Conditions: Coronavirus Disease 2019
Keywords: COVID-19
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 484
Healthy volunteers: no

Brief summary:
The purpose of this study was assess the safety and efficacy of leronlimab (PRO 140) administered as weekly subcutaneous injection in subjects with severe or critical COVID-19 disease.

Detailed description:
This was a Phase 2b/3, two-arm, randomized, double blind, placebo controlled, adaptive design multicenter study to evaluate the safety and efficacy of leronlimab (PRO 140) in patients with severe or critical symptoms of respiratory illness caused by coronavirus 2019 infection. Patients will be randomized to receive weekly doses of 700 mg leronlimab (PRO 140), or placebo. Leronlimab (PRO 140) and placebo will be administered via subcutaneous injection.

A single arm, non-randomized, open-label phase was added to the protocol after completion of enrollment in the randomized phase of the study.

The study had three phases: Screening Period, Treatment Period, and Follow-Up Period.

Arms:
arm 1: Syringes containing normal saline for injection were prepared by an unblinded pharmacist at the clinical sites for use as the placebo. arm 2: Each vial of active contains 350mg of leronlimab at a concentration of 175mg/ml (nominal 2mL fill volume) in formulation buffer containing histidine, glycine, sodium chloride, sorbitol, polysorbate 20 and sterile water for injections. arm 3: Each vial of active contains 350mg of leronlimab at a concentration of 175mg/ml (nominal 2mL fill volume) in formulation buffer containing histidine, glycine, sodium chloride, sorbitol, polysorbate 20 and sterile water for injections.

Interventions: intervention 1: Placebo intervention 2: Leronlimab (700mg)
Intervention descriptions: intervention 1: Placebo intervention 2: Leronlimab (PRO) 140 is a humanized IgG4, monoclonal antibody (mAb) to the C-C chemokine receptor type 5 (CCR5)

Protocol document:
ICF_002.pdf: 
 
 
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Protocol CD12_COVID-19 
RESEARCH SUBJECT INFORMATION AND CONSENT FORM AND 
AUTHORIZATION TO USE AND DISCLOSE PROTECTED HEALTH INFORMATION 
 
TITLE: 
A Phase 2b/3, Randomized, Double Blind, Placebo 
Controlled, Adaptive Design Study to Evaluate the Efficacy 
and Safety of Leronlimab for Patients with Severe or Critical 
Coronavirus Disease 2019 (COVID-19) 
 
PROTOCOL NO.: 
CD12_COVID-19 
IRB Protocol#20200923 
 
SPONSOR: 
CytoDyn, Inc. 
 
<<CF-Main Header Block - Investigator>> 
STUDY RELATED 
PHONE NUMBER(S): 
<<CF-Main User Defined #1>> 
 
In this consent form “you” generally refers to the research subject. If you are being 
asked as the legally authorized representative to permit the subject to take part in the 
research, “you” in the rest of this form generally means the research subject. 
 


 
 
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INTRODUCTION 
You are being invited to take part in a clinical research study because you have been 
diagnosed with Coronavirus Disease 2019, known as COVID-19. This research study is 
using an investigational drug as a possible treatment for this diagnosis.   
 
The name of the study drug involved in this study is: 
 
• Leronlimab (PRO 140). It belongs to a class (group) of drugs called CCR5 
antagonist. 
 
For purposes of this research, you will be referred to as a “participant”.   
 
CytoDyn, Inc., a pharmaceutical company is supporting this research study by providing 
funding for this research study.  
 
This research consent form explains why this research study is being done, what is 
involved in participating in the research study, the possible risks and benefits of 
participation, alternatives to participation, and your rights as a research participant.  The 
decision to participate is yours.  If you decide to participate, please sign and date at the 
end of this form. We will give you a copy so that you can refer to it while you are 
involved in this research study. If you choose not to participate in this research study, 
the research doctors will discuss other treatment options with you and/or refer you back 
to your primary doctor.  
 
Before you decide to take part in this study, it is important for you to understand why the 
research is being done and what it will involve. 
 
WHY IS THIS RESEARCH STUDY BEING DONE?  
This research study is a Phase 2b/3 clinical trial. Phase 2b/3 clinical trials test the safety 
and effectiveness of an investigational drug to learn whether the drug works in treating a 
specific disease.   
 
Your study doctor and medical team are conducting a research study with CytoDyn, Inc. 
This study will help determine the safety and efficacy of leronlimab (PRO 140) in the 
treatment of coronavirus disease 2019 (COVID-19). 
 
The safety of leronlimab (PRO 140) has been previously evaluated in over 750 people 
in previous studies. The product you will be using is an investigational drug. 
“Investigational” means that the drug is being studied.  The FDA (the U.S. Food and 
Drug Administration) has not approved this drug, leronlimab (PRO 140) as a treatment 
for any disease. The results of these studies will be used to design future studies to 
improve treatment of patients suffering from COVID-19. 
 
In the Randomized part of this study, 390 subjects were randomly assigned (by chance, 
like drawing straws) to receive two doses of leronlimab (PRO 140) or placebo. Patients 


 
 
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had 2 chances in 3 (67%) of receiving the study drug and 1 chance in 3 (33%) of 
receiving the placebo.  Neither patients nor the study doctor were aware of the 
treatment assignment. About 390 subjects were enrolled in the randomized study 
across 30 centers. 
 
After the completion of enrollment in the Randomized Phase of the study,  an Open-
label Phase is added to provide access to leronlimab for the eligible patients while 
waiting for the results for the randomized portion of the study. If you are eligible, you will 
be assigned to receive Leronlimab (PRO 140) in this open-label phase of the study. 
Approximately, 100 patients are expected to be enrolled in this open-label phase. 
Enrollment will remain open until the decision is made by CytoDyn and/or regulatory 
authorities to close the recruitment. 
You will be allowed to continue to receive the standard treatment in combination with 
leronlimab (PRO 140) or placebo. This includes hydroxychloroquine or chloroquine with 
or without azithromycin, Veklury (remdesivir), Dexamethasone (or other corticosteroids), 
monoclonal antibodies (such as bamlanivimab, casirivimab, imdevimab), 
immunomodulatory agents (such as baricitinib, sarilumab, clazakizumab, tocilizumab, 
anakinra), or Convalescent plasma therapy if already prescribed to you by your doctor.  
 
 
 
HOW DOES Leronlimab (PRO 140) WORK? 
Leronlimab (PRO 140) belongs to the monoclonal antibody class of medicines. 
Monoclonal antibodies are synthetic versions of the disease-fighting proteins 
(antibodies) that are naturally produced by the body. Antibodies that are normally 
circulating in the blood typically react to any foreign organisms or materials that enter 
our body. However, leronlimab (PRO 140) binds to a protein (CCR5) that is present on 
the surface of one kind of our blood cells. By doing so, it is hoped that it prevents the 
bad inflammation and damage to the lungs that result from infection with the 
coronavirus, and thus might be useful in the treatment of COVID-19. 
 
In the disease COVID-19, the body may respond to the viral infection by overproducing 
immune cells and their signaling molecules in a dangerous phenomenon called cytokine 
storm, which is often associated with a surge of activated immune cells into the lungs. 
This can lead to acute respiratory distress syndrome (ARDS).  
 
In ARDS, fluid builds up in the tiny, elastic air sacs (alveoli) in your lungs. The fluid 
keeps your lungs from filling with enough air, which means less oxygen reaches your 
bloodstream. This deprives your organs of the oxygen they need to function. ARDS has 
known to be one of the main reasons for death in patients with COVID-19. 
 
Leronlimab (PRO 140) does not kill the novel coronavirus. It acts as a CCR5 antagonist 
by blocking pro-inflammatory cytokines, which prevents cytokine storm and thus could 
be useful in treatment of COVID-19. 
  


 
 
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A small Phase II study of 86 patients with mild to moderate coronavirus disease 2019 
(COVID-19) did not meet its study goal to demonstrate difference between Leronlimab 
and placebo as the vast majority of the patients with mild to moderate COVID-19 
recover with supportive care. However, some additional analyses of the data indicated a 
possibility of benefit in more severe patients. Safety results showed no new safety risk 
was identified in patients receiving Leronlimab.  
 
This document uses words such as treatment, drug, medication, and patient. Please 
remember this is a research study and the use of these terms does not mean the use of 
the leronlimab (PRO 140) has been found to be safe or effective for your condition. 
 
WHAT OTHER OPTIONS ARE THERE? 
Taking part in this research study is voluntary. There is no specific antiviral treatment 
recommended for COVID-19. Instead of being in this research study, you have other 
options which may include the following:  
 
• Other standard supportive care to help relieve symptoms 
• Take part in another research study being explored for antiviral treatment 
 
Please talk to the research doctor about your options and their risks and benefits before 
you decide whether you will take part in this research study. 
 
WHAT IS INVOLVED IN THE RESEARCH STUDY? 
• You will take once weekly dose of 700 mg leronlimab (PRO 140) for two weeks.  
• Leronlimab (PRO 140) or placebo will be injected via a very thin needle slightly 
below the surface of your skin in your stomach, by the research staff or visiting 
nurse. You will receive two injections (of 2 mL) or four injections (of 1 mL), every 
week for two weeks. Placebo was used in the randomized part but is not used in 
the open-label part of this study, 
• Your participation involves 3 periods: 
 
o Screening will take up to 1 week and may include more than one visit. 
o Treatment will last for two weeks and include four visits. You will receive 
treatment with leronlimab (PRO 140) twice during the two-week Treatment 
Phase.  
o Follow-up phase will last for four weeks. The follow-up phase includes two 
visits, two weeks apart. Visits during the follow-up phase can be 
conducted as telephone or video contact visits. 
 
• In total, the expected study duration is 42 days (6 weeks).  
• At visits conducted at the hospital, you and the study staff will be provided the 
appropriate protective gear (e.g., masks, gloves) to prevent the spread of the 
infection. If you are discharged from the hospital at any point during the study, 
study visits can be conducted at your home by a visiting nurse or a trained 
member of the study team. 


 
 
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• Sometimes it is hard to keep track of all of the details and procedures that are 
part of a research study.  We will describe them in this consent form and you can 
refer to this at any time during the research study. 
 
Before the research starts (screening):   
After signing this consent form, you will be asked to undergo some screening tests or 
procedures to find out if you can participate in the research study. If you have had some 
of these tests or procedures recently, they may not have to be repeated. 
 
The screening period may last up to seven days (1 week). 
 
Screening Visit 
The following procedures will be done at the screening visit: 
 
• You will be asked a number of general questions about your age, race, ethnicity, 
your medical and surgical history, including any illnesses or health problems, and 
your prior or current medications. 
• Your study doctor will give you a Physical Exam. 
• Your height, weight, heart rate, temperature, blood pressure, and breathing rate 
will also be assessed. 
• Your study doctor will assess your clinical status based on your hospitalization 
status and if you have any limitations.  
• Your study doctor will measure the ratio between the oxygen level in your blood 
and the amount of oxygen you breathe in. 
• You doctor will perform a test (pulse oximetry) to measure your blood oxygen 
level 
• If you are intubated within 72 hours of this visit (using a tube to help you 
breathe), your doctor will measure the pressure in your lungs. 
• Your doctor will perform an assessment (Sequential Organ Failure Assessment 
(SOFA) Score) to determine the severity of your health status. The assessment 
score is based on lab results and clinical status. 
• Your doctor will determine your National Early Warning Score 2 (NEWS2) by 
checking your blood oxygen levels as well as assessing your breathing, your 
need for oxygen, heart and breathing rate, and your consciousness level. (Not 
done in the open-label part of this study) 
• Your study doctor will perform an ECG (electrocardiogram – a test to check your 
heart). 
• A series of blood tests will be performed. The amount of blood needed for these 
tests is about 3-4 teaspoons. 
 
o A blood test for general health screening, such as chemistry and complete 
blood count. 
 
• If you are a female and able to become pregnant, a pregnancy test will be 
required. If the pregnancy test is positive, you will not be able to be in the study. 


 
 
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• A urine sample will be needed for lab tests.  
• A nasal swab will be taken to test for the level of coronavirus in your body. (Not 
done in the open-label part of this study) 
• If needed, you will have a computed tomography (CT) scan, or chest X-ray test 
done to allow your study doctor to take images of your body or lungs. 
• An assessment to test your requirement for breathing or oxygen assistance, 
renal replacement therapy, or any hospital stay.  
 
Note that all of the procedures listed above may not be done if at any point during the 
evaluation, you fail eligibility. If you are not eligible for the study, your study doctor will 
explain the reasons and arrange for your prescribed standard care to continue. 
 
Within this 1-week period, you will be informed if you are eligible to enter the study. If 
Visit 2 takes place on the same day as the Screening Visit, scheduled assessments 
performed under screening (V1) do not need to be repeated. 
 
Treatment Period 
 
Visit 2 (Day 0) 
The treatment will start within 1 week of the Screening Visit.  
 
Before you receive any study treatment, your study doctor will reconfirm your study 
eligibility by completing the following procedures: 
 
• Your pulse rate, respiratory rate, temperature, and blood pressure will be 
assessed.  
• Your study doctor will measure your weight and give you a physical exam based 
on any changes reported in your health. 
• Your study doctor will assess your clinical status based on your hospitalization 
status and if you have any limitations.  
• Your study doctor will measure the ratio between the oxygen level in your blood 
and the amount of oxygen you breathe in. 
• You doctor will perform a test (pulse oximetry) to measure your blood oxygen 
level 
• If you are intubated (using a tube to help you breathe), your doctor will measure 
the pressure in your lungs. 
• Your doctor will perform an assessment (Sequential Organ Failure Assessment 
(SOFA) Score) to determine the severity of your health status. The assessment 
score is based on lab results and clinical status. 
• Your doctor will determine your National Early Warning Score 2 (NEWS2) by 
checking your blood oxygen levels as well as assessing your breathing, your 
need for oxygen, heart and breathing rate, and your consciousness level. (Not 
done in the open-label part of this study) 


 
 
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• A blood test to check the levels of certain proteins and substances in your blood 
cells (Not done in the open-label part of this study) 
• A blood test to check level of CCR5 receptors on the specialized white blood 
cells (Treg and macrophages) and any changes to the CCR5 gene 
(polymorphism). (Not done in the open-label part of this study) 
• A nasal swab will be taken to test for the level of coronavirus in your body. (Not 
done in the open-label part of this study) 
• An assessment to test your requirement for breathing or oxygen assistance, 
renal replacement therapy, or any hospital stay.  
 
Once all of the above assessments have been completed, your study doctor will 
perform for the following procedures: 
• You will receive your treatment injections of leronlimab (PRO 140) or placebo.  
• Your essential body functions like pulse rate, temperature, respiration rate, and 
blood will be recorded 
• You will be asked to report any symptoms that you experienced.  
 
Leronlimab (PRO 140) will be given under your skin as two 2mL shots on opposite sides 
of the stomach or as four 1mL injections at the clinic or at your home. 
 
Visit 3 (Day 3) 
The following assessments will be performed at Visit 3: 
 
• Your doctor will perform a physical exam based on any changes reported in your 
health  
• You will be asked about any change in current medications 
• Your pulse rate, respiratory rate, temperature, and blood pressure will be 
assessed.  
• Your study doctor will assess your clinical status based on your hospitalization 
status and if you have any limitations.  
• Your study doctor will measure the ratio between the oxygen level in your blood 
and the amount of oxygen you breathe in. 
• You doctor will perform a test (pulse oximetry) to measure your blood oxygen 
level 
• If you are intubated (using a tube to help you breathe), your doctor will measure 
the pressure in your lungs. 
• Your doctor will perform an assessment (Sequential Organ Failure Assessment 
(SOFA) Score) to determine the severity of your health status. The assessment 
score is based on lab results and clinical status. 
• A nasal swab will be taken to test for the level of coronavirus in your body. (Not 
done in the open-label part of this study) 
• An assessment to test your requirement for breathing or oxygen assistance, 
renal replacement therapy, or any hospital stay.  
• You will be asked to report any symptoms that you experienced 


 
 
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• A series of blood tests will be performed. The amount of blood needed for these 
tests is about 3-4 teaspoons. 
 
o A blood test for general health screening, such as chemistry and complete 
blood count 
o A blood test to check the levels of certain proteins and substances in your 
blood cells (Not done in the open-label part of this study) 
o A blood test to check level of CCR5 receptors on the specialized white 
blood cells (Treg and macrophages) and any changes to the CCR5 gene 
(polymorphism). (Not done in the open-label part of this study) 
 
Continuation of Treatment, Visit 4 (Day 7) 
For Visit 4, the following assessments will be performed: 
 
• Your study doctor will give you a physical exam. 
• You will be asked if there have been any changes to the medications you are 
taking  
• Your weight, heart rate, temperature, blood pressure, and breathing rate will also 
be assessed. 
• Your study doctor will assess your clinical status based on your hospitalization 
status and if you have any limitations.  
• Your study doctor will measure the ratio between the oxygen level in your blood 
and the amount of oxygen you breathe in. 
• You doctor will perform a test (pulse oximetry) to measure your blood oxygen 
level 
• If you are intubated (using a tube to help you breathe), your doctor will measure 
the pressure in your lungs. 
• Your doctor will perform an assessment (Sequential Organ Failure Assessment 
(SOFA) Score) to determine the severity of your health status. The assessment 
score is based on lab results and clinical status. 
• Your doctor will determine your National Early Warning Score 2 (NEWS2) by 
checking your blood oxygen levels as well as assessing your breathing, your 
need for oxygen, heart and breathing rate, and your consciousness level. (Not 
done in the open-label part of this study) 
• A nasal swab will be taken to test for the level of coronavirus in your body. (Not 
done in the open-label part of this study) 
• Your study doctor will check your clinical symptoms regarding any fever, muscle 
pain, breathing difficulties, and cough. 
• A series of blood tests will be performed. The amount of blood needed for these 
tests is about 3-4 teaspoons. 
 
o A blood test for general health screening, such as chemistry and complete 
blood count. 
o A blood test to check the levels of certain proteins and substances made 
by a kind of your blood cells (Not done in the open-label part of this study) 


 
 
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o A blood test to check level of CCR5 receptors on the specialized white 
blood cells (Treg and macrophages) and any changes to the CCR5 gene 
(polymorphism). (Not done in the open-label part of this study) 
o A urine sample will be needed for lab tests 
 
• You will be asked to report any symptoms that you experienced 
• You will receive your treatment injections of leronlimab (PRO 140) or placebo. 
 
Visit 5, End of Treatment (Day 14) 
One week after your last treatment, you will be asked to visit the clinic for the end of 
treatment (EOT) visit during which the following assessments will be performed: 
 
• You will be asked to report any symptoms that you experienced 
• You will be asked if there have been any changes to the medications you are 
taking 
• Your study doctor will give you a Physical Exam. 
• Your weight, heart rate, temperature, blood pressure, and breathing rate will also 
be assessed. 
• Your study doctor will assess your clinical status based on your hospitalization 
status and if you have any limitations.  
• Your study doctor will measure the ratio between the oxygen level in your blood 
and the amount of oxygen you breathe in. 
• You doctor will perform a test (pulse oximetry) to measure your blood oxygen 
level 
• If you are intubated (using a tube to help you breathe), your doctor will measure 
the pressure in your lungs. 
• Your doctor will perform an assessment (Sequential Organ Failure Assessment 
(SOFA) Score) to determine the severity of your health status. The assessment 
score is based on lab results and clinical status. 
• Your doctor will determine your National Early Warning Score 2 (NEWS2) by 
checking your blood oxygen levels as well as assessing your breathing, your 
need for oxygen, heart and breathing rate, and your consciousness level. (Not 
done in the open-label part of this study) 
• A nasal swab will be taken to test for the level of coronavirus in your body. (Not 
done in the open-label part of this study) 
• A urine sample will be needed for lab tests 
• A series of blood tests will be performed. The amount of blood needed for these 
tests is about 3-4 teaspoons. 
 
o A blood test for general health screening, such as chemistry and complete 
blood count. 
o A blood test to check the levels of certain proteins and substances made 
by a kind of your blood cells (Not done in the open-label part of this study) 
 


 
 
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• If you are a female and able to become pregnant, a pregnancy test will be 
required. If the pregnancy test is positive, you will not be able to be in the study. 
• A blood test to check level of CCR5 receptors on the specialized white blood 
cells (Treg and macrophages) and any changes to the CCR5 gene 
(polymorphism). (Not done in the open-label part of this study) 
• If needed, you will have a computed tomography (CT) scan, or chest X-ray test 
done to allow your study doctor to take images of your body or lungs. 
• An assessment to test your requirement for breathing or oxygen assistance, 
renal replacement therapy, or any hospital stay.  
 
Follow-Up Period  
 
Visit 6 and Visit 7 (Day 28 and Day 42) 
The follow-up period will last up to four weeks and include two visits. The following 
assessments will be performed at each visit: 
 
• You will be asked to report any symptoms that you experienced.  
• You will be asked if there have been any changes to the medications you are 
taking.  
• Your study doctor will give you a physical exam. 
• Your heart rate, temperature, blood pressure, and breathing rate will also be 
assessed. 
• Your study doctor will assess your clinical status based on your hospitalization 
status and if you have any limitations (Visit 6 only).  
• A urine sample will be needed for lab tests 
• A series of blood tests will be performed. The amount of blood needed for these 
tests is about 3-4 teaspoons. 
 
o A blood test for general health screening, such as chemistry and complete 
blood count. 
 
• A nasal swab will be taken to test for the level of coronavirus in your body. (Not 
done in the open-label part of this study) 
 
HOW LONG WILL I BE IN THIS RESEARCH STUDY? 
This research study lasts for a total of 42 days. You can participate for as long as you 
do not have serious side effects and your disease does not get worse. 
 
You may be taken off the research study for many reasons including if: 
 
• It is considered to be in your best interest 
• The study treatment or procedures are found to be unsafe or ineffective 
• There is any problem with following study treatments and procedures 
• Your condition worsens 


 
 
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• Or for other unforeseen reasons that make it necessary to stop your participation 
in the research study 
• You become pregnant 
• If you miss two consecutive doses of the investigational drug 
• The study is canceled by the sponsor or the FDA 
 
If you are removed from the research study, the research doctor will explain to you why 
you were removed.   
 
In addition, you can stop participating in the research study at any time, however, the 
FDA requires that any information collected up to the point of your withdrawal cannot be 
removed from the study.  If you decide to stop participating in this research study, we 
encourage you to talk to the research doctor and your primary doctor first. 
 
WHAT ARE THE RISKS/SIDE EFFECTS OF TAKING PART? 
There are risks to taking part in any research study. One risk is that you may get a study 
drug that does not help treat your disease or that makes your condition or disease 
worse.  Another risk is that there may be side effects. You need to tell your doctor or 
a member of the study team immediately if you experience any side effects.  
 
