-2 serology (both based on central lab testing) at baseline. 
Subjects will be analyzed based on the randomized treatment assignment. The 
efficacy endpoints for cohort B1 will be analyzed using the seronegative 
mFAS-B1 unless specified otherwise. 
Primary Efficacy Analysis (Cohort A)  
The primary efficacy endpoint will be analyzed in the seronegative mFAS-A 
population. In order to account for the correlation among subjects within a 
household and control the associated type 1 error inflation, a generalized linear 
model will be used to estimate the odds ratio between the treatment groups by 
using the GEE approach.  This model estimates a single within-household 
correlation coefficient. The model will include the fixed category effects of 
treatment group (placebo versus REGN10933+REGN10987), region (US vs ex-
US), and age (≥12 to <50, ≥50 years). The model will use a compound 
symmetry covariance matrix and estimate the odds ratio between the treatment 
groups and corresponding 95% CI and p-value.  If the GEE model fails to 
converge due to most households containing only a single study subject in 
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seronegative mFAS-A or the percentage of households with only a single study 
subject is 70% or more, then a logistic regression model will be used, with 
treatment, region, and age group as fixed effects.  
Subjects with COVID-19 symptoms that are missing a central lab determined 
RT-qPCR test during the EAP (eg. are too sick to go to the study site) but have 
a positive SARS-COV-2 test from a local lab (eg. in the hospital) will be 
considered as having a symptomatic infection if any of the symptoms occurred 
within 14 days of the positive SARS-COV-2 test.  
Additional sensitivity analyses for missing data are described in the protocol.  
Control of Multiplicity  
The overall type I error will be controlled in each of the seronegative mFAS-A 
and seronegative mFAS-B independently at a 2-sided 5% significance level.  
Seronegative mFAS-A Subjects 
The overall type I error will be controlled for the primary hypothesis in cohort 
A based on a 2-sided test at an alpha level of 0.05 as follows: 
H0: There is no treatment difference between REGN10933+REGN10987 
and placebo in the proportion of subjects with a symptomatic RT-qPCR 
confirmed SARS-CoV-2 infection during the EAP. 
H1: There is a treatment difference between REGN10933+REGN10987 
and placebo in the proportion of subjects with a symptomatic RT-qPCR 
confirmed SARS-CoV-2 infection during the EAP 
If the primary efficacy endpoint in cohort A is statistically significant, the alpha 
level of 0.05 will be released for the key secondary endpoints in cohort A. The 
hierarchy testing sequence of key secondary endpoints is presented in the 
protocol and statistical analysis plan (SAP). 
Cohort B: SARS-CoV-2 RT-qPCR Positive 
The overall type I error will be controlled for the primary hypothesis in cohort B 
based on a 2-sided test at an alpha level of 0.05 as follows: 
H0: 
There 
is 
no 
treatment 
difference 
between 
REGN10933+REGN10987 and placebo in the proportion of subjects 
who subsequently develop signs and symptoms (broad-term) within 
14 days of a positive RT-qPCR at baseline or during the EAP. 
H1: 
There 
is 
a 
treatment 
difference 
between 
REGN10933+REGN10987 and placebo in the proportion of subjects 
who subsequently develop signs and symptoms (broad-term) within 
14 days of a positive RT-qPCR at baseline or during the EAP. 
If statistical significance is established for the primary efficacy endpoint in 
cohort B, a hierarchical testing procedure will be applied to the key secondary 
endpoints in cohort B at a 2-sided 0.05 significance level. The order of testing 
sequence for key secondary endpoints is presented in the protocol and SAP. 
Safety Analysis 
Safety and tolerability will be summarized for each cohort and will also be 
summarized by baseline serology status for all adults, adolescent subjects, and 
pediatric subjects. 
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1. 
INTRODUCTION 
1.1. 
Emergence of SARS-CoV-2 and COVID-19 
Coronaviruses are a family of enveloped, single-stranded RNA viruses. In recent decades, two 
highly pathogenic strains of coronavirus were identified in humans: severe acute respiratory 
syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus 
(MERS-CoV). These viruses were found to cause severe, and sometimes fatal, respiratory illness 
(Cui, 2019) (Fehr, 2015). 
In December 2019, a pneumonia of unknown cause was identified in clusters of patients in 
Wuhan City, China. A novel enveloped RNA betacoronavirus – severe acute respiratory syndrome 
coronavirus 2 (SARS-CoV-2) – was identified in these patients, and the viral infection was later 
designated coronavirus disease 2019 (COVID-19) by the World Health Organization (WHO, 
2020b) (Zou, 2020).  As of June 2020, more than 7.6 million confirmed cases of COVID-19 have 
been reported globally (WHO, 2020a). This rapidly-spreading, worldwide outbreak prompted the 
WHO to declare COVID-19 a pandemic and public health emergency of international concern on 
11 March 2020. 
1.2. 
Populations at Increased Risk of SARS-CoV-2 Infection Among 
Household Contacts of a Person Infected with SARS-CoV-2 
Efforts to control the pandemic have resulted in widespread shelter-in-place orders.  Transmission 
of SARS-CoV-2 occurs primarily through person-to-person contact and respiratory droplet 
transmission (Lai, 2020).  Household contacts of a person infected with SARS-CoV-2 are at a high 
risk for acquiring infection, with transmission rates ranging from approximately 10% to 15%.  One 
US study reported a household attack rate of 29%, 42% among children (<18 years) of the 
SARS-CoV-2-infected patient, suggesting that children and adolescents are especially vulnerable 
to household transmission of SARS-CoV-2 (Lewis, 2020).  Pregnant women, in particular, are at 
increased risk for developing severe COVID-19 and have been shown to have a higher rate of 
hospitalization, need for mechanical ventilation, and ICU admission than non-pregnant women 
(Ellington, 2020) (Knight, 2020)(Woodworth, 2020).  Neonatal transmission of SARS-CoV-2 has 
also been reported (Vivanti, 2020).  Therefore, pregnant women should be considered for inclusion 
in COVID-19 prophylaxis efforts. Although it has been reported that the majority of individuals 
who acquire infection from household contacts develop symptoms of COVID-19 (Burke, 2020) 
(Jing, 2020), (Bi, 2020) (Li, 2020b), in a cruise ship setting, the majority of persons who are 
asymptomatic at the time of testing remain asymptomatic throughout the course of the infection 
(ie, until reverse transcription polymerase chain reaction (RT-PCR) results are negative (Sakurai, 
2020).  Prophylaxis is urgently needed to reduce transmission rates and/or reduce the occurrence 
of symptomatic disease.  Ideally, prophylaxis would need to be given as soon as possible after a 
known exposure, as the duration of time between symptomatic infection in the source individual 
and the development of symptoms in newly infected individual is thought to be approximately 5 
days, with a possible range of 2 to14 days (Lauer, 2020) (Li, 2020a).  Animal models suggest that 
SARS-CoV-2 RT-PCR in nasopharyngeal (NP) samples become positive within a few days after 
infection (Rockx, 2020).  An ideal agent for prophylaxis should be fast acting and highly effective 
and should protect against multiple viral variants.  A monoclonal antibody (mAb) combination 
therapy, with two different monoclonal antibodies that bind distinct regions of the portion of the 
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SARS-CoV-2 spike (S) protein that bind to and facilitate entry into host cells, has been developed 
in order to achieve these goals.  A mAb combination against SARS-CoV-2 for post-exposure 
prophylaxis that can either prevent the development of disease or reduce viral acquisition or viral 
load could be key to reducing transmission of the virus and limiting symptoms and adverse 
outcomes following infection. 
1.3. 
The Role of Spike Protein in SARS-CoV-2 Pathogenesis 
Coronaviruses consist of an RNA genome packaged in nucleocapsid (N) protein surrounded by an 
outer envelope. The envelope is comprised of membrane (M) protein and envelope (E) protein, 
which are involved in virus assembly, and spike (S) protein, which mediates entry into host cells. 
S proteins form large trimeric projections, providing the hallmark crown-like appearance of 
coronaviruses. S protein trimers bind to a host receptor and, after priming by cellular proteases, 
mediate host–virus membrane fusion (Li, 2016). The S protein appears to be central to viral 
infectivity by SARS-CoV-2. SARS-CoV-2 S protein binds the host protein angiotensin-converting 
enzyme 2 (ACE2) with high affinity, and in cell assays and animal models can utilize ACE2 as a 
functional receptor for host cell entry (Ou, 2020) (Hoffmann, 2020) (Walls, 2020).  
Blockade of host cell entry through the use of neutralizing antibodies against S protein is a viable 
mechanistic strategy shown to reduce viral infectivity of SARS-CoV and MERS-CoV (Jiang, 
2020). In light of the likely pivotal role of spike protein in the pathogenesis of SARS-CoV-2, a 
number of efforts are underway to develop antibodies and vaccines that target the S protein of this 
novel coronavirus. 
1.4. 
REGN10933+REGN10987: Fully Human Monoclonal Antibodies 
that Target SARS-CoV-2 S Protein 
Regeneron Pharmaceuticals, Inc (Regeneron) is currently developing fully human, neutralizing 
mAbs directed against the S protein of SARS-CoV-2, for the treatment and prevention of 
SARS-CoV-2 infection. REGN10933 and REGN10987 are fully human, IgG1 mAbs that bind to 
distinct regions of the receptor binding domain (RBD) of the SARS-CoV-2 S protein and block 
interaction 
with 
ACE2. 
REGN10933 
and 
REGN10987 
(also 
referred 
to 
as 
casirivimab+imdevimab) exhibit potent neutralization and can bind simultaneously to the S protein 
RBD. When co-administered as combination therapy, REGN10933+REGN10987 prophylaxis is 
anticipated to neutralize SARS-CoV-2 with a reduced likelihood of viral escape due to genetic 
mutations. In vitro experiments designed to specifically test for viral escape under selective 
pressure have shown that the combination of REGN10933+REGN10987 was resistant to escape 
while some single anti-Spike protein monoclonal antibodies were vulnerable to escape. 
REGN10933+REGN10987 combination therapy thus represents a promising prophylaxis strategy 
to reduce SARS-CoV-2 infection upon exposure to SARS-CoV-2. 
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1.5. 
A Randomized, Placebo-Controlled Study of Anti-Spike Protein 
Monoclonal Antibodies as Post-Exposure Prophylaxis and 
Pre-emptive Therapy in Household Contacts   
Many therapeutic agents have been studied in the context of other coronaviruses (SARS-CoV and 
MERS-CoV), including corticosteroids, type 1 interferons, convalescent plasma, ribavirin, 
lopinavir/ritonavir, proteases, and agents targeting viral entry proteins, with generally inconsistent 
findings of efficacy (Sanders, 2020). Several of these therapies, as well as a number of other 
potential treatments and vaccines, are currently under investigation for the treatment of 
SARS-CoV-2.  There is currently only 1 approved treatment for COVID-19, remdesivir, approved 
for use in patients 12 years of age and older requiring hospitalization or other comparable acute 
care setting.  Additionally, there are currently only 3 therapies for which the FDA has issued an 
Emergency Use Authorization (EUA): convalescent plasma for use in hospitalized patients, 
bamlanivimab (a monoclonal antibody against SARS-COV-2) for use in outpatients 12 years of 
age and older and who are at high risk for progressing to severe COVID-19 and/or hospitalization, 
and REGN10933+REGN10987 for use in outpatients 12 years of age and older with confirmed 
mild to moderate COVID-19 who are also at high risk for progressing to severe COVID-19 and/or 
hospitalization. Currently, however, there is no approved prophylaxis for COVID-19 nor for 
patients that are infected with SARS-CoV-2 but are asymptomatic. Given the speed at which this 
outbreak has spread and how it has impacted almost every community globally, there is an urgent 
need to develop safe and efficacious interventions to slow the spread of the SARS-CoV-2 virus 
and decrease adverse outcomes associated with symptomatic disease. 
This is a pivotal phase 3 randomized, double-blind, placebo-controlled study in adult subjects and 
pediatric subjects (<18 years of age) with household contact exposure to individuals with 
SARS-CoV-2 infection in geographic areas with an active COVID-19 outbreak. This study is 
designed to assess the efficacy and safety of co-administered REGN10933+REGN10987 
combination therapy (“REGN10933+REGN10987”) to reduce the proportion of SARS-CoV-2 
infections and prevent the development of COVID-19 disease (symptomatic SARS-CoV-2 
infection), after household exposure to individuals with SARS-CoV-2 infection. Safety, 
tolerability, pharmacokinetics (PK), and immunogenicity of REGN10933+REGN10987 will also 
be evaluated. 
For more information regarding the rationale for the study design and dose selection, refer to 
Section 3.2. Additional background information on the study drugs and the overall development 
program can be found in the Investigator’s Brochure (IB). 
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2. 
STUDY OBJECTIVES  
All subjects in the study will be household contacts of the first known household member to be 
infected with SARS-CoV-2 infection (index case) but who are themselves asymptomatic (having 
no active respiratory or non-respiratory symptoms consistent with COVID-19) at the time of 
screening. 
For analysis of endpoints, there are 4 defined cohorts based on the subjects’ SARS-CoV-2 
infection status at baseline, as measured by central lab SARS-CoV-2 RT-qPCR (quantitative 
reverse transcription polymerase chain reaction) and on the subject’s age:  
1. Cohort A: adult and adolescent subjects (≥12 years) who are SARS-CoV-2 RT-qPCR 
negative at baseline 
2. Cohort A1: pediatric subjects (<12 years) who are SARS-CoV-2 RT-qPCR negative at 
baseline  
3. Cohort B: adult and adolescent subjects (≥12 years) who are SARS-CoV-2 RT-qPCR 
positive at baseline 
4. Cohort B1: pediatric subjects (<12 years) who are SARS-CoV-2 RT-qPCR positive at 
baseline 
Results of the local diagnostic assay for SARS-CoV-2 from appropriate samples (eg NP, 
oropharyngeal [OP], or nasal or saliva) at baseline will be used as stratification factors for 
randomization and treatment group allocation, but not for the designation of cohorts for data 
analysis. 
Cohorts are described in Section 3.2.3 and are defined in Section 6.1.6. Study objectives and 
endpoints are specified based on their SARS-CoV-2 RT-qPCR results at baseline: cohort A and 
cohort A1 (negative results) or cohort B and cohort B1 (positive results).   
The “strict-term”, “broad-term”, and CDC definitions for signs/symptoms of SARS-CoV-2 
infection are presented in Section 9.2.2.2. 
2.1. 
Cohort A and Cohort A1:  SARS-CoV-2 RT-qPCR Negative at 
Baseline 
Objectives are for subjects who are seronegative at baseline (based on central lab test) unless 
stated otherwise. 
2.1.1. 
Primary Objectives 
2.1.1.1. 
Cohort A Primary Efficacy Objective 
• To evaluate the efficacy of REGN10933+REGN10987 compared to placebo in 
preventing symptomatic SARS-CoV-2 infection (broad-term) confirmed by RT-qPCR 
2.1.2. 
Cohort A and Cohort A1 Primary Safety Objective  
• To evaluate the safety and tolerability of REGN10933+REGN10987 following 
subcutaneous (SC) administration compared to placebo 
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2.1.3. 
Cohort A and Cohort A1 Secondary Objectives  
• To evaluate the efficacy of REGN10933+REGN10987 compared to placebo in 
preventing a SARS-CoV-2 infection with a high viral load (ie, viral load 
>4 (log10 copies/mL) 
• To evaluate the impact of REGN10933+REGN10987 compared to placebo on the 
duration of signs and symptoms in subjects with symptomatic SARS-CoV-2 infection 
(broad-term) confirmed by RT-qPCR 
• To evaluate the impact of REGN10933+REGN10987 compared to placebo on the 
duration of SARS-CoV-2 infection with a high viral load (ie, viral load 
>4 (log10 copies/mL) 
• To evaluate the impact of REGN10933+REGN10987 compared to placebo on the 
duration of SARS-CoV-2 infection 
• To evaluate the efficacy of REGN10933+REGN10987 compared to placebo in 
preventing asymptomatic or symptomatic SARS-CoV-2 infection confirmed by 
RT-qPCR 
• To evaluate the impact of treating the index case with REGN10933+REGN10987 on 
the incidence of SARS-CoV-2 infection among household contacts in the placebo 
group (This is a cross-study analysis based on only subjects in  placebo group of study 
R10933-10987-COV-2069 whose index cases participated in study R10933-10987-
COV-2067) 
• To evaluate the efficacy of REGN10933+REGN10987 compared to placebo in 
preventing symptomatic SARS-CoV-2 infection (Center for Disease Control [CDC] 
definition) confirmed by RT-qPCR 
• To evaluate the efficacy of REGN10933+REGN10987 compared to placebo in 
preventing symptomatic SARS-CoV-2 infection (strict-term) confirmed by RT-qPCR  
• To evaluate the impact of REGN10933+REGN10987 compared to placebo on SARS-
CoV-2 RT-qPCR viral load 
• To evaluate the impact of REGN10933+REGN10987 compared to placebo on 
SARS-CoV-2 infection:  
− On health care utilization 
− On absenteeism from daily responsibilities (where applicable) 
• To evaluate the impact of treating any SARS-CoV-2 RT-qPCR positive household 
member with REGN10933+REGN10987 on the incidence of SARS-CoV-2 infection 
among their household contacts in placebo group (note: This is a cross-study analysis 
based on only subjects in placebo group of study R10933-10987-COV-2069 whose  
index or other household member participated in study R10933-10987-COV-2067 or 
in cohort B ) 
• To characterize the drug concentration-time profiles of REGN10933 and REGN10987 
in serum and selected PK parameters 
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• To assess the immunogenicity of REGN10933 and REGN10987  
• To evaluate the safety and tolerability of REGN10933+REGN10987 following SC 
administration in seropositive subjects  
• To estimate the incidence and severity of symptomatic SARS-CoV-2 infection over 
time, 
including 
the 
period 
following 
study 
drug 
treatment, 
in 
REGN10933+REGN10987-treated seronegative and seropositive subjects compared 
with placebo-treated subjects 
• To evaluate the efficacy of REGN10933+REGN10987 compared to placebo in 
preventing symptomatic SARS-CoV-2 infection (broad-term) confirmed by 
RT-qPCR (cohort A1) 
2.1.4. 
Cohort A and Cohort A1 Exploratory Objectives 
• To evaluate the efficacy of REGN10933+REGN10987 compared to placebo in 
preventing SARS-CoV-2 infection assessed by seroconversion in baseline seronegative 
subjects  
• To explore the impact of REGN10987+REGN10933 compared to placebo:  
− On humoral immune response to SARS-CoV-2 infection  
− On measures of infectivity of SARS-CoV-2 as assessed in experimental laboratory 
assays  
• To evaluate the impact of REGN10933+REGN10987 compared to placebo in 
SARS-CoV-2 infection in subjects who are seropositive at baseline:  
− Prevention of symptomatic infection (strict-term)  
− Prevention of symptomatic infection (broad-term)  
− Prevention of symptomatic infection (CDC definition) 
− Prevention of symptomatic infection (strict-term, CDC definition, or broad-term) 
or asymptomatic infection  
• To explore the relationships between REGN10933+REGN10987 exposure and 
selected clinical efficacy and safety endpoints and/or biomarkers in seropositive and 
seronegative subjects  
• To assess viral genetic variation in SARS-CoV-2 in subjects with a positive 
SARS-CoV-2 RT-qPCR  
• To explore biomarkers (including host genome variants) associated with safety and 
efficacy of REGN10933+REGN10987 and to study SARS-CoV-2 (cohort A only)  
• To evaluate the impact of treating any household member with anti-SARS-CoV-2 
monoclonal antibody on the incidence of SARS-CoV-2 infection among their 
household contacts. The monoclonal antibody treatment considered for this analysis are 
any 
EUA 
approved 
antibody 
any 
EUA 
approved 
antibody 
including 
REGN10933+REGN10987 (within or outside of the study R10933-R10987-COV-2067). 
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2.2. 
Cohort B and Cohort B1: SARS-CoV-2 RT-qPCR Positive at 
Baseline 
Objectives for cohort B and cohort B1 are for subjects who are seronegative at baseline (by 
central lab test) unless stated otherwise. 
2.2.1. 
Cohort B Primary Efficacy Objective 
• To evaluate the efficacy of REGN10933+REGN10987 compared to placebo in 
preventing COVID-19 symptoms (broad-term)  
2.2.2. 
Cohort B and Cohort B1 Primary Safety Objective  
• To evaluate the safety and tolerability of REGN10933+REGN10987 following SC 
administration compared to placebo 
2.2.3. 
Cohort B and Cohort B1 Secondary Objectives  
• To evaluate the efficacy of REGN10933+REGN10987 compared to placebo in 
preventing development of:  
− Symptomatic SARS-CoV-2 infection (strict-term) 
− Symptomatic SARS-CoV-2 infection (broad-term; cohort B1) 
− Symptomatic SARS-CoV-2 infection (CDC definition) 
• To evaluate the impact of REGN10933+REGN10987 compared to placebo on the 
duration of signs and symptoms in subjects with symptomatic SARS‑CoV-2 infection 
confirmed by RT-qPCR 
• To evaluate the impact of REGN10933+REGN10987 compared to placebo on the 
duration of SARS-CoV-2 infection with a high viral load 
• To evaluate the impact of REGN10933+REGN10987 compared to placebo on 
SARS-CoV-2 RT-qPCR viral load 
• To evaluate the impact of REGN10933+REGN10987 compared to placebo on 
SARS-CoV-2 infection:  
− On health care utilization  
− On absenteeism from daily responsibilities (where applicable) 
• To characterize the drug concentration-time profiles of REGN10933 and REGN10987 
in serum and selected PK parameters  
• To assess the immunogenicity of REGN10933 and REGN10987  
• To evaluate the safety and tolerability of REGN10933+REGN10987 following SC 
administration   
• To estimate the incidence and severity of symptomatic SARS-CoV-2 infection over 
time, 
including 
the 
period 
following 
study 
drug 
treatment, 
in 
REGN10933+REGN10987-treated subjects compared with placebo-treated subjects 
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2.2.4. 
Cohort B and Cohort B1 Exploratory Objectives 
• To evaluate the impact of REGN10933+REGN10987 compared to placebo in 
seropositive subjects in preventing:  
− Symptomatic SARS-CoV-2 infection (strict-term)  
− Symptomatic SARS-CoV-2 infection (broad-term)  
− Symptomatic SARS-CoV-2 infection (CDC definition) 
• To evaluate the impact of REGN10933+REGN10987 compared to placebo on the 
duration of signs and symptoms in seropositive subjects with symptomatic SARS‑CoV-
2 infection confirmed by RT-qPCR 
• To evaluate the impact of REGN10933+REGN10987 compared to placebo in 
seropositive subjects on SARS-CoV-2 RT-qPCR viral load  
• To evaluate the impact of REGN10933+REGN10987 compared to placebo in 
SARS-CoV-2 infection:  
− On health care utilization  
− On absenteeism from daily responsibilities (where applicable) 
• To explore the impact of REGN10987+REGN10933 compared to placebo in subjects, 
by their baseline serology test status (eg, seropositive or seronegative, based on central 
lab test) on SARS-CoV-2 infection:  
− On humoral immune response  
− On measures of infectivity of SARS-CoV-2 as assessed in experimental laboratory 
assays  
• To explore the relationships between REGN10933+REGN10987 exposure and 
selected clinical efficacy and safety endpoints and/or biomarkers in seropositive and 
seronegative subjects  
• To assess viral genetic variation in SARS-CoV-2 in subjects with a positive 
SARS-CoV-2 RT-qPCR.  
• To explore biomarkers (including host genome variants) associated with safety and 
efficacy of REGN10933+REGN10987 and to study SARS-CoV-2 
3. 
HYPOTHESIS AND RATIONALE 
3.1. 
Hypotheses 
Cohort A:  SARS-CoV-2 RT-qPCR Negative at Baseline 
Prophylaxis with SC administration of anti-spike REGN10933+REGN10987 will:  
1. Prevent the occurrence of symptomatic infection with SARS-CoV-2. 
2. Prevent the occurrence of asymptomatic and symptomatic infection with SARS-CoV-2. 
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3. Be well-tolerated. 
Cohort B:  SARS-CoV-2 RT-qPCR Positive at Baseline 
Preemptive therapy with SC administration of REGN10933+REGN10987 will: 
1. Prevent the development of symptomatic SARS-CoV-2 infection in household contacts 
who already have a positive SARS-CoV-2 RT-qPCR test at baseline 
2. Be well-tolerated. 
3.2. 
Rationale  
3.2.1. 
Study Design  
This randomized, double-blind, placebo-controlled, phase 3 study will assess the safety, 
tolerability, and efficacy of REGN10933+REGN10987 in adult subjects and pediatric subjects 
(<18 years of age) who are household contacts of the first known household member infected with 
SARS-CoV-2 (index case). Collection of clinical and virologic data using a standardized timeline 
will provide valuable information on the clinical course of SARS-CoV-2 infection and the impact 
of these mAbs to prevent infection and symptomatic disease associated with SARS-CoV-2.  The 
multicenter conduct of this study will enable generalizable evidence of the safety, tolerability, and 
efficacy of investigational mAbs.  Specifically, this study is intended to demonstrate the efficacy 
of REGN10933+REGN10987 to prevent SARS-CoV-2 infection (with or without symptoms) in 
uninfected subjects or prevent symptomatic disease (eg, preemptive therapy) in subjects already 
infected (ie, SARS-CoV-2 RT-qPCR positive) at baseline. The double-blind design serves to 
reduce potential bias introduced by knowing the study drug assignment. The comparator arm in 
this study will be placebo as no approved preventative treatments are currently available. The 
placebo arm will also provide an estimate of the background incidence of SARS-CoV-2 infection 
and disease, as well as of adverse event (AE) rates for both efficacy and safety analyses.  
Additionally, all subjects’ SARS-CoV-2 serology status, including baseline, will also remain 
blinded to study site personnel during the study to avoid potential bias introduced when evaluating 
and assessing subjects who are seropositive and to mitigate the possibility of less risk averse 
behaviors in which subjects might engage.  The study size and duration were driven by current 
epidemiological assumptions about study population and are detailed in Section 11.2.   
This study was preceded by safety review of data from other studies:  a safety sentinel group of 
30 adult patients with COVID-19 dosed with REGN10933+REGN10987 2400 mg IV, 
REGN10933+REGN10987 8000 mg IV or placebo in the leading phase 1 studies of 
REGN10933+REGN10987 in the treatment of COVID-19 patients. Randomization in this study 
began when the Independent Data Monitoring Committee (IDMC) for the treatment studies 
provided a "study may proceed" conclusion from the IV dosing sentinel group (Section 3.2.4). 
All subjects in the study will be household contacts of the first known household member to be 
infected with SARS-CoV-2 (index case) but who are themselves asymptomatic (having no active 
respiratory or non-respiratory symptoms consistent with COVID-19) at the time of screening.  
Randomization will be performed on an individual subject basis rather than by household, however 
all subjects randomized will be given a household identification number in the case that multiple 
members of the same household are enrolled and receive study drug.  This ensures that correlation 
among subjects within the same household may be considered in the statistical analysis. Some of 
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the household members of the study subjects in this study may receive EUA approved monoclonal 
antibody treatment for COVID-19 or may be participating in a separate treatment study assessing 
the 
efficacy 
of 
REGN10933+REGN10987 
in 
outpatients 
with 
COVID-19 
(study 
R10933-10987-COV-2067).  Therefore, EUA monoclonal antibody treatment of household 
members, as well as information from R10933-10987-COV-2067 and R10933-10987-COV-2069 
studies will be linked, where applicable, to assess the impact of monoclonal antibody treatment of 
the COVID-19 infected household members on infectivity of study subjects.  
The study will consist of a screening/baseline period that will occur on the same day, due to the 
short window (96 hours) between the collection of the index cases’ positive SARS-COV-2 
diagnostic test sample and randomization of the study subject(s). This same day screening/baseline 
period is expected to decrease the burden of study visits on the subject and might help to increase 
subject engagement. For the same reason, only a subset of subjects (by subject ordinal number as 
first subjects are randomized using the interactive web response system [IWRS]) will undergo PK 
and intensive safety laboratory testing throughout the study (approximately 30 subjects for dense 
PK sampling, approximately 400 subjects for sparse PK sampling, and intensive safety laboratory 
assessments).  The number of subjects selected for PK sampling and for intensive safety lab 
assessments are considered sufficient to provide an adequate evaluation of the different 
parameters. 
At the screening/baseline visit, subjects will have a local, diagnostic assay for SARS-CoV-2 from 
appropriate samples. The results of this local test will be used as a stratification factor for 
randomization for assigning subjects into 1 of 2 treatment groups. In the event that local testing 
result is not anticipated to be available in the time required during screening, subjects may be 
randomized (local test will be specified as "undetermined" in IRT).  Subjects will also have NP 
swab samples collected at baseline for central lab SARS-CoV-2 RT-qPCR tests. The results of the 
central lab RT-qPCR (the results of which may not be available on the same day due to time for 
shipping) will be used for cohort allocation into cohort A and cohort A1 (negative) or cohort B 
and cohort B1 (positive) for data analysis. 
Within this study, a sentinel safety group that consisted of the first 30 adult subjects who completed 
day 4 safety assessments was assessed. Subjects were observed at the study site for 4 hours after 
the single-dose SC study drug administration and were specifically monitored for acute 
hypersensitivity reactions or injection site reactions, which constitute the primary potential risks 
with SC injection of a fully human monoclonal antibody against an exogenous target. Subjects 
were then assessed daily for the first 4 days after study drug administration for evaluation of 
treatment-emergent adverse events (TEAEs) and adverse events of special interest (AESI). 
Blinded safety data was reviewed before progressing with enrollment of additional study subjects. 
This close observation of the first 30 subjects was considered sufficient to assess safety and allow 
further enrollment of study subjects as the risk for AEs or AESIs is highest during the first days 
following study drug administration.  This sentinel safety monitoring was considered adequate 
because REGN10933+REGN10987 was already cleared by a sentinel safety group who received 
higher doses (2400 mg and 8000 mg) administered IV. 
The Blinded Safety Data for the R10933-10987-COV-2069/COVID-19 Prevention Network 
(CoVPN) 3502 study was reviewed and the monitoring team met via teleconference on 
04 Aug 2020 to discuss the sentinel data. 
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After review of the totality of evidence the Blinded Safety Data Review team found no reasons to 
recommend alteration or termination of the study. Study R10933-10987-COV-2069/CoVPN 3502 
can continue enrolment as planned per protocol. 
Available clinical safety data (including adverse experiences, AESIs, injection site reactions and 
hypersensitivity reactions, vital signs, and safety labs) from the first 30 subjects who received a 
single dose of 600mg REGN10933+600mg REGN10987 SC or matching placebo SC and who 