Everyone in the research study will be watched carefully for side effects.  You will be 
monitored during the administration of study drugs to keep track of your essential body 
functions- blood counts and organ function, particularly your kidney and liver function.  If 
you experience side effects, they may go away after you stop taking the study drug.  
Some side effects can be mild; but others can be long lasting and may never go away.  
Some may be life-threatening or fatal.  
 
In other studies of leronlimab (PRO 140), possibly related side effects observed in 
subjects receiving the 700 mg dose included: 
 
• Reactions at the site of the injection such as: 
 
o Bruising 
o Redness of the skin 
o Fluid leakage 
o Itch 
o Rash 
 
• Headache 
• Diarrhea 
• Fatigue 
 
All of these side effects occurred in less than 2% of subjects.  
 


 
 
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Since the effect of the study drug(s) taken with other medications may not be known, it 
is important that you tell the research doctor about all prescription and non-prescription 
drugs, herbal preparations and nutritional supplements that you are taking or planning 
to take. There may also be some foods that you should avoid while on this research 
study and your research doctor will review this information with you. 
 
During the research study, you will be notified of newly discovered side effects or 
significant findings, which may affect your health or willingness to participate.  You may 
be asked to sign a new consent form that shows that you have been informed of new 
information relating to this research study. 
 
Side effects that you could experience during or after the leronlimab (PRO 140) 
treatment: 
 
• The most common potential study drug-related side effect that has been seen 
using the drug formulation that you will be using is mild headache. Other side 
effects likely to be related to the drug include mild to moderate diarrhea, nausea, 
and fatigue. There may be other side effects associated with leronlimab (PRO 
140) that we do not know about.  
• Leronlimab (PRO 140) belongs to the monoclonal antibody class of drugs. 
Monoclonal antibodies are sometimes associated with allergic reactions (fatigue, 
diarrhea, fever, vomiting, headache, nausea, pain at the site of injection, low 
blood pressure, rash, itching, and chills) or flu-like reactions such as fever, chills, 
and aches. These events usually do not last long if they occur at all. Severe 
allergic reactions, however, can be life-threatening. 
• Rare severe acute hypersensitivity reactions or anaphylaxis can occur. If 
anaphylaxis or severe allergic reactions occur, therapy with leronlimab (PRO 
140) will be permanently discontinued and appropriate medications (e.g., 
epinephrine) and supportive care will be provided. 
• People who take leronlimab (PRO 140) or other monoclonal antibodies can also 
develop an immune response to leronlimab (PRO 140) that may affect their 
ability to receive monoclonal antibodies, or to benefit from diagnosis or therapy 
with a monoclonal antibody in the future. 
• Side effects that may be associated within a short period of time after receiving 
drugs similar to leronlimab (PRO 140) through an injection include chills, 
headache, backache, overall feeling of being ill, fever, skin rash, nausea, tingling 
and high blood pressure. Your study doctor may give you medicine to help with 
these side effects. 
• People who lack a functional CCR5 gene are at increased risk for severe 
infection by West Nile virus. Please ask your study doctor about this. 
• Local pain, redness, tenderness, bruising, itching and rarely, an infection might 
occur at the site of injection in your stomach or at the site of the needle stick in 
your arm for blood draws or you may faint when blood is taken. 
• The nasal swab procedure to test for the level of coronavirus in your body may 
be uncomfortable. (Not done in the open-label part of this study) 


 
 
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• Studies on leronlimab (PRO 140) to determine its capability to cause harm to an 
unborn child have not been performed. If you are a woman of childbearing 
potential, you will be tested for pregnancy at the beginning of the study. 
• It is unknown if leronlimab (PRO 140) can pass through breast milk and it is 
unknown if this can cause harm to your child. 
 
In addition to the risks or discomforts listed here, there may be other risks that are 
currently not known.    
 
Reproductive Risks:  
The drug used in this research study may affect a fetus.  While participating in this 
research study, you should not become pregnant and should not nurse a baby.  We can 
provide counseling about preventing pregnancy. You must use at least one highly 
effective method of birth control (hormonal contraceptives such as implants, injectables, 
combined oral pills, patches or rings; intrauterine devices (IUDs), tubal ligation (two 
fallopian tubes that connect ovaries and uterus are blocked, tied, clamped, sealed, or 
cut) or sexual abstinence) throughout the course of this study. Let your doctor know 
immediately if you or your partner become pregnant. 
 
If you or your partner become pregnant during the course of this study, you will be 
followed until 3 months after the birth of the child. This will consist of telephone contact 
to determine what side effects may have happened 
 
Non-Physical Risks:  
Because of side effects or the time required for tests and clinic visits while you are on 
this research study, you may be unable to keep up with your normal daily activities.  
 
WHAT ARE THE POSSIBLE BENEFITS OF TAKING PART IN THIS STUDY? 
We do not know if taking part in this study will help you. This study may help 
researchers learn information that could help people in the future. If you receive 
leronlimab and it is effective, it may help prevent the bad inflammation and damage to 
the lungs that result from COVID-19 infection 
 
WILL I BE PAID TO TAKE PART IN THIS RESEARCH STUDY? 
You will not be paid for participating in this study.  
 
The study sponsor may reimburse you for qualifying study-related travel costs and/or 
expenses.  Study staff will review the reimbursement plan and any requirements for 
reimbursement with you.  
 
Patients will receive $XX for each completed study visit. If you do not complete the 
study, you will be paid for the visits which you have completed.  You will be paid at the 
end of the designated study visits.  
 
OR You will not receive any payment for taking part in this research study. 


 
 
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<<CF-Main Payment for Part. Paragraph>> 
 
WHAT IF SOMETHING IS DEVELOPED FROM THIS RESEARCH? 
We may use your samples and information to develop a new product or medical test to 
be sold.  The sponsor and hospital may benefit if this happens. There are no plans to 
pay you if your samples are used for this purpose. 
 
ARE THERE COSTS FOR PARTICIPATING IN THIS STUDY? 
Taking part in this research study might lead to added costs to you or your insurance 
company. 
 
You will not be charged for leronlimab (PRO 140).  It is possible that leronlimab (PRO 
140) may not continue to be supplied free for some reason.  If this would occur, your 
research doctor will talk with you about your options.  
 
You or your insurance company will be charged for portions of your care during this 
research study that are considered standard care. You may be responsible for co-
payments and deductibles that are typical for your insurance coverage. 
 
If you have questions about your insurance coverage, or the items you might be 
required to pay for, please call financial services of the hospital for information. You 
should also check with your insurance to see what services will be covered by your 
insurance and what you will have to pay. 
 
WHAT HAPPENS IF I AM INJURED OR BECOME SICK BECAUSE I TOOK PART IN 
THIS RESEARCH STUDY? 
If you think you have been injured as a result of taking part in this research study, tell 
the study doctor as soon as possible.  The research doctor’s name and phone number 
are listed in this consent form. The study doctor will treat you or refer you for care. 
 
The treating hospital will offer you the care needed to treat injuries directly resulting 
from taking part in this research.  These treatments will be billed to you or your 
insurance company. You will be responsible for deductibles and co-payments. There 
are no plans to pay you or give you other compensation for the injury. You do not give 
up your legal rights by signing this form.  
 
We will need to collect certain personal information about you for insurance or payment 
reporting purposes, such as your name, date of birth, gender, social security number or 
Medicare identification number and information related to this research study. We may 
be required to report this information to the Centers for Medicare & Medicaid Services. 
We will not use this information for any other purpose. 
 


 
 
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WILL MY TAKING PART IN THIS STUDY BE KEPT CONFIDENTIAL? 
We will take measures to protect the privacy and security of all your personal 
information, but we cannot guarantee complete confidentiality of study data. The 
information collected about you usually will not directly identify you (for example, by 
name, address, or social security number).  Instead, your initials and a code number will 
be used for your information.   
 
Medical information created by this research study may become part of your hospital 
medical record and may be forwarded to your primary doctor. Information that does not 
become part of your medical record will be stored in your study file. 
 
If you consent to take part in this study, your medical records may be reviewed by 
relevant employees of CytoDyn, Inc., the company sponsoring the study, or
 
LLC (Amarex), the company to which CytoDyn has given the management of this study, 
for purposes of analyzing the study results and monitoring the study. Regulatory 
authorities such as the U.S. Food and Drug Administration (FDA), the Institutional 
Review Board (IRB)<<CF-Main SMO Company 1>><<CF-Main Affiliated IN Language 
1>> and other foreign regulatory bodies may review study results and subject records to 
check that the study is being conducted correctly. They also want to make sure that 
your health information has been collected the right way, or for other reasons that are 
allowed under the law. Your identity and medical records will be kept confidential and 
will not be disclosed outside of the hospital/clinic/family physician’s office. 
 
The study team plans to publish the results of this research study and when we do, we 
may be asked to make the data we collect available to other researchers. We will not 
include information that identifies you in any publications or to the researchers who 
request the data to do additional research. 
      
The Genetic Information Nondiscrimination Act of 2008 (GINA) is a federal law that 
protects Americans from being treated unfairly because of differences in their DNA that 
may affect their health, and may prevent discrimination by health insurers and 
employers based on genetic information.   GINA is intended to ease concerns about 
discrimination that might keep some people from getting genetic tests that could benefit 
their health, and enable people to take part in research studies such as this without fear 
that their DNA information might be used against them by health insurers or their 
workplace.  This protection does not extend to disability or life insurance.  
 
Additional information can be found at http://www.genome.gov/10002328. 
 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as 
required by U.S. Law. This Web site will not include information that can identify you. At 
most, the Web site will include a summary of the results. You can search this Web site 
at any time. 
 


 
 
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WHAT IF NEW INFORMATION BECOMES AVAILABLE? 
During the course of a research study, new information may become available about 
your disease or the treatment that is being studied that might change your decision to 
be in this study. If this happens, your study doctor will discuss this with you and whether 
you want to continue in the study. If you decide to withdraw, your study doctor will make 
arrangements for your prescribed standard care to continue. If you decide to continue in 
the study you will be asked to sign an updated consent form. 
 
In addition, on receiving new information your study doctor might consider it to be in 
your best interest to withdraw you from the study. Your study doctor will explain the 
reasons and arrange for your prescribed standard care to continue. 
 
WHAT WILL HAPPEN TO THE RESULTS OF THE RESEARCH STUDY? 
This study is expected to start in 2020. Once the study has finished, the information will 
be analyzed and a clinical report will be written to record the results. This process can 
take about 6 months. Your study doctor will be kept informed of the results from the 
study, and a paper detailing these results will probably be published in an appropriate 
medical journal. You can also ask your study doctor for the results of the study. 
 
RESEARCH FUNDING 
The company sponsoring and funding this research is CytoDyn, Inc. 
 
The study center and/or your study doctor are receiving financial support from the 
sponsor for holding this study. <<CF-Main Financial Disclosure>> 
 
CAN I STOP BEING IN THE RESEARCH STUDY AND WHAT ARE MY RIGHTS? 
You have the right to choose not to sign this form. If you decide not to sign this form, 
you cannot participate in this research study.  
 
You can stop being in the research study at any time. Tell the research doctor if you are 
thinking about stopping or decide to stop.  He or she will tell you how to stop.  Leaving 
the research study will not affect your medical care outside of the research study.   
 
If you choose not to participate, are not eligible to participate, or withdraw from this 
research study, this will not affect your present or future care and will not cause any 
penalty or loss of benefits to which you are otherwise entitled.  
 
It is important to tell the research doctor if you are thinking about stopping so your 
research doctor can evaluate the risks from stopping leronlimab (PRO 140). In some 
cases, the abrupt stopping of a drug can have risks in itself. Another reason to tell your 
research doctor that you are thinking about stopping is to discuss what follow-up care 
and testing could be most helpful for you. 
 


 
 
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WHOM DO I CONTACT IF I HAVE QUESTIONS ABOUT THE RESEARCH STUDY? 
If you have questions, concerns, or complaints, or think this research has hurt you or 
made you sick, talk to the research team at the phone number(s) listed above on the 
first page. 
 
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 (888)-303-2224 or (800) 562-4789, irb@cgirb.com if: 
 
• 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. 
 
IRB will not be able to answer some study-specific questions, such as questions about 
appointment times. However, you may contact IRB if the research staff cannot be 
reached or if you wish to talk to someone other than the research staff. 
 
Do not sign this consent form unless you have had a chance to ask questions and have 
received satisfactory answers to all of your questions. 
 
If you agree to be in this study, you will receive a signed and dated copy of this consent 
form for your records. 
 
If you choose to participate in this study, please read the following and sign where 
indicated. 
 


 
 
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CONSENT 
I confirm that I have read this consent form (or it has been read to me) and have had 
the opportunity to ask questions. I agree to participate in this study and comply with the 
requirements to the best of my ability. 
 
My signature below indicates: 
 
• I have had enough time to read the consent and think about participating in 
this study; 
• I have had all of my questions answered to my satisfaction; 
• I am willing to participate in this study; 
• I have been told that my participation is voluntary and I can withdraw at any 
time 
 
By signing this consent form, I have not given up any of my legal rights. I will receive a 
signed and dated copy of this consent form<<CF-Main California Bill of Rights>>. 
 
 
 
 
Printed Name of Subject 
 
 
 
 
 
 
 
 
Subject Signature 
Date 
Time 
 
 
 
 
Printed Name of Legally Authorized Representative, if applicable 
 
 
 
 
 
 
 
 
Signature of Legally 
Date 
Time 
Authorized Representative 
 
 
 
 
Relationship of Legally Authorized Representative to Subject 
 
STATEMENT OF PERSON CONDUCTING INFORMED CONSENT DISCUSSION 
I, the undersigned, certify that to the best of my knowledge that subject named above or 
the subject’s legally authorized representative had the study fully and carefully 
explained, including the nature, risks, and benefits of his/her participation in the 
research study; and all questions were answered to his/her satisfaction. I confirm that 
the he/she freely and voluntarily gave consent to participate in this research study 


 
 
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before any study-related procedures were performed. A medical problem or language or 
educational barrier has not precluded this understanding. 
 
I reviewed the consent form with the subject or the subject’s legally authorized 
representative and answered his/her questions. The subject or his/her legally authorized 
representative appeared to have understood the information and was able to answer 
the following questions correctly: 
 
• What is the purpose of this study? 
• If you decide to be in the study, what will you be asked to do? 
• What is the possible benefit of participating in this study? 
• What are the possible risks of participating in this study? 
• If you decide not to participate in this study, what options do you have? 
• Will participating in this study cost you anything? If so, what will you have to pay 
for? 
• Do you have to be in this study? 
• If you decide to be in the study, can you leave the study when you want to? 
 
 
 
 
 
 
 
 
Signature of Person Conducting 
Date 
Time 
Informed Consent Discussion 
 
 
 
 
Name of Person Conducting Informed Consent Discussion 
 
---------------------------- Use this witness section only if applicable ------------------------- 
If this consent form is read to the subject or the subject’s legally authorized 
representative because he/she is unable to read the form, an impartial witness not 
affiliated with the research or investigator must be present for the consent and sign the 
following statement: 
 
I confirm that the information in the consent form and any other written information was 
accurately explained to, and apparently understood by, the subject or the subject’s 
legally authorized representative. He/she freely consented to be in the research study. 
 
 
 
 
Printed Name of Impartial Witness 
 
 
 
 
 
 
Signature of Impartial Witness 
Date 
 


 
 
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An impartial witness is: 
 
• a person who is independent of the trial,  
• who cannot be unfairly influenced by people involved with the trial, 
• who attends the informed consent process, and  
• who reads the informed consent form and any other written information supplied 
to the subject or the subject’s legally authorized representative. 
 
Note: This signature block cannot be used for translations into another language. A 
translated consent form is necessary for enrolling subjects who do not speak English. 
 
Original for researcher; one copy for subject; one copy to be kept with medical 
records. 
 


 
 
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AUTHORIZATION TO USE AND DISCLOSE PROTECTED HEALTH 
INFORMATION 
 
While you are participating in this research study, the study doctor and his 
study staff will collect and create personal health information about you and 
record it on study forms. This information may include health histories, 
examinations and results of tests. The study doctor will keep this 
information in study records. He may also gather information regarding 
your past, present, and/or future medical conditions from your primary 
medical doctor. These records may also include personal information such 
as your birth date, social security number, or medical record numbers 
which could be used to identify you. This type of information is called 
“Protected Health Information” (PHI). 
 
The terms “you” and “your” in this Authorization refer to the research 
subject. 
 
Under a federal law called the “Privacy Rule” or Health Insurance 
Portability and Accountability Act of 1996 (HIPAA), your PHI that is 
gathered and obtained during research cannot be used to conduct the 
research or be given to anyone for research purposes without your 
permission. Because of this rule, you may not participate in this study 
unless you give your permission to use and disclose your PHI. You do not 
have to sign this form, but if you do not, you cannot participate in this study. 
 
By signing this consent form, you are giving permission for the study doctor 
and his study staff to use your PHI to conduct this study, to monitor your 
health status, and possibly to develop new tests, procedures and 
commercial products. 
 
You are also agreeing to allow your PHI to be disclosed to the study 
sponsor and any representatives working with them. The sponsor may also 
give your PHI to the FDA or other regulatory agencies which are 
responsible for ensuring that the research is being done correctly. 
 
Study staff will assign a code number to you for this study. This will help to 
protect your identity; however, the sponsor may look at your complete 
study records which will identify you. The sponsor will also send 
representatives to your study doctor’s office to oversee how the study is 


 
 
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being conducted. These representatives will review your PHI to make sure 
the information is correct. The Institutional Review Board (IRB)<<CF-Main 
SMO Company 2>><<CF-Main Affiliated IN Language 2>> may also have 
access to your PHI. These disclosures help to make sure that all 
information related to the research is available to those who need it. 
 
Your identity will remain confidential and except for the disclosures 
described above and detailed specifically in the consent page, will not be 
shared with others, unless it is required by law. If your PHI is given to the 
parties listed above or to anyone who is not required to follow federal law, 
your PHI will no longer be protected by the “Privacy Rule” and could 
possibly be used or disclosed in ways other than are listed here. 
 
You have the right to see and make copies of your PHI. You are agreeing, 
however, not to see or make copies of your PHI until all of the sponsor 
work has been completed. At that time, you may ask to see your records. 
 
This permission will be good until December 31, 2068. You have the right 
to cancel or withdraw this authorization at any time. If you cancel this 
authorization, your PHI will no longer be used for this study, unless it is 
necessary (based on your earlier authorization) to complete analysis (test) 
and reports for this research. If you withdraw your permission, no new 
health information will be gathered unless you have a side effect related to 
the study.   
 
If you withdraw from the study but do not withdraw your Authorization, new 
health information may be collected until this study ends.   
 
In the event of an adverse drug reaction/serious side effect following 
revocation of Authorization, your information may still be used and 
disclosed as necessary for study purposes. 
 
To cancel your permission to use PHI, you must send a written notice to 
your study doctor’s office stating that you are canceling your authorization 
to use or disclose your protected health information. If you cancel this 
authorization, you will not be allowed to continue in this study. 
 


 
 
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Your decision to withdraw your Authorization or not to participate will not 
involve any penalty or loss of access to treatment or other benefits to which 
you are otherwise entitled.   
 
AUTHORIZATION 
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. I will receive a signed and dated copy of this Authorization. 
 
 
 
 
Printed Name of Subject 
 
 
 
 
 
 
 
 
Subject Signature 
Date 
Time 
 
 
 
 
 
Printed Name of Legally Authorized Representative, if applicable 
 
 
 
 
 
 
 
 
Signature of Legally 
Date 
Time 
Authorized Representative 
 
 
 
 
 
Relationship of Legally Authorized Representative to Subject 
 


 
 
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Statement of the Witness (when applicable*) 
The information in the authorization was accurately explained to, and 
appeared to be understood by the subject or the subject’s legally 
authorized representative. Authorization was freely given. 
 
 
 
 
Printed Name of Impartial Witness  
 
 
 
 
Signature of Impartial Witness  
 
 
 
 
Date 
 
*Impartial Witness: If the subject or the subject’s legally authorized 
representative cannot read, the signature of an Impartial Witness is 
needed.   
 
An impartial witness is: 
 
• a person who is independent of the trial,  
• who cannot be unfairly influenced by people involved with the trial, 
• who attends the informed consent process, and  
• who reads the informed consent form and any other written 
information supplied to the subject or the subject’s legally authorized 
representative.  
 

Prot_000.pdf: 
CONFIDENTIAL 
 
  
 
Page 1 of 108 
 
 
 
A Phase 2b/3, Randomized, Double Blind, Placebo Controlled, Adaptive Design 
Study to Evaluate the Efficacy and Safety of Leronlimab for Patients with 
Severe or Critical Coronavirus Disease 2019 (COVID-19) 
 
Protocol Number: 
CD12_COVID-19 
Version: 
6.0 
Date: 
28-Dec-2020 
 
 
 
Sponsor: 
CytoDyn, Inc. 
1111 Main Street, Suite 660 
Vancouver, Washington 98660 
(360) 980-8524-Work 
(360) 980-8549-Fax 
www.cytodyn.com 
 
 
 
 
Confidentiality Statement 
 
This document is a confidential communication of CytoDyn, Inc. It is provided for the conduct 
of a clinical research study. The information contained in this document is confidential and, except 
to the extent necessary to obtain informed consent or IEC/IRB approval, cannot be disclosed unless 
required by governmental regulation. Persons to whom any portion of the contents of this 
document is disclosed must be informed that the information is confidential and may not be further 
disclosed by them. 


 
 
Protocol #CD12_COVID-19 
                                                                                                   Version 6.0 
 
 
   Date: 28-Dec-2020 
CONFIDENTIAL 
 
  
 
Page 2 of 108 
PROTOCOL APPROVAL PAGE 
 
 
 
 
Protocol Number:  
CD12_COVID-19 
 
Version: 
 
6.0 
 
Date: 
 
28-Dec-2020 
 
We, the undersigned, have reviewed this protocol and agree that it contains all relevant information 
required to meet FDA, GCP and all applicable regulatory guidelines and statutes. 
PROTOCOL APPROVAL FOR USE 


 
 
Protocol #CD12_COVID-19 
                                                                                                   Version 6.0 
 
 
   Date: 28-Dec-2020 
CONFIDENTIAL 
 
  
 
Page 3 of 108 
INVESTIGATOR’S SIGNATURE PAGE 
 
 
 
Protocol Number:  
CD12_COVID-19 
 
Version: 
 
6.0 
 
Date: 
 
28-Dec-2020 
 
I have read the protocol specified above and agree to participate in and comply with the procedures, 
as outlined herein for the conduct of this clinical trial. I also agree to comply with US Food and 
Drug Administration (FDA) and other global regulatory authority regulations and Investigational 
Review Board/Institutional Ethics (IRB/IEC) requirements for testing on human subjects. I agree 
to ensure that the requirements for obtaining informed consent are met.  
 
 
 
 
 
Principal Investigator’s Signature 
 
 
 
 
Date 
Print Name 
 
 
 
 
 
 
 
Site Number 
 
 
 


 
 
Protocol #CD12_COVID-19 
                                                                                                   Version 6.0 
 
 
   Date: 28-Dec-2020 
CONFIDENTIAL 
 
  
 
Page 4 of 108 
SPONSOR INFORMATION 
Sponsor Office: 
CytoDyn, Inc. 
 
 
 
 
 
1111 Main Street, Suite 660 
 
 
 
 
 
Vancouver, Washington 98660 
 
 
 
 
 
(360) 980-8524-Work 
 
 
 
 
 
(360) 980-8549-Fax 
 
 
 
 
 
www.cytodyn.com 
 
 
CONTRACT RESEARCH ORGANIZATION INFORMATION 






















 
 
Protocol #CD12_COVID-19 
                                                                                                   Version 6.0 
 
 
   Date: 28-Dec-2020 
CONFIDENTIAL 
 
  
 
Page 15 of 108 
TABLE OF CONTENTS 
PROTOCOL SYNOPSIS ..............................................................................................................5 
TABLE OF CONTENTS ............................................................................................................15 
List of Tables .................................................................................................................................20 
List of Figures ...............................................................................................................................21 
List of Abbreviations .....................................................................................................................22 
1 INTRODUCTION AND BACKGROUND ..........................................................................24 
1.1. Statement of Intent ..............................................................................................................24 
1.2. Background of the Disease ..................................................................................................24 
1.3. Leronlimab (PRO 140) ........................................................................................................24 
1.4. Summary of Prior Pre-Clinical and Clinical Studies ...........................................................25 
1.4.1. 
Pre-Clinical Studies with PRO 140 ...................................................................25 
1.4.2. 
Clinical Studies with PRO 140 ..........................................................................25 
1.5. Treatment Rationale for this Study .....................................................................................36 
1.5.1. 
Study Rationale .................................................................................................36 
1.5.2. 
Rationale for Dose Selection and Treatment Duration .....................................39 
1.6. Risks / Benefits Assessment ................................................................................................41 
2. STUDY OBJECTIVES ..........................................................................................................43 
3. STUDY DESIGN ....................................................................................................................44 
3.1. Study Center ........................................................................................................................45 
3.2. Study Population .................................................................................................................45 
3.3. Eligibility Criteria ................................................................................................................45 
3.3.1. 
Inclusion Criteria ...............................................................................................45 
3.3.2. 
Exclusion Criteria ..............................................................................................47 
4. STUDY SCHEDULE .............................................................................................................48 
4.1. Screening Phase ...................................................................................................................54 
4.1.1. 
Screening Visit (V1) ..........................................................................................54 
4.2. Treatment Phase ..................................................................................................................55 


 
 
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4.2.1. 
Visit 2 (V2) ........................................................................................................55 
4.2.2. 
Visits 3 and 4, (V3 and V4) ...............................................................................56 
4.2.3. 
End of Treatment – EOT (V5) ..........................................................................57 
4.3. Follow-Up Phase .................................................................................................................59 
4.3.1. 
Visits 6 and 7 (V6 and V7) ................................................................................59 
4.4. Unscheduled Visits ..............................................................................................................60 
5. SUBJECT COMPLETION, WITHDRAWAL AND CRITERIA FOR STOPPING THE 
STUDY ....................................................................................................................................61 
5.1. Subject Completion .............................................................................................................61 
5.2. Early Stopping Rules ...........................................................................................................61 
5.3. Removal of Subjects from Study Treatment and/or Study as a Whole ...............................61 
5.4. Data Collected from Withdrawn Subjects ...........................................................................62 
5.5. Screen Failures ....................................................................................................................62 
6. STUDY TREATMENT .........................................................................................................63 
6.1. Leronlimab (PRO 140) ........................................................................................................63 
6.1.1. 
Leronlimab (PRO 140) - Packaging and Labeling ............................................63 
6.1.2. 
Leronlimab (PRO 140) - Storage and Handling ................................................65 
6.1.3. 
Leronlimab (PRO 140) - Administration ..........................................................65 
6.1.4. 
Leronlimab (PRO 140) - Post Injection Monitoring .........................................66 
6.1.5. 
Leronlimab (PRO 140) – Toxicity Management ..............................................66 
6.1.6. 
Leronlimab (PRO 140) - Disposition ................................................................67 
6.1.7. 
Leronlimab (PRO 140) - Accountability ...........................................................67 
7. DESCRIPTION OF PROTOCOL ASSESSMENTS AND PROCEDURES ...................68 
7.1. Informed Consent ................................................................................................................68 
7.2. Assessment of Eligibility .....................................................................................................68 
7.2.1. 
Re-screening ......................................................................................................68 
7.3. Demographic Information ...................................................................................................68 
7.4. Medical History ...................................................................................................................69 
7.5. Physical Examination ..........................................................................................................70 
7.6. Vital Signs, Height and Weight ...........................................................................................70 


 
 
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7.7. Concomitant Medications ....................................................................................................70 
7.7.1. 
Excluded Medications .......................................................................................71 
7.7.2. 
Allowable Medications and Therapies ..............................................................71 
7.8. Clinical Laboratory Assessments ........................................................................................72 
7.9. Study Treatment Application ..............................................................................................73 
7.10. Clinical Status –Ordinal Scale Assessment .........................................................................73 
7.11. PaO2/FiO2 Measurement ....................................................................................................74 
7.12. Pulse Oxygen Saturation (SpO2) ........................................................................................74 
7.13. Positive End-Expiratory Pressure (PEEP), if intubated ......................................................74 
7.14. Sequential Organ Failure Assessment (SOFA) score ..........................................................74 
7.15. National Early Warning Score 2 Assessment ......................................................................74 
7.16. Assessment of Clinical Recovery ........................................................................................74 
7.17. 12-Lead Electrocardiogram .................................................................................................74 
7.18. Nasopharyngeal Swab Sample Collection ..........................................................................75 
7.19. Chest Radiograph or Computed Tomography Scan ............................................................75 
7.20. Requirement of Mechanical Ventilation, Non-Invasive Ventilation, Supplemental Oxygen, 
Vasopressors Use, Renal Replacement Therapy, ICU Admission,   and Hospital Stay ................75 
7.21. Randomization .....................................................................................................................75 
8. STATISTICAL ANALYSIS .................................................................................................76 
8.1. Treatment Groups ................................................................................................................76 
8.2. Description of Study Outcomes (Endpoints) .......................................................................76 
8.2.1. 
Primary Endpoint ..............................................................................................76 
8.2.2. 
Secondary Endpoints .........................................................................................76 
8.2.3. 
Exploratory Outcome Measures (Endpoints) ....................................................76 
8.2.4. 
Safety Measures ................................................................................................78 
8.3. Sample Size Determination and Rationale ..........................................................................78 
8.4. Randomization .....................................................................................................................79 
8.5. Stratification ........................................................................................................................79 
8.6. Blinding ...............................................................................................................................79 
8.7. Time to Unblinding .............................................................................................................80 


 
 
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8.7.1. 
Interim Analysis ................................................................................................80 
8.7.2. 
Emergency Unblinding......................................................................................80 
8.7.3. 
Final Analysis ....................................................................................................80 
8.8. Interim Analysis ..................................................................................................................80 
8.9. General Statistical Considerations .......................................................................................81 
8.9.1. 
Analysis Populations .........................................................................................81 
8.9.2. 
Covariates ..........................................................................................................81 
8.9.3. 
Missing Data......................................................................................................82 
8.10. Analysis Methods ................................................................................................................82 
8.10.1. 
Subject Disposition ...........................................................................................82 
8.10.2. 
Demographic and Baseline Characteristics .......................................................82 
8.10.4. 
Efficacy Analyses ..............................................................................................82 
9. ADVERSE EVENTS (DEFINITIONS AND REPORTING) ............................................85 
9.1. Adverse event (AE) .............................................................................................................85 
9.2. Reporting of Adverse Events ..............................................................................................85 
9.2.1. 
Impact on Study Treatment ...............................................................................85 
9.2.2. 
CTCAE Grade (Intensity) Assessment ..............................................................85 
9.2.3. 
Causality Assessment ........................................................................................86 
9.2.4. 
Treatment Given as a Result of the Event .........................................................87 
9.2.5. 
Outcome Assessment ........................................................................................87 
9.3. Serious Adverse Events .......................................................................................................87 
9.4. Reporting of Serious Adverse Events (SAE) ......................................................................88 
9.5. SAE Follow-Up ...................................................................................................................88 
9.6. Expected/anticipated events ................................................................................................89 
10. DIRECT ACCESS TO SOURCE DATA/DOCUMENTATION ......................................90 
11. QUALITY CONTROL AND QUALITY ASSURANCE ...................................................91 
11.1. Monitoring Requirements ....................................................................................................91 
11.2. Acceptability of Case Report Forms (CRFs) ......................................................................91 
11.3. Modification of Protocol .....................................................................................................91 
11.4. Reporting Protocol Deviations ............................................................................................92 


 
 
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11.4.1. 
Major Protocol Deviation or Violation .............................................................92 
11.4.2. 
Minor Protocol Deviation or Violation .............................................................92 
12. DATA SAFETY MONITORING COMMITTEE (DSMC) ...............................................94 
13. ETHICS AND REGULATORY REQUIREMENTS .........................................................95 
13.1. Institutional Review Board/Independent Ethics Committee (IRB/IEC) .............................95 
13.2. Investigator’s Responsibilities ............................................................................................95 
13.3. Subject Informed Consent Requirements ............................................................................96 
14. DATA HANDLING AND RECORD KEEPING ................................................................97 
14.1. Recording and Collection of Data .......................................................................................97 
14.2. Clinical Data Management ..................................................................................................97 
14.3. Archiving .............................................................................................................................98 
15. PUBLICATION PLAN .......................................................................................................100 
16. REFERENCES .....................................................................................................................101 
17. APPENDIX ...........................................................................................................................103 
17.1. Appendix 1: National Early Warning Score 2 (NEWS2) ..................................................103 
17.2. Appendix 2: Common Terminology Criteria for Adverse Events v5.03 ..........................106 
17.3. Appendix 3: Sequential Organ Failure Assessment (SOFA) Score ..................................107 


 
 
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LIST OF TABLES 
Table 1-1: 
List of Completed Clinical Studies with Leronlimab (PRO 140) ...........................34 
Table 1-2: 
List of Ongoing Clinical Studies with Leronlimab (PRO 140) ...............................35 
Table 1-3: 
Immunologic Status - Post Leronlimab Therapy in COVID-19 Patients ................37 
Table 1-4: 
Cytokine Levels - Post Leronlimab Therapy in COVID-19 Patients ......................37 
Table 4-1: 
Treatment Groups ....................................................................................................49 
Table 4-2: 
Schedule of Assessments .........................................................................................51 
Table 6-1: 
Treatment Administration Summary .......................................................................63 
Table 6-2: 
Investigational Product - Leronlimab (PRO 140) ...................................................63 
Table 6-3: 
Leronlimab (PRO 140) - Management for Injection Site Reactions .......................66 
Table 6-4: 
Leronlimab (PRO 140) - Management for all Other Potential Toxicities (Attributable 
to Leronlimab) .........................................................................................................67 
Table 7-1: 
Lab Parameters ........................................................................................................72 
Table 9-1: 
CTCAE v5.0 General Guidelines ............................................................................86 
 


 
 
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LIST OF FIGURES 
Figure 1-1: 
Dose-response curve for inhibition of CC-chemokine-induced calcium mobilization 
by PRO 140 .............................................................................................................40 
Figure 3-1: 
Study Schematic ......................................................................................................44 
Figure 6-1: 
Investigational Product - Vial Label .......................................................................64 
Figure 6-2: 
Investigational Product - Syringe Label ..................................................................64 
Figure 6-3: 
Investigational Product - Kit Label .........................................................................64 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
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LIST OF ABBREVIATIONS 
Abbreviation 
Term 
AE 
Adverse Event 
ALT 
Alanine Transaminase 
ARDS 
Acute Respiratory Distress Syndrome 
ART 
Antiretroviral Therapy 
AST 
Aspartate Aminotransferase 
BUN 
Blood Urea Nitrogen 
CCR5 
C-C chemokine receptor type 5 
CD 
Cluster of Differentiation 
CFR 
Code of Federal Regulations 
Cmax 
Maximal Concentration  
CNS 
Central Nervous System 
COVID-19 
Coronavirus Disease 2019 
CRF 
Case Report Form 
CRO 
Contract Research Organization 
CS 
Clinically Significant 
CTCAE 
Common Terminology Criteria for Adverse Events 
eCRF 
Electronic Case Report Form 
CV 
Curriculum Vitae 
DSMC 
Data Safety Monitoring Committee 
ECG 
Electrocardiogram 
ECMO 
Extracorporeal Membrane Oxygenation 
EOT 
End of Treatment 
FDA 
U.S. Food and Drug Administration 
FDP 
Finished Drug Product 
FUV 
Follow-up Visit 
GCP 
Good Clinical Practice 
GFR 
Glomerular Filtration Rate 
GMP 
Good Manufacturing Practice 
HEENT 
Head, Ears, Eyes, Nose, and Throat 
HIPAA 
Health Insurance Portability Accountability Act 
HIV 
Human Immunodeficiency Virus 
IA 
Interim Analysis 
IC 
Inhibitory Concentration 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization 


 
 
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Abbreviation 
Term 
ICU 
Intensive Care Unit 
IEC 
Independent Ethics Committee 
IND 
Investigational New Drug 
IP 
Investigational Product 
IRB 
Institutional Review Board 
ISR 
Injection Site Reaction 
ITT 
Intent to Treat 
IV 
Intravenous 
IWRS 
Interactive Web Based Response System 
LAR 
Legally Authorized Representative 
LTF 
Lost to Follow-Up 
MedDRA 
Medical Dictionary for Regulatory Activities  
mg 
Milligram 
MTD 
Maximum Tolerated Dose 
NEWS 
National Early Warning Score 2 
OBT 
Optimized Background Therapy 
PD 
Pharmacodynamic 
PEEP 
Positive End-Expiratory Pressure 
PK 
Pharmacokinetic 
PI 
Principal Investigator 
RRT 
Renal Replacement Therapy 
SAE 
Serious Adverse Event 
SARS-CoV-2 
Severe Acute Respiratory Syndrome Coronavirus 2 
SC 
Subcutaneous 
SOFA 
Sequential Organ Failure Assessment 
SOP 
Standard Operating Procedure 
SpO2 
Peripheral Capillary Oxygen Saturation 
SV 
Screening Visit 
TEAE 
Treatment Emergent Adverse Event 
TNBC 
Triple Negative Breast Cancer 
Treg 
T regulatory cell 
TV 
Treatment Visit 
V 
Visit 
VL 
Viral Load 


 
 
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1 INTRODUCTION AND BACKGROUND 
1.1. 
STATEMENT OF INTENT 
The design, conduct and reporting of this study shall be conducted in compliance with the protocol, 
International Conference on Harmonization/Good Clinical Practice (ICH/GCP), and all appropriate 
regulatory requirements. Investigator(s) participating in this study will have documented training 
in GCP. Independent monitoring of the trial will be accomplished utilizing a Contract Research 
Organization (CRO). 
1.2. 
BACKGROUND OF THE DISEASE 
Coronavirus disease 2019 (COVID-19) is a respiratory illness that can spread from person to 
person. The infectious agent that causes COVID-19 is a novel Coronavirus, named ‘SARS-CoV-
2’, was first identified during a recent outbreak in December 2019, in Wuhan, China. Patients with 
COVID-19 have had mild to severe respiratory illness with symptoms of fever, cough, and 
shortness of breath along with non-specific symptoms including myalgia and fatigue. Some patients 
were more likely to develop a severe respiratory illness similar to severe acute respiratory syndrome 
(SARS), or even die from the disease.  
Current standard of care treatment includes oxygen therapy. There is no specific antiviral treatment 
recommended for COVID-19 by Centers for Disease Control and Prevention (CDC). People with 
COVID-19 should receive supportive care to help relieve symptoms. For severe cases, treatment 
should include care to support vital organ functions. 
The aim of this study is to test efficacy and safety of leronlimab (PRO140) for treatment of adult 
patients with severe or critical symptoms of respiratory illness caused by ‘SARS-CoV-2’ 
coronavirus infection. 
1.3. 
LERONLIMAB (PRO 140) 
Leronlimab (PRO) 140 is a humanized IgG4,κ monoclonal antibody (mAb) to the C-C chemokine 
receptor type 5 (CCR5), under development as a therapy for human immunodeficiency virus (HIV) 
infection. 
Leronlimab (PRO 140) has been shown to bind to the N terminus (Nt) and the extracellular loop 2 
(ECL2) domain of the CCR5 cell surface receptor that HIV-1 uses to gain entry to a cell. 
Leronlimab (PRO 140) (binding to CCR5 blocks viral entry by interfering with the final phase of 
viral binding to the cell surface prior to fusion of the viral and cell membranes. Leronlimab (PRO 
140) has been administered intravenously or subcutaneously to more than 750 healthy and HIV-1 
infected individuals in Phase I/II/III studies. The drug has been well tolerated following intravenous 
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(SC) injection. Overall, 324 subjects have been exposed to leronlimab (PRO 140) 350 mg SC weekly 
dose with the longest duration of exposure lasting 4 years. Similarly, more than 250 and 150 subjects 
have been exposed to leronlimab (PRO 140) 525 mg and 700 mg SC weekly dose, respectively. 
1.4. 
SUMMARY OF PRIOR PRE-CLINICAL AND CLINICAL STUDIES 
1.4.1. Pre-Clinical Studies with PRO 140 
In vitro and in vivo preclinical studies have been conducted to determine the pharmacokinetic, 
immunogenicity, and toxicity profiles of leronlimab (PRO 140) following IV and SC 
administration. Several acute and chronic toxicity studies have been conducted to support the 
clinical development plan.  
Acute toxicity of leronlimab (PRO 140) was evaluated in New Zealand rabbits, following IV 
administration of 5 or 15 mg/kg. Chronic toxicity was evaluated in cynomolgus monkeys following 
biweekly administration of IV doses up to 10 mg/kg for six months and biweekly administration of 
various SC doses up to 50 mg/kg for 24 weeks. The drug was generally well tolerated. Biweekly 
administration of IV doses up to 10 mg/kg for six months resulted in minimum to mild lymphoid 
hyperplasia in assorted lymph nodes and spleen, which was considered an expected immune 
response to a foreign protein. Biweekly administration of SC doses up to 50 mg/kg for 24 weeks 
resulted in minimum injection-site reactions (minimal, multifocal, mononuclear cell infiltrates in 
the subcutis), which were considered due to an inflammatory response to the injected antigen. 
Monkeys tolerated treatment with leronlimab (PRO 140) for 24 weeks without evidence of local or 
systemic toxicity. Leronlimab (PRO 140) caused no mortality, cageside observations, in-life 
injection-site observations, or gross pathologic findings. Chronic treatment with leronlimab (PRO 
140) did not affect body weight, food consumption, hematology, clinical chemistry or coagulation 
parameters. 
Both IV and SC administration resulted in elimination half-lives of approximately 200 hours, and 
overall exposure increased with increasing doses. Following SC administration of leronlimab (PRO 
140) in monkeys, the maximal concentration (Cmax) was achieved within 56 hours and 
bioavailability for leronlimab (PRO 140) after SC dosing was approximately 70%. 
1.4.2. Clinical Studies with PRO 140 
Current human experience with leronlimab (PRO 140) consists of nine completed and six ongoing 
clinical trials, mostly on healthy subjects or HIV-1 positive subjects. These studies are summarized 
in Table 1-1 and Table 1-2. In all clinical trials, the majority of adverse events (AEs) have been 
mild or moderate. No dose-limiting toxicities or patterns of drug-related toxicities were observed. 
Antiviral activity was potent, rapid, prolonged, dose-dependent, and highly significant. 