completed safety assessment visits through day 4 were reviewed. Also, laboratory results available 
to date were reviewed including samples collected through day 2 for 27 subjects, and samples 
collected through day 4 for 18 subjects.  Neither SAEs, nor AESIs were reported among the 
30 subjects. No reported injection site reactions or hypersensitivity reactions occurred among the 
30 subjects. There were 12 TEAEs reported in 7 subjects, all grade ≤2.  No TEAEs were deemed 
related to study drug.  There were no patterns of clinically concerning changes in vital signs or 
safety laboratory parameters among 600mg REGN10933+600mg REGN10987/placebo treated 
subjects.  In summary, treatment with 600mg REGN10933+600mg REGN10987/placebo when 
administered as a single SC dose was sufficiently well tolerated to warrant continued enrolment as 
planned per protocol. 
Inclusion of Subjects Under 18 years of Age and Pregnant and Breastfeeding Women 
Adolescent subjects (12 to <18 years) enrollment was initiated in this study because this population 
is vulnerable to infection with SARS-CoV-2 in the household (Lewis, 2020), and 
REGN10933+REGN10987 appears well tolerated in adults, with over 1000 adult subjects having 
already received REGN10933+REGN10987, either in the treatment studies (single dose of 
2400 mg 
intravenous 
(IV) 
or 
8000 
mg 
IV 
[R10933-10987-COV-2066, 
R10933-10987-COV-2067]), or the prophylaxis study (1200 mg subcutaneous (SC) as a single 
dose [R10933-10987-COV-2069]), or the healthy subject safety study (1200 mg SC as multiple 
doses every 4 weeks (Q4W) for 6 doses [R10933-10987-COV-2093]).  Upon review of safety data 
from approximately the first 20 adolescent subjects (≥12 to <18 years of age) enrolled, pediatric 
subjects aged birth to <12 years of age will also be enrolled.  The pediatric subjects will be 
analyzed as separate cohorts (cohort A1 and cohort B1) to assess the safety, PK, immunogenicity, 
and efficacy of REGN10933+REGN10987.  
Pregnant women and breastfeeding women are being included in this study because pregnant 
women are at increased risk of developing severe COVID-19 (Ellington, 2020) (Knight, 
2020)(Woodworth, 2020).  The risks of REGN10933+REGN10987 treatment for pregnancy and 
a developing fetus are unknown.  Because REGN10933+REGN10987 mAbs are directed against 
an exogenous antigen, administration of REGN10933+REGN10987 is not anticipated to affect 
endogenous pathways.  Addition of pregnant women to the study is also supported by the results 
of nonclinical studies that show no changes to reproductive organs in nonhuman primates and an 
absence of human tissue cross reactivity with REGN10933 or REGN10987 in human or monkey 
tissues evaluated (see the IB).  Because pregnant women are allowed in the study, contraception 
for women of childbearing potential (WOCBP) is no longer required as an exclusion criterion; 
however, all WOCBP will undergo pregnancy testing prior to dosing and at the end of study.  
Women who are pregnant or who become pregnant during the study will be followed for the 
outcome of their pregnancy.  Also, because pregnant women are allowed in the study, 
contraception for men is no longer required as an exclusion criterion.  We will not solicit 
information regarding pregnancies occurring in the female partners of male study subjects as the 
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risk of exposure is negligible in this scenario.  The safety profile in pediatric subjects <12 years 
and pregnant and breastfeeding women is expected to be similar to that observed in adults and 
adolescents.  Safety data is reviewed in a continuous manner by the sponsor (blinded data) and by 
the Data and Safety Monitoring Board (DSMB) (unblinded data).   
The study has a 28-day efficacy assessment period (EAP) after the single dose of active study drug 
or placebo administered SC to capture all infections as detected by SARS-CoV-2 RT-qPCR 
positivity (both asymptomatic and symptomatic), symptomatic infection (ie, those individuals that 
experience symptoms consistent with SARS-CoV-2 infection and progression of COVID-19 
disease).  A 28-day assessment period is expected to be sufficient to accrue an adequate number 
of primary endpoint events within the planned sample size.  The incubation period of SARS-CoV-2 
after exposure is approximately 2 to 14 days (Li, 2020a) (Lauer, 2020).  The duration of mild to 
moderate symptoms, including time to hospitalization, is approximately 11.5±5.7 days (Lechien, 
2020).  Following the 28-day EAP, subjects will undergo a 7-month follow-up period to assess for 
TEAEs, PK, and anti-drug antibodies (ADA) and neutralizing antibodies (NAbs).  This duration 
is based on a half-life of 21-days for a typical mAb.  This follow-up period is expected to allow an 
assessment of safety after discontinuing treatment.  The length of the follow-up period may be 
modified based on the observed PK and ongoing nonclinical data as it becomes available. The 
occurrence and severity of any suspected COVID-19 related AEs (including SAEs) that occur as 
drug concentrations wane will be monitored, and subjects who received active drug or placebo will 
be assessed for any signal of ADE.  
3.2.2. 
Subject Population  
The study population will consist of approximately 3500 adult and adolescent subjects and 
approximately 250 pediatric subjects <12 years old, with household contact exposure to individual 
with a confirmed SARS-CoV-2 infection.  In this study, the household contact must share the same 
residence and have a close exposure to the first individual in the household with a known 
SARS-CoV-2 infection (index case).  In the case where more than 1 index case is the first known 
SARS-CoV-2 infected individual in the household (eg, 2 people are tested at the same time), this 
is allowed, and 1 index case should be chosen, at the discretion of the investigator, to be labeled 
“index case” in the household CRF. The study was originally planned to enroll 2000 adult and 
adolescent subjects.  However, a blinded analysis of approximately 25% of enrolled subjects in 
this study was performed, demonstrating that higher than expected seropositivity was observed in 
cohort A.  Therefore amendment 4 for the protocol increased the sample size for the study to 
account for the higher than expected seropositivity in cohort A.  Amendment 5 for the protocol 
increased the sample size further to accommodate the administrative assessment of assumption 
verification and sample size estimation. 
A household is defined as a group of people who live together at the same residence and share 
multiple living spaces (eg, living room, bedroom, kitchen, bathroom). In case there is uncertainty 
that the characteristics of the residence meets the definition of a ‘household’, the investigator and 
the Regeneron Medical Monitor should discuss prior to randomization.  
To be included in the study, subjects must be randomized within 96 hours of collection of the index 
cases’ positive SARS-COV-2 diagnostic test sample. Household contacts of individuals infected 
with SARS-CoV-2 are at a high risk for acquiring infection, with transmission rates ranging from 
approximately 10% to 15% in these settings (Burke, 2020) (Jing, 2020) (Li, 2020b). Therefore, 
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approximately 15% of subjects were expected to develop symptomatic disease in follow-up after 
a household contact transmission event (Li, 2020b). A minority of subjects were expected to be 
seropositive at baseline, as seropositivity in the general population, outside of hard-hit areas like 
New York City, was expected to be less than 10% (Burke, 2020). Upon blinded review of 
approximately the first 25% of subjects enrolled into this study, baseline seropositivity rates in 
cohort A subjects were approximately 3 times higher than anticipated and a minority of cohort A 
subjects who became infected during the 28 day efficacy assessment period were symptomatic.  
Subjects with positive rapid SARS-CoV-2 RT-PCR at the time of randomization, who are either 
seronegative or seropositive at baseline will also be included in the study, but only subjects who 
are both seronegative and negative for SARS-CoV-2 infection by central lab RT-qPCR at baseline 
will be included in the primary efficacy analysis. 
3.2.3. 
Enrollment by Baseline SARS-CoV-2 Infection  
This study will include asymptomatic subjects regardless of baseline SARS-CoV-2 infection status 
or serologic status. Including all-comers into the study will provide important information on 
infection prevention through prophylaxis as well as the impact of pre-emptive therapy in infected 
but asymptomatic individuals. Since the primary efficacy objective in cohort A is focused on the 
prevention of symptomatic SARS-CoV-2 infection (broad-term), the primary population of 
interest are subjects that are seronegative and SARS-CoV-2 RT-PCR negative at baseline.  It was 
estimated that approximately 10% of the study population for cohort A would be seropositive at 
baseline.  However, blinded data review of approximately the first 25% of subjects enrolled shows 
that approximately 30% of subjects in cohort A are seropositive at baseline. Therefore, the majority 
of subjects enrolled are expected to be allocated to the primary study population of interest, 
seronegative and SARS-CoV-2 RT-PCR negative at baseline (ie, cohort A).  
On day 1 and prior to randomization, subjects will have a local diagnostic assay for SARS-CoV-2 
from an appropriate sample.  Samples will also be collected for central lab SARS-CoV-2 RT-qPCR 
and serology tests.  The results of the local lab tests will be available the same day and will be used 
as stratification for randomization to allow administration of study drug.  In the event that local 
testing results are not anticipated to be available in the time required during screening, subjects 
may be randomized. 
For data analysis, adult and adolescent subjects will be divided into 2 independent study cohorts: 
cohort A or cohort B. This allocation will be based on a central lab SARS-CoV-2 RT-qPCR test 
result performed during the screening/baseline visit. While stratification and randomization will 
be based on local test results, data analyses will be based on the central lab results of baseline 
SARS-CoV-2 RT-qPCR results from NP swab sample and the serological status. 
The analysis of the adult and adolescent subject populations that are not part of the primary study 
population of interest (ie, those subjects in cohort A who are seropositive at baseline) will not 
contribute to a primary study objective or endpoint. These individuals will be analyzed separately 
either through secondary or exploratory objectives and endpoints.  
Adult and adolescent subjects in cohort B (ie, asymptomatic subjects who are SARS-CoV-2 
RT-qPCR positive at baseline, irrespective of the serology status being positive or negative) will 
be analyzed separately from cohort A with a primary study objective and endpoint, secondary and 
exploratory objectives and endpoints.  The primary efficacy objective in cohort B is focused on 
the prevention of COVID-19 symptoms (broad-term) in the subjects who are seronegative but 
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SARS-CoV-2 RT-qPCR positive at baseline.  The analysis of the adult and adolescent subject 
populations that are not part of the primary study population of interest (ie, those subjects in cohort 
B who are seropositive at baseline) will not contribute to a primary study objective or endpoint. 
These individuals will be analyzed separately either through secondary or exploratory objectives 
and endpoints.   
Pediatric subjects (<12 years) will be divided into 2 independent study cohorts, cohort A1 or cohort 
B1. This allocation will be based on a central lab SARS-CoV-2 RT-qPCR test result performed 
during the screening/baseline visit. 
To mitigate enrollment of a high percentage of subjects that are either seropositive or 
SARS-CoV-2 RT-qPCR positive at baseline, those with a known prior history of a positive 
SARS-CoV-2 RT PCR test, a positive serology test, or COVID-19 will be excluded. 
All subjects’ SARS-CoV-2 qualitative diagnostic and RT-qPCR test results will be unblinded 
during the study. This will ensure SARS-CoV-2 infected individuals take the appropriate 
precautions necessary to prevent spread of disease. However, all subjects’ SARS-CoV-2 serology 
results will remain blinded to study site personnel during the study to avoid potential bias 
introduced when evaluating and assessing subjects who are seropositive and to avoid encouraging 
higher risk behaviors through disclosure of seropositivity.  
3.2.4. 
Sentinel Safety Group and Subsequent Safety Reviews 
Driven by the medical urgency of the COVID-19 pandemic, the process described below is 
designed to maximize efficient enrollment of eligible subjects while optimizing the safety of the 
first SC administration of REGN10933+REGN10987.  Clinical safety and tolerability data from 
the pooled sentinel cohorts from treatment studies (R10933-10987-COV-2066 and 
R10933-10987-COV-2067) 
in 
COVID-19 
patients 
receiving 
IV 
administration 
of 
REGN10933+REGN10987 were available prior to first SC dosing in this study. 
A safety review of data from an adult sentinel safety group was conducted by the unblinded 
IDMC/DSMB as a precondition for further enrollment across the REGN10933+REGN10987 
clinical development program. The sentinel group consisted of 30 subjects pooled across the 
2 treatment studies of REGN10933+REGN10987 administered as a single IV dose in patients with 
COVID-19 (R10933-10987-COV-2066 and R10933-10987-COV-2067). Patients in this sentinel 
group were randomized to receive a single IV dose of REGN10933+REGN10987 (at 1200 mg per 
mAb, at 4000 mg per mAb), or placebo. The IDMC/DSMB approved the continuation of the 
treatment studies and the initiation of the prophylaxis study. Additionally, a blinded Sponsor 
analysis of the adult treatment study data showed that REGN10933+REGN10987 was sufficiently 
well-tolerated to warrant continued enrollment as planned per protocol, with no hypersensitivity 
reactions or infusion-related reactions reported. Vital signs, and laboratory assessments did not 
identify any safety signals. 
The description of the sentinel groups, safety monitoring of sentinel subjects (adult and pediatric 
[<12 years]), and data review for this study is provided in Section 6.1.1 and Section 6.1.2. 
A blinded Sponsor analysis of the sentinel data for adult subjects in this study 
(R10933-10987-COV-2069) showed that REGN10933+REGN10987 was well-tolerated, with no 
hypersensitivity reactions or injection site reactions reported. The continuous review of blinded 
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safety data for the study, eg, AEs, vital signs, and laboratory assessments, have not identified any 
safety signals.  
3.2.5. 
Primary Objective 
The primary objectives of this study are: 
• Cohort A:  To evaluate the efficacy of REGN10933+REGN10987 compared to 
placebo in preventing symptomatic SARS-CoV-2 infection (broad-term) confirmed 
by RT-qPCR in asymptomatic subjects at risk who are seronegative at baseline.  
• Cohort B:  To evaluate the efficacy of REGN10933+REGN10987 compared to 
placebo in preventing COVID-19 symptoms (broad-term) in asymptomatic subjects 
that are SARS-CoV-2 RT-qPCR positive and seronegative at baseline. 
The FDA Guidance on COVID-19 recommends that in prevention trials, the primary endpoint 
should be the occurrence of laboratory-confirmed SARS-CoV-2 infection, with or without 
symptoms. A descriptive administrative analysis of seronegative subjects in cohort A (n=409) 
demonstrated a 100% reduction in broad-term symptomatic PCR-positive infection with 8/223 
(3.6%) placebo treated subjects developing symptomatic infection versus 0/186 (0%) 
REGN10933+REGN10987 treated subjects; OR 0.00 (0.00, 0.69) p<0.01. The revised primary 
objectives and endpoints for cohort A are informed by these results. Thus, these revisions are 
applied to objectives and endpoints for cohort B as well. The final primary objectives and 
endpoints for the completed study will be assessed in the final study population enrolled, excluding 
those that were already unblinded and assessed in the descriptive administrative analysis 
(Section 11.4.9). Protocol amendment 6 specifies a single primary objective and endpoint for each 
cohort which consists of the prevention of laboratory confirmed symptomatic SARS-CoV-2 
infection (broad term)(Section 2.1.1.1 and Section 4.1.1).  
Clinical efficacy: The ability of REGN10933+REGN10987 administration to prevent 
symptomatic SARS-CoV-2 infection (broad-term) will be evaluated through weekly inquiry by 
the investigator to assess if subjects experienced or are experiencing commonly reported clinical 
signs/symptoms related to COVID-19. A broad definition of signs/symptoms associated with 
COVID-19 (see Section 9.2.2.2 for full definition) will be utilized for the primary endpoint. 
Commonly reported symptoms of COVID-19 include fever, cough and myalgias. However, 
SARS-CoV-2 infection has been associated with a wide variety of symptoms (eg, loss of taste and 
smell). In order to ensure all symptomatic SARS-CoV-2 infections are captured during the study, 
a broad term definition of any one of 23 symptoms will be reported by the investigator in 
association with a laboratory confirmed SARS-CoV-2 infection (see Section 9.2.2.2).  
3.2.6. 
Secondary Objectives 
The secondary objectives and endpoints are informed by results of the descriptive administrative 
analysis and include the assessment of laboratory confirmed SARS-CoV-2 infection with or 
without symptoms (strict term and CDC definition as described below),  the magnitude and 
duration of laboratory confirmed infection,  and the impact of treating a COVID-19 infected 
household member with REGN10933+REGN10987 on the incidence of SARS-CoV-2 infection. 
Clinical efficacy: While the primary objective captures symptomatic infections defined by a 
broad-term, secondary objectives include both a more strict definition of signs/symptoms 
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associated with COVID-19 and the CDC definition (see Section 9.2.2.2 for full definitions). Other 
secondary objectives will assess important clinical outcome measures including healthcare 
utilization (seeking an emergency room or urgent care facility, hospitalization, length of hospital 
stay, etc), the duration of disease in subjects who develop symptomatic infection, and the impact 
of index case treatment with REGN10933+REGN10987 on infection events in the study subject 
in this study. Similar objectives will be applied to subjects who are SARS-CoV-2 RT-PCR positive 
and/or seropositive at baseline (CDC, 2020b).   
Virologic efficacy: The primary mechanism of action of REGN10933+REGN10987 is blockade 
of the S protein RBD interaction with ACE2, leading to inhibition of SARS-CoV-2 host cell 
infection. The ability of REGN10933+REGN10987 treatment to prevent SARS-CoV-2 infection 
will be evaluated by SARS-CoV-2 RT-qPCR test results from weekly NP swab samples. Weekly 
sample collection is considered an adequate collection frequency to ensure early detection of viral 
load (SARS-COV-2 RT-qPCR positivity) in infected individuals; this is based on the average 
duration of viral positivity from NP swabs that ranges from 7 to 28 days (He, 2020) (Wölfel, 2020). 
All subjects will have SARS-CoV-2 RT-qPCR testing by NP sample. Nasopharyngeal swab testing 
has been shown to have good sensitivity and specificity for detecting SARS-CoV-2 RNA (Zou, 
2020) (Pere, 2020).  The administrative assessment of seronegative subjects (n=409) in cohort A 
demonstrated that the risk of becoming infected (ie, becoming SARS-CoV-2 RT-PCR positive) 
was reduced as early as the first week of study (10.3% in subjects in the placebo group versus 
5.4% in subjects in the REGN10933+REGN10987 group at day 8). The protection continued 
through the following weeks.  Both the magnitude and duration of infection were reduced by 
REGN10933+REGN10987 treatment. Infections occurring in subjects in the placebo group had, 
on average, more than 100-fold higher peak viral load.  Infections in subjects in the 
REGN10933+REGN10987 group lasted no more than 1 week, while approximately 40% of 
infections in subjects in the placebo group lasted 3 to 4 weeks. No infected subjects in the 
REGN10933+REGN10987 group had high viral loads (>104 copies/mL) compared to 62% of the 
infected subjects in the placebo group (13/21 placebo versus 0/9 REGN10933+REGN10987) 
(CDC, 2020b). (CDC, 2020b) 
3.2.7. 
Rationale for Dose Selection  
This study will assess a single SC dose of REGN10933+REGN10987 as combination therapy in a 
1:1 ratio. The 1:1 ratio for REGN10933+REGN10987 is thought to be appropriate as these are 
noncompeting mAbs targeting non-overlapping epitopes of the RBD of the S protein of 
SARS-CoV-2, with similar in vitro binding and neutralization properties (for more information, 
refer to the IB). The study will evaluate REGN10933+REGN10987 as combination therapy at a 
1200 mg (600 mg of each mAb) SC dose.  
Angiotensin converting enzyme subtype 2 expression has been reported in the lungs, particularly 
in type-2 alveolar epithelial cells and bronchial airway epithelium (Wu, 2020) (Xu, 2020) (Zhao, 
2020). The strategy taken for dose selection in this study was to identify a target concentration in 
lung epithelial lining fluid (ELF) that approximates the effective concentration required for 99% 
neutralization (EC99) of SARS-CoV-2 in vitro and to then identify a dose that will meet or exceed 
this concentration in lung ELF. The EC99 against SARS-CoV-2 in vitro is 0.14 µg/mL for 
REGN10933 and 0.80 µg/mL for REGN10987. 
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An average lung ELF-to-serum mean Cmax ratio of ~0.15 has been reported for other exogenous 
IgG1 mAbs for the treatment of Staphylococcus aureus lung infections (Magyarics, 2019). It is 
assumed that the lung ELF-to-serum Cmax ratio is 0.15 for REGN10933 and REGN10987. Dividing 
the target lung ELF concentration by this ratio, the associated serum concentration for these targets 
is therefore estimated to be ~at least 5 µg/mL for the combination of REGN10987+REGN10933. 
Taking into account uncertainties regarding mAb penetration into lung ELF, prediction of human 
PK, and effects of disease on PK, 20 µg/mL was selected as a target concentration in serum for 
subjects using the 600 mg SC per mAb REGN10933+REGN10987 combination dose. The goal 
for this REGN10933+REGN10987 combination dose is for ≥95% of subjects to exceed the target 
serum concentration for 28 days after dosing. To estimate the clinical SC dose required to achieve 
this goal, a population PK model developed for a typical Regeneron mAb administered SC was 
used to simulate mean and 5th percentile serum concentrations for a virtual population of 
2000 subjects (mean (SD) [min, max] body weight of 85 (17) [40, 150] kg) for various SC doses. 
For a single 600 mg per mAb SC dose, ≥95% of adult subjects are predicted to exceed the target 
serum concentration by approximately 1 day after the first dose and remain above the target serum 
concentration for the remainder of the 28-day treatment period, for each mAb. 
As the lower end of the proposed body weight range for adolescent subjects ≥12 years of age 
(40 kg) falls within the range of expected body weights for adult subjects, similar exposures are 
expected between these 2 populations for a single 1200 mg (600 mg of each mAb) SC dose of 
REGN10933+REGN10987. 
Similar to adults, the goal for dose selection in the pediatric population is for ≥95% of pediatric 
subjects within each weight-tiered group to exceed the 20 µg/mL target concentration in serum per 
mAb for 28 days after dosing. An additional consideration was to select doses for pediatric subjects 
that would achieve exposures within the range of those shown to be generally safe and well 
tolerated in adults. 
The same 2-compartment population PK model with linear clearance developed for adults was 
used to simulate concentrations in serum over time for various doses in each pediatric 
weight-tiered group using allometrically scaled estimates of clearance and volume of distribution 
(gestational-age corrected allometrically scaled estimates were used for subjects <10 kg) (Robbie, 
2012). The doses selected are predicted to result in ≥95% of subjects within each weight tier 
exceeding the 20 µg/mL target concentration in serum per mAb for 28 days after dosing (Table 1). 
Compared to predicted 95th percentiles of Cmax and AUC0-28 for REGN10933 and REGN10987 in 
adults after a single SC dose of 1200 mg (600 mg per mAb), the 95th percentiles of predicted Cmax 
and AUC0-28 across the different pediatric weight-tiered groups ranged from 18% to 88% higher 
than in adults, but lower than observed mean Cmax and AUC0-28 values for the lowest single IV 
dose (2.4 g) with an acceptable safety profile in adults with COVID-19.  For children < 10 kg, SC 
administration is not deemed feasible, and it is assumed that the concentration-time profile of 
REGN10933 and REGN10987 will be similar for intramuscular (IM) and SC administration. 
Table 1: 
REGN10933+REGN10987 Doses for Each Pediatric Weight-Tiered Groups 
Pediatric  
Weight-Tiered 
Groups 
Route of 
Administration 
Dose (mg) 
Total Dose (mg) 
REGN10933 
REGN10987 
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≥40 kg 
SC 
600 
600 
1200 
≥20 to <40 kg 
SC 
396 
396 
792 
≥10 to <20 kg 
SC 
204 
204 
408 
≥5 to <10 kg 
IM 
72 
72 
144 
≥2.5 to <5 kg 
IM 
48 
48 
96 
<2.5 kg 
IM 
24 
24 
48 
A 4-week GLP toxicology study in cynomolgus monkeys was conducted and assessed once weekly 
dosing of up to 150/150 mg/kg per mAb administered once weekly (for combination) to support 
safety of the anti-SARS-CoV-2 spike mAbs.  Throughout the 4-week dosing period the 
REGN10933+REGN10987 combination was well tolerated at all dose levels, with no drug-related or 
adverse effects evident (for more information, refer to the IB).  
3.3. 
Risk-Benefit 
This study represents the initial prophylaxis study planned to evaluate REGN10933+REGN10987 
as a SC injection in humans. Therefore, the potential clinical benefits and risks associated with the 
study drugs are yet to be determined. Several preclinical pharmacokinetic, pharmacologic, and 
toxicology studies are ongoing and/or planned, and findings from these studies will be 
appropriately communicated. While preclinical data are available (discussed below), the 
anticipated risks are based primarily on prior Sponsor experience with similar fully human 
monoclonal antibody development programs against exogenous targets and the potential risks 
associated with subcutaneous injection of fully human monoclonal antibodies in general. 
The positive efficacy results observed for REGN10933+REGN10987 administered IV to 
symptomatic patients with COVID-19 in R10933-10987-COV-2067 study are balanced by an 
acceptable safety profile.  Nonclinical toxicology studies in nonhuman primates showed that 
REGN10933+REGN10987 was well-tolerated without adverse findings.  Moreover, review of 
available clinical data from the 3 ongoing clinical studies (R10933-10987-COV-2066, 
R10933-10987-COV-2067, R10933+REGN10987-HV-2093) show that there are currently no 
identified risks with REGN10933+REGN10987. There are several potential risks, which are 
described below.  
A 4-week GLP toxicology study in cynomolgus monkeys is currently ongoing and assessing 
once-weekly IV and SC dosing of REGN10933+REGN10987 at up to 150 mg/kg per antibody. 
Findings from the completed 4-week dosing period of the toxicology study identified no clinically 
relevant risks or test article-related adverse effects and no changes to reproductive organs in 
nonhuman primates. Separately, findings from 2 tissue cross reactivity studies was notable for by 
the absence of any tissue cross reactivity with either REGN10933 or REGN10987 in any of the 
human or monkey tissues or human fetal tissues evaluated.  Reproductive and developmental 
toxicology studies have not been conducted; therefore, the effects of REGN10933, REGN10987, 
and REGN10933+REGN10987 combination therapy on the fetus and reproductive organs in males 
and females are unknown. 
REGN10933 and REGN10987 target the SARS-CoV-2 S protein, an exogenous protein. The 
Sponsor has significant experience with prior development programs for fully human mAbs 
against exogenous targets, including atoltivimab, odesivimab, and maftivimab (Ebola), 
REGN3048 and REGN3051 (MERS-CoV), REGN5713, REGN5714 and REGN5715 (Bet v 1 
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birch tree allergen), and REGN1908 and REGN1909 (Fel d 1 cat dander allergen). No significant 
safety findings were observed in any of the associated toxicology studies conducted and the mAbs 
demonstrated an acceptable safety profile in the clinical studies.  
Important Potential Risks:  The important potential risks are those typically associated with a 
mAb administered by SC route: injection site reactions, hypersensitivity reactions, 
immunogenicity, and potential embryo-fetal toxicity (see the IB). REGN10933 and REGN10987 
are fully human IgG1 mAbs, and correspondingly the risk of injection site reactions, 
hypersensitivity reactions, or immunogenicity is expected to be low.  However, given the limited 
experience with these mAbs and the evolving understanding of SARS-CoV-2 infections, all 
TEAEs will be collected during the study to adequately characterize the safety profile of 
REGN10933+REGN10987.  Clinical safety and tolerability data from the pooled sentinel cohorts 
from treatment studies (R10933-10987-COV-2066 and R10933-10987-COV-2067) in COVID-19 
patients receiving IV administration of REGN10933+REGN10987 were available prior to first SC 
dosing in this study.  These data showed that a single IV dose of REGN10933+REGN10987 or 
placebo (at 1200 mg per mAb, at 4000 mg per mAb) was well-tolerated, with no hypersensitivity 
reactions or infusion-related reactions reported. Vital signs and laboratory assessments did not 
identify any safety signals (Section 3.2.4).  Protein therapeutics carry the potential risk of an 
immunogenic response in the form of ADA and NAb development following administration, with 
possible consequences on safety and efficacy. Therefore, blood samples for immunogenicity 
assessment will be collected during the studies.  
Reproductive and developmental toxicology studies have not been conducted; therefore, the 
effects of REGN10933, REGN10987, and REGN10933+REGN10987 combination therapy on the 
fetus and reproductive organs in males and females are unknown. Human immunoglobulin G1 
(IgG1) antibodies are known to cross the placental barrier and are present in breast milk; therefore, 
the REGN10933+REGN10987 combination therapy have the potential to be transferred from the 
mother to the developing fetus or a breastfed child. Given the high affinity and specificity of 
REGN10933 and REGN10987, off-target pharmacological effects are not anticipated in either the 
mother, the fetus, or breastfed child and no off-target binding of REGN10933 or REGN10987 was 
observed in any of the human or monkey tissues evaluated ex vivo in tissue cross-reactivity studies. 
However, it is unknown whether the potential transfer of the combination of 
REGN10933+REGN10987 therapy provides any treatment benefit or risk to the developing fetus 
or breastfed child. 
There is currently limited clinical experience in the use of REGN10933, REGN10987, and 
REGN10933+REGN10987 combination therapy in female subjects who are pregnant or 
breastfeeding. The combination of REGN10933+REGN10987 therapy should be used during 
pregnancy or breastfeeding only if the potential benefit justifies the potential risk for the mother 
and the fetus or breastfed child considering all associated health factors. If a female subject is 
pregnant or were to become pregnant while receiving REGN10933+REGN10987 combination, 
the pregnancy should be followed until outcome and any safety issue observed get reported.  
Other Theoretical Considerations: Antibody-dependent enhancement (ADE) has also been 
observed for some therapeutics targeting exogenous viral proteins. For antibody therapies, ADE is 