 
 
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1.4.2.1. 
PRO 140 1101 Study 
For the first-in-human trial, PRO 140 1101, the drug was administered IV at 0.1, 0.5, 2.0, or 5.0 
mg/kg to healthy subjects and was generally well tolerated, non-immunogenic, and without 
clinically relevant toxicity. Treatment Emergent Adverse Events (TEAEs) did not increase with 
rising PRO 140 dose levels. Seventy-five percent (75%) of subjects reported TEAEs, most of which 
were deemed unrelated to study treatment by the investigator. 
1.4.2.2. 
PRO 140 1102 Study 
For PRO 140 1102, the majority of AEs, other than injection-site reactions, were considered mild 
and possibly related to drug administration. The majority of injection-site reactions were considered 
mild, self-resolving, and definitely related to drug administration. PRO 140 derived from Chinese 
Hamster Ovary (CHO) cells and administered at 100 mg/mL was generally well tolerated in 
healthy, normal volunteers. Overall, PRO 140 administered SC using Autoject® 2 appeared better 
tolerated than manual injection. 
1.4.2.3. 
PRO 140 1103 Study  
In PRO 140-1103, administration of PRO 140 at 350 mg using Autoject® 2 appeared well tolerated. 
Manual injections, on the other hand, were associated with a greater number of AEs. There did not 
appear, however, to be any substantial difference in subject perception of pain or discomfort related 
to site of drug administration. No anti-PRO 140 antibodies were detected in any subjects in this 
study. There was a tendency of higher exposure associated with SC administration of PRO 140 at 
350 mg in the abdomen and the thigh. A higher number of AEs were associated with injections in 
the arm. Based on these observations, thigh and abdominal administration of PRO 140 were 
preferred over arm injection. 
1.4.2.4. 
PRO 140 1302 Study 
The initial proof-of-concept study was a randomized, double-blind, placebo-controlled study in 
subjects with early-stage, asymptomatic HIV infection, only R5 HIV-1 detectable, and no 
antiretroviral therapy for 12 weeks [Jacobson, 2008]. Subjects (n=39) were randomized to receive 
a single IV injection of placebo or PRO 140 at doses of 0.5, 2, or 5 mg/kg. Subjects were monitored 
for antiviral effects, safety, and PRO 140 pharmacokinetics (PK) for 58 days.  
PRO 140 demonstrated potent, rapid, prolonged, and dose-dependent antiviral activity. Intravenous 
PRO 140 was generally well tolerated. No drug-related serious events or dose-limiting toxicity was 
observed [Jacobson, 2008]. The most common adverse events (headache, lymphadenopathy, 
diarrhea, and fatigue) were observed at similar frequencies across the placebo and PRO 140 dose 


 
 
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groups. There was no significant effect on QTc intervals or other electrocardiographic parameters, 
and there were no remarkably laboratory findings. 
1.4.2.5. 
PRO 140 2301 Study 
PRO 140 2301 was a multi-center, randomized, double-blind, placebo-controlled, parallel group 
study in 30 male and female adult subjects infected with HIV-1 [Jacobson, 2010]. Subjects were 
randomized to one of three groups (N=10/group), each receiving one of three treatments: (i) a single 
IV dose of 5 mg/kg by 30-minute IV infusion; (ii) a single IV dose of 10 mg/kg by 30-minute IV 
infusion; (iii) a single placebo dose by 30-minute IV infusion. The objective of the study was to 
assess and characterize the PK and PD of PRO 140 administered by IV infusion, assess efficacy at 
a new dosage level, and safety and tolerability of single doses of PRO 140. 
All PRO 140-treated subjects had more than 10-fold reduction in viral loads [Jacobson, 2010]. Both 
the 5 mg/kg and 10 mg/kg doses have shown favorable tolerability and no dose-limiting toxicity 
has been observed. High levels of receptor occupancy (>85% reduction in the number of cells 
detected) were observed for 29 days after treatment with both 5 and 10 mg/kg doses.  
1.4.2.6. 
PRO 140 2101 Study 
A subcutaneous (SC) form of PRO 140 was tested in HIV-infected subjects. The trial was a 
randomized, double-blind, placebo-controlled study in subjects (n=44) with early-stage, 
asymptomatic HIV infection, only R5 HIV-1 detectable, and no antiretroviral therapy for 12 weeks 
[Thompson, 2009]. Placebo (n=10) and three PRO 140 doses were examined: 162 mg weekly for 
three weeks (n=11), 324 mg weekly for three weeks (n=11), and 324 mg biweekly (every other 
week) for two doses (n=12). Subjects were followed for 44 days after the final dose.  
Potent, dose-dependent and highly statistically significant antiviral activity was observed. The trial 
established the first antiviral proof of concept for a long-acting, self-administrable drug for HIV-1 
infection [Thompson, 2009]. 
Subcutaneous PRO 140 was generally well tolerated both locally and systemically. There was no 
obvious dose-related pattern of toxicity. The most common adverse events (diarrhea, headache, 
lymphadenopathy and hypertension) were mild to moderate and self-resolving. These events are 
common in HIV infection and were reported with similar frequencies in the placebo and PRO 140 
treatment groups. Administration-site reactions were mild, transient, and observed in a fraction of 
subjects.  
1.4.2.7. 
PRO 140_CD01 Study 
PRO 140_CD01 study (open-label, 43 subjects, multi-center) evaluated the efficacy, safety, and 
tolerability of PRO 140 monotherapy (350 mg subcutaneous injection weekly for up to 12 weeks) 
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infected patients (with exclusive CCR5-tropic virus). Participants in this study were experienced 
HIV-infected individuals who were virologically suppressed on combination antiretroviral therapy. 
Consenting patients were shifted from combination antiretroviral regimen to PRO 140 monotherapy 
for 12 weeks.  
Forty-three (43) subjects (M/F: 37/3) with median age of 54.5 years (26-72) and median CD4 T-
cell count of 604.5 cells/mm3 (365-1240) were enrolled in the CD01 study. Overall, twenty-two 
out of 40 (55%) enrolled subjects completed 12 weeks of PRO140 monotherapy without 
experiencing virologic failure. Virologic failure was defined as two consecutive HIV-1 RNA levels 
of ≥ 400 copies/mL separated by at least 3 days. Of the 43 enrolled subjects, 3 subjects were found 
to have Dual/Mixed (D/M) tropism [1 at baseline and 2 at the time of virologic failure] and 37 
subjects were found to have exclusive CCR5-tropic virus. A letter of amendment was filed to 
increase the planned number of subjects from 40 to 43 subjects to compensate for the 3 Dual/Mixed 
subjects enrolled in the study. 
All virologic failure subjects who had available lab data in both studies achieved viral suppression 
to < 400 HIV-1 RNA copies/mL, as well as viral suppression to ‘Non Detectable’ or < 50 HIV-1 
RNA copies/mL after re-initiation of ART.  
The by-subject analysis of PhenoSense® Entry Assay data for PRO140, maraviroc, and AMD3100 
shows no significant changes in the post-treatment IC50 and IC90 values were noted when 
compared with baseline values in virologic failure and non-virologic failure groups of subjects. As 
the aggregate analysis shows for initial 40 subjects, the subjects who experienced virologic failure 
had higher IC90 value for PR0140 at baseline compared to subjects without virologic failure. The 
mean IC90 for subjects who experienced virologic failure was higher (10.84 µg/mL) than the IC90 
for subjects without virologic failure (6.70 µg/mL) in the CD01 study (p=0.0115).  
Anti-PRO140 antibodies were not identified in any post-treatment sample and data derived from 
the CD01 study further supports the favorable PRO140 PK profile data generated from both pre-
clinical as well as prior Phase 1/2 clinical trials. 
Safety data were analyzed for all 43 enrolled subjects. One (1) of 43 subjects experienced an SAE 
that was deemed not related to the study drug by the Principal Investigator. Twenty-eight (28) of 
43 subjects (67%) experienced one or more adverse events (AEs) after receiving at least one dose 
of PRO140. The most commonly occurring AEs were infections and infestation conditions which 
were reported by 14 of 43 (32.5%) subjects. The majority of the reported AEs (62/87; 71.2%) were 
deemed either unlikely or not related to study treatment by the Investigator. Similarly, the majority 
of the reported AEs (70/87; 80.4%) were deemed mild in nature.  
1.4.2.8. 
PRO 140 CD01 Extension Study 


 
 
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PRO 140_CD01-Extension study (open-label, 28 subjects, multi-center) seeks to evaluate the 
efficacy, safety, and tolerability of PRO 140 monotherapy (350 mg subcutaneous injection weekly) 
for the continued maintenance of viral suppression following substitution of antiretroviral therapy 
in HIV patients (with exclusive CCR5-tropic virus). Participants in this study were HIV-infected 
individuals who were virologically suppressed on combination antiretroviral therapy and completed 
the first 12 weeks of CD01 study without experiencing virologic failure. As with the CD01 study, 
virologic failure was defined as two consecutive HIV-1 RNA levels of ≥ 400 copies/mL separated 
by at least 3 days. Consenting patients may remain on PRO 140 monotherapy until PRO 140 
receives marketing approval or IND is withdrawn by Sponsor.  
A total of 17 subjects participated in the CD01-Extension study of which one subject was 
considered not eligible as subject experienced virologic failure prior to first extension treatment. 
Sixteen (16) eligible subjects (M/F: 14/2) with median age of 54.9 years (26-68) and median CD4 
T-cell count of 593 cells/mm3 (365-1059) were enrolled in an extension study. One patient 
discontinued at week 37 (with viral load of <40 copies/mL) due to relocation. Two subjects were 
withdrawn due to non-treatment related SAEs at week 140 and 149, respectively. One subject was 
withdrawn due to re-starting their ART at week 99. Two subjects withdrew consent at week 81 and 
139, respectively. Five (5) subjects experienced virologic failure (VF) (two consecutive viral load 
of ≥400 copies/mL). The mean time to virologic failure was 329 days (106-691).  
Five (5) subjects are currently receiving weekly 350 mg PRO140 SC monotherapy and have 
completed more than three years of treatment (176 - 198 weeks). Overall, 12 subjects completed at 
least one year of treatment and 9 subjects completed at least two years of treatment in this study 
PRO140 was generally well tolerated, and no drug-related SAEs were observed.  
This clinical study is currently ongoing. 
1.4.2.9. 
PRO 140_CD02 Study 
PRO 140_CD02 study (double blind, placebo controlled, 52 subjects, multi-center) seeks to 
evaluate the efficacy, safety, and tolerability of PRO 140 in combination with either existing ART 
(failing regimen) or Optimized Background Therapy (OBT) in patients infected with HIV-1. The 
study population includes 52 adult patients with a documented history of genotypic or phenotypic 
resistance to ART drugs within two or more drug classes who demonstrate evidence of HIV-1 
replication despite ongoing antiretroviral therapy and have limited treatment options. The options 
may be limited as a result of drug antiviral class cross-resistance, documented treatment intolerance, 
documented objective assessments such as renal or hepatic insufficiency (e.g. high creatinine at 
baseline, limiting treatment options due to potential for toxicity), past adverse reactions such as 


 
 
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hypersensitivity reactions or neuropsychiatric issues that could limit use of currently approved 
drugs. 
In Part 1 of double-blind treatment period, virally non-suppressed subjects will be randomized and 
treated with either PRO 140 or Placebo in combination with the failing ART regimen for 7 days 
until HIV-1 genotypic drug resistance assay results are available to construct an OBT. The primary 
efficacy endpoint is proportion of participants with ≥ 0.5 log10 reduction in HIV-1 RNA viral load 
from baseline at the end of the 7 day functional monotherapy period. 
In Part 2 of double-blind treatment period, subjects will continue treatment with PRO 140 in 
combination with OBT within the 24-week open-label period.  
Fifty-two subjects with a mean age of 52.4 years, 73.1% male, 48.1% non-white and mean duration 
of HIV-1 infection of 20.4 years were randomized 1:1 to the PRO 140 SC or placebo arm. Subjects 
had been previously exposed to an average of 11 ART drugs and had documented resistance to >9 
ART drugs. Mean baseline VL and CD4 cell count were 21,104 c/mL and 297.8 c/mm3, 
respectively. The primary efficacy endpoint- the proportion of patients with ≥0.5 log10 reduction 
in HIV-1 VL from baseline at the end of the 1-week double-blind, randomized, placebo-controlled 
treatment period- was met (16/25 vs 6/26 [p-value <0.0032, ITT population]). Forty seven (47) of 
52 patients have completed the 25-week study. Approximately 81% of patients completing 25-
weeks of PRO 140 SC treatment demonstrated HIV-1 VL <50 c/mL and 92% had HIV-1 VL <400 
c/mL. Continued access to PRO 140 SC was provided through a rollover study and 40 patients 
entered the extension protocol after completing the CD02 study. PRO 140 SC was generally well 
tolerated. No drug-related SAEs or treatment discontinuations were reported in the study. 
This clinical study is completed. 
1.4.2.10. 
PRO 140 CD02 Extension Study 
PRO 140_CD02 Extension study (open label, 40 subjects, multi-center) seeks to evaluate the long 
term efficacy, safety and tolerability of PRO 140 weekly injection in combination with Optimized 
Background Therapy (OBT) in patients infected with HIV-1. The study population includes 40 
treatment-experienced HIV-infected adult patients with CCR5-tropic virus who successfully 
completed PRO 140_CD02 study and continue to demonstrate HIV-1 viral suppression. 
This clinical study is currently ongoing. 
1.4.2.11. 
PRO 140 CD03 HIV Study 
PRO 140_CD03 HIV (open-label, 350 subjects, multi-center) is a three part study enrolling virally 
suppressed HIV-1 patients with CCR5-tropic HIV-1 receiving combination antiretroviral (cART) 
therapy. Patients received weekly doses of PRO 140 on single-agent maintenance therapy following 
one week of overlap of the existing cART regimen that is then discontinued. In part 1, 156 


 
 
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participants received 350 mg PRO 140 SC in a single-arm design. In part 2, 147 participants 
received 350 or 525 mg PRO 140 SC in a 1:1 ratio as randomized controlled, two-arm study. In an 
ongoing part 3, 51 participants have been randomized to receive 525 or 700 mg PRO 140 SC in a 
1:1 ratio.  
Despite reaching the enrollment target of 350 subjects for the PRO140_CD03 HIV study, the 
enrollment is ongoing as the goal of enrolling 20 subjects for the CNS sub-study have not achieved. 
As a result, sites that are currently participating in the CNS sub-study are permitted to continue 
enrollment in the CD03 HIV study. 
Of the 354 patients enrolled, median age was 51 yrs (21-77) with the majority reported as male 
(79%) and 37% were non-white. A total of 27 subjects have been randomized to 700 mg dose. In 
addition, another 18 subjects have been exposed to 700 mg dose after rescuing from the lower doses 
(350 mg or 525mg). On average, participants were diagnosed with HIV-1 infection for 16.8 yrs and 
were on cART regimen for 14.8 yrs. The frequency and severity of injection site reactions were 
comparable between the three dose groups (350, 525 and 700mg) and the incidence or severity of 
injection site reactions was not increased in patients receiving higher doses. Overall, PRO 140 SC 
was generally well tolerated at all dose levels in this study. 
This clinical study is currently ongoing. 
1.4.2.12. 
PRO 140 CD03 HIV Extension Study 
PRO 140_CD03 study (open-label, 350 subjects, multi-center) seeks to evaluate the long term 
efficacy, safety and tolerability of PRO 140 SC as long-acting single-agent maintenance therapy in 
virologically suppressed subjects with CCR5-tropic HIV-1 infection. The study population includes 
up to 300 treatment-experienced HIV-infected adult patients who successfully completed PRO 
140_CD03 HIV study and continue to demonstrate HIV-1 viral suppression. 
This clinical study is currently ongoing. 
1.4.2.13. 
PRO 140 CD06 Study 
PRO 140_CD06 study (double-blind, 80 subjects, single-center) seeks to evaluate the evaluate 
comparability of PRO 140 formulation Batch Lot # 3-FIN-3143 versus formulation Batch Lot# 3-
FIN-2618 as a one-time subcutaneous (SC) injection in healthy subjects under non-fasting 
conditions.  
1.4.2.14. 
PRO 140 CD07 Study 
CD07_TNBC study (open-label, two-part [Phase Ib: Up to 18 subjects; Phase II: 30 Subjects], 
multi-center) seeks to evaluate the efficacy, safety, tolerability and maximum tolerate dose (MTD) 


 
 
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of leronlimab (PRO 140) when combined with carboplatin in patients with CCR5+ metastatic triple-
negative breast cancer (mTNBC). 
The study population includes patients with CCR5-positive, locally advanced or metastatic triple-
negative breast cancer (mTNBC) who are naïve to chemotherapy in metastatic setting but have been 
exposed to anthracyclines and taxane in neoadjuvant and adjuvant settings (first-line). 
This clinical study is currently ongoing. 
1.4.2.15. 
 CD08 mCRC Study 
CD08_mCRC study (open-label, 30 subjects, multi-center) seeks to evaluate the effect on overall 
response rate (ORR) of Leronlimab (PRO 140) when combined with Regorafenib in patients with 
CCR5+, Microsatellite Stable (MSS), Metastatic Colorectal Cancer (mCRC).  
The study population includes patients with CCR5+, Microsatellite Stable (MSS), metastatic 
Colorectal Cancer (mCRC) who have been previously treated with fluoropyrimidine-, oxaliplatin- 
and irinotecan-based chemotherapy, an antiVEGF therapy, and, if RAS wild type, an anti-EGFR 
therapy.  
1.4.2.16. 
CD07_Compassionate Use 
CD07_Compassionate Use study (open-label, two-part, multi-center) seeks to evaluate the efficacy, 
safety, and tolerability of leronlimab (PRO 140) when combined Treatment of Physician’s Choice 
in the treatment of patients with CCR5+ Metastatic Triple Negative Breast Cancer (mTNBC). The 
study population includes patients with CCR5-positive, locally advanced or metastatic triple-
negative breast cancer (mTNBC). 
This clinical study is currently ongoing. 
1.4.2.17. 
CD09_Basket Study 
CD09_Basket study (open-label, 30 subjects, multi-center) seeks to evaluate the anti-tumor activity 
of leronlimab (PRO 140) in patients with CCR5+, locally advanced or metastatic solid tumors who 
have disease progression on standard therapy, or receiving a standard anticancer treatment but no 
subsequent approved treatment would be available upon progression, or unable to receive standard 
therapy, or for whom standard therapy does not exist. 
This clinical study is currently ongoing. 
1.4.2.18. 
CD10_COVID-19 
CD10_COVID-19 (two-arm, randomized, double blind, placebo controlled) study seeks to evaluate 
the safety and efficacy of leronlimab (PRO 140) in patients with mild-to-moderate symptoms of 
respiratory illness caused by coronavirus 2019 infection. Patients were randomized to receive 2 


 
 
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weekly doses of 700 mg leronlimab (PRO 140), or placebo via subcutaneous injection at Day 0 and 
Day 7. 
The study population was 60.7% female and 39.3% male, with an average age of 54.85 years. There 
were 56 subjects treated with leronlimab (PRO 140) and 28 with placebo.  
CD10 study did not meet the pre-defined primary endpoint (change in symptom score at Day 14 
analyzed as a continuous variable) or any of the pre-defined secondary efficacy endpoints (time to 
clinical resolution; change from baseline NEWS score at Days 3, 7, and 14 analyzed by ANCOVA 
method; change from baseline in pulse oxygen saturation Days 3, 7, 14; change from baseline health 
status by 7-point category ordinal scale at Days 3, 7, and 14; Incidence and Duration of 
hospitalization; incidence and duration of mechanical ventilation; incidence and duration of oxygen 
use; mortality at Day 14, or time to return to normal activity). 
Post-hoc analyses described below, however did provide additional insights and information which 
helped design the further development of PRO 140 in COVID-19 
• Day 3 total symptom score results:  
62.96% of the 56 subjects in PRO 140 group showed improvement in total symptom score, 
compared to 56% of the 28 subjects in the placebo group. In the sub-population of subjects with 
baseline total symptom score of ≥4, 90% of subjects treated with leronlimab (PRO 140) were 
reported with improvement in total symptom score, compared to 71% of subjects in the placebo 
group. 
• National Early Warning Score 2 (NEWS2) (reported as proportion):  
24 of 56 (50%) of subjects treated with leronlimab (PRO 140) showed improvement from 
baseline in NEWS2 score at EOT visit, compared to 5 of 28 (20.83%) of subjects in the placebo 
group . 
Safety was assessed primarily via reporting of adverse events (AEs) and serious adverse events 
(SAEs) throughout the study. In total, 34% (19 of 56 subjects) treated with leronlimab compared to 
50% (14 of 28 patients) treated with placebo reported at least one AE. Additionally, 9% of subjects 
(5/56) reported SAEs in leronlimab group  compared to 21% of subjects (6/28) in the placebo group. 
The vast majority of the patients with mild to moderate COVID-19 recover with supportive care. 
The study sample size was not large enough to evaluate the effect of PRO 140 in this patient 
population. Post-hoc analyses indicate the potential for benefit of PRO 140 in patients with more 
severe (total symptom score of ≥4) COVID-19. Safety data shows that leronlimab (PRO 140) was 
well tolerated by subjects. The incidence, frequency, and severity of AEs and SAEs were not 
increased in the leronlimab (PRO 140) group compared to the placebo group. 
 












 
 
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The changes in the cytokine milieu influence CCR5 expression and may explain emergence of 
tropism-specific strains facilitating coronavirus transmission and disease progression similar to 
HIV transmission [Patterson 1999]. Chen et al. study on BALB/c mice showed that depletion of 
CD4+ T cells resulted in an enhanced immune-mediated interstitial pneumonitis and delayed 
clearance of SARS-CoV from the lungs, which was associated with reduced neutralizing antibody 
and cytokine production and reduced pulmonary recruitment of lymphocytes [Chen-2010]. 
Leronlimab (PRO 140) is a humanized IgG4, κ monoclonal antibody (mAb) specific for the type 5 
C-C chemokine receptor (CCR5). Leronlimab (PRO 140) inhibits migration of Tregs into areas of 
inflammation which can inhibit the innate immune response against pathogens and most 
importantly, the migration of macrophages [Glass 2001] and release of pro-inflammatory cytokines 
in lungs. CCR5 engagement of macrophages changes them into effector cells rather than mediators 
of inflammation. In addition, the role of CCR5 antagonists in helping the innate immune response 
which is critical for infections the body has not been introduced to before (e.g. COVID-19), is 
discussed in Halama et al (2016). 
The ARDS has known to be one of the main reasons for mortalities in patients with COVID-19. 
CytoDyn believes that leronlimab, CCR5 antagonist, is a potential therapeutics in inhibiting pro-
inflammatory cytokines (cytokine storm) responses as observed in ARDS and thus could be useful 
in treatment of COVID-2019. 
1.5.2. Rationale for Dose Selection and Treatment Duration 
Leronlimab (PRO 140) is currently under development for the indication of HIV, Graft versus host 
disease (GVHD), metastatic triple negative breast cancer (mTNBC), and metastatic colorectal 
cancer (mCRC).  
The safety profile of leronlimab (PRO 140) has been extensively evaluated in clinical trials. PRO 
140 has been administered intravenously or subcutaneously to more than 750 healthy and HIV-1 
infected individuals thus far, in Phase I/II/III studies. The drug has been well tolerated following 
intravenous administration of single doses of 0.5 to 10 mg/kg or up to 700 mg weekly doses as 
subcutaneous (SC) injection. Overall, 324 subjects have been exposed to PRO 140 350 mg SC 
weekly dose with the longest duration of exposure lasting 4 years. Similarly, more than 250 and 
150 subjects have been exposed to PRO 140 525 mg and 700 mg SC weekly dose, respectively. 
Available safety data from 131 subjects that received 700 mg dose in the ongoing PRO 140_CD03 
study shows that less than 10% of subjects reported AEs considered definitely related to study 
treatment. All of these AEs were injection site reactions and considered to be mild or moderate in 
severity.  
By severity, three subjects (2.3%, 3/131) reported AEs that were considered severe and two subjects 
(1.5%, 2/131) reported events that were deemed to be life-threatening. No events were considered 
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Serious adverse events (SAEs) were reported for six subjects (4.6%, 6/131). None of SAEs were 
considered related to the study treatment.  
Additionally, there have been four patients with severe COVID-19 infection treated with 700 mg 
leronlimab (PRO 140) under individual patient, emergency use INDs. The current data from these 
patients are provided in the Investigational Brochure (IB).  
Leronlimab (PRO 140) 700mg will be administered once weekly for two weeks only in this study 
as most patients with mild to moderate COVID-19 disease fully recovery within 2 weeks of 
developing initial symptoms. 
While leronlimab showed weak activity relative to the positive control (2D7, an anti-CCR5 
antibody) in Study 300-TD-018, the IC50 values were: 59.1 µg/mL for RANTES, 21.2 µg/mL for 
MIP-1α and 39.6 µg/mL for MIP-1β. The modeled Cmax* for the proposed 700 mg weekly dose is 
267.2 µg/mL which is 4.5-12.6-fold higher than the IC50 values for these cytokines. In addition, at 
leronlimab concentrations greater than 75 µg/ml for RANTES and greater than 100 µg/ml for MIP-
1α and MIP-1β, inhibition of 80% or more was seen for these cytokines (Appendix, Figure 2 of 
Study 300-TD-018). Therefore, leronlimab is anticipated to inhibit these cytokines following the 
700 mg once weekly dose regimen. 
Figure 1-1: 
Dose-response curve for inhibition of CC-chemokine-induced calcium 
mobilization by PRO 140 
 
 
*The human Cmax was modeled for a dose of 700 mg once weekly in a 70 kg human subject. An interspecies population 
pharmacokinetic model was fit to available monkey and adult human data (concentration-time). Simulations were 
carried out to identify leronlimab serum concentration-time profiles (approximate to adults receiving 700 mg SC once 
weekly). 
Leronlimab’s role in the binding and signaling of chemokines MIP-1α(CCL3), MIP-1β(CCL4), and 
RANTES (CCL5) will be further evaluated in the Phase 2b/3 study. In addition, Cytokine and 
Chemokine Panel will include assessment of sCD40L, EGF, Eotaxin (CCL11), FGF-2, Flt-3 ligand, 
Fractalkine, G-CSF, GM-CSF, GRO alpha (CXCL1), IFN-alpha2, IFN-gamma, IL-1 alpha, IL-1 


 
 
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beta, IL-1RA, IL-2, IL-2R, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8 (CXCL8), IL-9, IL-10, IL-12 
(p40/p70) IL-13, IL-15, IL-17A, IL-17E/IL-25, IL-17F, IL-18, IL-22, IL-27, IP-10 (CXCL10), 
MCP-1 (CCL2), MCP-3, M-CSF, MDC (CCL22), MIG (CXCL9), MIP-1 alpha  (CCL3), MIP-1 
beta (CCL4), PDGF-AA, PDGF-AB/BB, RANTES (CCL5), TGF-alpha, TNF-alpha, TNF-beta, 
and VEGF-A. 
1.6. 
RISKS / BENEFITS ASSESSMENT 
Allergic Reaction 
Leronlimab (PRO 140) belongs to the monoclonal antibody class of drugs. Monoclonal antibodies 
are sometimes associated with allergic reactions or flu-like reactions (such as fever, chills, and 
aches) or injection-site reactions. These events are usually of short duration if they occur at all. 
Severe allergic reactions, however, can be life-threatening. Although anaphylaxis has not been 
observed in prior trials of leronlimab (PRO 140), the protein infusion always carries theoretical 
risk for anaphylactic shock. Accordingly, whenever leronlimab (PRO 140) is administered to 
subjects, procedures should be available and in place to manage the occurrence of anaphylactic 
shock. 
Immune Response 
People who take leronlimab (PRO 140) or other monoclonal antibodies can also develop an 
immune response to leronlimab (PRO 140) that may affect their ability to receive monoclonal 
antibodies, or to benefit from diagnosis or therapy with a monoclonal antibody in the future. 
Pregnancy 
Risks to unborn babies exposed to leronlimab (PRO 140) are unknown at this time; thus pregnant 
females will be excluded from this study. Females of childbearing potential must have a negative 
pregnancy test prior to enrollment. Both male and female patients and their partners of 
childbearing potential must agree to use appropriate birth control methods throughout the study 
duration (excluding women who are not of childbearing potential and men who have been 
sterilized).  
Venipuncture 
Blood sampling is required as part of the study protocol. Blood sampling carries a minimal risk 
of minor discomfort and the possibility of minor bruising at the site of the needle puncture and, 
rarely, the possibility of infection at the needle puncture site. 
Unknown Risks 
As with all research, there is the remote possibility of risks that are unknown or that cannot be 
foreseen based on current information.  