thought to occur when binding of antibody to the target viral protein enhances FcγR-mediated host 
cell entry of the virus (Iwasaki, 2020). This could potentially lead to worsening of disease and, in 
the case of SARS, acute lung injury (Liu, 2019).  REGN10933 and REGN10987 retain the Fc 
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region, as this may play a role in protecting against viral infection (Yasui, 2014). However, there 
is no strong evidence of ADE in other coronavirus models (Kam, 2007) (Liu, 2019) (Luo, 2018) 
(Wang, 2016) (Weingartl, 2004). To date, Fc-containing mAbs developed by the Sponsor for Ebola 
virus, and MERS-CoV have demonstrated specificity to their exogenous targets with no significant 
unexpected safety findings in preclinical or clinical studies.  All subjects will be monitored for 
TEAEs during the drug elimination period.  Theoretical risks of administration of the 
REGN10933+REGN10987 combination include interference with the subject’s endogenous 
immune response to either SARS-CoV-2 infection or vaccination against SARS-CoV-2.   
With respect to efficacy, the currently available in vitro data (see the IB) show that 
REGN10933+REGN10987 is anticipated to be pharmacologically active at the planned dose, with 
expected neutralization and effector functions against the SARS-CoV-2 S protein. Additionally, 
the only control measures that are currently available against this virus is practicing rigorous 
infection control. There is no therapeutic option for the prevention of SARS-CoV-2 infection and 
there is an urgent need for a preventative treatment given the wide reaching, devastating effects of 
this global outbreak (Woodworth, 2020).   
Emerging data suggest that the pediatric population is equally vulnerable to SARS-COV-2 
infection and may contribute significantly to transmission (Szablewski, 2020) (Lewis, 2020) 
(Viner, 2020)and that pregnant women are at increased risk for developing severe COVID-19 and 
have been shown to have a higher rate of hospitalization, need for mechanical ventilation, and ICU 
admission than non-pregnant women (Ellington, 2020) (Knight, 2020)(Woodworth, 2020).  
Neonatal transmission of SARS-CoV-2 has also been reported (Vivanti, 2020). Therefore, all 
adults and children should be considered for inclusion in COVID-19 prophylaxis efforts.  
In summary, based on prior experience with other fully human mAbs against exogenous targets, 
the available clinical and nonclinical data for REGN10933+REGN10987 to date, and the unmet 
need for a preventative therapy in advance of an approved vaccine, it is the opinion of the Sponsor 
that the overall risk-benefit balance for REGN10933+REGN10987 is acceptable to allow 
evaluation of this mAb combination in all populations, including adults, pregnant and 
breastfeeding women, and children who are household contacts of an infected individual and 
therefore at high risk for SARS-CoV-2 infection.  
For more details, refer to the IB. 
4. 
ENDPOINTS  
Endpoints are specified for study cohorts (as defined in Section 6.1.6).  
Symptomatic SARS-CoV-2 infection is determined by a positive central lab SARS-CoV-2 
RT-qPCR result during the EAP with signs/symptoms occurring within ±14 days of a positive 
RT-qPCR.  
The “strict-term”, “broad-term” and CDC definitions for signs/symptoms of SARS-CoV-2 
infection is presented in Section 9.2.2.2. 
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4.1. 
Cohort A and Cohort A1: SARS-CoV-2 RT-qPCR Negative at 
Baseline 
The endpoints are for subjects who are seronegative at baseline (based on central lab test), unless 
stated otherwise.  
4.1.1. 
Cohort A Primary Endpoints  
Cohort A Primary Efficacy Endpoint 
• Proportion of subjects who have a symptomatic RT-qPCR confirmed SARS-CoV-2 
infection (broad-term) during the EAP 
Cohort A and Cohort A1 Primary Safety Endpoints 
• Proportion of subjects with TEAEs and severity of TEAEs 
4.1.2. 
Cohort A Key Secondary Endpoints  
• Proportion of subjects with viral load >4 (log10 copies/mL) in NP swab samples 
during the EAP 
• Number of weeks of symptomatic RT-qPCR confirmed SARS-CoV-2 infection 
(broad-term) during the EAP 
• Number of weeks of high viral load >4 (log10 copies/mL) in NP swab samples during 
the EAP 
• Number of weeks of RT-qPCR confirmed SARS-CoV-2 infection (regardless of 
symptoms) during the EAP 
• Proportion of subjects who have a RT-qPCR confirmed SARS-CoV-2 infection 
(regardless of symptoms) during the EAP 
• Proportion of subjects in placebo group with a RT-qPCR confirmed SARS-CoV-2 
infection 
during 
the 
EAP 
with 
an index 
case 
participating 
in 
study 
R10933-10987-COV-2067 (comparison of those whose index cases receive 
REGN10933+REGN10987 versus placebo in study R1033-10987-COV-2067)  
4.1.3. 
Cohort A and Cohort A1 Other Secondary Endpoints  
• Proportion of subjects who have a symptomatic RT-qPCR confirmed SARS-CoV-2 
infection (CDC definition) during the EAP 
• Number of weeks of symptomatic RT-qPCR-confirmed SARS-CoV-2 infection (CDC 
definition) during the EAP  
• Proportion of subjects who have a symptomatic RT-qPCR confirmed SARS-CoV-2 
infection (strict-term) during the EAP 
• Number of weeks of symptomatic RT-qPCR-confirmed SARS-CoV-2 infection 
(strict-term) during the EAP  
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• Proportion of subjects who have a RT-qPCR confirmed SARS-CoV-2 infection at each 
week in the EAP 
• Proportion of subjects who have a symptomatic RT-qPCR confirmed SARS-CoV-2 
infection (broad term) at each week in the EAP 
• Time-weighted average of viral load (log10 copies/mL) from the first positive 
SARS-CoV-2 RT-qPCR in NP swab samples (that has an onset during the EAP) until 
the third weekly visit after the first positive test during the EAP (Note: Only for 
RT-qPCR positive subjects during the EAP in the seronegative modified full analysis 
set for cohort A [seronegative mFAS-A]) 
• Time-weighted average of viral load (log10 copies/mL) from the first positive 
SARS-CoV-2 RT-qPCR in NP swab samples (that has an onset during the EAP) until 
the second weekly visit after the first positive test during the EAP (Note: Only for 
RT-qPCR positive subjects during the EAP in the seronegative mFAS-A 
• Maximum SARS-CoV-2 RT-qPCR viral load (log10 copies/mL) in NP swab samples 
among individuals with ≥1 RT-qPCR positive that has an onset during the EAP 
• SARS-CoV-2 RT-qPCR viral load (log10 copies/mL) in NP swab samples 
corresponding to the onset of first positive RT-qPCR during the EAP 
• Area under the curve (AUC) in viral load (log10 copies/mL) from the first positive 
SARS-CoV-2 RT-qPCR NP swab samples detected during the EAP until the first 
confirmed negative test (testing that occurs after the EAP will be included if necessary 
to achieve a negative test result)  (Note: Only for RT-qPCR positive subjects during the 
EAP in the seronegative mFAS-A) 
• Number of medically attended visits in emergency rooms or urgent care centers related 
to a RT-qPCR confirmed SARS-CoV-2 infection that has an onset during the EAP 
• Proportion of subjects with at least 1 COVID-19-related hospitalization or emergency 
room visit associated with a positive RT-qPCR during the EAP, or all-cause death 
• Proportion of subjects requiring medically attended visits in emergency rooms or 
urgent care centers related to a RT-qPCR confirmed SARS-CoV-2 infection that has 
an onset during the EAP 
• Proportion of subjects hospitalized related to a RT-qPCR confirmed SARS-CoV-2 
infection that has an onset during the EAP 
• Number of days of hospital and intensive care unit (ICU) stay in subjects hospitalized 
for a RT-qPCR confirmed SARS-CoV-2 infection that has an onset during the EAP 
• Number of days missed for daily responsibilities (where applicable), including work 
(employed adults) or school (students), daycare or family obligations/responsibilities 
(childcare or eldercare) due to a RT-qPCR confirmed SARS-CoV-2 infection that has 
an onset during the EAP 
• Proportion of subjects in the placebo group with a RT-qPCR confirmed SARS-CoV-2 
infection during the EAP with at least 1 household member participating either in study 
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members 
receive 
REGN10933+REGN10987 
versus 
placebo 
in 
study 
R1033-10987-COV-2067 or in cohort B)  
Additional Cohort A1 Secondary Efficacy Endpoint 
• Proportion of subjects who have a symptomatic RT-qPCR confirmed SARS-CoV-2 
infection (broad-term) during the EAP.  
• Proportion of subjects with viral load >4 (log10 copies/mL) in NP swab samples during 
the EAP 
• Number of weeks of symptomatic RT-qPCR confirmed SARS-CoV-2 infection 
(broad-term) during the EAP 
• Number of weeks of high-viral load >4 (log10 copies/mL) in NP swab samples during 
the EAP 
• Number of weeks of RT-qPCR confirmed SARS-CoV-2 infection (regardless of 
symptoms) during the EAP 
• Proportion of subjects who have a RT-qPCR confirmed SARS-CoV-2 infection 
(regardless of symptoms) during the EAP 
•  Proportion of subjects in placebo group with a RT-qPCR confirmed SARS-CoV-2 
infection 
during 
the 
EAP 
with 
an index 
case 
participating 
in 
study 
R10933-10987-COV-2067 (comparison of those whose index cases receive 
REGN10933+REGN10987 versus placebo in study R1033-10987-COV-2067)  
Cohort A and Cohort A1 Safety Endpoints 
• Proportion of baseline seropositive subjects (based on central lab test) with TEAEs and 
severity of TEAEs 
• Incidence and severity of symptomatic SARS-CoV-2 infection in seronegative and 
seropositive subjects (based on central lab test) in both the EAP and follow-up periods 
Cohort A and Cohort A1 Pharmacokinetic and Immunogenicity Endpoints 
• Concentrations of REGN10933 and REGN10987 in serum over time and selected PK 
parameters in both seronegative and seropositive subjects (based on baseline central 
lab test) 
• Immunogenicity as measured by ADAs and NAbs to REGN10933 and REGN10987 
over time in both seronegative and seropositive subjects (based on baseline central lab 
test) 
4.1.4. 
Cohort A and Cohort A1 Exploratory Endpoints  
The exploratory endpoints for cohort A are: 
• Proportion of baseline-seronegative subjects who have a first RT-qPCR confirmed 
SARS-CoV-2 infection in the follow-up period (ie, after day 29 visit) 
• Proportion of baseline seronegative subjects who become seropositive (based on 
central lab test) up to day 57 
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• Proportion of baseline-seropositive subjects (based on central lab test) who 
subsequently have a positive SARS-CoV-2 RT-qPCR and symptomatic (strict-term) 
SARS-CoV-2 infection during the EAP 
• Proportion of subjects with negative RT-qPCR (based on central lab test) regardless of 
the serology status at baseline who subsequently have a positive SARS-CoV-2 
RT-qPCR and symptomatic (strict-term) SARS-CoV-2 infection during the EAP 
• Proportion of baseline-seronegative or baseline-seropositive subjects with negative 
RT-qPCR (based on central lab test) who subsequently have a positive SARS-CoV-2 
RT-qPCR and symptomatic (strict-term) SARS-CoV-2 infection during EAP 
• Proportion of baseline-seropositive subjects (based on central lab test) who 
subsequently have a positive SARS-CoV-2 RT-qPCR and symptomatic (broad-term) 
SARS-CoV-2 infection during the EAP 
• Proportion of subjects with negative RT-qPCR (based on central lab test) regardless of 
the serology status at baseline who subsequently have a positive SARS-CoV-2 
RT-qPCR and symptomatic (broad-term) SARS-CoV-2 infection during the EAP 
• Proportion of baseline-seronegative or baseline-seropositive subjects with negative 
RT-qPCR (based on central lab test) who subsequently have a positive SARS-CoV-2 
RT-qPCR and symptomatic (broad-term) SARS-CoV-2 infection during the EAP 
• Proportion of baseline-seropositive subjects (based on central lab test) who 
subsequently have a positive SARS-CoV-2 RT-qPCR and symptomatic (CDC 
definition) SARS-CoV-2 infection during the EAP 
• Proportion of subjects with negative RT-qPCR (based on central lab test) regardless of 
the serology status at baseline who subsequently have a positive SARS-CoV-2 
RT-qPCR and symptomatic (CDC definition) SARS-CoV-2 infection during the EAP 
• Proportion of baseline-seronegative or baseline-seropositive subjects with negative 
RT-qPCR (based on central lab test) who subsequently have a positive SARS-CoV-2 
RT-qPCR and symptomatic (CDC definition) SARS-CoV-2 infection during the EAP 
• Proportion of baseline-seropositive subjects (based on central lab test) who 
subsequently have a positive SARS-CoV-2 RT-qPCR during the EAP 
• Time-weighted average of viral load (log10 copies/mL) from the first positive 
SARS-CoV-2 RT-qPCR in NP swab samples (that has an onset during the EAP) until 
third weekly visit after the first positive test in seropositive subjects (based on central 
lab test) during the EAP 
• Time-weighted average of viral load (log10 copies/mL) from the first positive 
SARS-CoV-2 RT-qPCR in NP swab samples (that has an onset during the EAP) until 
the second weekly visit after the first positive test in seropositive subjects (based on 
central lab test) during the EAP 
• Area under the curve (AUC) in viral load (log10 copies/mL) in NP swab samples from 
the first positive SARS-CoV-2 RT-qPCR NP swab sample until the first confirmed 
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negative test, in seropositive subjects (based on central lab test) that has an onset during 
the EAP 
• Proportion of subjects in the placebo group who have a RT-qPCR confirmed 
SARS-CoV-2 infection (regardless of symptoms) during the EAP by the status of 
household members participating in study R10933-10987-CoV-2067 and receiving 
REGN10933+REGN10987 or whose household member did not receive treatment with 
REGN10933+REGN10987 
• Proportion of subjects who have a RT-qPCR confirmed SARS-CoV-2 infection 
(regardless of symptoms) during the EAP by the status of household members 
participating 
in 
study 
R10933-10987-CoV-2067 
and 
receiving 
REGN10933+REGN10987 
• Proportion of subjects who have a RT-qPCR confirmed SARS-CoV-2 infection 
(regardless of symptoms) during the EAP by the status of household members receiving 
an approved monoclonal antibody treatment for COVID-19 
• Proportion of subjects who have a RT-qPCR confirmed SARS-CoV-2 infection 
(regardless of symptoms) during the EAP by the status of household members receiving 
an 
approved 
monoclonal 
antibody 
treatment 
for 
COVID-19 
or 
REGN10933+REGN10987 in study R10933-10987-CoV-2067  
• Maximum RT-qPCR viral load (log10 copies/mL) in NP swab samples during the EAP 
in subjects who have asymptomatic infection during the EAP 
• Maximum RT-qPCR viral load (log10 copies/mL) in NP swab samples during the EAP 
in subjects who have symptomatic infection during the EAP 
• Maximum RT-qPCR viral load (log10 copies/mL) in NP swab samples during the EAP 
in subjects who have a medically attended visit 
4.2. 
Cohort B and Cohort B1: SARS-CoV-2 RT-qPCR Positive at 
Baseline 
The endpoints are for all subjects who are seronegative at baseline (based on central lab test), 
unless stated otherwise. 
4.2.1. 
Cohort B Primary Efficacy Endpoint 
• Proportion of subjects who subsequently develop signs and symptoms (broad-term) 
within 14 days of a positive RT-qPCR at baseline or during the EAP 
4.2.2. 
Cohort B Key Secondary Efficacy Endpoints 
• Number of weeks of symptomatic SARS-CoV-2 infection (broad-term) within 
14 days of a positive RT-qPCR at baseline or during the EAP  
• Number of weeks of high viral load >4 (log10 copies/mL) in NP swab samples during 
the EAP 
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4.2.3. 
Cohort B and Cohort B1 Other Secondary Efficacy Endpoints 
• Proportion of subjects who subsequently develop signs and symptoms (CDC 
definition) within 14 days of a positive RT-qPCR at baseline or during the EAP 
• Proportion of subjects who subsequently develop signs and symptoms (strict-term) 
within 14 days of a positive RT-qPCR at baseline or during the EAP 
• Number of weeks of symptomatic SARS-CoV-2 infection (CDC definition) within 
14 days of a positive RT-qPCR at baseline or during the EAP 
• Number of weeks of symptomatic SARS-CoV-2 infection (strict-term) within 14 days 
of a positive RT-qPCR at baseline or during the EAP 
• Proportion of subjects with viral load >4 (log10 copies/mL) in NP swab samples during 
the EAP 
• Change in viral load (log10 copies/mL) from baseline to day 8 visit in NP swab samples 
• Change in viral load (log10 copies/mL) from baseline to day 15 visit in NP swab 
samples 
• Time-weighted average change from baseline in viral load (log10 copies/mL) in NP 
swab samples until the day 22 visit  
• Area under the curve (AUC) in viral load (log10 copies/mL) in NP swab samples from 
baseline to the first confirmed negative test 
• Maximum SARS-CoV-2 RT-qPCR viral load (log10 copies/mL) in NP swab samples 
during the EAP 
• Number of medically attended visits in emergency rooms or urgent care centers related 
to RT-qPCR confirmed SARS-CoV-2 infection that has an onset at baseline or during 
the EAP 
• Proportion of subjects requiring medically attended visits in emergency rooms or 
urgent care centers related to a RT-qPCR confirmed SARS-CoV-2 infection that has 
an onset at baseline or during the EAP 
• Proportion of subjects hospitalized related to a RT-qPCR confirmed SARS-CoV-2 
infection that has an onset at baseline or during the EAP 
• Number of days of hospital and ICU stay in subjects hospitalized for a RT-qPCR 
confirmed SARS-CoV-2 infection that has an onset at baseline or during the EAP 
• Number of days missed for daily responsibilities (where applicable), including work 
(employed adults) or school (students), or family obligations/responsibilities (childcare 
or eldercare) due to a RT-qPCR confirmed SARS-CoV-2 infection that has an onset at 
baseline or during the EAP 
• Proportion of subjects with at least one COVID-19 related hospitalization or emergency 
room visit associated with a positive RT-qPCR at baseline or during the EAP, or 
all-cause death 
Additional Cohort B1 Secondary Efficacy Endpoints 
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• Proportion of subjects who subsequently develop signs and symptoms (broad-term) 
within 14 days of a positive RT-qPCR at baseline or during the EAP 
• Number of weeks of symptomatic SARS-CoV-2 infection (broad-term) within 14 days 
of a positive RT-qPCR at baseline or during the EAP 
• Number of weeks with high viral load >4 (log10 copies/mL) in NP swab samples during 
the EAP 
Cohort B and Cohort B1 Safety Endpoints 
• Proportion of subjects with TEAEs and severity of TEAEs 
• Incidence and severity of symptomatic SARS-CoV-2 infection in both the EAP and 
follow-up periods 
Cohort B and Cohort B1 Pharmacokinetic and Immunogenicity Endpoints 
• Concentrations of REGN10933 and REGN10987 in serum over time and selected PK 
parameters in both seronegative and seropositive subjects (based on baseline central 
lab test)  
• Immunogenicity as measured by ADAs and NAbs to REGN10933 and REGN10987 
over time in both seronegative and seropositive subjects (based on baseline central lab 
test)  
4.2.4. 
Cohort B and Cohort B1 Exploratory Endpoints 
• Proportion of subjects who subsequently have symptomatic (strict-term) SARS-CoV-2 
infection confirmed by RT-qPCR within the EAP according to their baseline serology 
test status (ie, seropositive or other, based on central lab test) 
• Proportion of subjects who subsequently have symptomatic (broad-term) SARS-CoV-2 
infection confirmed by RT-qPCR within the EAP according to their baseline serology 
test status (ie, seropositive or other, based on central lab test) 
• Proportion of subjects who subsequently have symptomatic (CDC definition) 
SARS-CoV-2 infection confirmed by RT-qPCR within the EAP according to baseline 
serology test status (ie, seropositive or other, based on central lab test) 
• Number of weeks of symptomatic SARS-CoV-2 infection (strict-term) within 14 days 
of a positive RT-qPCR at baseline or during the EAP, according to baseline serology 
test status (ie, seropositive or other, based on central lab test) 
• Number of weeks of symptomatic SARS-CoV-2 infection (broad-term) within 14 days 
of a positive RT-qPCR at baseline or during the EAP, according to baseline serology 
test status (ie, seropositive or other, based on central lab test) 
• Number of weeks of symptomatic SARS-CoV-2 infection (CDC definition) within 
14 days of a positive RT-qPCR at baseline or during the EAP, according to baseline 
serology test status (ie, seropositive or other, based on central lab test) 
• Time-weighted average change and percent change from baseline viral load 
(log10 copies/mL) by SARS-CoV-2 RT-qPCR in NP swab samples until the day 22 visit 
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according to baseline serology test status (ie, seropositive or other, based on central lab 
test)  
• Area under the curve (AUC) in viral load (log10 copies/mL) in NP swab samples from 
baseline to the first confirmed negative test according to baseline serology test status 
(ie, seropositive or other, based on central lab test)  
• Maximum SARS-CoV-2 RT-qPCR (log10 viral copies/mL) in NP swab samples during 
the EAP according to baseline serology test status (ie, seropositive or other, based on 
central lab test) 
• Number of medically attended visits in emergency rooms or urgent care centers related 
to RT-qPCR confirmed SARS-CoV-2 infection at baseline or during the EAP, 
according to baseline serology test status (ie, seropositive or other, based on central lab 
test) 
• Proportion of subjects requiring medically attended visits in emergency rooms or 
urgent care centers related to a RT-qPCR confirmed SARS-CoV-2 infection at baseline 
or during the EAP, according to baseline serology test status (ie, seropositive or other, 
based on central lab test) 
• Proportion of subjects hospitalized related to a RT-qPCR confirmed SARS-CoV-2 
infection at baseline or during the EAP, according to baseline serology test status 
(ie, seropositive or other, based on central lab test) 
• Number of days of hospital and ICU stay in subjects hospitalized for a RT-qPCR 
confirmed SARS-CoV-2 infection at baseline or during the EAP, according to baseline 
serology test status (ie, seropositive or other, based on central lab test) 
• Number of days missed for daily responsibilities (where applicable), including work 
(employed adults) or school (students), or family obligations/responsibilities (childcare 
or eldercare) due to a RT-qPCR confirmed SARS-CoV-2 infection at baseline or during 
the EAP, according to baseline serology test status (ie, seropositive or other, based on 
central lab test) 
• Maximum RT-qPCR viral load (log10 copies/mL) in NP swab samples during the EAP 
in subjects who have asymptomatic infection during EAP 
• Maximum RT-qPCR viral load (log10 copies/mL) in NP swab samples during the EAP 
in subjects who have symptomatic infection during EAP 
• Maximum RT-qPCR viral load (log10 copies/mL) in NP swab samples during the EAP 
in subjects who have a medically attended visit related to a RT-qPCR confirmed 
SARS-CoV-2 infection at baseline or during the EAP 
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5. 
STUDY VARIABLES 
This section provides variables to be measured in the study. For description and rationale of 
corresponding study procedures, refer to Section 9.2. 
5.1. 
Demographic and Baseline Characteristics 
The variables for baseline characteristics include standard demography (eg, age, race, weight, 
height, body mass index [BMI], risk factors for SARS-CoV-2 infection, etc), medical history, 
medication history, and test results for local diagnostic assay for SARS-CoV-2 from appropriate 
samples (details in Section 9.2.1.2), central lab SARS-CoV-2 RT-qPCR and central lab serology 
(anti-SARS-CoV-2 antibodies) test results for each subject. 
5.2. 
Efficacy Variables 
The efficacy variables include measurements or test results for individual subjects of the 
following: 
• A positive SARS-CoV-2 infection (ie, a positive RT-qPCR) will be defined based on 
any available RT-qPCR result (either NP, nasal or saliva) which is reported as 
“detected”. A negative infection (ie, a negative RT-qPCR) will be defined based on all 
available RT-qPCR results (either NP, nasal or saliva) which are reported as “not 
detected” 
• Viral load (log10 copies/mL) from RT-qPCR test 
• Asymptomatic SARS-CoV-2 infection: positive RT-qPCR result of NP swab sample 
without any of the strict-term or broad-term SARS-CoV-2 infection signs and 
symptoms (specified in Section 9.2.2.2) within the EAP 
• Symptomatic infection based on strict-term SARS-CoV-2 infection signs and 
symptoms (for secondary endpoint): Positive strict-term symptomatic infection defined 
as SARS-CoV-2 infection signs and symptoms (specified in Section 9.2.2.2) and a 
positive RT-qPCR that occurs within the EAP 
• Symptomatic infection based on broad-term SARS-CoV-2 infection signs and 
symptoms (for secondary endpoints): Positive broad-term symptomatic infection 
defined as SARS-CoV-2 infection signs and symptoms (specified in Section 9.2.2.2) 
and a positive RT-qPCR that occurs within the EAP 
• Symptomatic infection based on CDC definition SARS-CoV-2 infection signs and 
symptoms (for secondary endpoints): Positive broad-term symptomatic infection 
defined as SARS-CoV-2 infection signs and symptoms (specified in Section 9.2.2.2) 
and a positive RT-qPCR that occurs within the EAP 
• Medically attended visits to ED or UCC due to SARS-CoV-2 infection: number of 
visits that occur after a positive RT-PCR result within the EAP 
• Hospitalization due to SARS-CoV-2 infection (hospitalization status and days in 
hospital) within the EAP 
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• Days absent from daily responsibilities (eg, days missed from work, school, childcare, 
or eldercare) due to SARS-CoV-2 infection within the EAP 
• Occurrence of laboratory-confirmed SARS-CoV-2 infection during follow-up period 
collected from spontaneously reported AEs 
Detailed descriptions for assessing COVID-19 signs and symptoms and their temporal 
relationship with lab confirmed SARS-CoV-2 infection is provided in Section 9.2.2.2. 
5.3. 
Safety Variables 
Safety variables include recording, measurements, or laboratory test results for individual subjects 
of the following: TEAEs; vital signs including heart rate, blood pressure, respiration rate, and body 
temperature, physical examination findings; results of laboratory tests including hematology, 
blood chemistry, and urinalysis (only for adult/adolescent subjects).  In addition, subjects with a 
positive RT-PCR result and a medically attended visit (ED, UCC, hospitalization) will be assessed 
for occurrence (worst or most abnormal finding) of abnormal vital signs, respiratory failure, 
evidence of shock, multiorgan dysfunction and admission to ICU; Section 9.2.3). 
5.4. 
Pharmacokinetic Variables 
The pharmacokinetic variables are the concentrations of REGN10933 and REGN10987 in serum 
at each time point and select PK parameters.  The sampling time points for dense and sparse 
collection schedules are specified in Table 4. 
5.5. 
Immunogenicity Variables 
The immunogenicity variables are ADA status, titer, NAb status, and time-point/visit. Samples in 
this study will be collected at the clinic visits specified in Table 4 and Table 6. 
6. 
STUDY DESIGN 
6.1. 
Study Description and Duration 
This is a phase 3 randomized, double-blind, placebo-controlled study in adults, adolescents, and 
children with household contact exposure to individuals with SARS-CoV-2 infection. This study 
is designed to assess the efficacy of the administration of REGN10933+REGN10987 to reduce the 
incidence of SARS-CoV-2 infection and prevent the development of disease (symptomatic 
SARS-CoV-2 infection) after household exposure to individuals with SARS-CoV-2 infection.  
Safety, tolerability, PK, and immunogenicity of REGN10933+REGN10987 will also be evaluated. 
Eligible subjects are those who are asymptomatic and household contacts with close exposure with 
the first household member with known SARS-CoV-2 infection (index case) but may be either 
positive or negative for SARS-CoV-2 during screening, as assessed by central laboratory 
RT-qPCR performed at baseline.  The index case will have a diagnosis of SARS-CoV-2 infection 
using a diagnostic test, eg, RT-PCR, antigen test, or other test format (approved or with EUA 
issued by the US FDA or by equivalent local health authority). Randomization will be performed 
by individual study subjects, not by households. 
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Approximately 3500 adult and adolescent subjects and approximately 250 pediatric subjects 
<12 years old will be enrolled.  Randomization will be performed by site and stratified for 
assignment of treatment group by test result of a local diagnostic assay for SARS-CoV-2 from 
appropriate samples and age group (<12 years, ≥12 years to <18 years, ≥18 to <50 years, or 
≥50 years) (Section 8.4).  For pediatric subjects (<12 years), the weight group (≥20 kg, ≥10 kg to 
<20 kg, and <10 kg) will be used as an additional stratification factor. Cohort allocation will be 
based on central lab baseline SARS-CoV-2 RT-qPCR for data analysis: cohort A or cohort A1 
(negative) and cohort B or cohort B1 (positive) (defined in Section 6.1.6).  For adult and adolescent 
subjects, approximately 3150 subjects are planned to be enrolled in cohort A and 350 subjects in 
cohort B.  At least 1248 cohort A subjects are expected to be seronegative and available for primary 
and secondary endpoint analysis (Section 11.2.1), excluding those cohort A subjects that were 
included in the administrative assessment. The subjects that are included the planned analyses are 
described in Section 11.4.9. For pediatric subjects (<12 years), approximately 225 subjects are 
planned to be enrolled in cohort A1 and 25 subjects in cohort B1. Statistical analyses will be 
conducted separately in each cohort.  For the purpose of the study analysis, cohorts A, A1, B, and 
B1 are independent.  
Subjects will be randomized in a 1:1 allocation ratio to 1 of 2 treatment groups (placebo or 
REGN10933+REGN10987) (Section 8.1). 
Adult subjects were enrolled into the first 2 subgroups and then adolescents were added to 
subgroup 3, as subgroups 1 and 2 had completed enrollment at the time the protocol was amended 
to add adolescents.  Subjects are assigned a subject number by IWRS (irrespective of allocation to 
cohort A or cohort B) (Table 4): 
1. Sentinel group (subset 1; first 30 adult subjects; completed) had samples collected in the 
EAP and Follow-Up periods for clinical laboratory tests (hematology, blood chemistry, 
urinalysis), drug concentration measurement (dense, PK), and immunogenicity analysis 
(ADA). 
2. Safety group (subset 2; 31st to 400th adult subject; completed) had samples collected in the 
EAP and Follow-Up periods for clinical laboratory tests (hematology, blood chemistry, 
urinalysis), drug concentration measurement (sparse, PK), and ADA. 
3. All other subjects (subset 3; 401st to last subject) will have samples collected at baseline 
and end of EAP for clinical laboratory tests (hematology, blood chemistry, urinalysis) and 
ADA. 
Pediatric subjects (<12 years) will be enrolled into 2 subgroups by subject number assigned by 
IWRS (irrespective of allocation to cohort A1 or cohort B1) (Table 6).   
1. Pediatric subject sentinel group (subset 4; first 12 subjects (6 active, 6 placebo); 4 per 
weight group (≥20 kg, ≥10 kg to <20 kg, and <10 kg) completed) will have samples 
collected (Schedule A) in the EAP and Follow-Up periods for clinical laboratory tests 
(hematology, blood chemistry), drug concentration measurement, and ADA. 
2. All pediatric subjects (subset 4 and subset 5) will have samples collected (Schedules A, B, 
C, and D) in the EAP and Follow-Up periods for clinical laboratory tests (hematology, 
blood chemistry), drug concentration measurement, and ADA. 
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For each subject, the study comprises 3 periods: a 1-day screening/baseline period, a 1-month 
EAP, and a 7-month follow-up period. 
The study flow diagram is provided in Figure 1. 
Figure 1: 
Study Flow Diagram 
 
6.1.1. 
Sentinel Subjects and Staggered Enrollment/Dosing:  
Enrollment into this study was gated by IDMC review of a sentinel group of 30 adult patients with 
COVID-19 dosed with REGN10933+REGN10987 2400 mg IV, REGN10933+REGN10987 
8000 mg IV or placebo in leading phase 1 studies of REGN10933+REGN10987 (Section 3.2.4). 
Enrollment in this study was carried out in 2 phases: 
1. Sentinel group comprised ~30 adult subjects (by subject number assigned by IWRS; 
irrespective of allocation to cohort A or cohort B):  Subjects were monitored for safety 
on-site for a minimum of 4 hours after administration of the first dose of study drug and 
then daily via visits to the study site or phone calls for the first 4 days (96 hours). Because 
REGN10933+REGN10987 will already have cleared an adult safety sentinel cohort at 
higher doses administered IV in previous studies (Section 3.2.4), the sentinel group in this 
study focused on safety evaluation for injection site reactions and hypersensitivity reactions 
and data were reviewed before progressing with enrollment of additional study subjects. 
The blinded safety data review was be led by a designated member of the Regeneron 
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clinical team (generally either the medical monitor or the clinical trial manager) and at a 
minimum the data review team included the Regeneron Medical Monitor, Study 
Biostatistician, Global Safety Lead or designee, and the Senior Vice President of Early 
Clinical Development & Experimental Sciences. 
2. Following a conclusion of the blinded safety data review that the study could proceed, the 
study resumed enrollment. 
In case of any safety concerns, the IDMC/DMSB may be consulted and requested to provide 
recommendations.  
6.1.2. 
Pediatric Subjects (<12 years)  
Approximately 250 pediatric subjects (<12 years) across all weight-tiered dose ranges will be 
enrolled.  However, since the enrollment of pediatric subjects (<12 years) will end once enrollment 
of adult and adolescent subjects is complete, the number of pediatric subjects may be adjusted.  
Enrollment of pediatric subjects in this study will be carried out in 2 steps, one for safety and 
another for confirmation of drug exposure for each weight group.  
Pediatric Subjects Safety Sentinel Group 
1. Sentinel group (subset 4) will comprise 12 pediatric subjects (by subject number assigned 
by IWRS; irrespective of allocation to cohort A1 or cohort B1) in 3 weight groups (≥20 kg; 
10 kg to <20 kg; <10 kg).  Each weight group will have 4 subjects randomized 1:1 to 1 of 
2 treatment groups (placebo or REGN10933+REGN10987) and study drug administered 
first.  After all 4 subjects in a weight group complete the sentinel review, enrollment of 
additional subjects in that weight group will proceed.  Pediatric subjects (<12 years) will 
be monitored for safety on-site for a minimum of 2 hours after administration of the first 
dose of study drug and then daily via visits to the study site or phone calls for the first 
4 days (96 hours). Because REGN10933+REGN10987 will already have cleared an adult 
safety sentinel cohort at higher doses administered IV in previous studies (Section 3.2.4), 
and the adult safety sentinel as well as the first 20 adolescent subjects (≥12 to <18 years) 
in this study, the pediatric (<12 years) sentinel group in this study is focused on safety 
evaluation for injection site reactions and hypersensitivity reactions and data will be 
reviewed before progressing with enrollment of additional pediatric subjects. The blinded 
safety data review will be led by a designated member of the Regeneron clinical team 
(generally either the medical monitor or the clinical trial manager) and at a minimum the 
data review team will include the Regeneron Medical Monitor, Study Biostatistician, 
Global Safety Lead or designee, and the Senior Vice President of Early Clinical 
Development & Experimental Sciences. 
2. Following a conclusion of the blinded safety data review that the study may proceed for a 
weight group, the enrollment of pediatric subjects in that weight group will resume; 
however, close monitoring by the Safety Review Committee will continue on a periodic 
cumulative aggregate basis, including stratification to facilitate early and periodic review 
of data for adolescent subjects (≥12 years to <18 years) and pediatric subjects (<12 years) 
in each of the weight groups. 
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1. All pediatric subjects (subset 4 and subset 5) will have samples collected (Schedules A, B, 
C, and D) in the EAP and Follow-Up periods for drug concentration measurement as well 
as ADA assessment and clinical laboratory tests (hematology, blood chemistry).  The drug 
concentration data from approximately the first 20 subjects per weight group (<10 kg, 10 to 
20 kg, ≥20 kg) will be evaluated to confirm that the REGN10933 and REGN10987 dose 
for the weight group is providing the expected exposure.   
2. Based on simulations using a population PK model using data from adult patients with 
COVID-19, the proposed doses for the pediatric subjects (Table 2) is expected to match 
the exposure in adult subjects at SC dose of 1200 mg (600 mg per mAb) in this study.  
Once the exposure for a dose is confirmed in a weight group, enrollment beyond 25 subjects 
for this weight group can continue.  Based on the results of the drug concentration analyses 
from up to 20 pediatric subjects receiving active drug in the weight groups, the dose for 
participating pediatric subjects may be adjusted in 1 or more of the weight group(s) to 
ensure drug exposure comparable to adult subjects in this study. If the dose for a particular 
weight group needs to be adjusted, the new dose for that weight group will used for 
approximately a subsequent 20 subjects for that weight group.  These subjects who 
received the new dose will have drug concentrations analyzed to confirm that it is providing 
the expected exposure.  When the new dose is started, the subjects will resume dosing 
according to the next sample collection schedule since the last subject received study drug. 
6.1.3. 
Screening/Baseline 
After subjects provide informed consent, they will be assessed for study eligibility.  The screening 
visit and randomization visit should occur on the same day.  If needed, a remote visit may occur 
to sign the ICF and collect medical history and concomitant medication use, on the day prior to, 
but within 24 hours of study drug administration, so that the in person screening and randomization 
visit may be abbreviated, due to COVID-19 considerations. Study drug administration must occur 
within 96 hours of the sample collection of the index cases’ positive SARS-CoV-2 diagnostic test 
sample.  Subjects will be provided with contact information for the clinical study site and will be 
given written and verbal instructions to call site personnel with any changes in their health status. 
On day 1, prior to randomization, a local diagnostic assay for SARS-CoV-2 (SARS-CoV-2 antigen 
or RT-PCR) from appropriate samples will be performed (details in Section 9.2.1.2).  The result 
of this assay will be used as a stratification factor for randomization to treatment groups (placebo 
or REGN10933+REGN10987) (Section 8.4).  The requirement for a local diagnostic assay for 
SARS-CoV-2 is waived when the results are not expected to be available in a timely manner for 
randomization.  Nasopharyngeal swab sample (swabbing through both nostrils) for central lab 
testing of SARS-CoV-2 RT-qPCR and blood sample for central lab serology will be collected and 
sent to central lab.  After completing baseline assessments and sample collection, all subjects will 
receive a single-dose of study drug (see details of study drug administration in Section 8.1).  The 
central lab results of baseline SARS-CoV-2 RT-qPCR will be used to allocate subjects into cohort 
A (negative result) or cohort B (positive result). 
Subjects will be monitored for vital signs and TEAEs after study drug administration as follows: 
• Adult subjects in the sentinel group (subset 1; completed) were monitored in the 
clinic for at least 4 hours after study drug administration on day 1 and then daily by 
phone call or site visit until day 4 (96 hours). 
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• Adult subjects in the safety group (subset 2; completed) were monitored in the clinic 
every hour for 2 hours after study drug administration and by a phone call on day 4. 
• All other adult and adolescent subjects (subset 3) will be monitored in the clinic for 
1 hour after study drug administration. 
• Pediatric subjects (<12 years) in the sentinel group (subset 4) will be monitored in 
the clinic for at least 2 hours after study drug administration on day 1 and then daily by 
phone call or site visit until day 4 (approximately 96 hours). 
• All other pediatric subjects (<12 years) (subset 5) will be monitored in the clinic for 
1 hour after study drug administration. 
All subjects will be advised to call the site if signs/symptoms of hypersensitivity occur.  During 
post-dose monitoring, Grade 3 or greater injection site reactions and hypersensitivity reactions that 
occur after study drug administration will be captured as an AESI to allow for expedited reporting 
to the sponsor (see AE grading system in Section 10.2.4 and list of AESIs in Section 10.1.3).  
6.1.4. 
Efficacy Assessment Period 
Efficacy, safety, sample collections, and other study assessments will be performed at specified 
time points throughout the EAP according to the Schedule of Events specified in Section 9.1. On 
day 1/baseline with study drug administration, sample collection must occur prior to study drug 
administration. 
If subjects are able to travel and can do so while maintaining social distancing guidelines, 
subsequent site visits will be conducted; alternatively, telemedicine visits, phone calls, mobile 
units or home health nurses may be utilized.  Throughout the study, biological samples will be 
obtained by adequately trained and delegated study personnel at study locations where appropriate 
personal protective equipment (PPE) are available to be used. 
At each weekly visit, assessments and procedures will be performed (Table 3 and Table 4). 
Subjects will be instructed to contact the study site staff for any new or changing symptoms or 
signs possibly related to COVID-19, including fever.  The investigator should recommend that 
subjects (themselves or by their parent/guardian) measure their temperature daily during EAP, 
approximately at the same time, and also every time when the subject feels feverish, chills, or sick 
(Section 10.1.1).  Adult subjects may receive automated reminders (eg, text messages to mobile 
phones; implemented as soon as technologically feasible and when subjects confirm to opt in) in 
between the weekly visits to prompt them to contact the study site staff as needed.  The NP swab 
sample will be collected for SARS-CoV-2 RT-qPCR to be tested at the central lab.  The 
investigator or designee will contact each subject weekly (site visit or telemedicine) to assess the 
subjects general health, and to document AEs in general and any signs and symptoms associated 
with SARS-CoV-2 infection since the last contact (see details of the procedure in Section 9.2.2.2). 
Any subject who develops fever, an acute respiratory illness, symptoms related to multisystem 
inflammatory syndrome in children ([MIS-C] [pediatric subjects <18 years only]), or other 
symptoms that they may feel could be related to COVID-19 should alert the study staff 
immediately.  If the subject experiences a true medical emergency, they should visit their local 
hospital ED or call the local emergency telephone number (eg, 911 in North America) and contact 
the clinical site personnel later.  Subjects’ symptoms must be evaluated by the investigator or 
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designee, which can occur through site visit, mobile unit, home visit, telemedicine, etc. If 
investigator or designee suspects SARS-CoV-2 infection, a NP swab sample should be collected 
and sent for central lab testing. The subject may also be asked to provide blood samples if it 
corresponds to a scheduled visit, according to the Schedule of Events (specified in Section 9.1). 
Subjects with laboratory confirmed SARS-CoV-2 infection should be informed as soon as possible 
and should undergo medical isolation to prevent contact with others to reduce the risk of further 
transmission. Since these subjects will likely be isolated, the study visits, assessments and sample 
collections may occur through a variety of methods.  For subjects who have a confirmed 
SARS-CoV-2 infection, the investigator will assess AEs weekly or more frequently than weekly, 
depending on the clinical status of the subject, as assessed by the investigator or designee (these 
more frequent AE assessments will be reported as unscheduled visits).  The investigator will also 
collect information for any SARS-CoV-2 infection-related medically attended visits to the ED, 
UCC, or hospitalization starting from the timepoint of SARS-CoV-2 RT-qPCR positive result (see 
detail in Section 9.2.2.3). 
For subjects who are positive for SARS-CoV-2 at any time during the EAP, including those 
positive at baseline, subsequent assessments/sample collections in the EAP should follow that 
specified in Table 3 until 2 consecutive confirmed negative SARS-CoV-2 RT-qPCR test results 
are achieved ≥24 hours apart.  A PK sample and an ADA sample will be collected (1) as soon as 
possible or within 7 days of receiving first positive SARS-CoV-2 RT-qPCR result for cohort A 
subjects and (2) as soon as possible or within 7 days of first new positive SARS-CoV-2 RT-qPCR 
result after achieving 2 consecutive negative results for all subjects. 
Subjects presenting with acute illness should be medically managed according to local standard of 
care as per the discretion of the treating physician. 
If a subject is hospitalized for suspected COVID-19, every effort should be made by the site 
personnel to collect, as soon as possible, a NP swab sample for central lab SARS-CoV-2 RT-qPCR 
testing. In subjects where it is not possible to have samples collected for assessment in the central 
laboratory, study site personnel will attempt to obtain and record information about all 
SARS-CoV-2 assays conducted in other medical facilities, including result(s), name of the assay(s) 
and whether the laboratory(ies) conducting the assays is a CLIA (Clinical Laboratory 
Improvement Amendments) certified (or equivalent) laboratory. The laboratory report for a 
positive SARS-CoV-2 test result, including the name of the test as well as information about 
laboratory certification, should be collected and stored as source documentation at the site. The 
positive SARS-CoV-2 assay result will be recorded in concomitant procedures related to the 
COVID-19 AE. Details on any symptoms and medically attended visits will also be collected. 
After discharge, as described above, all subjects with a positive SARS-CoV-2 RT-PCR will 
continue to follow the weekly planned study visits until 2 confirmed negative SARS-CoV-2 
RT-qPCR test results are achieved at least 24 hours apart.  
6.1.5. 
Follow-up Period 
Subjects who remain SARS-CoV-2 RT-qPCR negative throughout the EAP will complete the end 
of the EAP and enter the Follow-up Period to be followed for 7 months (Table 3, Table 4). 
Subjects who become SARS-CoV-2 RT-qPCR positive during the EAP will continue to have 
weekly NP swab samples for SARS-CoV-2 RT-qPCR tests until 2 confirmed negative 
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SARS-CoV-2 RT-qPCR test results are achieved at least 24 hours apart, even after they complete 
the EAP and enter the study Follow-up Period to be followed for 7 months.  In such situations, 
these visits for sample collection in the Follow-up Period should be characterized as unscheduled 
visits.  A PK sample and an ADA sample will be collected (1) as soon as possible or within 7 days 
of receiving first positive SARS-CoV-2 RT-qPCR result for cohort A subjects and (2) as soon as 
possible or within 7 days of first new positive SARS-CoV-2 RT-qPCR result after achieving 
2 consecutive negative results for all subjects. 
At each scheduled visit, the investigator or designee will contact each subject (site visit or 
telemedicine) to assess and document the subject’s general health, AEs in general and signs and 
symptoms associated with SARS-CoV-2 infection, including fever, since the last contact, as 
described for the EAP (Section 6.1.4).  For subjects who have a confirmed SARS-CoV-2 infection, 
the investigator will assess AEs weekly or more frequently than weekly, depending on the clinical 
status of the subject, as assessed by the investigator or designee (these more frequent AE 
assessments will be reported as unscheduled visits).  The investigator will also collect information 
for any SARS-CoV-2 infection-related medically attended visits to the ED, UCC, or 
hospitalization starting from the timepoint of SARS-CoV-2 RT-qPCR positive result (see details 
in Section 9.2.2.3). 
Any subject who, between the study visits, develops fever, an acute respiratory illness, symptoms 
related to MIS-C (pediatric subjects <18 years only), or other symptoms that they may feel could 
be related to COVID-19 should alert the study staff immediately. If the subject experiences a true 
medical emergency, they should visit their local hospital ED or call the local emergency telephone 
number (eg, 911 in North America) and contact the clinical site personnel later.  The subjects’ 
symptoms must be evaluated by the investigator or designee, which can occur through site visit, 
mobile unit, home visit, telemedicine, etc. If the investigator or designee deems the subject’s 
signs/symptoms require the collection of biological samples for central lab testing to assess or 
confirm SARS-CoV-2 infection, the subject will be advised to provide NP sample. The subject 
may also be asked to provide blood samples if it corresponds to a scheduled visit, according to the 
Schedule of Events (specified in Section 9.1). If a subject is hospitalized for suspected COVID-19, 
every effort should be made by the site personnel to collect, as soon as possible, a NP swab sample 
for central lab SARS-CoV-2 RT-qPCR testing. In subjects where it is not possible to have samples 
collected for assessment in the central laboratory, study site personnel will attempt to obtain and 
record information about all SARSCoV-2 assays conducted in other medical facilities, including 
result(s), name of the assay(s) and whether the laboratory(ies) conducting the assays is a CLIA 
certified (or equivalent) laboratory. The laboratory report for a positive SARSCoV-2 test result, 
including the name of the test as well as information about laboratory certification, should be 
collected and stored as source documentation at the site. The positive SARS CoV-2 assay result 
will be recorded as concomitant procedures related to the COVID-19 AE. Details on any symptoms 
and medically attended visits will also be collected. 
6.1.6. 
Description of Study Cohorts 
The study has 4 independent cohorts, cohort A and cohort B for adult and adolescent subjects and 
cohort A1 and cohort B1 for pediatric subjects <12 years. 
All subjects enrolled in the study will be household contacts of the first household members with 
a diagnosis of SARS-CoV-2 (index case) and asymptomatic at the time of screening.  The subjects’ 
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SARS-CoV-2 infection status, positive or negative by SARS-CoV-2 RT-qPCR (central lab) at 
baseline, determines the study procedures they follow (SOE) and the analysis of endpoints. 
• Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline:  Approximately 3150 adult 
and adolescent subjects with a negative SARS-CoV-2 RT-qPCR result who are 
asymptomatic at baseline.  Cohort A will evaluate the efficacy of a single dose of 
REGN10933+REGN10987 as prophylaxis to prevent SARS-CoV-2 symptomatic 
infection.   
• Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline:  Approximately 350 adult 
and adolescent subjects with a positive SARS-CoV-2 RT-qPCR result who are 
asymptomatic at baseline.  Cohort B will evaluate the effect of a single-dose of 
REGN10933+REGN10987 as preemptive therapy to prevent or modify symptomatic 
disease.   
• Cohort A1: SARS-CoV-2 RT-qPCR Negative at Baseline:  Approximately 
225 pediatric subjects (<12 years) with a negative SARS-CoV-2 RT-qPCR result who 
are asymptomatic at baseline. 
• Cohort B1: SARS-CoV-2 RT-qPCR Positive at Baseline:  Approximately 
25 pediatric subjects (<12 years) with a positive SARS-CoV-2 RT-qPCR result who 
are asymptomatic at baseline.   
Study objectives and endpoints are specified for each cohort (Section 2 and Section 4). 
The statistical analysis sets for the cohorts are defined in Section 11.3.1. 
6.1.7. 
Study Stopping Rules 
6.1.7.1. 
Study Stopping Criteria 
The IDMC, which may also be referred to Data and Safety Monitoring Board (DSMB), will 
monitor unblinded data on a regular basis to assess the risk/benefit profile of 
REGN10987+REGN10933. If at any time the IDMC has significant concerns regarding a 
meaningful imbalance in TEAEs or treatment-emergent SAEs, including in relation to safety data 
by pediatric groups, the IDMC may make a recommendation to the Sponsor to halt the study or 
make recommendations for other changes in the study conduct. This will prompt a review by the 
Sponsor who will decide to implement, modify, or reject the recommendation. Applicable 
regulatory procedures will be adhered to as required by local laws in relation to any decisions 
related to a change in study conduct, temporary halt, study termination, or study restart.   
Pre-specified stopping rules for early termination (ET) of the study for efficacy will be documented 
in the Statistical Analysis Plan (SAP) and IDMC Charter. 
6.1.8. 
End of Study Definition 
The end of study is defined as the date the last subject completes the last study visit, withdraws 
from the study, or is lost to follow-up (ie, the study subject can no longer be contacted by the 
investigator). 
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6.2. 
Planned Interim Analysis 
There is no interim analysis planned after the administrative assessment.   
6.3. 
Study Committees  
6.3.1. 
Independent Data Monitoring Committee/Data and Safety Monitoring Board 
The terms IDMC and DSMB employed during the conduct of this study refers to the safety 
committee that will perform safety monitoring for this study and the terms are interchangeable in 
this protocol.  
The IDMC/DSMB, will be utilized to evaluate the safety of REGN10933+REGN10987 on a 
regular basis. The IDMC/DSMB is important for this prophylaxis study, given the limited amount 
of safety data currently available, and because the study will enroll a large number of adults. The 
IDMC/DSMB may also be asked to perform a formal interim evaluation of efficacy (Section 11.5) 
and/or sample size re-estimation to be conducted when 25% of the originally planned number of 
subject complete the EAP (Section 11.2.1). The details of such evaluation will be described in the 
IDMC/DSMB Charter. 
6.3.2. 
Safety Review Committee for REGN 2069/ CoVPN 3502 
The Safety Review Committee (SRC) for REGN 2069/CoVPN 3502 will include Regeneron 
members (Medical/Study Director(s), Global Patient Safety, and Biostatistics and Data 
Management), National Institute of Allergy and Infectious Diseases (NIAID) members (Medical 
Officers), and CoVPN members (Protocol Chairs, and the CoVPN Physician.  The CoVPN is 
supported by NIAID. The SRC for 2069/CoVPN 3502 will be utilized to evaluate the safety of 
REGN10933+REGN10987 on a regular basis.  Safety monitoring will be performed for blinded 
data on an ongoing basis (eg, individual review of SAEs and AESIs) and on a periodic cumulative 
aggregate basis, including stratification to facilitate early and periodic review of data for 
adolescent subjects (≥12 years to <18 years), pediatric subjects (<12 years), and pregnant and 
breastfeeding subjects.  The details of the safety monitoring will be described in the SRC for 
2069/CoVPN 3502 safety monitoring collaborative plan. 
7. 
SELECTION, WITHDRAWAL, AND REPLACEMENT OF 
SUBJECTS 
7.1. 
Number of Subjects Planned 
Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline- Approximately 3150 adult and 
adolescent subjects will be enrolled.  Cohort A is expected to include the majority of study subjects.  
Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline- Approximately 350 adult and 
adolescent subjects will be enrolled.  
Cohort A1: SARS-CoV-2 RT-qPCR Negative at Baseline- Approximately 225 pediatric 
subjects (<12 years) will be enrolled. 
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Cohort B1: SARS-CoV-2 RT-qPCR Positive at Baseline- Approximately 25 pediatric subjects 
(<12 years) will be enrolled. 
7.2. 
Study Population  
Eligible subjects for this study consist of asymptomatic, healthy adults and children who are 
household contacts to the first known household member with a diagnosis of SARS-CoV-2 
infection (index case). 
7.2.1. 
Inclusion Criteria 
A subject must meet the following criteria to be eligible for inclusion in the study: 
1. Adult subjects 18 years of age (irrespective of weight) and above at the signing of informed 
consent or adolescent subjects ≥12 to <18 years of age, or pediatric subjects <12 years of 
age at the signing of the assent (parent/guardian sign the informed consent) (see 
Section 13.2)  
2. Asymptomatic household contact with exposure to an individual with a diagnosis of 
SARS-CoV-2 infection (index case).  To be included in the study, subjects must be 
randomized within 96 hours of collection of the index cases’ positive SARS-COV-2 
diagnostic test sample 
3. Subject anticipates living in the same household with the index case until study day 29 
4. Is judged by the investigator to be in good health based on medical history and physical 
examination at screening/baseline, including subjects who are healthy or have a chronic, 
stable medical condition 
5. Willing and able to comply with study visits and study-related procedures/assessments. 
6. Provide informed consent signed by study subject or legally acceptable representative. 
7.2.2. 
Exclusion Criteria 
A subject who meets any of the following criteria will be excluded from the study: 
1. Subject-reported history of prior positive SARS-CoV-2 RT-PCR test or positive 
SARS-CoV-2 serology test at any time before the screening 
2. Subject has lived with individuals who have had previous SARS-CoV-2 infection or 
currently lives with individuals who have SARS-CoV-2 infection, with the exception of 
the index case(s), the first individual(s) known to be infected in the household 
3. Active respiratory or non-respiratory symptoms consistent with COVID-19  
4. History of respiratory illness with sign/symptoms of SARS-CoV-2 infection, in the opinion 
of the investigator, within the prior 6 months to screening 
5. Nursing home resident 
6. Any physical examination findings, and/or history of any illness, concomitant medications 
or recent live vaccines that, in the opinion of the study investigator, might confound the 
results of the study or pose an additional risk to the subject by their participation in the 
study 
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7. Current hospitalization or was hospitalized (ie, >24 hours) for any reason within 30 days 
of the screening visit 
8. Has a history of significant multiple and/or severe allergies (eg, latex gloves), or has had 
an anaphylactic reaction to prescription or non-prescription drugs or food.  This is to avoid 
possible confounding of the safety analysis and not due to any presumed increased risk of 
these individuals to a reaction to the investigational product 
9. Treatment with another investigational agent in the last 30 days or within 5 half-lives of 
the investigational drug, whichever is longer, prior to the screening visit 
10. Received an investigational or approved SARS-CoV-2 vaccine 
11. Received investigational or approved passive antibodies for SARS-CoV-2 infection 
prophylaxis (eg, convalescent plasma or sera, monoclonal antibodies, hyperimmune 
globulin) 
12. Use of hydroxychloroquine/chloroquine for prophylaxis/treatment of SARS-CoV-2 or 
anti-SARS-viral agents, eg, remdesivir, within 60 days of screening  
NOTE: hydroxychloroquine/chloroquine for other uses, eg, for use in autoimmune diseases 
is allowed 
13. Member of the clinical site study team and/or immediate family  
14. Exclusion criterion #14 excluding sexually active men who are unwilling to use the 
following forms of medically acceptable birth control during the study drug follow-up 
period and for 8 months after single dose of study drug was removed since enrollment was 
expanded to include all women in protocol amendment 4.  
15. Exclusion criterion #15 excluding pregnant or breastfeeding women was removed since 
enrollment was expanded to all women in protocol amendment 4.   
16. Exclusion criterion #16 excluding women of childbearing potential (WOCBP)* and girls 
at or beyond menarche (≥12 to <18 years of age) who were unwilling to practice highly 
effective contraception prior to the initial dose/start of the first treatment, during the study, 
and for at least 8 months after the last dose was removed since enrollment was expanded 
to all women in protocol amendment 4.  
  *WOCBP are defined as women who are fertile following menarche until becoming 
postmenopausal, unless permanently sterile. Permanent sterilization methods include 
hysterectomy, bilateral salpingectomy, and bilateral oophorectomy.  
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7.3. 
Premature Withdrawal from the Study 
A subject or pediatric subject’s parent/guardian has the right to withdraw from the study at any 
time, for any reason, and without repercussion. 
The investigator and/or Sponsor have the right to withdraw a subject from the study if it is no 
longer in the interest of the subject to continue in the study, or if the subject’s continuation in the 
study places the scientific outcome of the study at risk (eg, if a subject does not or cannot follow 
study procedures).  An excessive rate of withdrawals would render the study uninterpretable; 
therefore, unnecessary withdrawal of subjects should be avoided. 
Subjects who are withdrawn prematurely from the study will be asked to complete the ET visit, as 
described in Section 9.1.5. 
7.4. 
Replacement of Subjects 
Subjects prematurely discontinued from study will not be replaced. 
8. 
STUDY TREATMENTS 
8.1. 
Investigational and Reference Treatments 
The following drug product will be provided. Instructions on dose preparation are provided in the 
pharmacy manual. 
REGN10933 and REGN10987, to be co-administered: 
• REGN10933:  Supplied as a 120 mg/mL solution for SC or IM injection 
• REGN10987:  Supplied as a 120 mg/mL solution for SC or IM injection 
Matching placebo:   
• Supplied as matching solution for SC or IM injection.  
All adult or adolescent subjects will receive 4 SC injections of study drug on day 1, each injection 
containing 2.5 mL of active study drug or placebo.  The REGN10987 and REGN10933 dose is 
1200 mg (600 mg of each mAb) SC single dose on day 1. 
Pediatric subjects (<12 years of age) will receive between 1 to 4 SC or IM injections of study drug, 
active or placebo, depending on the weight-tiered dose group on day 1 (Table 2). Subjects <5 kg 
should not receive an injection with more than 1 mL, subjects between 5 and 10 kg should not 
receive an injection with more than 1.25 mL.  Subjects <10 kg may receive IM injection(s)at the 
discretion of the investigator, as children less than 10 kg have smaller amounts of subcutaneous 
tissue and IM injection may be better tolerated than SC.  In addition, in children <10 kg, the 
combined volume containing both mAbs may be administered in a single syringe.  The total 
volume of study drug per syringe and the number of injections will be recorded in the CRF. For 
subjects who weigh ≥10 kg, study drug may be administered SC using an infusion pump, 
containing the combined volume containing both mAbs, which may improve tolerability of 
administration as only 1 injection may be required. 
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Table 2: 
Weight-Tiered Dose Groups for Pediatric Subjects <12 Years of Age 
Weight-Tiered 
Dose Group 
Total Dose (mg) 
Route of 
Administration 
Total Number 
of Injections 
Total Volume (mL) of 
Injection 
≥40 kg 
1200 (600 per mAb) 
SC1 
4 
10 (5 per mAb) 
≥20 to <40 kg 
792 (396 per mAb) 
SC1 
4 
6.6 (3.3 per mAb) 
≥10 to <20 kg 
408 (204 per mAb) 
SC1 
2 or 4 
3.42 (1.7 per mAb) 
≥5 to <10 kg3 
144 (72 per mAb) 
IM 
1 or 2 
1.24 (0.6 per mAb) 
≥2.5 to <5 kg3 
96 (48 per mAb) 
IM 
1 
0.8 (0.4 per mAb) 
<2.5 kg3 
48 (24 per mAb) 
IM 
1 
0.4 (0.2 per mAb) 
1.  Investigators have the option to use an infusion pump for SC administration of study drug containing the 
combined volume with both mAbs. 
2.  If the Investigators prefers not to exceed 1 mL per syringe, then study drug may be administered using 2 syringes 
for each mAb (ie, 4 injections), one with 0.8 mL and another with 0.9 mL for each mAb. If the Investigator prefers 
to use only 2 syringes (ie, 2 injections), the 1.7 mL administered in each syringe will contain a different mAb.   
3.  Investigators have the option to administer the dose in a single syringe containing the combined volume with 
both mAbs. 
4.  If the Investigator prefers not to exceed 1 mL per syringe, then study drug may be administered using 1 syringe 
for each mAb.  If the Investigator prefers to use 1 syringe, the1.2 mL administered in 1 syringe should be 
combined volume of 0.6 mL of each mAb. 
For study drug administration which requires multiple SC injections, it is recommended to use 
different quadrants of the abdomen (avoiding navel and waist areas) and upper thighs.  During the 
dose administration, each injection must be given in a different anatomical location (eg, 1 injection 
administered in the right lower quadrant of the abdomen, another in the left lower quadrant of the 
abdomen, etc).  For pediatric subjects (<12 years) only, a numbing cream may be used at the 
planned site(s) of injection.  Adolescent (≥12 years) and adult subjects should not use numbing 
cream at the sites of injection as this will interfere with the safety assessment, ie, evaluation of 
injection site reactions.   
A pharmacist or qualified personnel at the site, not otherwise associated with the conduct of the 
study, will prepare the drug for SC administration or IM administration. The prepared syringe must 
be provided in identical form for active and placebo treatments, so that they remain 
indistinguishable to both study personnel and subject. Details for study drug administration are 
provided in the pharmacy manual. 
8.2. 
Dose Modification and Study Treatment Discontinuation Rules 
8.2.1. 
Dose Modification 
This is a single dose study; dose modification is not allowed. 
8.2.2. 
Study Drug Discontinuation 
This is a single dose study; study drug discontinuation is not applicable.  
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8.3. 
Management of Acute Reactions  
8.3.1. 
Acute Injection Reactions 
8.3.1.1. 
Systemic Injection Reactions 
Emergency equipment and medication for the treatment of systemic reactions must be available 
for immediate use.  All injection reactions must be reported as AEs (as defined in Section 10.2.1) 
and graded using the grading scales as instructed in Section 10.2.4. 
Acute systemic reactions following injection of study drug (subcutaneous [SC]) should be treated 
using clinical judgment to determine the appropriate response according to typical clinical practice.  
8.3.1.2. 
Local Injection Site Reactions 
Local injection site reactions must be reported as AEs and graded according to Section 10.2.4. 
8.4. 
Method of Treatment Assignment 
Subjects will be randomized in a 1:1 ratio to receive REGN10987+REGN10933 or placebo 
according to a central randomization scheme provided by an interactive web response system 
(IWRS) to the designated study pharmacist (or qualified designee).  Randomization will be 
performed by individual study subjects, not by households.  In addition to a randomization number, 
all subjects randomized will be given a household identification number in the case that multiple 
members of the same household are enrolled and receive study drug.  This ensures that any 
correlation among subjects within the same household may be considered in the statistical analysis.  
The REGN10987 and REGN10933 dose for adult, adolescent, and pediatric subjects is described 
in Section 8.1. 
Randomization will be performed by site and stratified as follows: 
• Local diagnostic assay for SARS-CoV-2 from appropriate samples (positive, negative, 
or undetermined) 
• Age and/or weight: 
− <12 years and <10 kg,  
− <12 years and ≥10 kg to <20 kg, 
− <12 years and ≥20 kg  
− ≥12 years and <18 years 
− ≥18 years and <50 years 
− ≥50 years 
Note that the cohorts used in the analysis are defined by the baseline central lab SARS-CoV-2 
RT-qPCR results, not by the local diagnostic assay.  
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8.5. 
Blinding 
Study subjects, the principal investigators, and study site personnel will remain blinded to all 
randomization assignments throughout the study.  The Regeneron Medical/Study Director, Study 
Monitor, and any other Regeneron and contract research organization (CRO) personnel who are 
in regular contact with the study sites will remain blinded to all subject randomization assignments. 
No interim analyses were conducted (Section 11.5) and an unblinded administrative assessment of 
study assumptions (Section 11.2) was conducted. No study personnel involved in the day-to-day 
conduct of the study will have access to any subject-level unblinded data before the final database 
is locked for this study.  
Anti-drug antibody, drug concentration results, and central lab serology results will not be 
communicated to the sites. The Sponsor’s blinded study team will not have access to post-baseline 
results associated with subject identification until after the database is locked for the respective 
study part. 
8.6. 
Emergency Unblinding  
Unblinding of treatment assignment for a subject may be necessary due to a medical emergency 
or any other significant medical event and when a treatment decision is contingent on knowing the 
subject’s treatment assignment. 
• If unblinding is required: 
− Only the investigator will make the decision to unblind the treatment assignment. 
− Only the affected subjects will be unblinded. 
− The designated study pharmacist(s)/designee at the study site will provide the 
treatment assignment to the investigator.  If there is no study pharmacist, the 
investigator for the site will unblind the subject. Unblinding is performed using the 
IVRS/IWRS which will notify Regeneron. 
• The investigator will notify Regeneron and/or designee as soon as possible after 
unblinding the subject for safety or other important medical decisions, however, 
unblinding performed for the purpose of COVID-19 vaccine decision making does 
not need to be discussed with the medical director. 
Treatment assignment is not to be provided to site personnel, other than the unblinded study 
pharmacist (when applicable), at any time during the conduct of the study, except in the case of a 
true emergency and when a treatment decision is contingent on knowing the subject's treatment 
assignment.  In the event that there is no study pharmacist, the individual at the site fulfilling that 
role will be the only unblinded member of the site personnel. 
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8.7. 
Treatment Logistics and Accountability 
8.7.1. 
Packaging, Labeling, and Storage 
A medication numbering system will be used to label blinded investigational study drug.  Lists 
linking medication numbers with product lot numbers will be maintained by the groups (or 
companies) responsible for study drug packaging.  In order to maintain the blind, these lists will 
not be accessible to individuals involved in study conduct. 
Study drug will be stored at the site at a temperature of 2ºC to 8ºC; storage instructions will be 
provided in the pharmacy manual.  
8.7.2. 
Supply and Disposition of Treatments 
Study drug will be shipped at a temperature of 2ºC to 8ºC to the investigator or designee at regular 
intervals or as needed during the study.  At specified time points during the study (eg, interim site 
monitoring visits), at the site close-out visit, and following drug reconciliation and documentation 
by the site monitor, all opened and unopened study drug will be destroyed at the site with approval 
by the Sponsor or returned to the Sponsor or designee. 
8.7.3. 
Treatment Accountability 
All drug accountability records must be kept current. 
The investigator must be able to account for all opened and unopened study drug.  These records 
should contain the dates, quantity, and study medication 
• dispensed to each subject 
• disposed of at the site or returned to the sponsor or designee. 
All accountability records must be made available for inspection by the sponsor and regulatory 
agency inspectors; photocopies must be provided to the sponsor at the conclusion of the study. 
8.7.4. 
Treatment Compliance 
All drug compliance records must be kept current and made available for inspection by the Sponsor 
and regulatory agency inspectors. 
8.8. 
Concomitant Medications and Procedures 
Any treatment administered from the single dose of study drug to final study visit will be 
considered concomitant medication.  This includes medications that were started before the study 
and are ongoing during the study. 
As per Section 6.1.4 and Section 6.1.5, a positive SARS-CoV-2 test which is associated with a 
symptomatic SARS-CoV-2 infection and is conducted in a local laboratory associated with a 
medical facility, should be recorded as a concomitant procedure and associated with the 
COVID-19 AE.  
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8.9. 
Prohibited Medications  
Treatment with the following concomitant medications as prophylaxis is prohibited in uninfected 
subjects or for treatment of asymptomatic infection during the EAP and Follow-Up Period and 
may result in permanent discontinuation from the study. 
1. Other investigational drugs  
2. Investigational SARS-CoV-2 vaccine  
3. Approved or EUA approved SARS-CoV-2 vaccine (prohibited only during the EAP) 
4. Investigational or approved passive antibodies for SARS-CoV-2 infection prophylaxis 
(eg, convalescent plasma or sera, monoclonal antibodies, hyperimmune globulin) 
5. Hydroxychloroquine/chloroquine prescribed for the prophylaxis or treatment of COVID19 
(Note Hydroxychloroquine/chloroquine used for other indications eg, autoimmune 
therapies are permitted.) 
6. Remdesivir or anti-SARS-viral agents  
8.10. 
Permitted Medications  
Other than the prohibited medications listed in Section 8.9, treatment with concomitant 
medications is permitted during the study. If there is any question regarding whether a concomitant 
medication may be used during the study, the study site should contact the medical monitor.  
Subjects with symptomatic RT-qPCR confirmed SARS-CoV-2 infection during the study will be 
treated according to local standard of care as per the discretion of the investigator or treating 
physician. Any medication used by the study subject should be captured in the concomitant 
medication eCRF. 
Subjects are permitted to receive an approved or EUA approved COVID-19 vaccine after they 
complete the EAP.  
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9. 
STUDY SCHEDULE OF EVENTS AND PROCEDURES 
9.1. 
Schedule of Events 
Study assessments and procedures for adult and adolescent subjects and pediatric subjects 
<12 years old are presented by study period and visit in Table 3 and Table 5 for the period from 
screening/baseline to end of the EAP and the Follow-up Period, and in Table 4 and Table 6 for 
sample collection for assay of drug concentration and ADA, as well as for safety clinical labs 
during the entire study. 
Refer to Section 6.1.4 for conducting study assessments and sample collection when a subject is 
positive for SARS-CoV-2 infection based on rapid RT-PCR or RT-qPCR and when a subject is 
hospitalized. 
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Table 3: 
Schedule of Events Cohorts A and B ([Adult / Adolescent Subjects], RT-qPCR-Negative and Positive) 
Visit 
Screening / 
Baseline1 
Additional Safety 
(Sentinel Only)2 
Efficacy Assessment 
Period (EAP)3 
Follow-up Period 
ET Unsche
dVisit4 
Visit Location Site (S), Phone (P)5 
S 
S 
S 
P 
S 
S 
S 
S 
S 
S 
S 
S 
S 
S 
S 
S 
Visit Number 
1 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 EOS 
 