 
 
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Theoretical risk for increased severity of West Nile virus infection 
Individuals who lack a functional CCR5 gene are at increased risk for severe infection by West 
Nile virus [Thompson, 2009]. Because of this, treatment with CCR5 co­receptor antagonists poses 
a theoretical risk for increased severity of West Nile virus infection. However, this concern is 
mitigated by several factors. First, no increased risk was observed for individuals who possess 
one functional and one non-functional CCR5 gene, indicating that an intermediate amount of 
CCR5 is sufficient for defense against West Nile virus [Thompson, 2009]. Second, use of CCR5 
co-receptor antagonists is unlikely to completely abrogate CCR5 function, and there has been no 
association reported to date between CCR5 co-receptor use and severe West Nile virus. 
Additionally, leronlimab (PRO 140) weakly antagonizes the natural activity of CCR5 and thus is 
less likely to adversely affect immune function. However, patients enrolled in this study may have 
immune suppression and therefore, DSMB and the investigators will be alerted to risks of West 
Nile infections. Furthermore, this has not been established to be a risk with maraviroc, the other 
FDA-approved anti-CCR5 drug already. 
Collectively, the experience with both IV and SC, simulation modeling and the recent 
confirmation that a higher concentration of leronlimab (PRO 140) synthesized using a highly 
efficient CHO cell line can be conveniently and safely administered has resulted in the design of 
the current study. 
 
 
 
 
 
 
 
 
 


 
 
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2. 
STUDY OBJECTIVES 
Primary Objective: 
The purpose of this study is to assess the safety and efficacy of Leronlimab administered as weekly 
subcutaneous injection in subjects with severe or critical Coronavirus 2019 (COVID-2019) disease. 
 
 


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3. 
STUDY DESIGN
This study is a Phase 2b/3, two arm, randomized, double blind, placebo controlled, adaptive design 
study to evaluate the safety and efficacy of leronlimab (PRO 140) in patients with severe or critical 
symptoms of respiratory illness caused by Coronavirus disease 2019 (COVID-19). Patients will be 
randomized 2:1 to receive leronlimab (PRO 140) or placebo. Subjects will receive weekly 700 mg 
leronlimab (PRO 140) or placebo via subcutaneous injection for two weeks. The study will enroll 
390 subjects.  
A single arm, non-randomized, open-label phase is added to the protocol after completion of 
enrollment in the Randomized Phase of the study. Up to 100 subjects will be enrolled in the non-
randomized phase.  
The study flow diagram is presented in Figure 3-1. 
Figure 3-1: 
Study Schematic 
Screening Visit 
Visit 1 (V1)
SCREENING 
PERIOD
TREATMENT PERIOD
V2-V5 Visits
FOLLOW-UP PERIOD
V6 to V7 Visits
No
Yes
Does 
Subject Meet 
Inclusion/Exclusion 
Criteria?
Screen 
Failure
Informed 
Consent
Up to 4 Weeks
Up to 2 Weeks
4 Weeks
Visit 2 (V2)
Day 0
Within 7 Days of Screening Visit
Visit 3 (V3)
Day 3
3 (±1) days after V2
Visit 4 (V4)
Day 7
7 (±1) days after V2
Visit 5 (V5) / EOT
Day 14
7 (±1) days after V4
End of Study
Visit 6 (V6)
(14 ± 3 Days after EOT Visit)
Visit 7 (V7)
(28 days ±3 Days after EOT Visit)
First Leronlimab dose
Second Leronlimab dose


 
 
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3.1. 
STUDY CENTER 
Up to 30 multinational centers. Centers must have the capability of implementing appropriate 
infection-control measures to prevent infection of study staff and others who share the clinical site 
space. 
3.2. 
STUDY POPULATION 
The target population for this study is adult subjects with severe or critical symptoms of respiratory 
illness caused by coronavirus disease 2019 (COVID-19). 
3.3. 
ELIGIBILITY CRITERIA 
3.3.1. Inclusion Criteria 
Potential subjects are required to meet all of the following criteria for enrollment into the study: 
1. Male or female adult ≥ 18 years of age at time of screening. 
2. Subjects hospitalized with severe or critical illness caused by coronavirus 2019 infection as 
defined below: 
Severe Illness: 
• Diagnosed with COVID-19 by standard RT-PCR assay or equivalent testing within 5 days 
of screening 
AND 
• Symptoms of severe systemic illness/infection with COVID-19: 
o At least 1 of the following: fever, cough, sore throat, malaise, headache, muscle pain, 
shortness of breath at rest or with exertion, confusion, or symptoms of severe lower 
respiratory symptoms including dyspnea at rest or respiratory distress 
AND 
• Clinical signs indicative of severe systemic illness/infection with COVID-19, with at least 
1 of the following: 
o RR ≥ 30, HR ≥ 125, SaO2 <93% on room air or requires > 2L oxygen by NC in order 
maintain SaO2 ≥93%, PaO2/FiO2 <300 
AND 
• No criteria for Critical Illness: 
o None of the following: Respiratory failure (defined by endotracheal intubation and 
mechanical ventilation, oxygen delivered by high-flow nasal cannula, noninvasive 
positive pressure ventilation, or clinical diagnosis of respiratory failure in setting of 
resource limitations), Septic shock (defined by SBP < 90 mm Hg, or Diastolic BP < 
60 mm Hg), Multiple organ dysfunction/failure 
 


 
 
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Critical Illness: 
• Diagnosed with COVID-19 by standard RT-PCR assay or equivalent testing within 5 days 
of screening 
AND 
• Evidence of critical illness, defined by at least 1 of the following: 
o Respiratory failure defined based on resource utilization requiring at least 1 of the 
following: 
Endotracheal intubation and mechanical ventilation, oxygen delivered by high-flow 
nasal cannula, noninvasive positive pressure ventilation, ECMO, or clinical diagnosis 
of respiratory failure (in setting of resource limitation) 
OR 
• Shock (defined by SBP < 90 mm Hg, or Diastolic BP < 60 mm Hg or requiring 
vasopressors) 
OR 
• Multiple organ dysfunction/failure 
3. Subject, if intubated, positive end-expiratory pressure (PEEP) <15 cmH2O with PaO2/FiO2 
>150 mmHg. 
4. Electrocardiogram (ECG) with no clinically significant findings as assessed by the 
Investigator.  
Note: Below are the examples of clinically significant and non-clinically significant ECG 
abnormalities: 
− ECG findings indicative of acute myocardial infarction or acute ischemic changes 
would be considered clinically significant abnormalities.  
− ECG finding such as atrial fibrillation, atrial flutter, paced rhythms in individuals who 
have undergone permanent pacemaker placement, evidence of prior infarction, 
unchanged stable conduction abnormalities e.g. right bundle branch block, or any other 
finding which does not significantly impact mortality would be considered non-
clinically significant findings and subjects with these abnormal findings would be 
allowed to enroll in the study. 
5. Subject (or legally authorized representative) provides written informed consent prior to 
initiation of any study procedures. 
6. Understands and agrees to comply with planned study procedures. 
7. Women of childbearing potential and their partner must agree to use at least one highly 
effective method of contraception (e.g., hormonal contraceptives [implants, injectables, 


 
 
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combination oral contraceptives, transdermal patches, or contraceptive rings], intrauterine 
devices, bilateral tubal occlusion, or sexual abstinence) for the duration of the study. 
3.3.2. Exclusion Criteria 
Potential subjects meeting any of the following criteria will be excluded from enrollment: 
1. Subjects with do-not-resuscitate (DNR) and/or do-not-intubate (DNI) orders or expected to 
be made DNR/DNI in setting of resource limitations or family wishes. 
2. Not a candidate for dialysis or continuation of care (or full medical support) in setting of 
resource limitations. 
3. Subject on continuous vasopressors (at the dose of norepinephrine >20µg/min and/or 
vasopressin >0.04 units/kg/min) for >48 hours at time of screening. 
4. Subjects who have a history of allergic reactions attributed to compounds of similar 
chemical or biologic composition to leronlimab (PRO 140) are not eligible. 
5. Inability to provide informed consent or to comply with test requirements 
6. Consideration by the investigator, for safety reasons, that the subject is an unsuitable 
candidate to receive study treatment 
7. Pregnancy or breast feeding 
8. Subject participating in another study with for an investigational treatment for COVID-19. 
Note: Subject who were prescribed (1) hydroxychloroquine or chloroquine with or without 
azithromycin, (2) Remdesivir, (3) convalescent plasma therapy, or (4) immunomodulatory 
treatments (including but not limited to sarilumab, clazakizumab, tocilizumab, and 
anakinra) for the off-label treatment of COVID-19 prior to study enrollment may be 
included and may continue to receive these agents as part of standard-of-care. 


 
 
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4. 
STUDY SCHEDULE 
The study will have three phases: Screening Period, Treatment Period, and Follow-Up Period. The 
study Schedule of Assessments in presented in Table 4-2. 
Screening Period (up to 1 week):  
Screening assessments will commence at Visit 1 (V1) after obtaining signed informed consent, and 
will include review of medical and medication history, eligibility evaluation, subject demographics, 
physical examination, vital signs, clinical status – ordinal scale assessment, PaO2/FiO2 
measurement, pulse oxygen saturation (SpO2), positive end-expiratory pressure (PEEP) (for 
intubated subjects),  National Early Warning Score 2 (NEWS2) assessment, electrocardiogram 
(ECG), nasopharyngeal swab sample collection, chest radiograph or CT (if clinically indicated), 
assessment for the requirement of: mechanical ventilation, non-invasive ventilation, supplemental 
oxygen, vasopressors use, renal replacement therapy, ICU admission and hospital stay and 
laboratory sample collection for routine serum biochemical, hematologic, coagulation, urinalysis, 
and serum/urine pregnancy (if applicable). These assessments must be conducted within 7 days of 
the First Treatment Visit (V2).  
All subjects who fail to meet eligibility criteria are considered screen failures, and are exited from 
the study without further evaluation. 
Treatment Period (2 weeks ± allowed windows):  
The schedule of visits during Treatment Period is as follows:  
- Visit 2 (V2) [first treatment]: Within 1 week of the Screening Visit 
- Visit 3 (V3): 3 (±1) day after V2 
- Visit 4 (V4) [second treatment]: 7 (±1) days after V2 
- Visit 5 (V5) / End of Treatment (EOT) Visit: 7 (±1) days after V4.  
Subjects who meet the eligibility criteria will have completed the following evaluations and 
assessments at V2 prior to treatment: review of any changes in medical and medication history, 
physical examination, vital signs, clinical status – ordinal scale assessment, PaO2/FiO2 
measurement, pulse oxygen saturation (SpO2), positive end-expiratory pressure (PEEP) (for 
intubated subjects),  sequential Organ Failure Assessment (SOFA) score,  National Early Warning 
Score 2 (NEWS2) assessment, nasopharyngeal swab sample collection,  baseline assessment for 
the requirement of: mechanical ventilation, non-invasive ventilation, supplemental oxygen, 
vasopressors use, renal replacement therapy, ICU admission and hospital stay, assessment for any 
new infections, blood sample collection for CD3+, CD4+ and CD8+ T cell count, CCR5 receptor 
occupancy for Treg and macrophages, serum cytokine and chemokine levels, and CCR5 gene 
polymorphisms. After administration of leronlimab subjects will be assessed for vital sign, adverse 
event and concomitant medications. If Visit 2 (V2) takes place on the same day as the Screening 




 
 
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not be performed. In such cases, missed blood sample collection will not be captured as protocol 
deviation. 
Note: During visits conducted at the study clinic, subjects and site personnel will use appropriate 
protective gear (e.g., masks, gloves) to prevent the spread of the infection. If the subject is 
discharged from the hospital prior to Visit 7 (Day 42), scheduled study visits can be conducted by 
a visiting nurse (or trained site staff) at the subject’s home to mitigate the risk of spreading COVID-
19.  
During visits conducted at the subject’s home, the visiting nurse (or trained site staff) will 
administer study drug (if applicable), monitor subjects for safety, perform blood draw, and all other 
assessments related to study outcomes measures. All procedures (except chest radiograph or CT 
scan) listed under the schedule of assessments can be performed by visiting nurse at visits taking 
place in the subject’s home.  






 
 
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[6] The SOFA score assessment will be based on PaO2/FiO2, platelets, Glasgow coma scale (GCS), bilirubin, Mean arterial pressure OR administration of vasoactive agents 
required, and creatine. 
[7] National Early Warning Score 2 (NEWS2) Assessment is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, 
systolic blood pressure, heart rate, level of consciousness) 
[8] Based on hospital discharge or normalization of fever, respiratory rate, alleviation of cough, and resolution of hypoxia. 
[9] Hemoglobin, Hematocrit (HCT), Red Blood Cells (RBC), White Blood Cells (WBC) with total and differential count, Absolute Neutrophil Count (ANC) and platelets. 
[10] Biochemistry  
Hepatic function indicators: total bilirubin, alkaline phosphatase, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total protein, albumin Lactate 
dehydrogenase (LDH) 
Renal function indicators: Serum creatinine, creatinine clearance, or eGFR 
Electrolytes: sodium, potassium, chloride, calcium and bicarbonate 
Other: glucose (random), cholesterol (total), Creatine kinase, C-reactive protein, serum ferritin, d-dimer 
[11] Prothrombin time (PT) and International Normalized Ratio (INR) 
[12] ONLY performed on women of childbearing potential. 
[13] Urine samples will be tested for color, appearance, specific gravity, pH, protein, glucose, occult blood, ketones, leukocyte esterase, nitrite, bilirubin, urobilinogen, and 
microscopic examination of urine sediment. 
[14] Blood samples collected for receptor occupancy testing will also be used for CCR5 gene polymorphism for PRO 140 susceptibility.  
[15] Assessment is recommended but not required. Swabs will be used for quantitative virologic testing. Samples are to be stored at -70°C. 
[16] Chest radiograph or CT will be performed if clinically indicated by the treating physician. 
[17] If Visit 2 (V2) takes place on the same day as the Screening Visit (V1), scheduled assessments performed under screening (V1) do not need to be repeated at V2. 
[18] Randomization via WebView CTMS system 
[19] Not applicable for the single arm, non-randomized, open-label phase of the study. 


 
 
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4.1. 
SCREENING PHASE 
The subject (or Legally Acceptable Representative (LAR)) will sign and date the informed consent 
form (ICF) and Health Insurance Portability Accountability Act (HIPAA) authorization (according 
to site policy and practices) prior to any study-related procedures. All study centers will be 
instructed to maintain the study-specific screening and enrollment logs at their sites. If a subject 
initially fails to meet inclusion/exclusion criteria and is later reconsidered for participation, the 
subject will be re-consented and assigned a new unique identification number at the time of re-
screening. Subjects who fail their first screening attempt may be re-screened a maximum of once 
and may be enrolled if they are found to meet all inclusion and no exclusion criteria when re-
screened. 
4.1.1. Screening Visit (V1) 
After the ICF has been signed, screening procedures and information will be obtained to confirm 
subject eligibility, including: 
• Demographic information (see Section 7.3); 
• A detailed medical history (see Section 7.4); 
• Physical examination (see Section 7.5); 
• Vital signs (see Section 7.6), 
• Clinical Status - Ordinal scale assessment (see Section 7.10); 
• PaO2/FiO2, if intubated (See Section 7.11) 
• Pulse oxygen saturation (SpO2) (see Section 7.12); 
• Positive End-Expiratory Pressure (PEEP), if intubated (See Section 7.13) 
• National Early Warning Score 2 (NEWS2) assessment (see Section 7.15); 
• 12-lead electrocardiogram (see Section 7.17); 
• Collection of blood specimens (see Section 7.8) for 
o Complete blood count; 
o Biochemistry; 
o Coagulation indices; 
o Serum/urine pregnancy test, for female subjects of childbearing potential; and 
o Urine sample for urinalysis parameters. 


 
 
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• Nasopharyngeal Swab Sample Collection (See Section 7.18) 
• Chest radiograph or computer tomography (CT) scan (if clinically indicated) (See Section 
7.19); 
• Assessment for the requirement of mechanical ventilation, Non-Invasive Ventilation, 
Supplemental Oxygen, Vasopressors Use, Renal Replacement Therapy, ICU Admission, 
and hospital stay (see Section 7.20); and 
• Prior medications assessment (see Section 7.7). 
All screening information will be fully documented in the subject’s medical records (i.e., source 
documents).  
• For consented subjects who do not meet eligibility criteria, a Screen Failure Case Report 
Form (CRF) will be completed. The Screen Failure CRF will contain the following details: 
the subject identification number, the date of ICF signature, demographic information (see 
Section 7.3), and the reason for screen failure. No additional information will be required 
for subjects who fail screening.  
• For consented subjects who meet eligibility criteria, all required screening information will 
be transcribed onto the appropriate page of the CRF. 
4.2. 
TREATMENT PHASE 
Subjects who meet all eligibility criteria, as per data gathered from Screening Period are to be 
treated. All subjects who fail to meet eligibility criteria will be considered screen failure and will 
exit the study without further evaluation 
4.2.1. Visit 2 (V2) 
The following assessments will be performed at the first treatment visit prior to the first treatment 
administration. If Visit 2 (V2) takes place on the same day as the Screening Visit (V1), scheduled 
assessments performed under screening (V1) do not need to be repeated at V2. 
• Physical examination (see Section 7.5); 
• Vital Signs (see Section 7.6), 
• Clinical Status - Ordinal scale assessment (see Section 7.10); 
• PaO2/FiO2, if intubated (See Section 7.11) 
• Pulse oxygen saturation (SpO2) (see Section 7.12); 
• Positive End-Expiratory Pressure (PEEP), if intubated (See Section 7.13) 
• Sequential Organ Failure Assessment (SOFA) score, if intubated  (See Section 7.14) 


 
 
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• National Early Warning Score 2 (NEWS2) Assessment (see Section 7.15); 
• Collection of blood specimens (see Section 7.8) for 
o CD3+, CD4+ and CD8+ T cell count; 
o CCR5 receptor occupancy for Treg and macrophage;  
o Serum cytokine and chemokine levels; and 
o CCR5 Gene Polymorphisms. 
• Nasopharyngeal Swab Sample Collection (See Section 7.18) 
• Assessment for the requirement of mechanical ventilation, Non-Invasive Ventilation, 
Supplemental Oxygen, Vasopressors Use, Renal Replacement Therapy, ICU Admission, 
and hospital stay (see Section 7.20);  
• Assessment for any new infections; and 
• Prior medications assessment (see Section 7.7). 
Subjects will be randomized 2:1 via WebView CTMS system to Leronlimab (PRO 140) or Placebo 
(see Section 7.21). 
• Leronlimab (PRO 140) 700 mg or 
• Placebo 
Note: In the single arm, non-randomized, open-label phase, all eligible subjects will be assigned to 
receive Leronlimab (PRO 140). 
Leronlimab (PRO 140) or placebo will be administered subcutaneously to all subjects at a weekly 
dose of 700 mg. After receiving the first leronlimab (PRO 140) dose, the following assessments 
will be performed: 
• Vital signs (see Section 7.6), 
• Concomitant medications assessment (see Section 7.7),  
• Review of adverse events (see Section 9) 
4.2.2. Visits 3 and 4, (V3 and V4) 
The following assessments will be performed during the remaining visits during the treatment 
period: 
• Physical examination (see Section 7.5); 
• Vital Signs (see Section 7.6), 


 
 
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• Clinical Status - Ordinal scale assessment (see Section 7.10); 
• PaO2/FiO2, if intubated (See Section 7.11) 
• Pulse oxygen saturation (SpO2) (see Section 7.12); 
• Positive End-Expiratory Pressure (PEEP), if intubated (See Section 7.13) 
• Sequential Organ Failure Assessment (SOFA) score, if intubated  (See Section 7.14) 
• National Early Warning Score 2 (NEWS2) assessment (see Section 7.15) 
• Assessment of Clinical Recovery (See Section 7.16) 
• Collection of blood specimens (see Section 7.8) for 
o Complete blood count; 
o Biochemistry; 
o Coagulation indices; 
o Urine sample for urinalysis parameters; 
o CD3+, CD4+ and CD8+ T cell count; 
o CCR5 receptor occupancy for Treg and macrophage;  
o Serum cytokine and chemokine levels; and 
o CCR5 Gene Polymorphisms 
• Nasopharyngeal Swab Sample Collection (See Section 7.18) 
• Leronlimab (PRO 140) or Placebo Administration – V4 only (see Section 6.1.3); 
• Assessment for the requirement of mechanical ventilation, Non-Invasive Ventilation, 
Supplemental Oxygen, Vasopressors Use, Renal Replacement Therapy, ICU Admission, 
and hospital stay (see Section 7.20);  
• Assessment for any new infections; 
• Prior medications assessment (see Section 7.7); and 
• Review of adverse events (see Section 9). 
4.2.3. End of Treatment – EOT (V5) 
The last visit during the treatment phase will be considered at the End of Treatment (EOT) visit. 
The assessments performed at this visit will include: 
• Physical examination (see Section 7.5); 


 
 
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• Vital Signs (see Section 7.6), 
• Clinical Status - Ordinal scale assessment (see Section 7.10); 
• PaO2/FiO2, if intubated (See Section 7.11) 
• Pulse oxygen saturation (SpO2) (see Section 7.12); 
• Positive End-Expiratory Pressure (PEEP), if intubated (See Section 7.13) 
• Sequential Organ Failure Assessment (SOFA) score, if intubated  (See Section 7.14) 
• National Early Warning Score 2 (NEWS2) assessment (see Section 7.15); 
• Assessment of Clinical Recovery (See Section 7.16) 
• 12-lead electrocardiogram (see Section 7.17); 
• Collection of blood specimens (see Section 7.8) for 
o Complete blood count; 
o Biochemistry; 
o Coagulation indices; 
o Serum/urine pregnancy test, for female subjects of childbearing potential; 
o Urine sample for urinalysis parameters; 
o CD3+, CD4+ and CD8+ T cell count; 
o CCR5 receptor occupancy for Treg and macrophage;  
o Serum cytokine and chemokine levels; and 
o CCR5 Gene Polymorphisms. 
• Nasopharyngeal Swab Sample Collection (See Section 7.18) 
• Chest radiograph or computer tomography (CT) scan (if clinically indicated) (See Section 
7.19); 
• Assessment for the requirement of mechanical ventilation, Non-Invasive Ventilation, 
Supplemental Oxygen, Vasopressors Use, Renal Replacement Therapy, ICU Admission, 
and hospital stay (see Section 7.20);  
• Assessment for any new infections;  
• Review of mortality status; 
• Prior medications assessment (see Section 7.7); and 




 
 
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4.4. 
UNSCHEDULED VISITS 
In the event that the subject will return to clinic at a time other than a regularly scheduled study 
visit, the visit will be regarded as an unscheduled visit. Assessments at unscheduled visits are at 
the discretion of the Investigator. All pertinent findings, including adverse events or changes in 
medications, will be noted in the eCRF. 


 
 
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5. 
SUBJECT COMPLETION, WITHDRAWAL AND CRITERIA FOR 
STOPPING THE STUDY 
5.1. 
SUBJECT COMPLETION 
A subject is considered to have completed the study once all follow-up visit assessments have been 
completed. 
5.2. 
EARLY STOPPING RULES 
Upon occurrence of any of the following events, data will be reviewed by the Medical Monitor and 
the Lead Principal Investigator. 
1. Death in any subject in which the cause of death is judged to be probably or definitely related 
to the study drug by the treating investigator; 
2. The occurrence in any subject of a life-threatening SAE whose causal relationship to study 
drug is judged to be probable or definite by the treating investigator; 
3. Two (2) occurrences of Grade 4 toxicities that are assessed to be probably or definitely related 
to the study drug by the treating investigator; 
4. Two (2) occurrences of a Grade 2 or higher allergic/hypersensitivity reaction directly related 
to the study drug that lead to permanent discontinuation of study drug. 
In case the above listed event(s) occurred, patient accrual will be suspended pending further review 
and the FDA and other global regulatory authority will be notified. The study will be stopped if any 
of these stopping criteria are met unless, after reviewing the safety events of interest, the medical 
monitor and Sponsor, agree to allow the study to proceed. The FDA and other global regulatory 
authority will be consulted for any protocol amendment before restarting the trial if a stopping rule is 
met. 
5.3. 
REMOVAL OF SUBJECTS FROM STUDY TREATMENT AND/OR STUDY AS A WHOLE 
Subjects can be taken off the study treatment and/or study as a whole at any time at their own 
request, or they may be withdrawn at the discretion of the investigator for safety, behavioral or 
administrative reasons. In the case that a subject is removed from the study due to safety reasons, 
the FDA and other global regulatory authority will be notified. The reason(s) for discontinuation 
must be clearly documented on the appropriate eCRF and may include: 
• Subject voluntarily withdraws from treatment (follow-up permitted) 
• Subject withdraws consent (no follow-up permitted) 
• Subject is unable to comply with protocol requirements 


 
 
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• Subject experiences unacceptable toxicity 
• Treating physician determines that continuation on the study would not be in the subject’s 
best interest 
• Subject becomes pregnant 
• Subject becomes lost to follow-up (LTF) 
• Subject will be withdrawn from the study if 2 consecutive injections of study drug are 
missed 
• Subject manifesting Grade 4 or Grade 3 toxicity attributable to the Leronlimab (PRO 140) 
If a subject fails to return for the scheduled study visit or is discontinued from the study, an attempt 
will be made to determine the reason(s). If the subject is unreachable by telephone, a registered 
letter will be sent to the subject requesting that he/she contact the clinic.  
All patients with an ongoing SAE or AE attributable (definitely, probably, or possibly related) to 
the study treatment at the Post-Study (Follow-up) Visit (scheduled or premature) must be followed 
until the event is resolved (with or without sequelae) or deemed stable. 
5.4. 
DATA COLLECTED FROM WITHDRAWN SUBJECTS 
Every attempt should be made to collect follow-up information. The reason for withdrawal from 
the study will be recorded in the source documents and on the appropriate page of the CRF. 
Before a subject is identified as lost-to-follow up, the site should make all reasonable efforts to 
contact the subject. These attempts must be documented and should include at a minimum one 
phone call and one certified letter.  
In the event that a subject is withdrawn from the study at any time due to an adverse event or SAE, 
the procedures stated in Section 9 (Safety) must be followed. 
5.5. 
SCREEN FAILURES 
A subject who signed a consent form, but did not meet the inclusion/exclusion criteria is classified 
as a screen failure. Subject number, demographics and reason for screen failure will be recorded. 
In the event that a subject initially fails to meet inclusion/exclusion criteria and is later reconsidered 
for participation, the subject will be re-consented and assigned a new screening number at the time 
of re-screening. Subjects who fail their first screening attempt may be re-screened again (i.e., up to 
two screenings) and may be enrolled if they are found to meet all inclusion and no exclusion criteria 
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Study drug will be prepared by Ajinomoto Althea, Inc. and will be packaged, labeled, and shipped 
by Sherpa Clinical Packaging, LLC. 
The contents of each vial are described in Section 6.1. Leronlimab (PRO 140) kits will be labeled 
with information such as: study protocol #; fill volume; concentration; storage condition; a “use as 
per study protocol” statement; a cautionary statement; sponsor’s name and address; and the kit 
number. 
Below are representative samples of the Investigational Product, finished drug product (FDP) 
individual vial (Figure 6-1), syringe label (Figure 6-2), and kit labels (Figure 6-3) designated for 
use in this clinical protocol. Each kit contains two labeled vials and two syringe labels.  
Figure 6-1: 
Investigational Product - Vial Label 
Protocol: CD12_COVID-19               Kit No. xxx 
Subject No. _________        
Single use 3 mL vial contains 2.4 mL of PRO 140 (175 
mg/mL) solution for subcutaneous injection 
Store at 2oC to 8oC (36oF to 46oF) 
USE AS PER STUDY PROTOCOL 
Caution: New Drug – Limited by Federal (or United States) 
Law to Investigational Use 
CytoDyn Inc., Vancouver, WA, USA 
Protocol: CD12_COVID-19                    Kit No. xxx 
Subject No. _________        
Single use 3 mL vial contains 2.4 mL of PRO 140 (175 
mg/mL) solution for subcutaneous injection 
Store at 2oC to 8oC (36oF to 46oF) 
USE AS PER STUDY PROTOCOL 
Caution: New Drug – Limited by Federal (or United States) 
Law to Investigational Use 
CytoDyn Inc., Vancouver, WA, USA 
 
Figure 6-2: 
Investigational Product - Syringe Label 
Protocol: CD12_COVID-19                   
This syringe contains 2 mL PRO 140 (175 mg/mL) or placebo solution for 
subcutaneous injection 
USE AS PER STUDY PROTOCOL 
Caution: New Drug – Limited by Federal (or United States) Law to 
Investigational Use 
CytoDyn Inc., Vancouver, WA, USA 
 
Figure 6-3: 
Investigational Product - Kit Label 
Protocol: CD12_COVID-19                            Kit No. xxx 


 
 
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Site No. ____________              Subject No. ________________   
This kit contains 2 single-use vials 
Each 3 mL vial contains 2.4 mL of PRO 140 (175 mg/mL) solution for 
subcutaneous injection 
Store at 2oC to 8oC (36oF to 46oF) 
USE AS PER STUDY PROTOCOL 
Caution: New Drug – Limited by Federal (or United States) Law to Investigational 
Use 
CytoDyn Inc., Vancouver, WA, USA 
The pharmacy manual provides the criteria regarding vial acceptance or rejection, as well as 
instructions for the preparation of the IP syringes to be used to administer drug.  
6.1.2. Leronlimab (PRO 140) - Storage and Handling 
Study drug will be shipped at 2°C to 8°C (refrigerated [36°F to 46°F]) to the investigator’s site. 
Upon receipt at the site, the responsible site staff or pharmacist should verify the integrity of the 
vials. Study drug should be stored at 2°C to 8°C (refrigerated [36°F to 46°F]). The contents of the 
vial should appear as a clear to opalescent, colorless to yellow solution; fine translucent particles 
may be present. This is normal.  
The investigator must maintain an accurate record of the shipment, storage, and dispensing of the 
study drug in a drug accountability log. An accurate record including the date and amount of study 
drug dispensed to each subject must be available for inspection at any time. A study CRA assigned 
to monitor the investigational site will review these documents once study drug has been received 
by the investigational site. Study drug will be accounted for on an ongoing basis during the study. 
6.1.3. Leronlimab (PRO 140) - Administration 
Guidelines for dose preparation can be found in the pharmacy manual. 
Leronlimab (PRO 140) or placebo will be provided to the administering personnel in single-use 
syringes prepared from vials of study drug stored at 2-8°C at the site pharmacy prior to use. Syringes 
will be prepared by an unblinded pharmacist or designated site staff. Each of two syringes is filled 
to deliver 2 mL of study drug.  
Equivalent volumes of PRO 140 will be administered subcutaneously on opposite sides of the 
abdomen.  






 
 
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7. 
DESCRIPTION OF PROTOCOL ASSESSMENTS AND PROCEDURES 
7.1. 
INFORMED CONSENT 
A written informed consent will be obtained for this study by the Investigator or designee from all 
subjects prior to performance of any protocol-specific procedure. This study will be conducted in 
accordance with the provisions of the Declaration of Helsinki.  
The Investigator must comply with applicable regulatory requirements and must adhere to the Good 
Clinical Practice (GCP) in the process of obtaining and documenting the informed consent. The 
Investigator, or designee, must also inform subjects of all pertinent aspects of the study. Before 
written informed consent is obtained from the subject, the Investigator or a person designated by 
the Investigator, must provide the subject enough time and opportunity to inquire about the details 
of the study and to decide whether or not to participate in the trial. All questions addressed by the 
subject about the study must be answered to the satisfaction of the subject. Prior to the subject’s 
participation in the trial, the written informed consent must be signed and personally dated by the 
subject and by the person who conducted the informed consent discussion. Authorization for release 
of protected health information must also be obtained, as per local policies.  
7.2. 
ASSESSMENT OF ELIGIBILITY 
The Investigator must assess subject’s continued eligibility for the study as per the Inclusion and 
Exclusion criteria, during the Screening Phase. The eligibility criteria are described in Section 3.3.1 
(Inclusion Criteria) and Section 3.3.2 (Exclusion Criteria). In the event that the subject is not 
suitable or eligible for the study, the subject will be considered “screen failure”.  
7.2.1. Re-screening 
If a subject fails initially to meet the eligibility criteria, and is later reconsidered for participation, 
the subject will be re-consented and assigned a new screening number at the time of re-screening. 
Subjects who fail their first screening attempt may be re-screened a maximum of once and may be 
enrolled in the study only if they meet all Inclusion and no Exclusion criteria when re-screened. 
7.3. 
DEMOGRAPHIC INFORMATION 
In this study the demographic information will include: 
• Dates of ICF signature  
• Date of birth 
• Gender 


 
 
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• Race (American Indian or Alaska Native, Asian, Black or African American, Native 
Hawaiian or Other Pacific Islander, White, Not Reported, or Unknown) 
• Ethnicity (Hispanic or Latino,  Not Hispanic or Latino, Not Reported, or Unknown) 
• Use of tobacco products 
7.4. 
MEDICAL HISTORY 
A medical history will be recorded during the Screening Phase and will include: 
• All ongoing medical conditions 
• All previously resolved medical conditions that are relevant in the judgment of the 
Investigator  
• Any prior medical conditions that have resolved within the last year  
Events that emerge prior to the first treatment will be recorded in the medical history and not as 
AEs. Aside from being used to determine subject eligibility, this information will permit the 
Investigator to record the nature, duration and severity of any ongoing baseline medical conditions 
prior to the subject’s receiving investigational product treatment.  
Medical histories will be recorded using the body system categories outlined below: 
• HEENT 
• Lymphatic 
• Cardiovascular 
• Musculoskeletal and Extremities 
• Endocrinal 
• Hematological 
• Respiratory 
• Immunological 
• Gastrointestinal 
• Dermatologic 
• Substance Abuse 
• Psychiatric-Psychological 
• Neurologic 
• Other 
• Genitourinary 
 
 
For each relevant history, the following will be documented:  
• Disease/disorder/condition 
• Date of diagnosis 
• History status (resolved or ongoing). 
Note: For COVID-19 diagnosis, the number of days between the onset of symptoms and the 
initiation of treatment for each subject will be documented.  


 
 
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7.5. 
PHYSICAL EXAMINATION 
The physical examination will include routine examinations for the following: 
• Constitutional/General Appearance 
• Head, Ears, Eyes, Nose, Throat (HEENT) 
• Neurologic  
• Cardiovascular 
• Musculoskeletal and Extremities 
• Dermatologic 
• Respiratory  
• Gastrointestinal 
• Genitourinary  
• Lymphatic 
• Psychiatric  
Each abnormality will be recorded and the Investigator will record an assessment of its clinical 
significance.  
7.6. 
VITAL SIGNS, HEIGHT AND WEIGHT 
The following will be collected:  
o Systolic Blood Pressure  
o Diastolic Blood Pressure 
o Heart Rate 
o Temperature 
o Respiratory Rate  
• Height  
• Weight 
• Body Mass Index  
7.7. 
CONCOMITANT MEDICATIONS 


 
 
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All medications and therapies administered or taken by the subject beginning 30 days prior to 
Screening Visit and throughout the study will be recorded in the source documents and on the 
appropriate page of the Case Report Form (CRF). Additionally, all other investigational and off-
label therapies for COVID-19 will be recorded. Subjects must be questioned at each study visit 
concerning any new medications or changes in current medications including over-the-counter 
medication and topical medication. 
For each medication and non-study treatment, the following will be documented: 
• Medication/treatment name (generic name may be used if trade name is unknown) 
• Dose, unit, and frequency of dosing (individual dosages, not total daily dose).  
o Note: Each new dose of medication should be recorded as a separate entry, with the 
exception of medications that are given on a sliding scale. For these, it is acceptable 
to enter the range of the dosage, including the start and stop dates for which the 
specified dosage range was used. 
• Route of dosing  
• Indication for use 
• The start date  
• The stop date (if medication/therapy is not ongoing).  
7.7.1. Excluded Medications 
The following medications are prohibited while on study drug: 
• Other CCR5 antagonists 
• Other investigational products 
7.7.2. Allowable Medications and Therapies 
The following medications and therapies are allowed: 
• Patients with underlying chronic viral illnesses will be allowed to receive antiviral therapy. 
Note: Subjects infected with chronic hepatitis B virus or hepatitis C virus will be eligible 
for the study if they have no signs of hepatic decompensation.  
Note: Subjects infected with HIV-1 will be eligible for the study with undetectable viral load 
and are on a stable ART regimen. Investigators are required to review the subjects’ medical 
records to confirm HIV-1 RNA suppression within the previous 3 months. 
• Organ transplant patients will be allowed to continue baseline immunosuppressive therapy 
during the course of study. 


 
 
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• Empirical antibiotic treatment for secondary bacterial infections is allowed during the 
course of study. 
• Intravenous immunoglobulin (IVIG) 
• Treatment for COVID-19 in accordance with standards of care and/or institutional policy 
• Hydroxychloroquine or chloroquine with or without azithromycin for the off-label 
treatment of COVID-19 prescribed prior to study enrollment is permitted for continued use 
during the trial. 
• Remdesivir and convalescent plasma therapy prescribed prior to study enrollment is 
permitted for continued use during the trial. 
• Off-label immunomodulatory treatments for COVID-19 including but not limited to 
sarilumab, clazakizumab, tocilizumab, and anakinra prescribed prior to study enrollment is 
permitted for continued use during the trial. 
7.8. 
CLINICAL LABORATORY ASSESSMENTS 
Blood samples will be collected for analysis of the following parameters described in Table 7-1. 
• Biochemistry and Complete Blood Count (CBC): At Screening (V1), V3, V4, V5 (EOT), 
and V7.  
• Serum/urine pregnancy test (for female subjects of childbearing potential): At Screening 
(V1) and V5 (EOT) 
All laboratory reports will be reviewed by the Investigator. Abnormal results that are considered by 
the Investigator to be clinically significant will be recorded as adverse events. If in the Investigator 
judgment, in order to make the determination of clinical significance the testing may be needed to 
be repeated. Validated, quality-controlled laboratory data will be transferred to the main database 
for analyses. 
 
 
 
 
 
 
Table 7-1: 
Lab Parameters 




 
 
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(2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation 
(ECMO);  
(3) Hospitalized, on non-invasive ventilation or high flow oxygen devices;  
(4) Hospitalized, requiring supplemental oxygen;  
(5) Hospitalized, not requiring supplemental oxygen;  
(6) Not hospitalized, limitation on activities;  
(7) Not hospitalized, no limitations on activities. 
7.11. PAO2/FIO2 MEASUREMENT  
PaO2/FiO2 will be measured at Screening and at V2 (pre-dose), V3, V4, and V5 (EOT).   
7.12. PULSE OXYGEN SATURATION (SPO2) 
Pulse Oxygen Saturation (SPO2) will be measured at Screening and at V2 (pre-dose), V3, V4, and 
V5 (EOT).   
7.13. POSITIVE END-EXPIRATORY PRESSURE (PEEP), IF INTUBATED 
If the subject is intubated, positive end-expiratory pressure (PEEP) will be measured at Screening 
and at V2 (pre-dose), V3, V4, and V5 (EOT).   
7.14. SEQUENTIAL ORGAN FAILURE ASSESSMENT (SOFA) SCORE 
The SOFA score assessment will be based on PaO2/FiO2, platelets, Glasgow coma scale (GCS), 
bilirubin, Mean arterial pressure OR administration of vasoactive agents required, and creatine (See 
Appendix 17.3) 
7.15. NATIONAL EARLY WARNING SCORE 2 ASSESSMENT 
The National Early Warning Score 2 (NEWS2) Assessment is based on 7 clinical parameters 
(respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, 
heart rate, level of consciousness). See Appendix 17.1. 
7.16. ASSESSMENT OF CLINICAL RECOVERY 
The assessment of clinical recovery is based on hospital discharge or normalization of fever, 
respiratory rate, alleviation of cough and resolution of hypoxia. 
7.17. 12-LEAD ELECTROCARDIOGRAM 


 
 
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A resting supine 12-lead ECG will be conducted at the Screening Visit (V1) and Visit 5 (End of 
Treatment). A 12-lead ECG will be repeated during the study only if clinically indicated and at the 
discretion of the treating physician. The results will be evaluated by the Investigator. The following 
parameters will be recorded: ventricular rate (beats per minute), PR interval (msec), QRS interval 
(msec), QT interval (msec), and QTc interval (msec). Additionally, the Investigator will record the 
overall results of the ECG reading as either normal or abnormal, and as either not clinically 
significant or clinically significant. If abnormalities are observed, each will be recorded.  
7.18. NASOPHARYNGEAL SWAB SAMPLE COLLECTION 
Nasopharyngeal swabs will be used for quantitative virologic testing. Sample collection is 
recommended but no required. The subject will be followed and samples will be collected for the 
entire duration of the study.  
Samples are to be stored at -70°C. 
7.19. CHEST RADIOGRAPH OR COMPUTED TOMOGRAPHY SCAN 
If clinically indicated by the treating physician, a chest radiograph or CT scan will be performed at 
Screening Visit (V1) and V5 (EOT) 
7.20. REQUIREMENT 
OF 
MECHANICAL 
VENTILATION, 
NON-INVASIVE 
VENTILATION, 
SUPPLEMENTAL OXYGEN, VASOPRESSORS USE, RENAL REPLACEMENT THERAPY, ICU 
ADMISSION,   AND HOSPITAL STAY 
The incidence and duration, in days, of mechanical ventilation, non-invasive ventilation, 
supplemental oxygen, vasopressors use, renal replacement therapy, ICU admission and hospital 
stay will be assessed at Screening (V1) and V3, V4, and V5 (EOT). 
7.21. RANDOMIZATION 
Subjects who are eligible to participate in the trial will be randomized to one of the treatment groups 
via IWRS (Interactive Web Based Randomization System) at Visit 2 prior to IP administration. The 
randomization will be central with a 2:1 ratio of Active Treatment to Control Treatment to ensure 
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8. 
STATISTICAL ANALYSIS  
This section presents general information about statistical considerations and concepts and a brief 
discussion on analysis methodology, as well as some data conventions. Detailed descriptions of the 
statistical analysis methods and data conventions that will be used in this study will be in a separate 
document; i.e., the Statistical Analysis Plan (SAP). 
8.1. 
TREATMENT GROUPS 
There will be two treatment groups in the study:  
• 700 mg Leronlimab (PRO 140) 
• Placebo 
8.2. 
DESCRIPTION OF STUDY OUTCOMES (ENDPOINTS) 
8.2.1. Primary Endpoint 
The primary endpoint for the study is: 
• 
All-cause mortality at Day 28 
Note: Day 0 refers to the date of randomization/first treatment. 
8.2.2. Secondary Endpoints 
The secondary efficacy endpoints for the study are: 
• All-cause mortality at Day 14 
• Proportion of patients achieving a category of 6 or higher at Days 14 and 28 (on a 7 point 
ordinal scale). 
• Change in clinical status of subject at Days 14 and 28 (on a 7 point ordinal scale) 
A 7-category ordinal scale of patient health status ranges from: 1) Death; 2) Hospitalized, 
on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) 
Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, 
requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen; 6) Not 
hospitalized, limitation on activities; 7) Not hospitalized, no limitations on activities. 
• Length of hospital stay (days) 
8.2.3. Exploratory Outcome Measures (Endpoints) 
• All-cause mortality at Day 42 
• Change in clinical status of subject at Days 3 and 7 (on a 7 point ordinal scale) 