 
Day 
1 
1 
2 
3 
4 
8 
15 
22 
29 
57 
85 
113 141 169 197 225 
 
 
Week 
0 
0 
0 
0 
0 
1 
2 
3 
4 
8 
12 
16 
20 
24 
28 
32 
 
 
Window (day) 
 
 
 
 
 
±1 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Screening/Baseline: 
Inclusion/exclusion 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Informed consent (adult subject or parent/guardian)/pediatric 
assent (adolescent subject) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Informed consent(adults or parent/guardian)/pediatric assent 
for PGx sub-study(optional)6 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics and risk factors for SARS-CoV-2 infection 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Household assessment 
X16 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
Appropriate sample, diagnostic assay for SARS-CoV-2 (local 
lab)  
X7 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Randomization 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Treatment: 
Study drug administration 
X8 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Efficacy (Virology): 
NP swab, SARS-CoV-2 RT-qPCR (central lab)7,17 
X8 
 
 
 
 
X 
X 
X 
X 
X3,4,9 X3,4,9 X3,4,9 X3,4,9 X3,4,9 X3,4,9 X3,4,9 X 
X 
Efficacy (Subject-Reported) only for RT-qPCR positive subjects: 
Assessment of ED, UCC, hospital visits18 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Absenteeism assessment18 
 
 
 
 
 
X 
X 
X 
X 
 
 
 
 
 
 
X 
 
 
Safety: 
 
 
 
 
Vital signs 
X2,11 
X2 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
 
X 
Targeted PE11 
X 
 
X 
 
X 
 
 
 
X 
 
 
 
 
 
 
X 
 
X 
Adverse events15,19 
X 
X2 X2 X2 X2,10 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Con Meds, Procedures 
X 
X X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urine pregnancy test for WOCBP (dipstick, local lab)12 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
X 
Laboratory Testing13: 
Clinical Laboratory, Hematology, Blood Chemistry, 
Urinalysis  
Refer to Table 4  
Pharmacokinetics and Immunogencity13: 
Drug concentration  
Refer to Table 4 
Anti-drug antibodies (ADA) 
Biomarkers: 
Serum for serology (central lab)14 
X 
 
 
 
 
 
 
 
X 
X 
 
 
 
 
 
X 
 
 
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Research plasma 
X 
 
 
 
 
 
 
 
X20 
X20 
 
 
 
 
 
X20 
 
 
Research serum 
X 
 
 
 
 
 
 
 
X20 
X20 
 
 
 
 
 
X20 
 
 
Pharmacogenomics Sub-Study: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Whole Blood for RNA (Optional)6 
X 
 
 
 
 
 
 
 
X20 
X20 
 
 
 
 
 
X20 
 
 
Whole Blood for DNA (Optional)6  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
EAP, Efficacy assessment period; EOS, end of study; ED, emergency departments; ET, Early termination; UCC, urgent care centers; PE, physical exam; PGx, pharmacogenomics; 
RT-PCR, reverse transcription polymerase chain reaction; RT-qPCR, quantitative reverse transcription polymerase chain reaction; SARS-CoV-2, severe acute respiratory 
syndrome coronavirus 2; WOCBP, women of childbearing potential. 
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9.1.1. 
Schedule of Events Table 3 (Cohorts A and B [Adult / Adolescent Subjects], 
RT-qPCR-Negative and Positive) Footnotes  
1. The screening visit and baseline visit should both occur on the same day. If needed, a 
remote visit may occur to sign the ICF and collect medical history and concomitant 
medication use, on the day prior to, but within 24 hours of study drug administration, so 
that the in-person screening and randomization visit may be abbreviated, due to COVID-19 
considerations. Study drug administration must occur within 96 hours of collection of the 
index cases’ positive SARS-CoV-2 diagnostic test sample. 
2. The sentinel group (see Section 6.1.1) had additional safety monitoring on day 1 and 
through day 4. 
Vital signs: On day 1, vital signs (blood pressure, pulse rate, body temperature, and 
respiratory rate) will be measured at predose, approximately every 30 minutes during the 
first 2 hours after dose, at hour 3, and at hour 4 before dismissal. 
Adverse Events (injection site reactions and hypersensitivity): after the administration 
of the first dose of study drug, subjects will be monitored on site for a minimum of 4 hours 
and then by daily visits to the study site or phone calls for the first 4 days (96 hours), 
particularly focusing on the assessment of injection site reactions and hypersensitivity after 
study drug administration. 
3. Subjects who have a positive RT-PCR result during screening, or who have a positive 
RT-qPCR result any time after screening, will have the additional assessments done as 
indicated (RT-qPCR positive subjects only). A PK sample and an ADA sample will be 
collected (1) as soon as possible or within 7 days of receiving first positive SARS-CoV-2 
RT-qPCR result for cohort A subjects and (2) as soon as possible or within 7 days of first 
new positive SARS-CoV-2 RT-qPCR result after achieving 2 consecutive negative results 
for all subjects. 
For subjects who become RT-qPCR positive after screening, the visit schedule will proceed 
as follows: (a) If the positive RT-qPCR result is from a scheduled visit for sample 
collection, the next weekly visit will occur as planned.  (b) If the positive RT-qPCR result 
is from an unscheduled sample collection (eg, between scheduled visits) but within the 
window (±3 days) of the next weekly visit, this visit will be recorded as the scheduled next 
weekly visit.  (c) If the positive RT-qPCR result is from an unscheduled sample collection 
(eg, between scheduled visits) and not within the window (±3 days) of the next weekly 
visit, this visit will be recorded as an unscheduled visit, and the next weekly visit will occur 
as planned. 
4. Unscheduled visits: If, at any time after randomization until end of study, a subject 
develops fever, an acute respiratory illness or other symptoms they may feel could be 
related to COVID-19 or is hospitalized for suspected COVID-19, the subject or 
parent/guardian (adolescent pediatric subject) should alert the investigator or designee 
immediately who will assess the subject’s symptoms and condition (can be performed by 
phone contact, telemedicine, online meeting, home health care, etc) to decide if the subject 
should have an unscheduled visit for collection of NP swab sample for RT-qPCR testing.  
The subject or parent/guardian (adolescent pediatric subject) may also be asked to provide 
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blood samples if it corresponds to a scheduled visit, according to the Schedule of Events 
(specified in Section 9.1).  The investigator or designee should query the subject about AEs 
in general and AEs consistent of COVID-19 and record the information on CRF (see 
detailed description of the procedure in Section 9.2.2.2). 
(a) If the positive RT-qPCR result is from a scheduled visit for sample collection, the next 
weekly visit will occur as planned.  (b) If the positive RT-qPCR result is from an 
unscheduled sample collection (eg, between scheduled visits) but within the window 
(±3 days) of the next weekly visit, this visit will be recorded as the scheduled next weekly 
visit.  (c) If the positive RT-qPCR result is from an unscheduled sample collection 
(eg, between scheduled visits) and not within the window (±3 days) of the next weekly 
visit, this visit will be recorded as an unscheduled visit, and the next weekly visit will occur 
as planned. 
5. Visit may occur by phone or electronic means 
6. Separate consent (adult subject or parent/guardian of adolescent pediatric subject)/pediatric 
assent is required for participation in the optional genomic sub-study and collection of 
blood samples for DNA and RNA. The sample for RNA, should be collected on day 
1/baseline (pre-dose). Genomic DNA should be collected on day 1/baseline. If not 
collected at baseline, the sample for genomic DNA may be collected at any visit. 
7. Sample for diagnostic assay for SARS-CoV-2 (local lab) (see Section 9.2.1.2) and 
RT-qPCR (NP swab; central lab) should be collected before administration of study drug. 
Samples for RT-qPCR (NP swab) will be collected by swabbing through both nostrils 
(see Section 9.2.2.1). The remnant samples may additionally be used for exploratory viral 
RNA sequencing and viral infectivity analyses.  The requirement for a local diagnostic 
assay for SARS-CoV-2 may be waived if the results are not expected to be available in a 
timely manner for randomization. 
8. Study drug should be administered after all biological samples at screening/baseline have 
been collected. 
9. Subjects who are RT-qPCR positive at the end of the EAP will continue to have samples 
collected weekly (NP swab; central lab) for RT-qPCR.  Subjects will continue 
assessments/sample collections until 2 negative RT-qPCR test results have been obtained 
≥24 hours apart (all samples must be negative).  Subjects who are RT-qPCR negative at 
the end of the EAP will have samples collected only if they become symptomatic with 
COVID-19 in the follow-up period. If a subject is hospitalized for suspected COVID-19, 
every effort should be made by the site personnel to collect, as soon as possible, a NP swab 
sample for central lab SARS-CoV-2 RT-qPCR testing. In subjects where it is not possible 
to have samples collected for assessment in the central laboratory, study site personnel will 
attempt to obtain and record information about all SARS-CoV-2 tests conducted in local 
laboratories associated with other medical facilities, including result(s), name of the 
assay(s)  and whether the laboratory(ies) conducting the assays is a CLIA certified (or 
equivalent) laboratory. The positive test result should be recorded as concomitant 
procedures. 
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10. For subjects who are not in the sentinel group (subset 1; completed), vital signs will be 
monitored on site as follows: Safety group (subset 2; completed): at baseline predose and 
then every hour for 2 hours after study drug administration and a phone call on day 4 to 
assess AEs, specifically injection site reactions and hypersensitivity; all other subjects 
(subset 3): at baseline and 1 hour after study drug administration.  All subjects will be 
advised to call the site if signs/symptoms of injection site or hypersensitivity reactions 
occur.  If the subject experiences a true medical emergency, they should visit their local 
hospital ED and contact the site personnel later. 
11. The investigator may perform a targeted physical exam, request an exam and/or vital signs 
at any time.  These assessments can be performed using a clinic visit or a remote visit with 
the investigator or sub-investigator, or designee (ie, nurse practitioner in countries where 
allowed by local law). 
12. For all women of childbearing potential (WOCBP) and girls at or beyond menarche, except 
subjects with a confirmed pregnancy.  If the local urine pregnancy test is positive, the site 
must perform a serum pregnancy test for confirmation.  
13. Samples for drug concentration and, immunogenicity, and laboratory testing will be 
collected based on the subject subset designation as indicated in Table 4 
14. The serology test results will not be communicated to the sites. The sponsor’s blinded study 
team will not have access to post-baseline results associated with subject identification 
until after the database is locked. 
15. During each scheduled or unscheduled visit/contact, the investigator or designee will query 
subject about AEs in general (see Section 10.1.1) and evaluate if the AEs are associated 
with SARS-CoV-2 infection, including fever (see Section 9.2.2.2).  The investigator should 
recommend that subjects (themselves or by their parent/guardian) measure their 
temperature daily during EAP, approximately at the same time, and also every time when 
the subject feels feverish, chills, or sick.  Subjects with symptomatic SARS-CoV-2 
infection should be queried on their symptoms weekly until symptoms resolve, even during 
follow-up period, then follow the regular schedule.  
16. The information for the household assessment, including household members who receive 
an EUA approved monoclonal antibody treatment for COVID-19 or household members 
participating in the R10933-10987-COV-2067 study, should preferably be collected at the 
baseline visit. There will be a follow-up assessment at day 29.  
17. All subjects will have a weekly NP swab sample collected during the EAP.  Only subjects 
who are RT-qPCR positive will continue to have weekly NP swab samples collected during 
the follow-up period until 2 consecutive negative (≥24 hr) RT-qPCR results or the end of 
study visit.  
18. Only for RT-qPCR positive subjects (cohort A and cohort B): Complete assessments from 
the time the subject first becomes RT-qPCR positive or from the time they develop 
symptoms suspected to be COVID-19 (later confirmed by RT-qPCR positive results) until 
the subject has had 2 negative tests or COVID-19 related symptoms have resolved 
(whichever lasts longer), or until the end of study visit.  
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19. All subjects or parent/guardians of adolescent pediatric subjects will complete the TEAE 
assessment weekly during the EAP.  Subjects who are RT-qPCR negative will complete 
the TEAE assessment monthly during the follow-up period.  Subjects who have 
symptomatic SARS-CoV-2 infection will complete the TEAE assessment weekly during 
the follow-up period until the COVID-19 related symptoms resolve after which the subject 
will complete the TEAE assessment monthly until the end of study visit. 
20. Samples will be collected only from RT-qPCR positive subjects (cohort A and cohort B) 
from the time the subject first becomes RT-qPCR positive until the end of study. Note: this 
includes subjects who have returned to RT-qPCR negative by this visit.   
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Table 4: 
Schedule of Events: Cohorts A and B (Adult / Adolescent Subjects) for Drug Concentration, Immunogenicity, 
and Laboratory Testing  
Samples for drug concentration (dense PK, sparse PK), immunogenicity assessment (ADA), and clinical laboratory testing (hematology, blood 
chemistry, and urinalysis) will be collected based on subset designation using subject number (assigned by IWRS): 
• 
Sentinel group (Subset 1; completed): First 30 subjects 
• 
Safety group (Subset 2; completed): 31st to 400th subject 
• 
All other subjects (Subset 3): 401st to last subject 
 
Visit 
Screening / 
Baseline1 
Sentinel 
Group Only  
Efficacy Assessment 
Period (EAP) 
Follow-up Period 
ET 
Visit5 
Unscheduled 
Visit 
Site (S) 
S 
S 
S 
S 
S 
S 
S 
S 
S 
S 
S 
S 
S 
 
Visit Number 
1 
2 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
EOS 15 
 
 
Day 
1 
2 
4 
8 
15 
22 
29 
57 
85 
113 
141 
169 
197 
225 
 
 
Week 
0 
0 
0 
1 
2 
3 
4 
8 
12 
16 
20 
24 
28 
32 
 
 
Window (day) 
 
 
±1 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
 
 
 
Sentinel Group (Subset 1) 
Dense PK2 
X1 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X6,7 
ADA2,3 
X1 
 
 
 
 
 
X 
 
 
X 
 
 
 
X 
X 
X6,7 
Hematology4 
X1 
X 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Blood chemistry4 
X1 
X 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Urinalysis4 
X1 
X 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Safety group (Subset 2) 
Sparse PK2 
X1 
 
 
 
 
 
X 
X 
 
X 
 
X 
 
X 
X 
X6,7 
ADA2,3 
X1 
 
 
 
 
 
X 
 
 
X 
 
 
 
X 
X 
X6,7 
Hematology4 
X1 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Blood chemistry4 
X1 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Urinalysis4 
X1 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
All other subjects (Subset 3) 
PK2 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X6,7 
ADA2,3 
X1 
 
 
 
 
 
X 
 
 
X 
 
 
 
X 
X 
X6,7 
Hematology4 
X1 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
Blood chemistry4 
X1 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
Urinalysis4 
X1 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
ADA, anti-drug antibodies; EAP, Efficacy assessment period; EOS, end of study; ET, Early termination; PK, Pharmacokinetics 
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9.1.2. 
Schedule of Events Table 4: All Cohorts A and B (Adult / Adolescent Subjects) 
for Drug Concentrations, Immunogenicity, and Laboratory Testing  
1. Samples should be collected before the administration of study drug. Administration of 
study drug must be performed on the on same day as sample collection.  
2. Actual dosing time and dense PK, sparse PK, and ADA sample collection times will be 
recorded.  
3. At the screening/baseline visit, the window for baseline pre-dose ADA sample collection 
is as close to administration of study drug as is reasonable. Actual dosing times and ADA 
sample collection times will be recorded. 
4. Whole blood samples for hematology and blood chemistry and urine samples for urinalysis 
will be analyzed at central lab. 
5. Subjects who prematurely discontinue the study should have sample collection listed in the 
ET visit before exiting the study. 
6. A PK serum sample and an ADA serum sample will be collected as soon as possible or 
within 7 days of receiving the first positive SARS-CoV-2 RT-qPCR result for cohort A 
subjects.  The ADA serum samples may be analyzed for ADA and NAb, if feasible. 
7. A PK serum sample and an ADA serum sample will be collected as soon as possible or 
within 7 days of first new positive SARS-CoV-2 RT-qPCR result after achieving 
2 consecutive negative results for all subjects. 
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Table 5: 
Schedule of Events: Cohorts A1 and B1 (Pediatric Subjects [<12 years], RT-qPCR-Negative and Positive) 
Visit 
Screening / 
Baseline1 
Additional Safety 
(Sentinel Only)2 
Efficacy Assessment 
Period (EAP)3 
Follow-up Period 
ET Unsche
dVisit4 
Visit Location Site (S), Phone (P)5 
S 
S 
S 
P5 
S 
S 
S 
S 
S 
S 
S 
S 
S 
S 
S 
S 
Visit Number 
1 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
EOS 
 
 
Day 
1 
1 
2 
3 
4 
8 
15 22 29 
57 
85 
113 141 169 197 
225 
 
 
Week 
0 
0 
0 
0 
0 
1 
2 
3 
4 
8 
12 
16 
20 
24 
28 
32 
 
 
Window (day) 
 
 
 
 
 
±1 
±3 ±3 ±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Screening/Baseline: 
Inclusion/exclusion 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Informed consent (parent/guardian)/pediatric assent (subject) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Informed consent(adults or parent/guardian)/pediatric assent for 
PGx sub-study(optional)19 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics and risk factors for SARS-CoV-2 infection 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Household assessment 
X15 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
Appropriate sample, diagnostic assay for SARS-CoV-2 (local lab)  
X6 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Randomization 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Treatment: 
Study drug administration 
X7 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Efficacy (Virology): 
NP swab, SARS-CoV-2 RT-qPCR (central lab)6,16 
X7 
 
 
 
 
X 
X 
X 
X X3,4,8 X3,4,8 X3,4,8 X3,4,8 X3,4,8 X3,4,8 X3,4,8 X 
X 
Efficacy (Subject-Reported) only for RT-qPCR positive subjects: 
Assessment of ED, UCC, hospital visits17 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Absenteeism assessment17 
 
 
 
 
 
X 
X 
X 
X 
 
 
 
 
 
 
X 
 
 
Safety: 
 
 
 
 
Vital signs 
X2,10 
X2 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
 
X 
Targeted PE10 
X 
 
X 
 
X 
 
 
 
X 
 
 
 
 
 
 
X 
 
X 
Adverse events14,18 
X9 
X2 X2 X2 X2 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Con Meds, Procedures 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urine pregnancy test for WOCBP (dipstick, local lab)11 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
 
Laboratory Testing12: 
Clinical Laboratory, Hematology, Blood Chemistry 
Refer to Table 6 
Pharmacokinetics and Immunogencity12: 
Drug concentration / Anti-drug antibodies (ADA) 
Refer to Table 6 
Biomarkers: 
Serum for serology (central lab)12,13 
Refer to Table 6 
Pharmacogenomics Sub-Study: 
 
Whole Blood for RNA (Optional)12,19 
Refer to Table 6 
Whole Blood for DNA (Optional)12,19  
Refer to Table 6 
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EAP, Efficacy assessment period; EOS, end of study; ED, emergency departments; ET, Early termination; UCC, urgent care centers; PE, physical exam; RT-PCR, reverse 
transcription polymerase chain reaction; RT-qPCR, quantitative reverse transcription polymerase chain reaction; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2;  
WOCBP, women of childbearing potential.  
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9.1.3. 
Schedule of Events Table 5 Cohorts A1 and B1 (Pediatric Subjects [ <12 years], 
RT-qPCR-Negative and Positive) Footnotes  
1. The screening visit and baseline visit should both occur on the same day. If needed, a 
remote visit may occur to sign the ICF and collect medical history and concomitant 
medication use, on the day prior to, but within 24 hours of study drug administration, so 
that the in-person screening and randomization visit may be abbreviated, due to COVID-19 
considerations. Study drug administration must occur within 96 hours of collection of the 
index cases’ positive SARS-CoV-2 diagnostic test sample. 
2. The pediatric sentinel group (subset 4) (see Section 6.1.2) will have additional safety 
monitoring on day 1 and through day 4. 
Vital signs: On day 1, vital signs (pulse rate, respiratory rate, body temperature and blood 
pressure [if feasible, according to the child’s age]) will be measured at predose, 
approximately every 30 minutes during the first 2 hours after dose before dismissal. 
Adverse Events (injection site reactions and hypersensitivity): after the administration 
of the first dose of study drug, subjects will be monitored on site for a minimum of 2 hours 
and then by daily visits to the study site or phone calls for the first 4 days (96 hours), 
particularly focusing on the assessment of injection site reactions and hypersensitivity after 
study drug administration. 
3. Pediatric subjects who have a positive RT-PCR result during screening, or who have a 
positive RT-qPCR result any time after screening, will have the additional assessments 
done as indicated (RT-qPCR positive pediatric subjects only).  A PK sample and an 
ADA sample will be collected (1) as soon as possible or within 7 days of receiving first 
positive SARS-CoV-2 RT-qPCR result for cohort A1 pediatric subjects and (2) as soon as 
possible or within 7 days of first new positive SARS-CoV-2 RT-qPCR result after 
achieving 2 consecutive negative results for all pediatric subjects. 
For pediatric subjects who become RT-qPCR positive after screening, the visit schedule 
will proceed as follows: (a) If the positive RT-qPCR result is from a scheduled visit for 
sample collection, the next weekly visit will occur as planned.  (b) If the positive RT-qPCR 
result is from an unscheduled sample collection (eg, between scheduled visits) but within 
the window (±3 days) of the next weekly visit, this visit will be recorded as the scheduled 
next weekly visit.  (c) If the positive RT-qPCR result is from an unscheduled sample 
collection (eg, between scheduled visits) and not within the window (±3 days) of the next 
weekly visit, this visit will be recorded as an unscheduled visit, and the next weekly visit 
will occur as planned. 
4. Unscheduled visits: If, at any time after randomization until end of study, a pediatric 
subject develops fever, an acute respiratory illness or other symptoms they may feel could 
be related to COVID-19 or is hospitalized for suspected COVID-19, the pediatric subject 
and/or parent/guardian should alert the investigator or designee immediately who will 
assess the subject’s symptoms and condition (can be performed by phone contact, 
telemedicine, online meeting, home health care, etc) to decide if the pediatric subject 
should have an unscheduled visit for collection of NP swab sample for RT-qPCR testing. 
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The pediatric subject and/or parent/guardian may also be asked to provide blood samples 
if it corresponds to a scheduled visit, according to the Schedule of Events (specified in 
Section 9.1).  The investigator or designee should query the subject and/or 
parents/guardians about AEs in general and AEs consistent of COVID-19 and record the 
information on CRF (see detailed description of the procedure in Section 9.2.2.2). 
(a) If the positive RT-qPCR result is from a scheduled visit for sample collection, the next 
weekly visit will occur as planned.  (b) If the positive RT-qPCR result is from an 
unscheduled sample collection (eg, between scheduled visits) but within the window 
(±3 days) of the next weekly visit, this visit will be recorded as the scheduled next weekly 
visit.  (c) If the positive RT-qPCR result is from an unscheduled sample collection 
(eg, between scheduled visits) and not within the window (±3 days) of the next weekly 
visit, this visit will be recorded as an unscheduled visit, and the next weekly visit will occur 
as planned. 
5. Visit may occur by phone or electronic means 
6. Sample for diagnostic assay for SARS-CoV-2 (local lab) (see Section 9.2.1.2) and 
RT-qPCR (NP swab; central lab) should be collected before administration of study drug. 
Samples for RT-qPCR (NP swab) will be collected by swabbing a single nostril 
(see Section 9.2.2.1). The remnant samples may additionally be used for exploratory viral 
RNA sequencing and viral infectivity analyses.  The requirement for a local diagnostic 
assay for SARS-CoV-2 may be waived if the results are not expected to be available in a 
timely manner for randomization. 
7. Study drug should be administered after all biological samples at screening/baseline have 
been collected. 
8. Pediatric subjects who are RT-qPCR positive at the end of the EAP will continue to have 
samples collected weekly (NP swab; central lab) for RT-qPCR.  Pediatric subjects will 
continue assessments/sample collections until 2 negative RT-qPCR test results have been 
obtained ≥24 hours apart (all samples must be negative).  Subjects who are RT-qPCR 
negative at the end of the EAP will have samples collected only if they become 
symptomatic with COVID-19 in the follow-up period. 
9. All other pediatric subjects (subset 5) will have additional safety monitoring on day 1 at 
baseline and 1 hour after study drug administration.  All pediatric subjects or their 
parent/guardian will be advised to call the site if signs/symptoms of injection site or 
hypersensitivity reactions occur.  If the pediatric subject experiences a true medical 
emergency, they and their parent/guardian should visit their local hospital ED and contact 
the site personnel later. 
10. The investigator may perform a targeted physical exam, request an exam and/or vital signs 
at any time.  These assessments can be performed using a clinic visit or a remote visit with 
the investigator or sub-investigator, or designee (ie, nurse practitioner in countries where 
allowed by local law). 
11.  For all girls at or beyond menarche.  If the local urine pregnancy test is positive, the site 
must perform a serum pregnancy test for confirmation. 
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12. Samples for drug concentration, immunogenicity, laboratory testing, serology, and 
pharmacogenomics sub-study will be collected based on the pediatric subject subset 
designation as indicated in Table 6. 
13. The serology test results will not be communicated to the sites. The sponsor’s blinded study 
team will not have access to post-baseline results associated with pediatric subject 
identification until after the database is locked. 
14. During each scheduled or unscheduled visit/contact, the investigator or designee will query 
the pediatric subject and/or parent/guardian about AEs in general (see Section 10) and 
evaluate if the AEs are associated with SARS-CoV-2 infection (see Section 9.2.2.2). 
Pediatric subjects and/or parent/guardian with symptomatic SARS-CoV-2 infection should 
be queried on their symptoms weekly until symptoms resolve, even during follow-up 
period, then follow the regular schedule.  
15. The information for the household assessment, including household members who 
received EUA approved monoclonal antibody treatment for COVID-19 or household 
members participating in the R10933-10987-COV-2067 study should preferably be 
collected at the baseline visit. There will be a follow-up assessment at day 29.  
16. All pediatric subjects will have a weekly NP swab sample collected during the EAP.  Only 
pediatric subjects who are RT-qPCR positive will continue to have weekly NP swab 
samples collected during the follow-up period until 2 consecutive negative (≥24 hr) 
RT-qPCR results or the end of study visit.  
17. Only for RT-qPCR positive subjects (cohort A1 and cohort B1): Complete assessments 
from the time the subject first becomes RT-qPCR positive or from the time they develop 
symptoms suspected to be COVID-19 (later confirmed by RT-qPCR positive results) until 
the subject has had 2 negative tests or COVID-19 related symptoms have resolved 
(whichever lasts longer), or until the end of study visit.  
18. All pediatric subjects and/or parent/guardian will complete the TEAE assessment weekly 
during the EAP.  Subjects who are RT-qPCR negative will complete the TEAE assessment 
monthly during the follow-up period.  Pediatric subjects and/or parent/guardian who have 
symptomatic SARS-CoV-2 infection will complete the TEAE assessment weekly during 
the follow-up period until the COVID-19 related symptoms resolve after which the 
pediatric subject and/or parent/guardian will complete the TEAE assessment monthly until 
the end of study visit. 
19. Separate consent (parent/guardian of pediatric subject)/pediatric assent is required for 
participation of pediatric subjects who weigh ≥10 kg in the optional genomic sub-study 
and collection of blood samples for DNA and RNA.  
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Table 6: 
Schedule of Events: Cohorts A1 and B1 (Pediatric Subjects [<12 years]) for Drug Concentration, 
Immunogenicity, and Laboratory Testing  
Samples for drug concentration (PK), immunogenicity assessment (ADA), and clinical laboratory testing (hematology, blood chemistry, and 
serology) will be collected based on subset designation and sample schedule (A, B, C, D) using subject number (assigned by IWRS): 
• 
Pediatric sentinel group (Subset 4): First 12 pediatric subjects (4 subjects per weight group (≥20 kg; 10 kg to <20 kg; <10 kg)  
• 
All other pediatric subjects (Subset 5): All other pediatric subjects  
Visit 
Screening / 
Baseline1 
Sentinel 
Group Only  
Efficacy Assessment 
Period (EAP) 
Follow-up Period 
ET 
Visit5 
Unscheduled 
Visit 
Site (S) 
S 
S 
S 
S 
S 
S 
S 
S 
S 
S 
S 
 
Visit Number 
1 
2 
5 
6 
8 
9 
10 
11 
12 
13 
14 
EOS 15 
 
 
Day 
1 
2 
8 
15 
29 
57 
85 
113 
141 
169 
197 
225 
 
 
Week 
0 
0 
1 
2 
4 
8 
12 
16 
20 
24 
28 
32 
 
 
Window (day) 
+2 
±1 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
 
 
 
Sentinel Group (Subset 4) 
PK-ADA2,3,9; Hematology4; Blood Chemistry4, Serology4,8 
Schedule A 
X1,8 
X 
 
 
X8 
 
 
 
 
 
 
 
X 
X6,7 
All other subjects (Subset 5) 
PK-ADA2,3,9; Hematology4, Blood Chemistry4, Serology8 
Schedule A 
X1,8 
X 
 
 
X8 
 
 
 
 
 
 
 
X 
X6,7 
Schedule B 
X1,8 
 
X 
 
X8 
 
 
 
 
 
 
 
X 
X6,7 
Schedule C 
X1,8 
 
 
X 
X8 
 
 
 
 
 
 
 
X 
X6,7 
Schedule D 
X1,8 
 
 
 
X8 
 
 
X8 
 
 
 
 
X 
X6,7 
Pharmacogenomics Sub-Study (only subjects ≥10 kg) 
Whole Blood for RNA 
(Optional) 
X10 
 
 
 
 
 
 
 
 
 
 
 
 
 
Whole Blood for DNA 
(Optional)  
X10 
 
 
 
 
 
 
 
 
 
 
 
 
 
ADA, anti-drug antibodies; EAP, Efficacy assessment period; EOS, end of study; ET, Early termination; PK, Pharmacokinetics 
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9.1.4. 
Schedule of Events Table 6: Cohorts A1 and B1 (Pediatric Subjects [<12 years]) 
for Drug Concentration, Immunogenicity, and Laboratory Testing 
1. Samples should be collected before the administration of study drug. Administration of 
study drug must be performed on the on same day as sample collection.  
2. Actual dosing time and sample collection times will be recorded for PK-ADA samples.   
3. At the screening/baseline visit, the window for baseline pre-dose PK-ADA sample 
collection is as close to administration of study drug as is reasonable. 
4. Whole blood samples for hematology and blood chemistry will be analyzed at central lab. 
5. Pediatric subjects who prematurely discontinue the study should have sample collection 
listed in the ET visit before exiting the study. 
6. A PK-ADA serum sample will be collected as soon as possible or within 7 days of 
receiving the first positive SARS-CoV-2 RT-qPCR result for cohort A pediatric subjects. 
7. A PK-ADA serum sample will be collected as soon as possible or within 7 days of first 
new positive SARS-CoV-2 RT-qPCR result after achieving 2 consecutive negative results 
for all pediatric subjects. 
8. Serum samples for serology will be collected at baseline and day 29.  For pediatric subjects 
<10 kg, the serum sample for serology on the day 29 visit will not be collected due to 
restrictions in total blood volumes collection.  For pediatric subjects <3 kg, the serum 
sample for serology on the baseline and day 29 visit will not be collected due to restrictions 
in total blood volumes collection.  
9. The PK-ADA serum samples may be analyzed for ADA and NAb, if feasible. 
10. Only for pediatric subjects who weigh ≥10 kg:  The whole blood sample for RNA, should 
be collected on day 1/baseline (pre-dose).  The whole blood for genomic DNA should be 
collected on day 1/baseline. If not collected at baseline, the sample for genomic DNA may 
be collected at any visit. 
9.1.5. 
Early Termination Visit 
Subjects who are withdrawn from the study will be asked to provide final blood samples for drug 
concentration and immunogenicity analysis. 
9.1.6. 
Unscheduled Visits 
All attempts should be made to keep subjects on the study schedule.  Unscheduled visits may be 
necessary to repeat testing following abnormal laboratory results, for follow-up of AEs, for 
SARS-CoV-2 RT-qPCR and serology testing when subjects experience symptoms consistent with 
SARS-CoV-2 infection (per the broad-term list specified in Section 9.2.2.2), or for any other 
reason, as warranted. 
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9.2. 
Study Procedures 
This section describes the procedures and collections that will be performed in this study. 
Procedures and collections will occur according to the schedule of events (Table 3 and Table 4). 
9.2.1. 
Procedures Performed Only at the Screening/Baseline Visit 
The following procedures will be performed for the sole purpose of determining study eligibility 
or characterizing the baseline population: demographics (eg, age, sex, race, weight, height, etc), 
medical history, local diagnostic assay for SARS-CoV-2, query for risk factors for SARS-CoV-2 
infection (eg, first responder or healthcare worker; presence in outdoor or indoor crowed or public 
places [without keeping distance >6 feet] in the last 14 days, with or without a mask and/or eye 
protection; attendance to any social events with more than 10 people in the last 14 days, with or 
without a mask and/or eye protection; exposure to someone believed to have COVID-19; exposure 
to someone diagnosed with COVID-19; receipt of influenza vaccine as of July 2020), and 
household assessment in which subjects will be asked to provide general information about the 
household members (including their general demographic information, COVID-19 status, their 
risk of exposure to COVID-19, and treatment with an EUA approved monoclonal antibody 
treatment for COVID-19). 
9.2.1.1. 
Informed Consent 
Informed consent (adults and parents/guardians) and pediatric assent must be obtained according 
to the requirements described in Section 13.2. Optional informed consent may be obtained for 
participation in the pharmacogenomics sub-study (refer to Section 9.2.7 for more information on 
this sub-study or inclusion in the R10933-10987-COV-2067 study). 
9.2.1.2. 
Local Diagnostic Assay for SARS-CoV-2  
The investigator or sub-investigator will verify that the subjects tests negative or positive by a local 
diagnostic assay for SARS-CoV-2 (eg, molecular assay such as RT-PCR assay for SARS-CoV-2 
or a SARS-CoV-2 antigen test using an appropriate sample such as NP, nasal, OP, or saliva). The 
local diagnostic assay for SARS-CoV-2 must be considered acceptable for clinical use by local 
standards. If the test has not been approved or received EUA issued by the US FDA or by the 
equivalent local health authority, then the Sponsor should be consulted. The use of a RT-PCR 
assay is highly recommended.  
The local diagnostic test result, specimen type (eg, nasal swab), assay type, and date of test will be 
recorded in the CRF. The sample type collected is dependent on local lab requirements.  
9.2.2. 
Efficacy Procedures 
9.2.2.1. 
Nasopharyngeal Swab SARS-CoV-2 RT-qPCR Test (Central Lab) 
Nasopharyngeal swab sample will be collected from subjects to determine presence or absence of 
SARS-CoV-2 virus and to determine the relative quantification of viral load.  For adult and 
adolescent subjects (≥12 years of age), NP swab samples will be collected by swabbing through 
both nostrils on all planned timepoints (Table 3). For pediatric subjects (<12 years of age), NP 
swab samples will be collected by swabbing through a single nostril on all planned timepoints 
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(Table 5).  Detailed instructions for sample collections are in the laboratory manual provided to 
study sites.  
9.2.2.2. 
COVID-19 Symptomology (Strict Terms, Broad Terms, and CDC Definition) 
During each scheduled or unscheduled visit/contact, the investigator or sub-PI investigator, or 
designee (ie, nurse practitioner in countries where allowed by local law) will query the subject 
and/or subject’s parent or guardian about adverse events the subject is experiencing or has 
experienced since the last visit/contact (eg, within the prior week if it is a weekly scheduled visit) 
and ask about all of the signs and symptoms associated with these adverse events including the 
start date, end date and severity of each. The investigator should avoid querying the subject and/or 
subject’s parent or guardian by running a check-list of signs and symptoms, but rather allow the 
subject and/or subject’s parent or guardian to spontaneously report everything that they presented.  
All signs and symptoms related to the AEs, along with the corresponding start date, end date and 
severity should be documented in the subject’s medical records (source document). As signs and 
symptoms may appear and resolve on different days and may precede or occur after the collection 
of NP swab sample for the SARS-CoV-2 RT-qPCR test, it is important that this detailed 
information be captured in the source document. 
Independent of the results (positive or negative) of the SARS-CoV-2 RT-qPCR tests performed 
on samples collected from study subjects during the weekly or unscheduled visits, all adverse 
events must be documented in the AE CRF. Signs and symptoms related to the adverse events 
reported in the AE CRF and confirmed to be temporally related to a positive SARS-CoV-2 
RT-qPCR test collected from the subject’s NP swab sample will be reported on a separate CRF 
(individual sign or symptom with start date and end date, and associated severity). 
For the purpose of the study’s primary and secondary objectives, the assessment of association of 
symptomatic disease with SARS-CoV-2 infection (ie, diagnosis of strict term COVID-19, broad 
term COVID-19, and CDC definition of COVID-19) will be based on the strict term, broad term, 
and CDC COVID-19 definitions described below (Table 7) and the temporal relationship of the 
signs and symptoms with lab confirmed SARS-CoV-2 infection (based on central lab RT-qPCR 
test result).   
Temporal Relationship of Signs and Symptoms with Positive RT-qPCR for Diagnosis of 
COVID-19 
The onset date of signs/symptoms will utilize a ±14 days window from the date of the positive 
SARS-CoV-2 RT-qPCR, so long as the signs/symptom onset does not precede a negative 
SARS-CoV-2 RT-qPCR test. That is, the onset date of symptomatic SARS-CoV-2 infection is 
defined as the date of the first sign/symptom that is consistent with a diagnosis of COVID-19 as 
determined by the investigator. The onset date must be after the last negative SARS-CoV-2 
RT-qPCR and no more than 14 days prior to the first positive SARS-CoV-2 RT-qPCR or must 
occur on or before 14 days after the last positive SARS-CoV-2 RT-qPCR. 
Definitions of COVID-19 Signs and Symptoms used for the Secondary Efficacy Endpoints:  
1. Strict term: as described in Section 4.1.2 and  Section 4.2.2 , a secondary endpoint will 
utilize a strict definition of signs and symptoms of COVID-19 (see Table 7). 
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2. Broad term: as described in Section 4.1.2 and Section 4.2.2, a secondary endpoint will 
utilize a broad term COVID-19 signs and symptoms defined as any of the 23 symptoms 
listed in Table 7 or fever (≥38°C). 
3. CDC definition:  as described in Section 4.1.2 and Section 4.2.2, a secondary endpoint 
will utilize the CDC COVID-19 2020 Interim Case Definition (approved 5 Aug 2020) 
(see Table 7) to allow for comparability across studies in the field (CDC, 2020a).  
Table 7: 
Strict-Terms, Broad-Terms, and CDC Definition COVID-19 Signs and 
Symptoms 
Strict-term defined by: 
Broad-term defined as any of the 
following: 
CDC definition 
Fever (≥38°C) PLUS ≥1 
respiratory symptom (sore 
throat, cough, shortness of 
breath) 
OR 
2 respiratory symptoms (sore 
throat, cough, shortness of 
breath) 
OR 
1 respiratory symptom (sore 
throat, cough, shortness of 
breath) PLUS ≥2 non-
respiratory symptoms (chills, 
nausea, vomiting, diarrhea, 
headache, conjunctivitis, 
myalgia, arthralgia, loss of taste 
or smell, fatigue or general 
malaise) 
Fever ≥38°C 
• 
The signs and symptoms below: 
1. Feverish 
2. Sore throat 
3. Cough 
4. Shortness of breath/difficulty 
breathing (nasal flaring*) 
5. Chills 
6. Nausea 
7. Vomiting 
8. Diarrhea 
9. Headache 
10. Red or watery eyes 
(conjunctivitis) 
11. Body aches such as muscle pain 
or joint pain (myalgia, 
arthralgia) 
12. Loss of taste/smell 
13. Fatigue (fatigue or general 
malaise or lethargy*) 
14. Loss of appetite or poor 
eating/feeding 
15. Confusion 
16. Dizziness 
17. Pressure/tightness in chest 
18. Chest pain 
19. Stomach ache (abdominal 
pain*) 
20. Rash 
21. Sneezing 
22. Runny nose 
23. Sputum/phlegm 
Other 
 
*Signs and symptoms observed in pediatric 
subjects 
At least 2 of the following 
symptoms: fever (measured or 
subjective), chills, rigors, 
myalgia, headache, sore 
throat, nausea or vomiting, 
diarrhea, fatigue, congestion 
or runny nose 
OR 
Any 1 of the following 
symptoms: cough, shortness 
of breath, difficulty breathing, 
new olfactory disorder, new 
taste disorder 
OR 
Severe respiratory illness with 
at least 1 of the following, 
clinical or radiographic 
evidence of pneumonia, 
ARDS. 
 
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9.2.2.3. 
Assessment of Medically Attended Visits 
Only for RT-qPCR positive subjects (cohort A, cohort A1, cohort B, and cohort B1): Subjects 
and/or their parent/guardian (as appropriate) who are or become SARS-CoV-2 RT-PCR positive 
will be queried on any SARS-CoV-2 infection-related medically attended visits to the ED, UCC, 
or hospitalization (Table 3 and Table 5).  The assessment of medically attended visits to ED, UCC 
or hospitalization will be performed from the time the subject first becomes SARS-CoV-2 
RT-qPCR positive or from the time they develop symptoms suspected to be COVID-19 (later 
confirmed by RT-qPCR positive results) until the subject has had 2 negative tests or COVID-19 
related symptoms have resolved (whichever lasts longer), or until the end of study visit. Details 
associated with any SARS-CoV-2 infection-related medically-attended visit will be recorded and 
will include at minimum: 
• Nature of the visit (ED, UCC, hospital stay) 
• Date and length of visit 
• Primary reason for the visit should be recorded as an adverse event 
• Assessment of the following parameters or occurrences (worst or most abnormal 
finding) during the medically attended visit/stay: 
− Abnormal vital signs: respiratory rate ≥30 per minute, heart rate ≥125 per minute, 
peripheral capillary oxygen saturation (SpO2) ≤93% on room air at sea level, or 
oxygen partial pressure (PaO2)/fractional inspired oxygen (FiO2) <300 mm Hg)  
Note:  these limits for abnormal vital signs are for adult and adolescent subjects. 
− Respiratory failure: needing high-flow oxygen, noninvasive ventilation, 
mechanical ventilation, extracorporeal membrane oxygenation (ECMO) 
− Evidence of shock: systolic blood pressure (SBP) <90 mm Hg, diastolic blood 
pressure 
(DBP) 
<60 
mm 
Hg, 
or 
requiring 
vasopressors 
Note:  these limits for abnormal vital signs are for adult and adolescent subjects.  
− Multiorgan dysfunction: Significant acute renal, hepatic, or neurologic dysfunction 
− Multisystem 
inflammatory 
syndrome 
in 
children 
(MIS-C)  
Note:  for pediatric subjects <18 years only 
− Admission to an ICU 
9.2.2.4. 
Absenteeism Assessment 
Only for RT-qPCR positive subjects (cohort A, cohort A1, cohort B, and cohort B1): Subjects 
and/or their parent/guardian who are or become SARS-CoV-2 RT-PCR positive during the EAP 
will be queried on any SARS-CoV-2 infection-related absenteeism (Table 3 and Table 5). 
Absenteeism is defined as number of days missed for daily responsibilities, including work 
(employed adults) or school (students), daycare, or family obligations/responsibilities (childcare 
or eldercare).  The assessment of absenteeism will be performed from the timepoint the subject 
first becomes SARS-CoV-2 RT-qPCR positive until the end until the subject has had 2 negative 
tests or COVID-19 related symptoms have resolved (whichever lasts longer), or until the end of 
study visit.   
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9.2.3. 
Safety Procedures  
9.2.3.1. 
Targeted Physical Examination and Vital Signs 
The targeted physical examination and vital signs include measurements of temperature, blood 
pressure (measured after the subject has been resting quietly for at least 5 minutes and may be 
obtained from a seated or supine position), pulse rate, and respiratory rate, and examination of the 
oropharynx, skin, heart, lungs and any other system(s) depending on any complaints or concerns 
expressed by the subjects. 
Vital signs consisting of blood pressure, pulse rate, body temperature, and respiratory rate will be 
collected pre-dose and after dose administration as follows: 
• Sentinel group (subset 1; completed):  approximately every 30 minutes during the 
first 2 hours after study drug administration, at hour 3, and at hour 4 before dismissal. 
• Safety group (subset 2; completed):  approximately every hour for 2 hours after study 
drug administration. 
• All other adult and adolescent subjects (subset 3):  approximately 1 hour after study 
drug administration. 
• Pediatric sentinel group (subset 4): approximately every hour for at least 2 hours 
after study drug administration (blood pressure will be measured, if feasible, 
according to the child’s age). 
• All other pediatric subjects (subset 5): approximately 1 hour after study drug 
administration (blood pressure will be measured, if feasible, according to the child’s 
age). 
9.2.3.2. 
Laboratory Testing 
Samples for laboratory testing will be collected at visits according to the Schedule of Events 
Table 4 and Table 6.  Samples will be analyzed by a central laboratory.  For pediatric subjects 
(<18 years) only, a numbing  cream may be used for blood sample collection.  Detailed instructions 
for blood sample collection are in the laboratory manual provided to study sites. 
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Tests will include:  
Blood Chemistry 
Sodium 
Total protein, serum 
Total bilirubin 
Potassium 
Creatinine 
Total cholesterol 
Chloride 
Blood urea nitrogen (BUN) 
Triglycerides 
Carbon dioxide 
Aspartate aminotransferase (AST) 
Uric acid 
Calcium 
Alanine aminotransferase (ALT) 
Creatine phosphokinase (CPK) 
Glucose 
Alkaline phosphatase 
 
Albumin 
Lactate dehydrogenase (LDH) 
 
Hematology 
Hemoglobin 
Differential:  
Hematocrit 
 
Neutrophils 
Red blood cells (RBCs) 
 
Lymphocytes 
White blood cells (WBCs) 
 