 
 
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A 7-category ordinal scale of patient health status ranges from: 1) Death; 2) Hospitalized, 
on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) 
Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, 
requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen; 6) Not 
hospitalized, limitation on activities; 7) Not hospitalized, no limitations on activities. 
• Change from baseline in Sequential Organ Failure Assessment (SOFA) score at Days 3 and 
7. 
• Proportion of subjects extubated within 14 days of start of study treatment. 
Note: This applies only for subjects who were intubated at the time of randomization 
• Proportion of subjects admitted into an intensive care unit (ICU) after randomization 
Note: This applies only for subjects who were hospitalized but not in an intensive care unit 
(ICU) at the time of randomization 
• Proportion of subjects requiring initiation of mechanical ventilation after randomization 
Note: This applies only for subjects who does not require mechanical ventilation at the time 
of randomization 
• Change from baseline in Sequential Organ Failure Assessment (SOFA) score at Day14. 
• Length of ICU stay (days) 
• Duration (days) of mechanical ventilation (if applicable) 
• Time to clinical recovery 
• Time from initiation of the study to discharge or to normalization of fever (defined as 
<36.6°C from axillary site, or < 37.2°C from oral site or < 37.8°C from rectal or tympanic 
site), respiratory rate (< 24 bpm while breathing room air), alleviation of cough (defined as 
mild or absent in a patient reported scale of 0=absent, 1=mild, 2=moderate, and 3=severe) 
and resolution of hypoxia (defined as SpO2 ≥ 93% in room air or P/F ≥ 300 mmHg). All 
these improvements must be sustained for at least 24 hours. 
• Change from baseline in pulse oxygen saturation (SpO2) at Days 3, 7, and 14 
• Change from baseline in National Early Warning Score 2 (NEWS2) at Days 3, 7, and 14.  
This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any 
supplemental oxygen, temperature, systolic blood pressure, heart rate, level of 
consciousness). 
• Incidence of transaminitis, defined as an increase in alanine aminotransferase (ALT) and/or 
aspartate aminotransferase (AST) to > 5 times the upper limit of normal. 
• Incidence of subjects requiring Renal Replacement Therapy (RRT) after randomization  


 
 
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• Incidence of new bacterial, invasive fungal, or opportunistic infection 
• Change in size of lesion area by chest radiograph or CT 
• Change from baseline in serum cytokine and chemokine levels at Days 3, 7, and 14 
• Change from baseline in CCR5 receptor occupancy levels for Tregs and macrophages at 
Days 3, 7, and 14 
• Change from baseline in CD3+, CD4+ and CD8+ T cell count at Days 3, 7, and 14 
8.2.4. Safety Measures 
Safety will be assessed using: 
• Incidence of treatment-related adverse events (TEAEs)  
• Incidence and severity of treatment-emergent adverse events (TEAEs) 
• Incidence of  serious adverse events (SAEs) 
• Incidence of TEAEs and SAEs leading to discontinuation of study medication.  
• Changes in blood chemistry, hematology and coagulation parameter results 
• Changes in vital signs including temperature, pulse, respiratory rate, systolic and diastolic 
blood pressure 
• Changes in physical examination results 
• Changes in electrocardiogram (ECG) results 
8.3. 
SAMPLE SIZE DETERMINATION AND RATIONALE 
This is a randomized study with two treatment groups. The subjects will be randomized to the 
treatment groups (leronlimab or placebo) in a 2:1 ratio.  
A total of three hundred ninty (390) subjects will be randomized in a 2:1 ratio to leronlimab or 
placebo groups with the goal of having 369 subjects (246 subjects in the leronlimab and 123 in the 
placebo group) complete the study.  
The sample size is obtained based on the assumption that there will be a clinically meaningful 
difference in the rate of Day 28 mortality (i.e., 15% which is 45% Day 28 mortality rate for the 
placebo group versus 30% Day 28 mortality rate in the leronlimab group). This sample size is based 
on using a 2-sided Z-tset test with 80% power and an overall significance level of 0.05. The 
expected dropout rate is 5%. To accommodate subject attritions due to the potential 
discontinuations, it is recommended randomizing an estimated 390 subjects (260 in the leronlimab 
group and 130 placebo group).  Sample size is estimated using PASS sample size software, tests 
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A single arm, non-randomized, open-label phase is added to the protocol after completion of 
enrollment in the Randomized Phase of the study in order to provide access to leronlimab for the 
eligible patients. Approximately, 100 subjects are expected to be enrolled in the non-randomized 
phase. Enrollment will remain open until the decision is made by Sponsor and/or FDA to close the 
recruitment. No statistical power calculation is used for the sample size calculation for the non-
randomized portion of the trial.  
8.4. 
RANDOMIZATION 
This is a multi-center randomized clinical trial. The randomization will use block size of 3 with a 
2:1 ratio of leronlimab group and placebo group to ensure balanced distribution of leronlimab group 
and placebo subjects. An individual, independent of the clinical trial team, will develop the 
randomization schedules. The actual randomization assignment will be made through an Interactive 
Web Based Response System (IWRS) called WebView®. Subjects who have provided written 
informed consent and have met all the inclusion criteria and none of the exclusion criteria will be 
randomized to one of the treatment groups. 
8.5. 
STRATIFICATION 
Randomization will be stratified into one of the three categories based on clinical status of the study 
at baseline: 
• Hospitalized, not in intensive care unit (ICU)  
• Hospitalized, in ICU, on mechanical ventilation, not on vasopressors 
• Hospitalized, in ICU, on mechanical ventilation, on vasopressors 
For the purpose of stratification, on vasoporessors dose is defined as: norepinephrine >20µg/min 
and/or vasopressin >0.04 units/kg/min. 
Subjects will also be stratified for the prior use of off-label immunomodulatory treatments for 
COVID-19.  
Additionally, randomization will be stratified by region (North America, Europe etc.) if 
multinational sites are involved in the study. 
8.6. 
BLINDING 
All subjects, Investigators and their staff (except unblinded pharmacist or designated site staff), and 
all Sponsor/CRO personnel involved in the management of the study will be blinded to treatment 
assignments.   
The 
Information Technology department will be unblinded to treatment. As noted above, 
the 
Technology department is not otherwise involved with the study. 


 
 
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Treatment unblinding for the study will occur after all clinical data have been received, data 
inconsistencies have been resolved, and the database is locked, except for safety reasons on a case-
by-case basis (i.e., emergency unblinding).  
The process for emergency unblinding will be outlined in details in the Randomization Plan.  In 
addition, any subject that is unblinded for any reason will be identified and discussed in the final 
clinical study report. 
8.7. 
TIME TO UNBLINDING 
8.7.1. 
Interim Analysis 
Unblinded treatment assignments for the interim analysis will only be given to an independent 
statistician who will conduct the analysis. For this analysis there will be no subject specific 
unblinding to any other personnel in the study.  
8.7.2. 
Emergency Unblinding   
Breaking the blind prematurely will be allowed only if the subject’s well-being requires knowledge 
of the subject’s treatment allocation. Every attempt will be made to maintain the blind throughout 
the study. 
In the event of an urgent safety issue where the randomized treatment of a subject is necessary to 
manage and treat the affected study subject (e.g., unblinding subjects because of SAEs that meet 
“expedited criteria” and requires reporting to FDA and other global regulatory authority), the 
Investigator will contact the Medical Monitor. The Medical Monitor, in consultation with sponsor, 
will make a decision to unblind. If the decision has been made to unblind, a prompt written 
notification will be provided to the Investigator. The reason for unblinding must be recorded; 
however the investigator must not record the subject’s treatment assignment in study documentation 
and must not reveal the subject’s treatment assignment to the clinical monitor. 
If reporting of an adverse event is to be performed unblinded as per regulatory authority guidelines, 
study-unrelated personnel will unblind the individual subject’s treatment group and will perform 
the unblinded reporting. No treatment group information would be shared with study personnel. 
8.7.3. 
Final Analysis 
Treatment unblinding and release of the randomization codes of the investigational product 
assignments for the study will occur immediately following database lock when all randomized 
subjects have completed the study or discontinued from the study and after all clinical data have 
been received and data inconsistencies have been resolved. 
8.8. 
INTERIM ANALYSIS 


 
 
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An Interim Analysis (IA) will be conducted when approximately 50% (~195 subjects) of the study 
participants have been in the study for at least 4 weeks after randomization or are withdrawn from 
the study, whichever occurs first. 
The main objectives of the IA are safety and sample size re-assessment.  
The IA will have prospectively assigned rules and a method to protect the type I error rate and the 
integrity of the trial, due to the unblinded look. The IA will be conducted under the auspices of an 
independent Data Safety Monitoring Committee (DSMC) according to a written Charter. The 
procedures for this IA will be based on a standard operating procedure (SOP) that has a well-
established a firewall to protect the integrity of the trial. The IA will be performed by an 
independent un-blinded statistician, who is not otherwise associated with the conduct of this trial.  
The details of the interim analysis will be included in the Statistical Analysis Plan. 
8.9. 
GENERAL STATISTICAL CONSIDERATIONS 
All collected study data will be presented in subject data listings. Statistical analyses will be 
performed using SAS® for Windows, version 9.4 or later. Descriptive statistics (n, mean, standard 
deviation, median, minimum and maximum) will be presented for continuous variables. 
Frequencies and percentages will be presented for categorical variables. 
8.9.1. Analysis Populations 
8.9.1.1. 
Intent-to-Treat Population 
The Intent-to-Treat (ITT) population is defined as all randomized subjects. This population will 
be used as the primary analysis population for analysis of the primary and secondary efficacy 
endpoints. 
8.9.1.2. 
PP Population 
The Per Protocol (PP) population is defined as the set of subjects who meet the ITT Population 
requirements and are not associated with any major protocol violations. This population will be 
identified before the database lock.  This population will be used as the supportive analysis 
population for analysis of the primary and secondary efficacy endpoints. 
8.9.1.3. 
Safety Population 
The Safety Population will include all subjects who have received one dose of leronlimab (PRO 
140) or placebo. This population will be used for the analysis of safety parameters or measurements. 
8.9.2. Covariates 
For efficacy analyses important prognostic factors that need adjustment will be specified in the 
Statistical Analysis Plan (SAP) for the study 


 
 
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8.9.3. Missing Data 
Every effort will be made to obtain required data at each scheduled evaluation from all subjects 
who have been randomized to minimize missing data. However, in the event when there is missing 
data the following imputation methods will be used. 
For efficacy evaluations, multiple imputation methods will be used to handle missing data. This 
imputation method is a robust method to impute missing measurements.  The imputation will be 
carried out in SAS version 9.4 or later using PROC MI. Each imputation model will include the 
stratification factor as a covariate in the model.  The details of multiple imputation will be included 
in the statistical analysis plan.  
8.10. ANALYSIS METHODS 
A Statistical Analysis Plan (SAP) will be developed and approved before the database is locked. 
The SAP will present the detailed statistical methodology to be used in analyzing the data from this 
trial. 
8.10.1. Subject Disposition 
The disposition of all subjects who signed an ICF will be provided. The number of subjects 
screened, screen failed, randomized, received at least one treatment, completed, and discontinued 
during the study, as well as the reasons for all discontinuations will be summarized by treatment 
group. Disposition and reason for study discontinuation will also be provided as a by-subject listing. 
8.10.2. Demographic and Baseline Characteristics 
Demographics and baseline characteristics including medical history, will be summarized by 
treatment group using appropriate descriptive statistics. 
8.10.3. Concomitant Medications/Therapies 
Concomitant medications/therapies will be summarized separately for the Safety population. All 
prior and concomitant medications recorded in the case report form will be coded to matching 
Anatomic Therapeutic Classification codes using the most recent version of the WHO Drug 
Dictionary. Descriptive summaries by treatment group will be prepared using the coded term. All 
concomitant medications/therapies recorded in the case report form will be listed. 
8.10.4. Efficacy Analyses 
Primary Analysis   
The ITT population will be the primary population for the analysis of the efficacy endpoints of the 
study.  
Primary Endpoint 


 
 
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The primary endpoint for this study is the proportion of subjects with Mortality at Day 28 between 
leronlimab and placebo. The difference in the Day 28 mortality between the leronlimab and placebo 
treatment groups will be compared using Logistic regression model.  
Secondary Endpoints  
To maintain the trial-wise Type I error rate at 0.05, a closed test procedure will be used for the 
secondary endpoints. The order of the secondary endpoints will prospectively specified in the SAP.  
Analysis of the secondary and exploratory endpoints will be summarized according to the variable 
type:  
• Continuous data summaries will include:  
o If the Normality assumption is met, Analysis of Covariance (ANCOVA) would be 
used.  
o If the Normality assumption is not met, a non-parametric method or a rank –
ANCOVA analysis i.e., an ANCOVA analysis on rank-transformed data will be 
used.  
• Categorical data summaries will be based on Logit model will be used. 
• Time-dependent data: Cox proportional hazards model will be used to analyze time 
dependent data and to depict the time to event data.  
8.10.5. Supportive Analysis  
To assess the consistency of the Primary Analysis results, supportive analysis will be conducted 
using the Intent to Treat (ITT) and Per Protocol (PP) populations. Statistical methodology for the 
supportive analyses will be the same as that of the primary analysis, with the exception of the 
analysis population used.  
8.10.6. Subgroup Analysis 
Subgroup analyses will be conducted for the predefined stratification factors (Section 8.5) for the 
study. Additional exploratory subgroup analysis will be conducted using the baseline clinical 
characteristics and laboratory parameters such as, CD4/CD8 ratio and IL-6. The details will be 
prospectively specified in the SAP. 
Safety Summaries  
8.10.6.1. 
Adverse Events 
Adverse events will be coded using the most recent version of Medical Dictionary for Regulatory 
Activities (MedDRA). Treatment Emergent AE’s (TEAE) are defined as events with an onset on 
or after the first treatment. TEAEs will be summarized by System Organ Class and preferred term 
by treatment group. The following TEAE summaries will be provided: 
• Overall (i.e., regardless of severity or relationship to treatment); 


 
 
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• By intensity  (mild, moderate, severe, life threatening or death); 
• By causality (definitely, probably, possibly, remotely or unrelated); 
• By impact on study treatment (dose increased, dose not changed, dose rate reduced, dose 
reduced, drug interrupted, drug withdrawn, not applicable, or unknown). 
In addition, separate summaries of serious adverse events, and adverse events resulting in 
discontinuation of study treatment will be presented. 
8.10.6.2. 
Clinical Laboratory Data 
All laboratory values will be listed. Laboratory measurements will also be summarized by treatment 
group and presented by time point. 
8.10.6.3. 
ECG 
All ECG values will be listed. ECG measurements will also be summarized by treatment group and 
presented by time point. 
8.10.6.4. 
Vital Signs 
All vital sign findings will be listed and/or summarized by treatment group. 
8.10.6.5. 
Physical Examination 
All physical examination findings will be listed and/or summarized by treatment group. 


 
 
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9. 
ADVERSE EVENTS (DEFINITIONS AND REPORTING)  
The Investigator is responsible for the detection and documentation of events meeting the criteria 
and definition of an AE or SAE, as provided in this protocol. During the study when there is a safety 
evaluation, the Investigator or site staff will be responsible for detecting, documenting and reporting 
AEs and SAEs as detailed in this Section of the protocol.  
9.1. 
ADVERSE EVENT (AE)  
An adverse event (AE) is defined as any unfavorable or unintended sign, symptom, or disease that 
occurs or is reported by the patient to have occurred, or a worsening of a pre-existing condition. An 
adverse event may or may not be related to the study treatment.  
AEs will be elicited through direct questioning and subject reports. Any abnormality in physical 
examination findings or laboratory results that the investigator believes is clinically significant (CS) 
to the research subject and that occurred after initiation of the first study treatment will be reported 
as AEs. Abnormal findings that are NOT clinically significant should not be recorded as an AE. 
9.2. 
REPORTING OF ADVERSE EVENTS 
Report initiation for all AEs and SAEs will begin at the time of the first treatment visit and continue 
until the end of final study visit.  All events will be followed to resolution or until the subject 
completes the study. A final assessment of outcome will be made at that time.  
All AEs must be recorded in the subject’s medical records and on the CRF. AEs will be reported 
using customary medical terminology along with the following information: the onset and end 
dates,  whether the event is considered to be a SAE (see Section 9.3), the impact the event had on 
study treatment (see Section 9.2.1), the Common Terminology Criteria for Adverse Events 
(CTCAE) grade (intensity) of the event (see Section 9.2.2), the causality of the event (see Section 
9.2.3), whether treatment was given as a result of the event (see Section 9.2.4), and the outcome of 
the event (see Section 9.2.5) 
9.2.1. Impact on Study Treatment 
The impact the event had on the study treatment will be assessed as either: dose increased, dose not 
changed, dose rate reduced, dose reduced, drug interrupted, drug withdrawn, not applicable, or 
unknown. The “not applicable” assessment will be used only when the subject is no longer in the 
Treatment Phase of the protocol. 
9.2.2. CTCAE Grade (Intensity) Assessment 
The guidelines outlined in CTCAE v5.0 will be used for assessing the intensity of the event (See 
Appendix 17.2). The general guidelines for assessing the AE grade appear below. Full guidelines 
may be obtained at 




 
 
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3. Possibly related: This category applies to those AEs which, after careful medical consideration 
at the time they are evaluated, are judged unlikely but cannot be ruled out with certainty to the 
study treatment. An AE may be considered possible if or when (must have two): (1) it follows 
a reasonable temporal sequence from administration of the study treatment. (2) It could not 
readily have been produced by subject’s clinical state, environmental or toxic factors, or other 
therapies administered to the subject. (3) Disappears or is decreased upon discontinuation of 
the study treatment. (4) It follows a known response pattern to treatment with the study 
treatment.  
4. Remotely related: In general this category can be considered applicable to those AEs which, 
after careful medical consideration at the time they are evaluated, are judged likely to be 
unrelated to the study treatment. An AE may be considered unlikely if or when (must have two): 
(1) it does not follow a reasonable temporal sequence from administration of the study 
treatment. (2) It could not readily have been produced by subject’s clinical state, environmental 
or toxic factors, or other therapies administered to the subject. (3) Disappears or is decreased 
upon discontinuation of the study treatment. (4) It does not follow a known response pattern to 
treatment with the study treatment.  
5. Unrelated: This category applies to those AEs which, after careful consideration at the time 
they are evaluated, are clearly and incontrovertibly due to extraneous causes (disease, 
environment, etc.) and determined with certainty to have no relationship to the study treatment.  
9.2.4. Treatment Given as a Result of the Event 
The event impact in terms of treatment provided will be as either: none, medication administered, 
non-drug therapy administered, surgery performed, hospitalization, or other (with a specification). 
9.2.5. Outcome Assessment 
The outcome of the event will be assessed as either: fatal, not recovered/not resolved, 
recovered/resolved, recovered/resolved with sequelae, recovering/resolving, or unknown. Only one 
AE per subject is allowed to have an outcome assessment as “death.” If there are multiple causes 
of death for a given subject, only the primary cause of death will have an outcome of death.  
9.3. 
SERIOUS ADVERSE EVENTS 
A SAE is defined as any AE that: 
• Results in death 
• Is life threatening (the subject is at immediate risk of dying from the adverse experience) 
• Requires subject’s hospitalization or prolongs existing hospitalization 
• Results in persistent or significant disability/incapacity 
• Is a congenital anomaly/birth defect 


 
 
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• Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered a serious adverse effect when, based upon appropriate 
medical judgment, they may jeopardize the subject or subject and may require medical or 
surgical intervention to prevent one of the outcomes listed in this definition. 
9.4. 
REPORTING OF SERIOUS ADVERSE EVENTS (SAE)  
The Investigator is required to report all SAEs that occur during the time period specified in 
Section 9.2.2. Once the Investigator becomes aware of an SAE, he/she must report the SAE to 
Medical Monitor within 24 hours. 
Medical Monitor 
Attn: Safety DepartmentAmarex Clinical Research, 
LLC 
20201 Century Boulevard, 4th Floor 
Germantown, MD 20874 
Email: saereporting@amarexcro.com 
Phone: +1 (240) 235-6852 
Fax: +1 (240) 454-6602 
The Medical Monitor may request additional supporting documentation as it becomes available, 
such as lab reports, ECG reports, discharge summary, hospital notes, etc, if applicable. Additional 
follow-up information as it becomes available must be reported to the Medical Monitor. 
The Investigator is also responsible for reporting all SAEs to the appropriate Institutional Review 
Board (IRB) in accordance with local laws and regulations. The Investigator is responsible for 
maintaining documentation in the study file that indicates the IRB has been properly notified.  
9.5. 
SAE FOLLOW-UP 
All subjects experiencing an SAE, including the discontinued subjects, must be closely followed 
until sufficient information is obtained to indicate a return to normal status or until the event 
stabilizes at a level acceptable to the investigator (i.e., recovery, return to baseline status, no further 
improvement expected, or death). 
For each SAE indicated as an unresolved event on the initial report, regardless of whether the 
subject completed the study or withdrew, the site should submit a follow-up report with updated 
information. 
Study participants should be instructed to notify the investigator and discontinue investigational 
product immediately if they become pregnant at any time during the study or if they become 
pregnant within 30 days of last investigational product dose. A participant whose partner has 
become pregnant or suspects she is pregnant during the study must report the information to the 
investigator. The Investigator is required to report any notification of pregnancy to CytoDyn, 
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until the conclusion of the pregnancy. Any complication experienced through the end of the 
pregnancy should be considered as an adverse event (AE), and should be recorded, and if it meets 
the seriousness criteria, it must be reported to CytoDyn, Inc/designated CRO promptly. Pregnancy 
outcomes will be reported in the clinical study report. 
9.6. 
EXPECTED/ANTICIPATED EVENTS 
Refer to Investigator Brochure for the expected/anticipated events. 
 