Monocytes 
Red cell indices 
 
Basophils 
Platelet count 
 
Eosinophils 
Urinalysis 
Color 
Glucose 
RBC 
Clarity 
Blood 
Hyaline and other casts 
pH 
Bilirubin 
Bacteria 
Specific gravity 
Leukocyte esterase 
Epithelial cells 
Ketones 
Nitrite 
Crystals 
Protein 
WBC 
Yeast 
Other Laboratory Tests 
Urine pregnancy test will be performed for WOCBP at baseline and prior to administration of 
study drug. If a subject has a positive urine pregnancy test, a serum pregnancy test should be 
performed to confirm.   
Abnormal Laboratory Values and Laboratory Adverse Events 
All laboratory values must be reviewed by the investigator or authorized designee. 
Significantly abnormal test results that occur after start of treatment may be repeated to confirm 
the nature and degree of the abnormality.  When necessary, appropriate ancillary investigations 
should be initiated.  If the abnormality fails to resolve or cannot be explained by events or 
conditions unrelated to the study medication or its administration, the Medical/Study Director must 
be consulted. 
The clinical significance of an abnormal test value, within the context of the disease under study, 
must be determined by the investigator. 
Criteria for reporting laboratory values as an AE are provided in Section 10.1.1. 
9.2.4. 
Drug Concentration and Measurements 
Serum samples for REGN10933 and REGN10987 drug concentration measurement will be 
collected per the schedule of events for adult and adolescent subjects (Table 4) and pediatric 
subjects (<12 years of age) (Table 6).  For pediatric subjects (<18 years) only, a numbing cream 
may be used for blood sample collection.   
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A subset of the first 30 adult subjects (by subject number by IVRS) will have frequent sample 
collection (dense PK).  The second subset will include the next 370 adult subjects (the 31st to 400th 
subjects) who will have less frequent sample collection (sparse PK).  Pediatric subjects will have 
3 serum samples collected.  In order to collect serum samples over the study duration, pediatric 
subjects will be assigned by IVRS to 1 of 4 sampling schedules (A, B, C, D) (Table 6).  Any unused 
samples may be kept for up 15 years (or for a shorter time period if required per regional laws and 
regulations) after study completion for use in exploratory research. 
9.2.5. 
Immunogenicity Measurements and Samples 
Immunogenicity will be assessed by ADA and NAb. Samples for ADA and NAb assessment will 
be collected for adult and adolescent subjects (<12 years) at time points listed in Table 4. Samples 
will be assessed for ADA and NAb using samples collected for subjects (<12 years) at the time 
points listed in Table 6, if feasible. For pediatric subjects (<18 years) only, a numbing cream may 
be used for blood sample collection.  Any unused samples may be kept for up 15 years (or for a 
shorter time period if required per regional laws and regulations) after study completion for use in 
exploratory research. 
9.2.6. 
Exploratory Pharmacodynamic/Biomarker Procedures 
A description of planned or potential exploratory analyses is provided below. Samples for 
assessment of pharmacodynamic and exploratory biomarkers will be collected from adult and 
adolescent subjects at time points indicated in Table 4.  Sample for serological assays will be 
collected from pediatric subjects (<12 years) at the time points indicated in Table 6.  For pediatric 
subjects (<18 years) only, a numbing cream may be used for blood sample collection.  Residual 
serum or plasma samples collected for other purposes may also be used to study how 
REGN10933+REGN10987 work and SARS-CoV-2 infection, including but not limited to, 
cytokines, complement pathways, and other factors emerging to be associated with disease or 
clinical prognosis. Any unused samples may be kept for up 15 years (or for a shorter time period 
if required per regional laws and regulations) after study completion for use in exploratory 
research. 
9.2.6.1. 
Virology 
9.2.6.1.1. Viral Sequencing  
In support of public health initiatives to track SARS-CoV-2 genetic variants, viral genome 
sequencing will be performed on all viral nucleic acid isolated from NP swab samples at baseline. 
Sequencing analyses will be of the entire viral genome, including the full gene sequence that 
encodes the SARS-CoV-2 S protein. 
The results of the viral sequencing will not be included in the clinical study report. 
9.2.6.1.2. Viral Resistance 
Subjects will be assessed for virologic resistance, defined as (1) those subjects who are positive at 
baseline and remain positive without a consistent decrease in viral load by 4 weeks, (2) those 
subjects who were negative and become positive during the EAP, and/or (3) those subjects who 
have 2 consecutive negative RT‑qPCR tests with a subsequent positive RT-qPCR test result. For 
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subjects who exhibit viral resistance, viral sequencing will be performed to understand the 
potential relationship between genetic mutations and mAb functional activity. Viral sequencing 
may also be done on a gender-matched placebo control group in order to determine whether any 
genetic mutations observed in the mAb treatment group are naturally emergent genetic variants. 
The results of the viral resistance will not be included in the clinical study report. 
9.2.6.1.3. Viral Infectivity  
To explore the effects of REGN10933+REGN10987 on infectivity of SARS-CoV-2, we may use 
viral culture assays or sub genomic viral mRNA transcript analyses. Subgenomic viral RNA 
transcripts potentially indicate the presence of actively replicating virus in samples, as viral 
subgenomic mRNA is transcribed only in infected cells and is not packaged into virions. These 
data may be associated to RT-qPCR data from matched samples for each group and compare to 
placebo or other clinical or other measures in the study. 
9.2.6.2. 
Serological Assays for Endogenous Anti-SARS-CoV-2 Antibodies 
In order to assess the impact of baseline humoral immunity/antibody response to SARS-CoV-2 on 
REGN10933+REGN10987 efficacy to prevent SARS-CoV-2 infection, serum anti-SARS-CoV-2 
will be measured at baseline, including but not limited to those which detect antibodies against the 
S protein and/or the N protein and/or neutralization assays. The impact of a positive serology result 
on drug efficacy will be assessed by associating seropositivity to positive SARS-CoV-2 RT-qPCR 
test from NP swabs. Association of seropositivity with clinical endpoints and other measures may 
also be explored. 
To explore whether REGN10933+REGN10987 affect the generation of a humoral immune 
response to SARS-CoV-2, serum anti-SARS-CoV-2 N protein antibodies will be measured using 
immunoassays in REGN10933+REGN10987 groups as compared to placebo control, as well as to 
baseline. 
Any unused samples may be kept for up 15 years after study completion for use in exploratory 
research (or for a shorter time period if required per regional laws and regulations). 
9.2.6.3. 
Serum and Plasma for Research 
Research serum and plasma are being collected and banked for exploratory research related to 
COVID-19, SARS-CoV-2, REGN10933+REGN10987, host and viral biological pathways and 
mechanisms related disease activity and clinical outcomes. The data from these exploratory 
analyses may not be included in the CSR. 
9.2.7. 
Pharmacogenomic Analysis (Optional) 
Adult and pediatric subjects (<18 years and ≥10 kg) who agree to participate in the genomics sub-
study will be required to consent to this optional sub-study before collection of the samples. Blood 
sample for RNA must be collected predose on day 1. Whole blood samples for DNA extraction 
should be collected on day 1/baseline (predose) but can be collected at a later study visit. For 
pediatric subjects (<18 years and ≥10 kg) only, a numbing cream may be used for blood sample 
collection. DNA and RNA samples will be collected for pharmacogenomics analyses to understand 
the genetic and/or transcriptional determinants of efficacy and safety associated with the 
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treatments in this study and the molecular basis of SARS-CoV-2 infection. These samples will be 
single-coded as defined by the International Council for Harmonisation (ICH) guideline E15.  
Samples will be stored for up to 15 years after the final date of the database lock (or for a shorter 
time period if required per regional laws and regulations). If there are specific site or country 
requirements involving the pharmacogenomic analyses which the Sponsor is unable to comply 
with, samples will not be collected at those sites. 
The purpose of the pharmacogenomic analyses is to identify genomic associations with clinical or 
biomarker response to REGN10933+REGN10987, other SARS-CoV-2 infection clinical outcome 
measures, and possible treatment-emergent adverse events. In addition, associations between 
genomic variants and prognosis or progression of SARS-CoV-2 infection as well as related viral 
pneumonia and respiratory diseases may also be studied. These data may be used or combined 
with data collected from other studies to identify and validate genomic and transcriptional markers 
related to the study drug, target pathway, or SARS-CoV-2 infection. These data may also be 
combined with viral sequence analyses to study host/virus genetic interactions. 
Analyses may include sequence determination or single nucleotide polymorphism studies of 
candidate genes and surrounding genomic regions. Other methods, including whole-exome 
sequencing, whole-genome sequencing, DNA copy number variation, and transcriptome 
sequencing (or other methods for quantitating RNA expression) may also be performed. The list 
of methods may be expanded to include novel methodology that may be developed during the 
course of this study or sample storage period. 
Results from the genomic and transcriptional analyses will not be reported in the CSR. 
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10. 
SAFETY EVALUATION AND REPORTING 
10.1. 
Recording and Reporting Adverse Events 
10.1.1. 
General Guidelines 
The investigator must promptly record all clinical events occurring during the study data 
collection, from the time of signing the ICF to the end of study (see Section 11.4.5.1). Medical 
conditions that existed or were diagnosed prior to the signing of the Informed Consent will be 
recorded as part of medical history. Abnormal laboratory values and vital signs observed at the 
time of Informed Consent should also be recorded as medical history.  Any subsequent worsening 
(ie, any clinically significant change in frequency and/or intensity) of a pre-existing condition that 
is temporally associated with the use of the study drug should also be recorded as an AE. 
At each visit, the investigator will determine whether any AEs have occurred by evaluating the 
subject.  Adverse events may be directly observed, reported spontaneously by the subject or 
adolescent subject’s parent or guardian, or by questioning the subject or the adolescent subject’s 
parent or guardian at each study visit. Subjects or the subject’s parent or guardian should be 
questioned in a general way, without asking about the occurrence of any specific symptoms. The 
Investigator must assess all AEs to determine seriousness, severity, and causality, in accordance 
with the definitions in Section 10.2. The investigator should recommend that subjects (themselves 
or by their parent/guardian) measure their temperature daily during efficacy assessment period, 
approximately at the same time, and also every time the subject feels feverish, chills, or sick. The 
Investigator’s assessment must be clearly documented in the site’s source documentation with the 
Investigator’s signature. The Investigator should follow-up on SAEs (and AESIs) until they have 
resolved or are considered clinically stable; AEs should be followed until they are resolved or last 
study visit, whichever comes first. 
Always report the diagnosis as the AE or SAE term. When a diagnosis is unavailable, report the 
primary sign or symptom as the AE or SAE term with additional details included in the narrative 
until the diagnosis becomes available. If the signs and symptoms are distinct and do not suggest a 
common diagnosis, report them as individual entries of AE or SAE. 
Laboratory results, vital signs, and other diagnostic results or findings should be appraised by the 
Investigator to determine their clinical significance. Isolated abnormal laboratory results, vital sign 
findings, or other diagnostic findings (ie, not part of a reported diagnosis) should be reported as 
AEs if they are symptomatic, lead to study drug discontinuation, dose reduction, require corrective 
treatment, or constitute an AE in the investigator’s clinical judgment. 
For events that are serious due to hospitalization, the reason for hospitalization must be reported 
as the serious adverse event (diagnosis or symptom requiring hospitalization). A procedure is not 
an AE or SAE, but the reason for the procedure may be an AE or SAE. Pre-planned (prior to 
signing the Informed Consent Form) procedures, treatments requiring hospitalization for pre-
existing conditions that do not worsen in severity, and admission for palliative or social care should 
not be reported as SAEs (see Section 10.2 for Definitions). 
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For deaths, the underlying or immediate cause of death should always be reported as an SAE. 
Any SAE that may occur subsequent to the reporting period (end of the on-treatment period) that 
the Investigator assesses as related to study drug should also be reported. 
All AEs, serious adverse events (SAEs), AESIs, and pregnancy reports are to be reported according 
to the procedures in Section 10.1.3. 
10.1.2. 
Reporting Procedure  
All events (serious and non-serious) must be reported with investigator’s assessment of the event’s 
seriousness, severity, and causality to the (when applicable: blinded) study drug. For SAEs and 
AESIs, a detailed narrative summarizing the course of the event, including its evaluation, 
treatment, and outcome should be provided on the AE CRF. Specific or estimated dates of event 
onset, treatment, and resolution should be included, when available.  Medical history, concomitant 
medications, and laboratory data that are relevant to the event should also be summarized in the 
narrative.  For fatal events, the narrative should state whether an autopsy was or will be performed 
and include the results if available. Information not available at the time of the initial report must 
be documented in a follow-up report. Source documents (including hospital or medical records, 
diagnostic reports, etc) will be summarized in the narrative on the AE CRF and retained at the 
study center and available upon request. 
Urgent safety queries must be followed up and addressed promptly. Follow-up information and 
response to non-urgent safety queries should be combined for reporting to provide the most 
complete data possible within each follow-up.  
10.1.3. 
Events that Require Expedited Reporting to Sponsor 
The following events also require reporting to the sponsor (or designee) within 24 hours of learning 
of the event: 
• SAEs. 
• Adverse Events of Special Interest (AESI; serious and nonserious):  Adverse events 
of special interest for this study include the following: (as defined in Section 10.2.3): 
− Grade 3 or greater injection site reactions or hypersensitivity reactions including 
but not limited to anaphylaxis, laryngeal/pharyngeal edema, severe bronchospasm, 
chest pain, seizure, or severe hypotension (AE grading system is provided in 
Section 10.2.4) 
• Pregnancy: 
Although pregnancy is not considered an AE, it is the responsibility of 
the investigator to report to the sponsor (or designee), within 24 hours of identification, 
any pregnancy occurring in a female study subject existing at the time of signing the 
informed consent form, during the study, and for 8 months following administration of 
the single dose of study drug. Any complication of pregnancy affecting a female study 
subject and/or fetus and/or newborn that meets the SAE criteria must be reported as an 
SAE. Outcome for all pregnancies should be reported to the sponsor. 
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10.2. 
Definitions 
10.2.1. 
Adverse Event 
An AE is any untoward medical occurrence in a subject administered a study drug which may or 
may not have a causal relationship with the study drug. Therefore, an AE is any unfavorable and 
unintended sign (including abnormal laboratory finding), symptom, or disease which is temporally 
associated with the use of a study drug, whether or not considered related to the study drug (ICH 
E2A Guideline. Clinical Safety Data Management: Definitions and Standards for Expedited 
Reporting, Oct 1994). 
10.2.2. 
Serious Adverse Event 
An SAE is any untoward medical occurrence that at any dose: 
• Results in death – includes all deaths, even those that appear to be completely unrelated 
to study drug (eg, a car accident in which a subject is a passenger). 
• Is life-threatening – in the view of the investigator, the subject is at immediate risk of 
death at the time of the event. This does not include an AE that had it occurred in a 
more severe form, might have caused death. 
• Requires in-subject hospitalization or prolongation of existing hospitalization.  
In-subject hospitalization is defined as a hospital admission (any duration) or an 
emergency room visit for longer than 24 hours. Prolongation of existing hospitalization 
is defined as a hospital stay that is longer than was originally anticipated for the event, 
or is prolonged due to the development of a new AE as determined by the investigator 
or treating physician. 
• Results in persistent or significant disability/incapacity (substantial disruption of 
one’s ability to conduct normal life functions). 
• Is a congenital anomaly/birth defect 
• Is an important medical event - Important medical events may not be immediately 
life-threatening or result in death or hospitalization, but may jeopardize the subject or 
may require intervention to prevent one of the other serious outcomes listed above (eg, 
intensive treatment in an emergency room or at home for allergic bronchospasm; blood 
dyscrasias or convulsions that do not result in hospitalization; or development of drug 
dependency or drug abuse). 
Criteria for reporting SAEs must be followed for these events.  
10.2.3. 
Adverse Events of Special Interest 
An adverse event of special interest (AESI; serious or non-serious) is one of scientific and medical 
interest specific to the sponsor’s product or program, for which ongoing monitoring and rapid 
communication by the investigator to the sponsor can be appropriate. Such an event might warrant 
further investigation in order to characterize and understand it. 
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10.2.4. 
Severity 
The severity of AEs (including test findings classified as AEs) and injection-site -related reactions 
will be graded using the current version of the NCI–CTCAE v5.0 0 (DCTD, 2017). The 
NCI-CTCAE severity grading systems for anaphylaxis, allergic reaction, and injection site reaction 
are specifically provided Table 8. 
Table 8: 
NCI-CTCAE Severity Grading System for Adverse Events for Anaphylaxis, 
Allergic Reaction, and Injection Site Reaction 
CTCAE Term 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Grade 5 
only grade 3, 4, and 5 are reportable as AESI for 
R10933-10987-COV-2069a 
Anaphylaxisb 
Not applicable 
Not applicable 
Symptomatic 
bronchospasm, with 
or without urticaria; 
parenteral 
intervention 
indicated; allergy-
related 
edema/angioedema; 
hypotension 
Life-threatening 
consequences; 
urgent 
intervention 
indicated 
Death 
Allergic reaction 
(hypersensitivity 
reaction)c 
Systemic 
intervention not 
indicated 
Oral 
intervention 
indicated 
Bronchospasm; 
hospitalization 
indicated for 
clinical sequelae; 
intravenous 
intervention 
indicated 
Life-threatening 
consequences; 
urgent 
intervention 
indicated 
Death 
Injection site 
reactiond 
Tenderness with 
or without 
associated 
symptoms (eg, 
warmth, erythema, 
itching) 
Pain; 
lipodystrophy; 
edema; 
phlebitis 
Ulceration or 
necrosis; severe 
tissue damage; 
operative 
intervention 
indicated 
Life-threatening 
consequences; 
urgent 
intervention 
indicated 
Death 
a See details in Section 10.1.3 
b Definition: A disorder characterized by an acute inflammatory reaction resulting from the release of histamine and 
histamine-like substances from mast cells, causing a hypersensitivity immune response. Clinically, it presents with 
breathing difficulty, dizziness, hypotension, cyanosis and loss of consciousness and may lead to death 
c Definition: A disorder characterized by an adverse local or general response from exposure to an allergen. 
d Definition: A disorder characterized by an intense adverse reaction (usually immunologic) developing at the site of 
an injection.  
Source: (DCTD, 2017) 
10.2.5. 
Causality 
The investigator must provide causality assessment as whether or not there is a reasonable 
possibility that the drug caused the adverse event, based on evidence or facts, his/her clinical 
judgment, and the following definitions. The causality assessment must be made based on the 
available information and can be updated as new information becomes available. 
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For double blinded studies using an active comparator, the investigator should consider all study 
drugs in determining event causality.   
The following factors should be considered when assessing causality: 
• Temporal relationship: time to onset vs time drug was administered 
• Nature of the reactions: immediate vs long term 
• Clinical and pathological features of the events  
• Existing information about the drug & same class of drugs  
• Concomitant medications  
• Underlying and concurrent illnesses  
• Subject’s medical and social history  
Causality to the study drug (including study drug administration): 
• Related: 
− The AE follows a reasonable temporal sequence from study drug administration, 
and cannot be reasonably explained by the nature of the reaction, subject’s clinical 
(eg, disease under study, concurrent diseases, concomitant medications), or other 
external factors. 
or 
− The AE follows a reasonable temporal sequence from study drug administration, 
and is a known reaction to the drug under study or its class of drugs, or is predicted 
by known pharmacology. 
• Not Related: 
− The AE does not follow a reasonable sequence from study drug administration, or 
can be reasonably explained by the nature of the reaction, subject’s clinical state 
(eg, disease under study, concurrent diseases, and concomitant medications) or 
other external factors. 
Causality to the study conduct (protocol specified procedure): 
• Related: 
− The AE follows a reasonable temporal sequence from a protocol specified 
procedure, and cannot be reasonably explained by the nature of the reaction, 
subject’s clinical (eg, disease under study, concurrent diseases, concomitant 
medications), or other external factors. 
• Not Related: 
− The AE does not follow a reasonable sequence from a protocol specified procedure, 
or can be reasonably explained by the nature of the reaction, subject’s clinical state 
(eg, disease under study, concurrent diseases, and concomitant medications) or 
other external factors. 
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10.3. 
Safety Monitoring 
The investigator will monitor the safety of study subject at his/her site(s) as per the requirements 
of this protocol and consistent with current Good Clinical Practice (GCP). Any questions or 
concerns should be discussed with the sponsor in a timely fashion.  The sponsor will monitor the 
safety data from across all study sites. The Medical/Study Director will have primary responsibility 
for the emerging safety profile of the compound, but will be supported by other departments (eg, 
Pharmacovigilance; Global Patient Safety; Biostatistics and Data Management). Safety monitoring 
will be performed on an ongoing basis (eg, individual review of SAEs) and on a periodic 
cumulative aggregate basis. 
10.4. 
Notifying Health Authorities, Institutional Review Board/Ethics 
Committee and Investigators 
During the study, the sponsor and/or the CRO will inform health authorities, IRBs/ECs, and the 
participating investigators of any SUSARs (Suspected Unexpected Serious Adverse Reactions) 
occurring 
in 
other 
study 
centers 
or 
other 
studies 
of 
the 
active 
study 
drug 
(REGN10933+REGN10987), as appropriate per local reporting requirements. In addition, the 
sponsor and/or CRO will comply with any additional local safety reporting requirements. All 
notifications to investigators will contain only blinded information.  
Upon receipt of the sponsor’s notification of a SUSAR that occurred with the study drug, the 
investigator will inform the IRB/EC unless delegated to the sponsor. 
Event expectedness for study drug (REGN10933+REGN10987) is assessed against the Reference 
Safety Information section of the IB that is effective for expedited safety reporting.   
At the completion of the study, the sponsor will report all safety observations made during the 
conduct of the trial in the Clinical Study Report to health authorities and IRBs/ECs as appropriate. 
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11. 
STATISTICAL PLAN 
This section provides the basis for the SAP for the study. The SAP will be revised prior to the end 
of the study to accommodate amendments to the clinical study protocol and to make changes to 
adapt to unexpected issues in study execution and data that may affect the planned analyses. The 
final SAP will be issued before the first database lock. 
Endpoints are listed in Section 4. Analysis variables are listed in Section 5.  
11.1. 
Statistical Hypothesis 
The following null and alternate hypotheses will be tested for the primary and secondary efficacy 
endpoints: 
H0: There is no treatment difference between REGN10933+REGN10987 and placebo 
H1: There is a treatment difference between REGN10933+REGN10987 and placebo  
11.2. 
Justification of Sample Size 
An administrative assessment for assumption verification and sample size estimation for cohort A 
was conducted using unblinded descriptive analyses without performing any formal statistical 
hypothesis testing.  Analyses were conducted in the group of cohort A subjects randomized from 
study initiation through the date of randomization that was associated with approximately 
30 RT-PCR events amongst cohort A seronegative subjects during the EAP (subjects overall 
regardless of baseline serology status [eg, seronegative, seropositive, or other]).  The subjects who 
were evaluated in this descriptive analysis will not be included for the final efficacy analyses, 
however, these subjects will be included in the safety analyses (Section 11.4.9). To maintain 
operational efficiencies and because of the progressive rollout of SARS-CoV-2 vaccination which 
may change the dynamics of virus transmission/infection in the near future, enrollment into the 
study was not paused while the administrative assessment was performed and was estimated that 
the total enrollment may reach approximately 3500 subjects. The justification of sample size in 
cohort A (Section 11.2.1) with the assumption of reduction of symptomatic infection is based on 
the results from the administrative assessment.  
11.2.1. 
Cohort A: Adult and Adolescent Subjects (≥12 years) Who Are SARS-CoV-2 
RT-qPCR Negative at Baseline 
In cohort A, subjects are randomized in a 1:1 allocation ratio to REGN10933+REGN10987 or 
placebo. The primary hypothesis is the reduction in the proportion of symptomatic RT-qPCR 
(broad-term) confirmed SARS-CoV-2 infections in seronegative subjects. To calculate the sample 
size required to achieve at least 90% power for seronegative subjects in cohort A, it is assumed 
that the statistical hypothesis will be tested in a 2-sided test. Based on the administrative 
assessment results among 409 seronegative subjects in cohort A, a 50% reduction of infections 
(symptomatic or asymptomatic) compared to the placebo group and a 100% reduction of 
symptomatic infections compared to placebo group was observed. Due to the small sample size in 
the administrative assessment, it is assumed, for the purpose of calculating study power, that an 
approximately 50% reduction or greater in symptomatic infections compared to placebo group will 
be expected for the final primary efficacy analysis. 
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In this household study design, the number of subjects per household, the correlation between 
subjects and symptomatic infection rates within a household are unknown.  To detect a relative 
risk of 0.5 (ie, 50% reduction of the assumed 10% attack rate in the placebo arm), equivalent to an 
odds ratio of 0.47, power was calculated compared to the p-value of 0.05 based on 2000 
simulations in 1248 subjects from 430 households (ie, assuming an average household size of 
2.9 seronegative subjects).  Table 9 provides power calculations by varying degrees of correlation 
within household.  In all cases, the power of the study is >90% using a generalized linear model 
with the generalized estimation equation (GEE) approach and assuming a compound symmetry 
covariance matrix. 
Table 9: 
Simulated Power for Household Design (1248 Subjects over 430 Households)  
Placebo  
Attack Rate 
REGN10933+ 
REGN10987 
Attack Rate 
Correlation 
within Household 
Average Odds Ratio 
REGN10933+REGN10987 
versus Placebo 
Power 
10% 
5% 
0.1 
0.485 
0.914 
10% 
5% 
0.2 
0.485 
0.934 
10% 
5% 
0.3 
0.480 
0.956 
10% 
5% 
0.4 
0.481 
0.972 
10% 
5% 
0.5 
0.476 
0.983 
10% 
5% 
0.6 
0.478 
0.999 
At least 1980 subjects will need to be enrolled in cohort A to have a minimum of 1248 seronegative 
subjects, assuming that 10% of subjects drop out and 30% of subjects are seropositive at baseline. 
11.2.1.1. Cohort A1: Pediatric Subjects (<12 years) Who Are SARS-CoV-2 RT-qPCR 
Negative at Baseline 
Approximately up to a total of 250 pediatric subjects (<12 years) will be enrolled in this study. Of 
the 250 subjects, 90% (225/250) are expected to be enrolled in this cohort (ie, central lab RT-qPCR 
negative at baseline) for evaluation of the drug concentration and exposure, and safety.  The actual 
number of subjects in this cohort will depend on the actual percentage of subjects with a baseline 
negative RT-qPCR enrolled. No statistical hypothesis tests will be performed. 
11.2.2. 
Cohort B: Adult and Adolescent Subjects (≥12 years) Who Are SARS-CoV-2 
RT-qPCR Positive at Baseline  
The primary endpoint in asymptomatic, seronegative subjects in cohort B is the proportion of 
subjects who subsequently develop signs and symptoms (broad-term) within 14 days of a positive 
RT-qPCR test result at baseline or during the EAP. 
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The sample size of cohort B is based on the frequency of finding positive subjects while enrolling 
cohort A and assumes that approximately 10% of subjects in a household are already positive for 
SARS-CoV-2 by RT-qPCR at baseline. Among approximately 3500 adult and adolescent subjects 
that are anticipated to be enrolled in cohort A or cohort B, the number of subjects expected in 
cohort B is approximately 220, including 200 seronegative subjects. Assuming that 50% of 
infected placebo subjects at baseline will develop symptoms, 200 seronegative subjects in cohort 
B will provide >90% power to detect a relative risk of 0.5 using a 2-sided Fisher’s exact test at an 
alpha level of 0.05.  
11.2.2.1. Cohort B1: Pediatric Subjects (<12 years) Who Are SARS-CoV-2 RT-qPCR 
Positive at Baseline 
Approximately up to a total of 250 pediatric subjects (<12 years) will be enrolled in this study. Of 
the 250 subjects, 10% (25/250) are expected to be enrolled in this cohort (ie, central lab RT-qPCR 
positive at baseline) for evaluating the drug concentration and exposure, and safety. No statistical 
hypothesis tests will be performed. The actual number of subjects in this cohort will depend on the 
actual percentage of subjects with a baseline positive RT-qPCR enrolled. No statistical hypothesis 
tests will be performed. 
11.3. 
Analysis Sets  
11.3.1. 
Efficacy Analysis Sets 
Seronegative Modified Full Analysis Set (Seronegative mFAS-A) - Cohort A 
The seronegative modified full analysis set for cohort A (seronegative mFAS-A) includes all 
randomized subjects aged 12 years and older who are laboratory confirmed negative for 
SARS-CoV-2 (per central lab PCR test) and who test negative for antibodies for SARS-CoV-2 
(per central lab serology testing) at baseline.   
Subjects included in the administrative assessment analysis are excluded from the seronegative 
mFAS-A population.  
Subjects will be analyzed based on the randomized treatment assignment. The seronegative 
mFAS-A population is the primary analysis population for the primary and secondary endpoints 
for cohort A of this study unless specified otherwise.   
Seronegative Modified Full Analysis Set (Seronegative mFAS-A1) - Cohort A1 
The seronegative modified full analysis set for cohort A1 (seronegative mFAS-A1) includes all 
randomized subjects aged less than 12 years who are laboratory confirmed negative for 
SARS-CoV-2 (per central lab PCR test) and who test negative for antibodies for SARS-CoV-2 
(per central lab serology testing) at baseline.  
Subjects will be analyzed based on the randomized treatment assignment. The efficacy endpoints 
for cohort A1 will be analyzed using the seronegative mFAS-A1 unless specified otherwise.  
Seronegative Modified Full Analysis Set (Seronegative mFAS-B) - Cohort B 
The seronegative modified full analysis set for cohort B (seronegative mFAS-B) includes all 
randomized subjects aged 12 years and older who have laboratory confirmed positive tests at 
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baseline for SARS-CoV-2 RT-qPCR and negative SARS-CoV-2 serology (both based on central 
lab testing) and are asymptomatic at baseline.   
Subjects will be analyzed based on the randomized treatment assignment. The primary and 
secondary endpoints for cohort B will be analyzed using the seronegative mFAS-B unless 
otherwise specified. 
Seronegative Modified Full Analysis Set (Seronegative mFAS-B1) - Cohort B1 
The seronegative modified full analysis set for cohort B1 (seronegative mFAS-B1) includes all 
randomized subjects aged less than 12 years who have laboratory confirmed positive tests at 
baseline for SARS-CoV-2 RT-qPCR and negative SARS-CoV-2 serology (both based on central 
lab testing) and are asymptomatic at baseline.  Subjects will be analyzed based on the randomized 
treatment assignment. The efficacy endpoints for cohort B1 will be analyzed using the 
seronegative mFAS-B1 unless otherwise specified. 
11.3.2. 
Safety Analysis Set 
The safety analysis set (SAF) includes all randomized subjects who received at least 1 dose or part 
of a dose of study drug. Subjects in the SAF will be analyzed based on the treatment received (as 
treated). In general, safety will be evaluated by study cohort: SAF-A (cohort A), SAF-B (cohort B), 
SAF-A1 (cohort A1), and SAF-B1 (cohort B1). However, injection site reactions will also be based 
on all cohorts combined.  
11.3.3. 
Pharmacokinetic Analysis Set 
The PK analysis population includes all subjects who received any study drug and who had at least 
1 non-missing drug concentration measurement following study drug administration. Subjects will 
be analyzed based on actual treatment received. 
11.3.4. 
Immunogenicity Analysis Sets 
The ADA analysis set (AAS) includes all subjects who received study drug and had at least 
1 non-missing ADA result after study drug administration. Subjects will be analyzed based on the 
actual treatment received.  
11.3.5. 
Neutralizing Antibody Analysis Set 
The NAb analysis set (NAS) includes all subjects who received any study drug and who are either 
negative in the ADA assay or positive for ADA with at least one non-missing result in the NAb 
assay after first dose of the study drug. Subjects who are ADA negative are set to negative in the 
NAb analysis set. Subjects will be analyzed according to the treatment actually received.  
11.4. 
Statistical Methods 
For continuous variables, descriptive statistics will include the following information: the number 
of subjects reflected in the calculation (n), mean, standard deviation, Q1, median, Q3, minimum, 
and maximum. For categorical or ordinal data, frequencies and percentages will be displayed for 
each category.  
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Baseline is defined as the last assessment obtained before the first dose of study drug unless 
specified otherwise.  
Statistical analyses will be conducted separately in each cohort. For the purpose of the study 
analysis, cohorts A, A1, B, and B1 are independent with separate type I error control for each 
cohort.   
11.4.1. 
Subject Disposition 
The following will be provided: 
• The total number of screened subjects, defined as signed the ICF 
• The total number of randomized subjects:  received a randomization number 
• The total number of subjects randomized but not receiving study treatment 
• The total number of subjects who discontinued the study, and the reasons for 
discontinuation 
• A listing of subjects treated but not randomized, subjects randomized but not treated, 
and subjects randomized but not treated as randomized 
• A listing of subjects prematurely discontinued from the study, along with reasons for 
discontinuation 
11.4.2. 
Demography and Baseline Characteristics 
Demographic and baseline characteristics will be summarized descriptively by treatment group, 
and by all subjects combined.  
11.4.3. 
Efficacy Analyses 
11.4.3.1. Primary Efficacy Analysis 
Cohort A 
The cohort A primary efficacy endpoint described in Section 4.1.1 will be analyzed in the 
seronegative mFAS-A population (Section 11.3.1). All post-baseline efficacy assessments 
obtained up to last scheduled visit (day 29) in EAP will be included for the primary analysis.  
In order to account for the correlation among subjects within a household and control the 
associated type 1 error inflation, a generalized linear model will be used to estimate the odds ratio 
between the treatment groups by using the GEE approach. This model estimates a single 
within-household correlation coefficient. The model will include the fixed category effects of 
treatment group (placebo versus REGN10933+REGN10987), region (US versus ex-US), and age 
(≥12 to <50, ≥50 years). The model will use a compound symmetry covariance matrix and estimate 
the odds ratio between the treatment groups and corresponding 95% CI and p-value.   
If the GEE model fails to converge due to most households containing only a single study subject 
in seronegative mFAS-A or the percentage of households in cohort A with only a single study 
subject is 70% or more, then a logistic regression model will be used, with treatment, region, and 
age group as fixed effects. The threshold of 70% was based on simulations of within-household 
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correlation which show the type I error rate is inflated and the power is decreased when the 
proportion of single-subject households is high. Additional details will be provided in the SAP. If 
the logistic regression model does not converge, an exact logistic regression will be used. The 
estimates of odds ratio, the corresponding 95% CI and p-value will be provided from logistic 
regression (or exact logistic regression) for comparison of REGN10933+REGN10987 against 
placebo group. 
In cohort A, a subject will be considered having a symptomatic RT-qPCR confirmed SARS-CoV-2 
infection (broad-term) during the EAP if any of the post-baseline RT-qPCR results during EAP 
are positive with at least 1 symptom within 14 days of a positive RT-qPCR result.   
Cohort B 
The cohort B  primary efficacy endpoint  described in Section 4.2.1 will be analyzed in the 
seronegative mFAS-B population (Section 11.3.1). The same statistical methods as described for 
cohort A will be used to obtain the estimate of odds ratio and p-value for comparison between the 
treatment groups. 
In cohort B, a subject will be considered having a symptomatic RT-qPCR confirmed SARS-CoV-2 
infection (broad-term) during the EAP if subjects have at least 1 symptom within 14 days of a 
positive RT-qPCR result at baseline or during the EAP. 
Handling of Missing Central Lab SAR-CoV-2 RT-qPCR Data for Both Cohort A and 
Cohort B  
Subjects with COVID-19 symptoms that are missing a central lab-determined RT-qPCR test 
during the EAP (eg, are too sick to go to the study site) but have a positive SARS-COV-2 test from 
a local lab (eg, in the hospital) will be considered as having a symptomatic infection if any of the 
symptoms occurred within 14 days of the positive SARS-COV-2 test(s). 
The graphical display using Kaplan-Meier curve for the time to first symptom will also be 
provided.  
11.4.3.1.1. Sensitivity Analyses  
Robustness of the primary analyses results in cohort A and cohort B will be assessed through 
sensitivity analyses as follows: 
Sensitivity analysis by excluding subjects who develop asymptomatic or symptomatic SARS-
CoV-2 infection within 72 hours of the study drug administration 
This analysis assesses for the sensitivity of the results to subjects who may have had undetected 
infections prior to dosing. That is, a subject had any onset of a positive RT-qPCR within 72 hours 
of the study drug administration will be excluded for this sensitivity analysis.  
This sensitivity analysis will only be performed for cohort A primary endpoint.  
Sensitivity analysis by excluding subjects from non-good clinical practice (GCP) Compliant 
Site(s) 
To access the impact of sites that had non-GCP compliance issues on the primary efficacy points, 
the primary analyses will be performed by excluding non-GCP compliant site(s).  
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This sensitivity analysis will be performed for both cohort A and cohort B primary endpoints.  
11.4.3.1.2. Subgroup Analyses  
To assess the homogeneity of the treatment effect across various subgroups, the primary analysis 
model with GEE approach will be applied to each subgroup if applicable; otherwise, the logistic 
regression model will be used. Odds ratio between the treatment groups and corresponding 95% CI 
will be provided, as well as the within-household correlation coefficient from GEE approach, 
within each subgroup.  
The subgroups of interest to be evaluated for cohort A primary endpoint include, but are not 
limited to: 
• Stratification age group (years) (≥12 to <18, ≥18 to <50, ≥50) and the additional age 
group: ≥12 to <18, ≥18 years 
• Sex  
• Race  
• Ethnicity 
• BMI (<30, ≥30)  
• Number of study subjects in cohort B within a household (0, ≥1) (cohort A only) 
• Total household size including the household member(s) not participating this study 
(2, and >2) 
• Region (US, ex-US) 
Additional subgroup analyses will be defined in the SAP. 
11.4.3.2. Key Secondary Efficacy Analyses  
For cohort A, the key binary endpoint of the proportion of subjects who have a RT-qPCR 
confirmed SARS-CoV-2 infection (regardless of symptoms) during the EAP, the same statistical 
method used in the primary analysis will be applied. If a subject’s overall infection status during 
the EAP cannot be determined due to missing RT-qPCR results, the following rules will be applied 
to impute the missing RT-qPCR data. 
1. For subjects satisfying the criteria specified in the handling of missing central lab 
SARS-CoV-2 RT-qPCR data of the analysis of primary efficacy variables, the 
corresponding visit(s) will be considered as having a positive RT-qPCR test.  
2. After the first step above, each planned visit with missing RT-qPCR data will be imputed 
100 times to generate 100 complete datasets based on the predicted probability using the 
fully conditional specification (FCS) (Van Buuren, 2006) through the logistic regression. 
The logistic regression model includes the fixed effect factors of treatment group, region, 
age group, and RT-qPCR testing status at other analysis visits during the EAP. This 
imputation will repeat by iterating for each analysis visit with missing RT-qPCR testing 
status.  Full details on details on the use of FCS from the SAS MI procedure will be 
provided in the SAP. 
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For the key binary endpoint of the proportion of subjects with viral load >4 (log10 copies/mL), if 
NP swab viral load data is missing for a visit, it will not be imputed regardless of symptoms. Only 
non-missing available NP swab viral load data will be used for the analysis of this endpoint. Only 
subjects with at least one post-baseline viral load (log10 copies/mL) data in NP swab samples will 
be included in the analysis. 
For 
cohort 
A 
the 
key 
binary 
endpoint 
regarding 
the 
index 
case 
linkage 
to 
R10933-10987-COV-2067, the Fisher's exact test will be used.  
For continuous key secondary endpoints in cohort A and cohort B (eg, number of weeks of high 
viral load >4 (log10 copies/mL) in NP swab samples and number of weeks of symptomatic 
RT-qPCR-confirmed SARS-CoV-2 infection (broad-term) during the EAP, etc), visits with 
missing viral load regardless of symptoms and visits with missing RT-qPCR that do not have any 
broad-term symptoms within 14 days will not be considered as meeting these endpoint criteria, 
respectively. These endpoints will be analyzed by the non-parametric method, a stratified 
Wilcoxon rank sum test (Van Elteren Test) with the region and age group. Descriptive statistics 
will be provided for number (%) of subjects with each interval of duration in weeks (ie, 0 week, 
> 0 to ≤ 1 week, > 1 to ≤2 weeks, etc) within each treatment group. The total weeks of infection 
and normalized duration (eg, average duration infection per 1000 subjects) per treatment group 
will also be reported. 
11.4.3.3. Other Secondary Efficacy Analyses  
Other secondary efficacy endpoints will be analyzed by type of endpoint for all cohorts. The 
analysis methods for key secondary efficacy endpoints in both cohort A and cohort B will also be 
applied to efficacy endpoints for exploratory endpoints in both cohort A and cohort B if 
appropriate. The primary approach to the data will be through descriptive statistics. For the 
comprehensive evaluation of efficacy, nominal p-values may be reported. Raw data descriptive 
statistics will also be presented. 
Other secondary efficacy endpoints and exploratory endpoints for cohort A1 and cohort B1 will 
also be analyzed by type of endpoint. If the sample size is sufficient, continuous variables will be 
summarized by the descriptive statistics (eg, n, mean, SD, Q1, median, Q3, minimum and 
maximum, etc.). Binary variables will be summarized using the number and percentage of subjects 
in each treatment group. No statistical hypothesis testing will be performed for cohort A1 and 
cohort B1.  This approach may also be applied to adolescent subjects. 
Binary Endpoints 
The binary endpoints in cohort A and cohort B will be analyzed applying the same approach used 
for the primary efficacy endpoints.  The details will be provided in the SAP. 
Continuous Endpoints  
The secondary and exploratory continuous efficacy endpoints such as TWA, AUC, and maximum 
viral load (log10 copies/mL) will be analyzed using the ANOVA including treatment group, 
region, and age group as fixed effects or using the ANCOVA if adjusting by the relevant baseline 
values as covariate and treatment-by-covariate interaction are needed.  For other endpoints with 
non-normal/skewed distribution, the Van Elteren test used in the key secondary endpoints will be 
applied. 
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11.4.4. 
Control of Multiplicity 
The overall type I error will be controlled in each of seronegative mFAS-A and seronegative 
mFAS-B independently at 2-sided 5% significance level.  
Seronegative mFAS-A Subjects 
The overall type I error will be controlled for the primary hypothesis in cohort A based on a 2-sided 
test at an alpha level of 0.05 as follows: 
H0: There is no treatment difference between REGN10933+REGN10987 and placebo in 
the proportion of subjects with a symptomatic RT-qPCR confirmed SARS-CoV-2 infection 
during EAP. 
H1: There is a treatment difference between REGN10933+REGN10987 and placebo in the 
proportion of subjects with a symptomatic RT-qPCR confirmed SARS-CoV-2 infection 
during the EAP 
If the primary efficacy endpoint in cohort A is statistically significant, the alpha level of 0.05 will 
be released for the key secondary endpoints in cohort A. The hierarchical testing sequence for key 
secondary efficacy endpoints is presented in Table 10. 
Table 10: 
Hierarchy Testing Sequence of Key Secondary Efficacy Endpoints in 
Seronegative mFAS-A 
Key Secondary Efficacy Endpoints 
Proportion of subjects with viral load >4 (log10 copies/mL) in NP swab samples during the EAP 
Number of weeks of symptomatic RT-qPCR-confirmed SARS-CoV-2 infection (broad-term) 
during the EAP  
Number of weeks of high-viral load >4 (log10 copies/mL) in NP swab samples during the EAP  
Number of weeks of RT-qPCR confirmed SARS-CoV-2 infection (regardless of symptoms) 
during the EAP 
Proportion of subjects who have a RT-qPCR confirmed SARS-CoV-2 infection (regardless of 
symptoms) during the EAP 
Proportion of subjects in placebo group with a RT-qPCR confirmed SARS-CoV-2 infection 
during the EAP with index case participating in study R10933-10987-COV-2067 (comparison 
of those whose index cases receive REGN10933+REGN10987 versus placebo in R1033-10987-
COV-2067) 
Seronegative mFAS-B Subjects 
The overall type I error will be controlled for the primary hypothesis in cohort B based on a 2-sided 
test at an alpha level of 0.05 as follows. 
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H0: There is no treatment difference between REGN10933+REGN10987 and placebo in 
proportion of subjects who subsequently develop signs and symptoms (broad-term) within 
14 days of a positive RT-qPCR at baseline or during the EAP 
H1: There is a treatment difference between REGN10933+REGN10987 and placebo in the 
proportion of subjects who subsequently develop signs and symptoms (broad-term) within 
14 days of a positive RT-qPCR at baseline or during the EAP 
If statistical significance is established for the primary efficacy endpoint in cohort B, a hierarchical 
testing procedure will be applied to the key secondary endpoints in cohort B at a 2-sided 0.05 
significance level. The order of testing sequence for key secondary endpoints is presented in 
Table 11.  
Table 11: 
Hierarchy Testing Sequence of Key Secondary Efficacy Endpoints in 
Seronegative mFAS-B 
Key Secondary Efficacy Variables 
Number of weeks of symptomatic SARS-CoV-2 infection (broad-term) within 14 days of a 
positive RT-qPCR at baseline or during the EAP 
Number of weeks of high viral load (log10 copies/mL) >4 in NP swab samples during the EAP 
 
11.4.5. 
Safety Analysis 
11.4.5.1. Adverse Events 
Definitions 
For safety variables, the following observation periods are defined: 
• The pretreatment period is defined as the time from signing the ICF to before the first 
dose of study drug. 
• The treatment-emergent EAP is defined as the day from first dose of study drug to 
28 days after the last dose of study drug. 
• The treatment-emergent follow-up period is defined from the day after the end of the 
treatment-emergent EAP to the end of the Follow-up Period (ie, last study visit). 
Treatment-emergent adverse events (TEAEs) are defined as those that are not present at baseline 
or represent the exacerbation of a pre-existing condition. 
Treatment-emergent adverse events (TEAEs) will be summarized for each of the following 
periods: treatment-emergent EAP, treatment-emergent follow-up period, and combined across the 
treatment-emergent EAP and treatment-emergent follow-up periods.  Adverse events that occur 
prior to treatment will be listed. 
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Analysis 
All AEs reported in this study will be coded using the currently available version of the Medical 
Dictionary for Regulatory Activities (MedDRA®), version 23.0 or greater.  Coding will be to 
lowest level terms.  The preferred term (PT), and the primary system organ class (SOC) will be 
listed. 
The number and percentage of subjects with TEAEs will be summarized by treatment group.  
Summaries will include: 
• Overview of TEAEs, ie, overall number (%) of subjects with any TEAE, Serious 
TEAE, TEAE leading to death, or TEAE leading to study drug withdrawn 
• TEAEs by primary SOC and PT 
• TEAEs by severity (according to the grading scale outlined in Section 10.2.4), 
presented by SOC and PT 
• TEAEs by relationship to treatment (related, not related), presented by SOC and PT 
• Treatment-emergent SAEs by primary SOC and PT  
• Treatment-emergent AESIs by primary SOC and PT  
• Treatment-emergent AEs leading to study drug withdrawn by primary SOC and PT  
Similar summaries as described above will also be provided for adult, adolescent and pediatric 
subjects (<12 years), respectively.  Deaths and other SAEs will be listed and summarized by 
treatment group. 
In addition, the number and percentage of subjects with symptomatic SARS-CoV-2 infections, 
and the severity of the infection will be summarized by treatment group. SARS-CoV-2 infection 
will be summarized for each of the following periods: EAP and Follow-up period. 
11.4.5.2. Other Safety (Vital Signs and Laboratory Tests) 
Definitions 
The following definitions will be applied to laboratory parameters and vital signs: 
• The potentially clinically significant value (PCSV) criteria are defined as abnormal 
values considered medically important by the Sponsor according to predefined 
criteria/thresholds based on literature review and defined by the Sponsor for clinical 
laboratory tests and vital signs. The PCSV criteria will be provided in the SAP. 
• PCSV criteria will determine which subjects had at least 1 PCSV during the respective 
TEAE periods, taking into account all evaluations performed during the respective 
TEAE periods, including unscheduled or repeated evaluations. The number of all such 
subjects will be the numerator for the PCSV percentage. 
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Analysis 
The incidence of PCSVs at any time during the TEAE period will be summarized regardless of the 
baseline level, and again according to the following baseline categories: 
• Normal/missing 
• Abnormal according to PCSV criterion or criteria 
Shift tables based on baseline normal/abnormal and other tabular and graphical methods may be 
used to present the results for laboratory tests of interest. 
Listings will be provided for subjects meeting PCSV criteria and subjects with any positive 
RT-qPCR test results, respectively. 
11.4.5.3. Treatment Exposure 
The duration of study treatment exposure will be defined as 28 days after the last dose for a subject 
in SAF. The follow-up period is defined as 8 months after the dose administration. 
11.4.5.4. Treatment Compliance 
Subject treatment compliance is not applicable for this study, since the study drug is administered 
once at the site and will be the same as treatment exposure. 
11.4.6. 
Pharmacokinetics 
11.4.6.1. Analysis of Drug Concentration Data 
Dense Samples for Drug Concentration 
The PK parameters to be determined for REGN10933 and REGN10987 may include, but are not 
limited to: 
Cmax, tax, tlast, Clast, AUCinf, t1/2, C28 (concentration in serum 28 days after dosing)   
Selected PK parameters will be summarized by descriptive statistics for each cohort. All 
parameters will be summarized (mean, SD, %CV, range, median, and number of samples).  
Sparse Samples for Drug Concentrations 
The concentrations of REGN10933 and REGN109877 in serum over time will be summarized by 
descriptive statistics for each cohort. 
No formal statistical hypothesis testing will be performed.  
11.4.7. 
Pharmacokinetics and Pharmacokinetics/Pharmacodynamics Analyses 
At a minimum, exposure-response analyses will be performed for selected virologic endpoints. 
Additional exposure response analyses will be performed for safety endpoints and/or biomarkers, 
as appropriate.  
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11.4.8. 
Analysis of Immunogenicity Data 
Immunogenicity will be characterized by ADA and NAb responses and titers observed in subjects 
in the ADA and NAb analysis sets. The ADA response categories and titer categories are defined 
as follows: 
ADA response categories: 
• ADA Negative, defined as ADA negative response in the ADA assay at all time points, 
regardless of any missing samples. 
• Pre-existing immunoreactivity, defined as either an ADA positive response in the ADA 
assay at baseline with all post first dose ADA results negative, or a positive response 
at baseline with all post first dose ADA responses less than 9-fold over baseline titer 
levels. 
• Treatment-emergent response, defined as an ADA positive response in the ADA assay 
post first dose when baseline results are negative or missing. 
• Treatment-boosted response, defined as a positive response in the ADA assay post first 
dose that is greater than or equal to 9-fold over baseline titer levels, when baseline 
results are positive 
Titer categories (Maximum titer values) 
• Low (titer <1,000) 
• Moderate (1,000 ≤ titer ≤ 10,000) 
• High titer >10,000) 
The following analysis will be provided: 
• Number (n) and percent (%) of ADA-negative subjects (pre-existing immunoreactivity 
or negative in the ADA assay at all time points) by treatment groups  
• Number (n) and percent (%) of treatment-emergent ADA positive subjects by treatment 
groups and ADA titer categories 
• Number (n) and percent (%) of treatment-boosted ADA positive subjects by treatment 
groups and ADA titer categories 
Listing of all ADA titer levels will be provided for subjects with pre-existing, treatment-emergent, 
and treatment-boosted ADA response. 
The absolute occurrence (n) and percent of subjects (%) with NAb status in the NAb analysis set 
will be provided by treatment groups. 
11.4.9. 
Timing of Statistical Analysis 
There are multiple steps of analyses planned for this study. 
• An administrative assessment based on approximately first 554 randomized cohort A 
subjects has been conducted. No formal statistical hypothesis testing was performed. 
(Section 11.2). The individuals who can access the subject treatment information will 
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be described in the communication plan. These 554 subjects will not be included in the 
first-step or second-step efficacy analyses described below. 
• The first step analysis (primary analysis): The database lock will occur when all cohort 
A and cohort B subjects complete the EAP. The data during the EAP has been collected 
and validated for all subjects who were randomized by 28 Jan 2021. Subjects who are 
randomized after 28 Jan 2021 (approximately 269 subjects) will not be included in this 
first-step analysis. The individual treatment codes will be unblinded and final analyses 
of the primary and some secondary efficacy endpoints of cohort A and cohort B will 
be conducted.  
Note: The results of primary and some secondary efficacy endpoints in the first step 
analysis maybe used for a submission dossier to health authorities. 
• The second step analysis (final analysis): The database lock will occur after the last 
subject completes the study. All treated subjects, including 554 subjects in the 
administrative assessment, subjects in the first step analysis, and those subjects 
(approximately 269 subjects) who were randomized after 28 Jan 2021, will be included 
in the safety analysis. The second-step analysis for efficacy will include all subjects 
except those subjects who were included in the administrative assessment. 
11.5. 
Interim Analysis 
No interim analysis will be conducted for this study.   
11.6. 
Statistical Considerations Surrounding the Premature Termination 
of a Study 
If the study is terminated prematurely, only those parameters required for the development 
program and/or reporting to regulatory authorities will be summarized. Investigator and sponsor 
responsibilities surrounding the premature termination of a study are presented in Section 15.1. 
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12. 
QUALITY CONTROL AND QUALITY ASSURANCE 
In accordance with ICH E6, the sponsor is responsible for quality assurance to ensure that the 
study is conducted and the data generated, recorded, and reported in compliance with the protocol, 
GCP, and any applicable regulatory requirement(s). The planned quality assurance and quality 
control procedures for the study are described in this section. 
12.1. 
Data Management and Electronic Systems 
12.1.1. 
Data Management 
A data management plan specifying all relevant aspects of data processing for the study (including 
data validation [quality-checking], cleaning, correcting, releasing) will be maintained and stored 
at Regeneron (Sponsor). 
A medical coding plan will specify the processes and the dictionary used for coding. All data 
coding (eg, AEs, baseline findings, medication, medical history/surgical history) will be done 
using internationally recognized and accepted dictionaries. 
The CRF data for this study will be collected with an electronic data capture (EDC)  
12.1.2. 
Electronic Systems 
Electronic systems that may be used to process and/or collect data in this study will include the 
following: 
• IWRS system – randomization, study drug supply 
• EDC system – data capture – Medidata Rave 
• Statistical Analysis System (SAS) – statistical review and analysis 
• Pharmacovigilance safety database 
12.2. 
Study Monitoring 
12.2.1. 
Monitoring of Study Sites 
Regeneron uses a study-specific risk based approach to study monitoring and oversight, aligned 
with risk based quality principles, outlined in ICH E6 (R2) Guideline for Good Clinical Practice. 
Risk-Based Quality Monitoring (RBQM) methodology focuses on employing a fit-for-purpose 
monitoring strategy, supported either directly by Regeneron as sponsor, or via our CRO partners. 
RBQM strategies include: reduced source data verification (SDV), targeted source data review 
(SDR), the use of off-site/remote and triggered on-site monitoring visits, and Centralized 
Monitoring to identify site level risks and study level trends. The investigator must allow 
study-related monitoring activities to occur. 
The study monitors will perform ongoing source data review to verify that data recorded in the 
CRF by authorized site personnel are accurate, complete, and verifiable from source documents, 
that the safety and rights of subjects are being protected, and that the study is being conducted in 
accordance with the current approved protocol version and any other study agreements, ICH GCP, 
and all applicable regulatory requirements. 
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12.2.2. 
Source Document Requirements 
Investigators are required to prepare and maintain adequate and accurate subject records (source 
documents).  The site is responsible to ensure quality within their records and systems and are 
accountable for ensuring that all source data and CRF data are timely, accurate and complete. 
The investigator must keep all source documents on file with the CRF (throughout this protocol, 
CRF refers to either a paper CRF or an electronic CRF).  Case report forms and source documents 
must be available at all times for inspection by authorized representatives of the sponsor and 
regulatory authorities. 
12.2.3. 
Case Report Form Requirements 
Study data obtained in the course of the clinical study will be recorded on electronic Case Report 
Forms (CRFs) within the EDC system by trained site personnel.  All required CRFs must be 
completed for each and every subject enrolled in the study.  The investigator must ensure the 
accuracy, completeness, and timeliness of the data reported to the sponsor in the CRFs.  After 
review of the clinical data for each subject, the investigator must provide an electronic signature.  
A copy of each subject CRF casebook is to be retained by the investigator as part of the study 
record and must be available at all times for inspection by authorized representatives of the sponsor 
and regulatory authorities. 
Corrections to the CRF will be entered in the CRF by the investigator or an authorized designee.  
All changes, including date and person performing corrections, will be available via the audit trail, 
which is part of the EDC system.  For corrections made via data queries, a reason for any alteration 
must be provided. 
12.3. 
Audits and Inspections 
This study may be subject to a quality assurance audit or inspection by the sponsor or regulatory 
authorities.  Should this occur, the investigator is responsible for: 
• Informing the sponsor of a planned inspection by the authorities as soon as notification 
is received, and authorizing the sponsor’s participation in the inspection 
• Providing access to all necessary facilities, study data, and documents for the inspection 
or audit 
• Communicating any information arising from inspection by the regulatory authorities 
to the sponsor immediately 
• Taking all appropriate measures requested by the sponsor to resolve the problems found 
during the audit or inspection 
Documents subject to audit or inspection include but are not limited to all source documents, CRFs, 
medical records, correspondence, ICFs, IRB/EC files, documentation of certification and quality 
control of supporting laboratories, and records relevant to the study maintained in any supporting 
pharmacy facilities.  Conditions of study material storage are also subject to inspection.  In 
addition, representatives of the sponsor may observe the conduct of any aspect of the clinical study 
or its supporting activities both within and outside of the investigator's institution. 
In all instances, the confidentiality of the data must be respected. 
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12.4. 
Study Documentation 
12.4.1. 
Certification of Accuracy of Data 
A declaration assuring the accuracy and content of the data recorded on the eCRF must be signed 
electronically by the investigator.  This signed declaration accompanies each set of subject final 
eCRF that will be provided to the sponsor. 
12.4.2. 
Retention of Records 
The investigator must retain all essential study documents, including ICFs, source documents, 
investigator copies of CRFs, and drug accountability records for at least 15 years following the 
completion or discontinuation of the study, or longer, if a longer period is required by relevant 
regulatory authorities.  The investigator must obtain written approval from the sponsor before 
discarding or destroying any essential study documents during the retention period following study 
completion or discontinuation.  Records must be destroyed in a manner that ensures 
confidentiality. 
If the investigator's personal situation is such that archiving can no longer be ensured, the 
investigator must inform the sponsor (written notification) and the relevant records will be 
transferred to a mutually agreed-upon destination.  
13. 
ETHICAL AND REGULATORY CONSIDERATIONS 
13.1. 
Good Clinical Practice Statement 
It is the responsibility of both the sponsor and the investigator(s) to ensure that this clinical study 
will be conducted in accordance with the ethical principles that have their origin in the Declaration 
of Helsinki, and that are consistent with the ICH guidelines for GCP and applicable regulatory 
requirements. 
13.2. 
Informed Consent 
The principles of informed consent are described in ICH guidelines for GCP. 
Adult Subjects 
The ICF used by the investigator must be reviewed and approved by the sponsor prior to 
submission to the appropriate IRB/EC.  A copy of the IRB/EC-approved ICF and documentation 
of approval must be provided to the sponsor before study drug will be shipped to the study site. 
It is the responsibility of the investigator or designee (if acceptable by local regulations) to obtain 
written informed consent from each subject prior to his/her participation in the study and after the 
aims, methods, objectives, and potential hazards of the study have been explained to the subject in 
language that he/she can understand.  The ICF should be signed and dated by the subject and by 
the investigator or authorized designee who reviewed the ICF with the subject. 
• Subjects who can write but cannot read will have the ICF read to them before signing 
and dating the ICF. 
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• Subjects who can understand but who can neither write nor read will have the ICF read 
to them in presence of an impartial witness, who will sign and date the ICF to confirm 
that informed consent was given. 
The original ICF must be retained by the investigator as part of the subject's study record, and a 
copy of the signed ICF must be given to the subject. 
If new safety information results in significant changes in the risk/benefit assessment, or if there 
are significant changes to the study procedures, the ICF must be reviewed and updated 
appropriately. All study subjects must be informed of the new information and provide their 
written consent if they wish to continue in the study. The original signed revised ICF must be 
maintained in the subject’s study record and a copy must be given to the subject. 
Pediatric Subjects: Adolescent and Children (<12 years) 
The ICF used by the investigator must be reviewed and approved by the sponsor prior to 
submission to the appropriate IRB/EC.  A copy of the IRB/EC -approved ICF and documentation 
of approval must be provided to the sponsor before study drug will be shipped to the study site. 
It is the responsibility of the investigator or designee (if acceptable by local regulations) to obtain 
written informed consent from each subject and his/her parent(s) or legal guardian(s) prior to the 
subject’s participation in the study and after the aims, methods, objectives, and potential hazards 
of the study have been explained to the fullest possible extent in language that the subject and the 
parent(s) or legal guardian(s) can understand.  The ICF should be signed and dated by the subject’s 
parent(s) or legal guardian(s) and the same investigator or designee who explained the ICF. 
Local law must be observed in deciding whether 1 or both parents/guardians consent is required.  
If only 1 parent or guardian signs the consent form, the investigator must document the reason the 
other parent or guardian did not sign.  The subject may also be required to sign and date the ICF, 
as determined by the IRB/EC and in accordance with the local regulations and requirements. 
• Subjects who can write but cannot read will have the assent form read to them before 
writing their name on the form. 
• Subjects who can understand but who can neither write nor read will have the ICF 
read to them in presence of an impartial witness, who will sign and date the ICF to 
confirm that informed consent was given. 
The original ICF must be retained by the investigator as part of the subject’s study record, and a 
copy of the signed ICF must be given to the subject’s parent(s) or legal guardian(s). 
13.3. 
Subjects Confidentiality and Data Protection 
The investigator must take all appropriate measures to ensure that the anonymity of each study 
subject will be maintained. Subjects should be identified by a subject identification number only, 
on CRFs or other documents submitted to the sponsor. Documents that will not be submitted to 
the sponsor (eg, signed ICF) must be kept in strict confidence.  Government agencies such as 
Health and Human Services, other health authorities, IRBs/ ECs, and staff/contractors may review 
these records, as appropriate. 
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The subject 's and investigator's personal data, which may be included in the sponsor database, 
will be treated in compliance with all applicable laws and regulations.  The sponsor shall take all 
appropriate measures to safeguard and prevent access to this data by any unauthorized third party. 
13.4. 
Institutional Review Board/Ethics Committee 
An appropriately constituted IRB/EC, as described in ICH guidelines for GCP, must review and 
approve: 
• The protocol, ICF, and any other materials to be provided to the subjects 
(eg, advertising) before any subject may be enrolled in the study 
• Any amendment or modification to the study protocol or ICF before implementation, 
unless the change is necessary to eliminate an immediate hazard to the subject, in which 
case the IRB/EC should be informed as soon as possible  
• Ongoing studies on an annual basis or at intervals appropriate to the degree of risk  
In addition, the IRB/EC should be informed of any event likely to affect the safety of subjects or 
the continued conduct of the clinical study. 
A copy of the IRB/EC approval letter with a current list of the IRB/EC members and their functions 
must be received by the sponsor prior to shipment of drug supplies to the investigator.  The 
approval letter should include the study number and title, the documents reviewed, and the date of 
the review. 
Records of the IRB/EC review and approval of all study documents (including approval of ongoing 
studies) must be kept on file by the investigator. 
13.5. 
Clinical Study Data Transparency 
Final study results will be published on a public clinical trial website according to applicable local 
guidelines and regulations.  Treatment codes will be disseminated to each investigation site 
thereafter. 
14. 
PROTOCOL AMENDMENTS 
The sponsor may not implement a change in the design of the protocol or ICF without an 
IRB/EC-approved amendment.  Where required per local legislation, regulatory authority approval 
will also be sought.  
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15. 
PREMATURE TERMINATION OF THE STUDY OR CLOSE-
OUT OF A SITE 
15.1. 
Premature Termination of the Study 
The sponsor has the right to terminate the study prematurely.  Reasons may include efficacy, 
safety, or futility, among others.  Should the sponsor decide to terminate the study, the 
investigator(s) will be notified in writing. 
15.2. 
Close-out of a Site 
The sponsor and the investigator have the right to close-out a site prematurely. 
Investigator’s Decision 
The investigator must notify the sponsor of a desire to close-out a site in writing, providing at least 
30 days’ notice.  The final decision should be made through mutual agreement with the sponsor.  
Both parties will arrange the close-out procedures after review and consultation. 
Sponsor’s Decision 
The sponsor will notify the investigator(s) of a decision to close-out a study site in writing.  
Reasons may include the following, among others:  
• The investigator has received all items and information necessary to perform the study, 
but has not enrolled any subject within a reasonable period of time 
• The investigator has violated any fundamental obligation in the study agreement, 
including but not limited to, breach of this protocol (and any applicable amendments), 
breach of the applicable laws and regulations, or breach of any applicable ICH 
guidelines  
• The total number of subjects required for the study are enrolled earlier than expected 
In all cases, the appropriate IRB/EC and Health Authorities must be informed according to 
applicable regulatory requirements, and adequate consideration must be given to the protection of 
the subjects’ interests. 
16. 
CONFIDENTIALITY 
Confidentiality of information is provided as a separate agreement. 
17. 
FINANCING AND INSURANCE 
Financing and insurance information is provided as a separate agreement. 
18. 
PUBLICATION POLICY 
Publication rights and procedures will be outlined in a separate clinical study agreement. 
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20. 
INVESTIGATOR’S AGREEMENT 
I have read the attached protocol: A Phase 3, Randomized, Double-Blind, Placebo-Controlled 
Study Assessing the Efficacy and Safety of Anti-Spike SARS-CoV-2 Monoclonal Antibodies in 
Preventing SARS-CoV-2 Infection in Household Contacts of Individuals Infected with 
SARS-CoV-2 and agree to abide by all provisions set forth therein. 
I agree to comply with the current International Council for Harmonisation Guideline for Good 
Clinical Practice and the laws, rules, regulations, and guidelines of the community, country, state, 
or locality relating to the conduct of the clinical study. 
I also agree that persons debarred from conducting or working on clinical studies by any court or 
regulatory agency will not be allowed to conduct or work on studies for the sponsor or a partnership 
in which the sponsor is involved.  I will immediately disclose it in writing to the sponsor if any 
person who is involved in the study is debarred, or if any proceeding for debarment is pending, or, 
to the best of my knowledge, threatened. 
This document contains confidential information of the sponsor, which must not be disclosed to 
anyone other than the recipient study staff and members of the IRB/EC.  I agree to ensure that this 
information will not be used for any purpose other than the evaluation or conduct of the clinical 
investigation without the prior written consent of the sponsor. 
 
 
 
 
 
 
(Signature of Investigator) 
 
(Date) 
 
 
 
(Printed Name) 
 
 
 
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SIGNATURE OF SPONSOR’S RESPONSIBLE OFFICERS 
(Medical/Study Director, Regulatory Representative, Clinical Study Lead, and 
Biostatistician) 
To the best of my knowledge, this report accurately describes the planned conduct of the study. 
Study Title: 
 A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Assessing the 
Efficacy and Safety of Anti-Spike SARS-CoV-2 Monoclonal Antibodies in Preventing 
SARS-CoV-2 Infection in Household Contacts of Individuals Infected with SARS-CoV-2 
Protocol Number: R10933-10987-COV-2069 
Protocol Version:  R10933-10987-COV-2069 Amendment 6 
 
See appended electronic signature page 
Sponsor’s Responsible Medical/Study Director 
 
 
See appended electronic signature page 
Sponsor’s Responsible Regulatory Liaison 
 
 
See appended electronic signature page 
Sponsor’s Responsible Clinical Study Lead 
 
 
See appended electronic signature page 
Sponsor’s Responsible Biostatistician 
 
 
                                        VV-RIM-00142963-1.0 Approved - 25 Mar 2021 GMT-5:00


Signature Page for VV-RIM-00142963 v1.0
Signature Page for VV-RIM-00142963 v1.0 Approved
ESig Approval
ESig Approval
ESig Approval
ESig Approval
ESig Approval
                                        VV-RIM-00142963-1.0 Approved - 25 Mar 2021 GMT-5:00