 
 
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10. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTATION 
Subjects will be identified on eCRFs by a unique subject identification number and on source 
documents by name and date of birth. No personal identifier will be used in any publication or 
communication used to support this research study. The subject identification number will be used 
if it becomes necessary to identify data specific to a single subject.  
The local IRB, FDA and other global regulatory authorities, the monitors, auditors and personnel 
authorized by the Sponsor are eligible to review the medical and research records related to this 
study as part of their responsibility to protect human subjects in clinical research. They will be 
given direct access to source data and documentation (e.g., medical charts/records, printouts etc.) 
for source data verification, provided that subject confidentiality is maintained in accordance with 
local requirements. Access to electronic medical records may be governed by institution policy and 
each site will be required to ensure access while remaining compliant with institutional 
requirements. 
 
 
 


 
 
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11. 
QUALITY CONTROL AND QUALITY ASSURANCE 
11.1. MONITORING REQUIREMENTS 
The specific obligations outlined in 21 Code of Federal Regulations (CFR) and ICH guidelines 
require the Sponsor to maintain current personal knowledge of the progress of a study. Therefore, 
the Sponsor's designated monitor will visit the site during the study as well as maintain frequent 
telephone and written communication. The Investigator will permit the Sponsor to monitor the 
study as frequently as is deemed necessary and provide access to medical records to ensure that 
data are being recorded adequately, that data are verifiable and that protocol adherence is 
satisfactory.  
As delineated above, the Investigator will permit representatives of the Sponsor and/or designated 
CRO to inspect all CRFs and corresponding study subject original medical records (source 
documents) at regular intervals throughout the study. Subject original medical records and other 
relevant data must be available to support all data recorded in the eCRF. In addition to the original 
medical records, these data may include but are not limited to study, laboratory reports, etc.  
In accordance with federal regulations, site inspections will serve to verify strict adherence to the 
protocol and the accuracy of the data that is being entered on the case report forms. A Monitoring 
Log will be maintained at each study site. The Monitoring Log will be signed by the monitor, dated 
and stated the type of visit. The Investigator should be aware that the study site and subject records 
may be inspected by the Sponsor and or representatives of the designated CRO, FDA or other 
regional regulatory authority. 
11.2. ACCEPTABILITY OF CASE REPORT FORMS (CRFS) 
For each subject who has signed an informed consent form, a CRF must be completed. For subjects 
who are screen failures, this would be limited to the screen failure CRF page. All source documents 
and CRFs will be completed as soon as possible after the subject's visit and corrections to data on 
the CRFs will be documented, if applicable. The Investigator will review the CRFs to indicate that, 
to his/her knowledge, they are complete and accurate. CRFs will be reviewed by the Sponsor’s or 
designated CRO’s monitor, who will make a decision as to their acceptability.  
11.3. MODIFICATION OF PROTOCOL 
The Investigator will not modify or alter this protocol without first obtaining the concurrence of the 
Sponsor. Approval by the Investigator’s IRB must also be obtained prior to implementation of the 
change, with two exceptions: 
1. When necessary to eliminate apparent immediate hazard to the subject; or 
2. When the modification does not involve the subject’s participation in the trial. 


 
 
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An amendment may also require modification of the informed consent form. The Investigator will 
provide an approval letter for the amendment and revised informed consent form, if applicable, to 
the Sponsor. An amendment must be provided in writing and it must be dated by both the Sponsor 
and the Investigator. If necessary, the Sponsor will submit protocol amendments to FDA and other 
appropriate regulatory authorities and notify other Investigators using this protocol. 
11.4. REPORTING PROTOCOL DEVIATIONS 
The Investigator is obligated to follow the protocol without departure from the requirements written 
in the protocol. If the Investigator deviates from the protocol requirements, the Sponsor will make 
the determination as to whether the subject will continue in the study. The Sponsor also has the 
right to discontinue the subject for protocol violations. The IRB may also have to be contacted if 
safety to the subject or if the scientific soundness of the study is involved. All protocol deviations 
must be documented in the CRFs. 
11.4.1. Major Protocol Deviation or Violation 
A major protocol deviation or violation is a deviation from the IRB approved protocol that may 
affect the subject's rights, safety, or well being and/or the completeness, accuracy and reliability of 
the study data. Examples of this include: 
• Failure to obtain informed consent prior to initiation of study-related procedures  
• A research subject does not meet the protocol's eligibility criteria but was enrolled without prior 
approval from the sponsor. 
• A research subject received the wrong treatment or incorrect dose. 
• A research subject met withdrawal criteria during the study but was not withdrawn. 
• A research subject received a prohibited concomitant medication. 
• Failure to treat research subjects per protocol procedures that specifically relate to primary 
efficacy outcomes. 
• Changing the protocol without prior sponsor and IRB approval. 
• Multiple minor violations of the same nature after multiple warnings. 
11.4.2.  Minor Protocol Deviation or Violation 
A minor protocol deviation is any change, divergence, or departure from the study design or 
procedures of a research protocol that has not been approved by the IRB and which DOES NOT 
have a major impact on the subject's rights, safety or well-being, or the completeness, accuracy and 
reliability of the study data.  Examples of this include: 


 
 
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• Follow-up visits that occurred outside the protocol required time frame because of the 
participant’s schedule. 
• Blood samples obtained at times close to but not precisely at the time points specified in the 
protocol. 
 
 
 


 
 
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12. 
DATA SAFETY MONITORING COMMITTEE (DSMC) 
A Data Safety and Monitoring Committee (DSMC), independent of the study operations will be 
established to consider safety data generated during the study and to make recommendations about 
IA data for sample size re-estimation once 50% of enrolled patients have been in the study for at 
least 4 weeks after randomization or are withdrawn from the study, whichever occurs first. The 
details of the DSMC responsibilities will be included in the DSMC charter. The DSMC charter will 
be developed and operated in adherence to the current FDA guidance on DSMC (Establishment 
and Operation of Clinical Trial Data Safety Monitoring Committees [March 2006]). The DSMC 
meetings will take place at least once after the IA, and at other time-points as determined by the 
DSMC charter. In addition to the pre-specified time-points, the DSMC may also decide to schedule 
a meeting whenever they decide a review of emergent safety data is warranted. The charter will 
detail the roles and responsibilities of the DSMC members once they have been appointed. The 
study data will be provided to the Committee members in the form of a data report. Meetings to 
discuss the data will be held in person or by teleconference, based on the DSMC Chair’s decision. 
The meetings will be in two stages: an “open stage” which will involve discussion on general 
aspects of the trial, and a “closed stage” between the DSMC members only. The remit of the DSMC 
will be primarily to assess the safety aspects of the trial. 
 


 
 
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13. 
ETHICS AND REGULATORY REQUIREMENTS 
This study is to be conducted in accordance with the specifications of this protocol and in 
accordance with principles consistent with Declaration of Helsinki, GCP, 21 CFR, ICH E6, HIPAA 
regulations in 45 CFR Part 164 (US only), and the Belmont Principles of respect for persons, 
beneficence, and justice. No protocol changes will be implemented without the prior review and 
approval of the IRB, except when the modification does not involve the subject’s participation in 
the trial or where it may be necessary to eliminate an immediate hazard to a research subject. In the 
latter case, the change will be reported to the IRB as soon as possible, according to IRB regulations.  
Additionally, the study product used in this study is manufactured, handled and stored in accordance 
with applicable GMP. The study product provided for this study will be used only in accordance 
with this protocol. 
13.1. INSTITUTIONAL REVIEW BOARD/INDEPENDENT ETHICS COMMITTEE (IRB/IEC) 
The Principal Investigator (PI) at each site will provide the Institutional Review Board/Independent 
Ethics Committee (IRB/IEC) with all appropriate materials as required by their IRB/IEC, including 
but not limited to the clinical study protocol, informed consent form, and any advertising materials. 
The study will not be initiated until the IRB/IEC provides written approval of the aforementioned 
documents and until approval documents have been obtained by the Principal Investigator and 
Sponsor or Sponsor designee. The Investigator will not participate in the decision. If the 
Investigator is an IRB or IEC member, documentation must be provided indicating recusal from 
the approval process. Appropriate reports on the progress of this study by the Principal Investigator 
will be made to the IRB/IEC as required by local and applicable government regulations and in 
agreement with policy established by the Sponsor. The Investigator is required to maintain an 
accurate and complete record of all written correspondence to and received from the IRB/IEC, and 
must agree to share all such documents and reports with the Sponsor. 
No changes from the final approved protocol will be initiated without the IRB/IEC’s prior written 
approval or favorable opinion of a written amendment, except when necessary to eliminate 
immediate hazards to the subjects or when the modification does not involve the subject’s 
participation in the trial.  
13.2. INVESTIGATOR’S RESPONSIBILITIES 
The Investigators are responsible for performing the study in full accordance with the protocol and 
the current revision of the Declaration of Helsinki, the Good Clinical Practice: Consolidated 
Guideline, approved by the ICH, and any applicable national and local laws and regulations. 


 
 
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Information regarding to the study center participating in this study that cannot comply with these 
standards will be documented. 
13.3. SUBJECT INFORMED CONSENT REQUIREMENTS 
All subjects participating in this study will be given to by the Investigator and/or designee, written 
and oral information about the study in a language understandable by the subject. Written informed 
consent will be obtained from each subject prior any procedures or assessments that would not 
otherwise be required for the care of the subject are done and after the aims, methods, anticipated 
benefits, potential hazards, and insurance arrangements in force are explained and the subject has 
been given sufficient time to ask questions and consider participation in the study. It will also be 
explained to the subjects that they are free to refuse entry into the study and free to withdraw from 
the study at any time without prejudice to future treatment. It is permissible for a third person (e.g., 
a family member) to be present during the explanation of the study. 
The written Informed Consent Form (ICF) will be in compliance with CFR 21 Part 50.27 and GCP 
guidelines. The Sponsor and/or designated CRO will approve the ICF and all amendments to the 
ICF prior to submission to the IRB/IEC. A copy of the ICF to be used will be submitted by the 
Investigator to the IRB/IEC for review and approval prior to the start of the study. The study site 
must provide the Sponsor with an unsigned copy of IRB/IEC-approved ICF along with applicable 
documentation to support this approval. The original signed ICF is retained in the subject's study 
records, and a copy is provided to the subject. A second copy may be filed in the subject’s medical 
record, if allowed by institutional policy.  
 


 
 
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14. 
DATA HANDLING AND RECORD KEEPING 
14.1. RECORDING AND COLLECTION OF DATA 
The primary source document for this study will be the subject's medical record. If separate research 
records are maintained by the Investigator(s), the medical record and the research records will be 
considered the source documents for the purposes of auditing the study.  
Applicable source data will be manually transcribed to approve case report forms (CRF). The 
Investigator is ultimately responsible for the accuracy of the data transcribed on the forms. All 
source documents and CRFs will be completed as soon as possible after the subject's visit. 
The Investigator will review the CRFs to indicate that, to his/her knowledge, they are complete and 
accurate. Designated source documents will be signed and dated by the appropriate study personnel. 
The Investigator must agree to complete and maintain source documents and CRFs for each subject 
participating in the study. 
All research data will be entered, either electronically or manually, into a computerized database. 
The clinical database will be designed by the clinical data manager in accordance with 21 CFR Part 
11 and based on protocol requirements defined by the Sponsor in association with the Lead 
Investigator.  
The Investigator will maintain a confidential list of study subjects that will include each subject’s 
study number, name, date of birth, and unique hospital identification number if applicable. This list 
will be kept by the Investigator and will not be collected by the Sponsor. A notation will be made 
in the subject’s case history/medical chart that he/she is participating in a clinical study and has 
provided a signed and dated ICF as well as a release for protected health information as required 
by local policies. The Investigator must also maintain a separate screening log of all the subjects 
screened for participation in the study; it should include gender, age, eligibility status, reason for 
ineligibility, if applicable; and study allocated subject number, if applicable.  
14.2. CLINICAL DATA MANAGEMENT 
The Sponsor and/or designated CRO will be responsible for the processing and quality control of 
the data. Data management will be carried out as described in the Sponsor’s or CRO’s standard 
operating procedures (SOPs) for clinical studies. 
The handling of data, including data quality control, will comply with regulatory guidelines 
(e.g., ICH E6 GCP, and local regulations where applicable) and the Sponsor’s or the CRO’s SOPs 
as well as provisions of the study-specific Data Management Plan. 
 
 


 
 
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14.3. ARCHIVING 
All study documentation at the Investigator site and Sponsor site will be archived in accordance 
with ICH GCP E6 and the Sponsor’s quality standards and SOPs. 
The Investigator will maintain all research records, reports, and case history reports for a period of 
two (2) years after regulatory approval of the investigational product. If no application is filed or if 
the application is not approved, records must be maintained for two (2) years after all investigations 
have been completed, terminated or discontinued and the FDA and other global regulatory 
authorities has been notified.  
These documents should be retained for a longer period however, if required by the applicable 
regulatory requirements or if needed by Sponsor or its authorized representative (as per 
GCP 5.5.11). 
At the completion of the study, details of the archival process must be provided to the Sponsor. 
Study records are subject to inspection by applicable health and regulatory agencies at any time.  
Records to be retained by the Investigator include, but are not restricted to: 
• Source data and the primary records upon which they are based (e.g., subject’s progress 
notes, adverse event data, test results, and any other diagnostic procedures required to 
evaluate the progress of the study) 
• Completed CRFs 
• Signed protocols and protocol amendments 
• Laboratory results, ranges, and certifications 
• IP and accountability records 
• Study personnel signature log 
• Monitoring logs 
• Correspondence to and from the Sponsor, designee and IRB 
• Investigator and sub-investigator CVs 
• Signed informed consent and protected health information consent forms 
• Subject screening  
• SAE reports 
• IRB approval and re-approval letters 
• Completed quality of life questionnaire 
• Other documents pertaining to the conduct of the study 
These documents must be maintained and kept on file by the Investigator so that the conduct of the 
study can be fully documented and monitored. 


 
 
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Study records should not be transferred from site or destroyed without prior written agreement 
between the Sponsor and the study Investigator. Study records are subject to inspection by 
applicable health and regulatory agencies at any time.  


 
 
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15. 
PUBLICATION PLAN 
All information supplied by CytoDyn, Inc. in connection with this study and not previously 
published, is considered confidential information. This information includes, but is not limited 
to, the Investigator’s Brochure, clinical protocol, case report forms and other scientific data. Any 
data collected during the study are also considered confidential. This confidential information 
shall remain the sole property of CytoDyn, Inc., shall not be disclosed to others without the 
written consent of CytoDyn, Inc., and shall not be used except in the performance of this study. 
It is understood by the Investigator that the Sponsor will use the information collected in this clinical 
trial in connection with the development of CytoDyn, Inc.. Therefore, this information may be 
disclosed as required to other Investigators or appropriate regulatory authorities. By agreeing to 
participate in this clinical trial, the Investigator understands that he/she has an obligation to provide 
the Sponsor with complete test results and all data developed during this trial. 
Publication and Disclosure: The site and Investigator agree to submit any proposed manuscript, 
presentation or other public disclosure regarding the study to Sponsor for review at least thirty (30) 
days prior to submitting such proposed manuscript to a publisher or delivering or making such 
presentation or other public disclosure to any third party. Within thirty (30) days of its receipt, 
Sponsor shall advise the site and/or Investigator, as the case may be, in writing of any information 
contained therein that is confidential information (other than research results included in a proposed 
manuscript) or that may impair Sponsor’s ability to obtain patent protection. Sponsor shall have the 
right to require the site and/or Investigator, as applicable, to remove specifically identified 
confidential information (but may not require removal of research results from a proposed 
manuscript) and/or to delay the proposed submission or delivery of the proposed manuscript or 
presentation, or other public disclosure, for an additional sixty (60) days to enable Sponsor to seek 
patent protection. The site and Investigator shall not publish, publicly disclose, present or discuss 
any results of or information pertaining to the site’s and Investigator’s activities prior to completion 
of the trial, even if the study is terminated before its completion and the final clinical study report 
is signed off, or with respect to any endpoints or analyses other than those specified in this protocol. 


 
 
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16. 
REFERENCES 
Center for Disease Control (CDC) (2020, March 3). Coronavirus Disease 2019 (COVID-19) 
Situation Summary Retrieved March 5, 2020, from https://www.cdc.gov/coronavirus/2019-
ncov/summary.html 
Chen, J., Lau, Y. F., Lamirande, E. W., Paddock, C. D., Bartlett, J. H., Zaki, S. R., & Subbarao, K. 
(2010). Cellular immune responses to severe acute respiratory syndrome coronavirus (SARS-CoV) 
infection in senescent BALB/c mice: CD4+ T cells are important in control of SARS-CoV 
infection. Journal of virology, 84(3), 1289-1301. 
Doerschuk, C. M., Tasaka, S., & Wang, Q. (2000). CD11/CD18-dependent and-independent 
neutrophil emigration in the lungs: how do neutrophils know which route to take?. American 
journal of respiratory cell and molecular biology, 23(2), 133-136. 
Glass, W. G., Liu, M. T., Kuziel, W. A., & Lane, T. E. (2001). Reduced macrophage infiltration 
and demyelination in mice lacking the chemokine receptor CCR5 following infection with a 
neurotropic coronavirus. Virology, 288(1), 8-17. 
Halama N, Zoernig I, Berthel A, Kahlert C, Klupp F, Suarez-Carmona M, Suetterlin T, Brand K, 
Krauss J, Lasitschka F, Lerchl T. Tumoral immune cell exploitation in colorectal cancer metastases 
can be targeted effectively by anti-CCR5 therapy in cancer patients. Cancer cell. 2016 Apr 
11;29(4):587-601. 
Jacobson, J. M., Lalezari, J. P., Thompson, M. A., Fichtenbaum, C. J., Saag, M. S., Zingman, B. S., 
... & Maddon, P. J. (2010). Phase 2a study of the CCR5 monoclonal antibody PRO 140 administered 
intravenously to HIV-infected adults. Antimicrobial agents and chemotherapy, 54(10), 4137-4142. 
Jacobson, J. M., Saag, M. S., Thompson, M. A., Fischl, M. A., Liporace, R., Reichman, R. C., ... & 
Murga, J. D. (2008). Antiviral activity of single-dose PRO 140, a CCR5 monoclonal antibody, in 
HIV-infected adults. Journal of Infectious Diseases, 198(9), 1345-1352. 
Kohlmeier, J. E., Miller, S. C., Smith, J., Lu, B., Gerard, C., Cookenham, T., ... & Woodland, D. L. 
(2008). The chemokine receptor CCR5 plays a key role in the early memory CD8+ T cell response 
to respiratory virus infections. Immunity, 29(1), 101-113. 
Patterson, B. K., Czerniewski, M., Andersson, J., Sullivan, Y., Su, F., Jiyamapa, D., ... & Landay, 
A. (1999). Regulation of CCR5 and CXCR4 expression by type 1 and type 2 cytokines: CCR5 
expression is downregulated by IL-10 in CD4-positive lymphocytes. Clinical Immunology, 91(3), 
254-262. 
Russkamp, N. F., Ruemmler, R., Roewe, J., Moore, B. B., Ward, P. A., & Bosmann, M. (2015). 
Experimental design of complement component 5a-induced acute lung injury (C5a-ALI): a role of 


 
 
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CC-chemokine receptor type 5 during immune activation by anaphylatoxin. The FASEB 
Journal, 29(9), 3762-3772. 
Thompson, M., Lalezari, J., Saag, M., Jacobson, J., Zingman, B., Stambler, N., ... & Morris, S. 
(2009, February). Weekly and biweekly subcutaneous PRO 140 demonstrates potent, sustained 
antiviral activity. In 16th Conference on Retroviruses and Opportunistic Infections (pp. 8-11). 
World Health Organization (WHO) (2020, March 1). Coronavirus disease 2019 (COVID-19) 
Situation Report -4 1 Retrieved March 5, 2020, from https://www.who.int/docs/default-
source/coronaviruse/situation-reports/20200301-sitrep-41-covid-19.pdf?sfvrsn=6768306d_2 
 
 


 
 
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17. 
APPENDIX 
17.1. APPENDIX 1: NATIONAL EARLY WARNING SCORE 2 (NEWS2) 
The National Early Warning Score 2 (NEWS2) determines the degree of illness of a patient and 
prompts critical care intervention. 






 
 
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17.2. APPENDIX 2: COMMON TERMINOLOGY CRITERIA FOR ADVERSE EVENTS V5.03 
 
For complete detailed information please refer to the link below: 
https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/CTCAE_v5_Quick_Re
ference_5x7.pdf 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
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17.3. APPENDIX 3: SEQUENTIAL ORGAN FAILURE ASSESSMENT (SOFA) SCORE 
Predicts ICU mortality based on lab results and clinical data 
Variable 
Points 
PaO2/FiO2, mmHg 
≥400 
0 
300-399 
+1 
200-299 
+2 
100-199 and mechanically ventilated 
+3 
<100 and mechanically ventilated 
+4 
Platelets, ×103/µL 
≥150 
0 
100-150 
+1 
50-99 
+2 
20-49 
+3 
<20 
+4 
Glasgow Coma Scale 
15 
0 
13–14 
+1 
10–12 
+2 
6–9 
+3 
<6 
+4 
Bilirubin, mg/dL (μmol/L) 
<1.2 (<20) 
0 
1.2–1.9 (20-32) 
+1 
2.0–5.9 (33-101) 
+2 
6.0–11.9 (102-204) 
+3 
≥12.0 (>204) 
+4 
Mean arterial pressure OR administration of vasoactive agents required (listed doses are 
in units of mcg/kg/min) 


 
 
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No hypotension 
0 
MAP <70 mmHg 
+1 
DOPamine ≤5 or DOBUTamine (any dose) 
+2 
DOPamine >5, EPINEPHrine ≤0.1, or norEPINEPHrine ≤0.1 
+3 
DOPamine >15, EPINEPHrine >0.1, or norEPINEPHrine >0.1 
+4 
Creatinine, mg/dL (μmol/L) (or urine output) 
<1.2 (<110) 
0 
1.2–1.9 (110-170) 
+1 
2.0–3.4 (171-299) 
+2 
3.5–4.9 (300-440) or UOP <500 mL/day) 
+3 
≥5.0 (>440) or UOP <200 mL/day 
+4 
 
 
 
 

SAP_001.pdf: