Clinical trial NCT04521114
Conditions: Nonalcoholic Steatohepatitis (NASH)
Keywords: NASH PRO 140 Leronlimab
Sponsor: CytoDyn, Inc.
Start date: 2020-12-01; Completion date: 2021-12-29
Enrollment: 87 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a phase II study of of Leronlimab (PRO 140)-Humanized monoclonal antibody to CCR5 in patients with Nonalcoholic Steatohepatitis (NASH).

Detailed description:
This is an exploratory phase II, multi-center, two-part study (Part 1: randomized, placebo-controlled, two-arm with 60 patients; Part 2: non-randomized, single-arm, open-label with 30 patients) designed to evaluate the safety and efficacy of leronlimab after subcutaneous (SC) administration in patients with NASH for 13 weeks.

A Follow Up visit was conducted 28 (± 3) days after receiving the last study treatment (i.e., after last dose of Leronlimab (PRO 140) or placebo.

Arms: arm 1: Leronlimab 700 mg SC weekly injection arm 2: Leronlimab 350 mg SC weekly injection arm 3: Placebo SC weekly injection
Interventions: intervention 1: Placebo intervention 2: leronlimab 700 mg intervention 3: leronlimab 350 mg
Intervention descriptions: intervention 1: Placebo will be administered subcutaneously every week for 13 weeks. intervention 2: 700 mg leronlimab will be administered subcutaneously every week for 13 weeks. intervention 3: 350 mg leronlimab will be administered subcutaneously every week for 13 weeks.

Protocol documents:
ICF_002.pdf: 
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RESEARCH PARTICIPANT INFORMATION AND CONSENT FORM 
AND 
AUTHORIZATION TO DISCLOSE HEALTH INFORMATION 
 
TITLE: 
A Phase II, Multi-center, Two-Part (Part 1: Randomized, Double-
Blind, Placebo-Controlled with Leronlimab 700mg and placebo; and 
Part 2: Open-Label, Single-Arm with Leronlimab 350mg), Three-
Arm, Dose-Ranging Study of the Safety and Efficacy of Leronlimab 
(PRO 140) in Adult Patients with Nonalcoholic Steatohepatitis 
(NASH) 
 
PROTOCOL NO.: 
CDI-NASH-01 
 
IRB Protocol #20203731 
 
SPONSOR: 
CytoDyn, Inc. 
 
INVESTIGATOR: 
Name 
 
Address 
 
City, State Zip 
 
Country 
 
STUDY-RELATED  
PHONE NUMBER(S): 
Phone Number 
 
Phone Number (24 hours) 
 
[24 hour number is required] 
 
 
This consent form contains important information to help you decide whether to participate 
in a research study. 
 
The study staff will explain this study to you. Ask questions about anything that is not clear at any 
time. You may take home an unsigned copy of this consent form to think about and discuss with 
family or friends. 
 
➢ Being in this study is voluntary – your choice. 
➢ If you join this study, you can still stop at any time. 
➢ No one can promise that a study will help you. 
➢ Do not join this study unless all of your questions are answered. 
 
After reading and discussing the information in this consent form you should know: 
 
➢ Why this research study is being done; 
➢ What will happen during the study; 
➢ Any possible benefits to you; 
➢ The possible risks to you; 


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➢ Other options you could choose instead of being in this study; 
➢ How your personal health information will be treated during the study and after the study is 
over; 
➢ Whether being in this study could involve any cost to you; and 
➢ What to do if you have problems or questions about this study. 
 
Please read this consent form carefully. 
 
Introduction 
 
You are being invited to take part in a clinical research study. 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. 
This consent form may contain words that you do not understand. Please take the time to read the 
following information carefully and feel free to take home an unsigned copy of this consent form to 
discuss this information with your family, friends, relatives and/or your study doctor or other 
Primary Care Physicians (PCP). Please ask the study doctor or one of the study staff to explain any 
words or information that you do not clearly understand. Feel free to request more information 
about the study.  
 
Once you have this information, understand the study procedures, and have had all your questions 
answered, you will need to decide if you will participate in this study. If you decide to participate, 
you will be asked to sign and date this consent form. Signed and dated copies of the consent form 
will be provided to you.  
 
Although an Institutional Review Board (IRB) has approved the information provided in this 
informed consent form and has granted approval for the study doctor to conduct the study, this does 
not mean IRB has approved your participation in the study. IRB is an independent committee 
established to help protect the rights of research participants. You must think about the information 
in this consent document for yourself. You must then decide if you want to be in the study. 
 
What is the purpose of the study? 
 
Your study doctor and his/her study staff are conducting a research study with CytoDyn, Inc., 
which is a pharmaceutical company supporting this research study by providing funding for this 
research study. You are being invited to take part in a clinical research study because you have 
been diagnosed with Nonalcoholic Steatohepatitis (NASH). Steatohepatitis is a type of liver disease 
known as fatty liver where the cells in the liver have abnormal accumulation of fat. One common 
form of fatty liver disease is caused by drinking too much alcohol. However, another form of fatty 
liver not caused by increased alcohol consumption is called nonalcoholic fatty liver. Liver fibrosis 
is a condition developed as a consequence of inflammation and build-up of scar tissue in the liver. 
This research study is designed to help us further understand if an investigational drug is safe and 
an effective 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 C-C Chemokine Receptor Type-5 (CCR5) antagonists. 


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For purposes of this research, you will be referred to as a “participant”. 
 
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 II clinical trial. Phase II 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 to determine how safe and effective the study product, Leronlimab (PRO 140), is for 
treatment of NASH. 
 
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 still 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 yet. The results of these studies will be 
used to design future studies to develop this investigational product for treatment of NASH. 
 
About 90 participants [60 participants for the randomized phase of the study (Part 1); 30 
participants for the non-randomized, open-label phase of the study (Part 2)] will enroll in the study 
across up to 20 centers within the USA. 
 
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 typically in the blood generally react to foreign 
organisms or materials (bacteria, viruses, etc.). However, Leronlimab (PRO 140) binds to a protein 
(CCR5) that may be present on the surface of liver cells. When Leronlimab (PRO 140) binds to the 
CCR5 receptor on these cells, inflammation, and fibrosis of liver cells might decrease. This study is 
designed to help us further understand if and how Leronlimab (PRO 140) affects liver cells, thus 
improving NASH. 


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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. 
 
Why have I been chosen? 
 
You have been chosen for consideration for this study because you are diagnosed with NASH and 
your study doctor thinks that you might be a good candidate for this study. About 90 participants 
with NASH [60 participants for the randomized phase of the study (Part 1); 30 participants for the 
non-randomized, open-label phase of the study (Part 2)] will enroll at about 20 sites within the 
United States. 
 
What other options are there? 
 
Taking part in this research study is completely voluntary. You will always be free to withdraw 
from the study at any time. If you withdraw during the study, you will be asked to come in for a 
final visit for study evaluations. You do not have to give a reason for your withdrawal from the 
study. This will not affect the standard of care that you will receive, and it will not result in any 
penalty or loss of benefits to which you are entitled. The data collected up to that point will be kept 
with your medical records and will be kept confidential. Your identity will not be disclosed. 
 
Instead of being in this research study, you have other options which may include the following: 
 
• Other available treatments for your condition such as weight loss, taking vitamin E, etc. as 
recommended by your doctor 
• Taking part in another research study 
• Receiving no therapy specific to your condition 
 
Please talk to the research doctor about your options before you decide whether you will take part 
in this research study. 
 
General Study Design and Duration of Study Involvement 
 
The duration of your participation in this study will be approximately 22 weeks with the total of 16 
study visits to the study site. The study will be conducted in 3 periods. After the initial screening 
period of the study (up to 4 weeks), you will enter the study treatment period (up to 14 weeks), 
concluded with the follow-up period [4 weeks after the End of Treatment Visit (or Early 
Termination Visit, if applicable)].  
 
If you are enrolled in Part 1, you will either receive 700 mg of Leronlimab (PRO 140) or placebo. 
If you are enrolled in Part 2 (Non-Randomized, open-label), you will receive Leronlimab (PRO 
140), 350mg. 


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Screening Period (before the research starts): 
 
During this part of the study you will be evaluated to determine if you would be eligible to enter the 
study. The screening period will take up to 4 weeks.  
 
Many of the tests and procedures are likely to be part of regular NASH care and may be done even 
if you do not take part in this research study. If you have had some of these tests or procedures 
recently, they may or may not have to be repeated. 
 
Screening Visit 
 
After signing this consent form, the following procedures will be done at the screening visit: 
 
• Review of your demographics, medical condition and medications: You will be asked a number 
of general questions about your age, race, ethnicity, alcohol use, your medical and surgical 
history, including any illnesses or health problems, and your prior or current medications. 
• Physical examination: Your study doctor will give you a physical exam. 
• Vital Signs, height and weight measurements: Your heart rate, body temperature, sitting blood 
pressure, and breathing rate will be assessed. These measurements will be taken in the sitting 
position after you have rested for at least 5 minutes. Your height and weight will also be 
measured. 
• Electrocardiogram: Your study doctor will perform an ECG (electrocardiogram – a routine test 
that records the heart’s electrical activity). 
• FibroScan: Your study doctor will perform a FibroScan (a specialized ultrasound - to check 
your liver) or another equivalent imaging test (such as Shear Wave). 
• Liver MRI: A liver MRI (an imaging exam – to check your liver) will be performed.  
• Laboratory assessments:  
➢ 
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, complete blood count, and 
some other tests for NASH.  
o A blood test for active Hepatitis B, C, A, and E (viruses that affect the liver) infection, 
and HIV (Human Immunodeficiency Virus), which can cause AIDS. If you test positive 
for HIV, hepatitis B or C, A or E you will be notified. It is required to notify state 
health authorities of positive results as required by state law. If you do not want to be 
tested, you should not take part in this research study. 
o If you are a female and able to become pregnant, a blood pregnancy test will be required 
at the Screening Visit. If the blood test is positive, you will not be able to be in the study. 
➢ 
A urine sample will be needed for lab tests. 
 
This visit will take about 2-4 hours of your time. 


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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.  
 
At the end of this 4-week period you will be informed if you are eligible to enter the study. 
 
If the results from the “Screening Visit” procedures are acceptable to the study doctor, you will be 
scheduled for study treatment period. 
 
Treatment Period 
 
Treatment Visit 1 (T1): 
 
The first visit of the treatment period (T1) will be conducted within 28 days from the Screening 
Visit. The treatment visits will occur every 7 days thereafter for a total of 14 weeks. 
 
At T1, the study doctor will check to see if you continue to be eligible to participate in this study. If 
you are not eligible for the study, the study doctor will explain the reasons and arrange for the 
prescribed standard conventional therapy to continue. If you continue to be eligible for the study, 
you will continue your participation in the study. 
 
Before you receive any study treatment, your study doctor will reconfirm your study eligibility by 
completing the following procedures: 
 
• Review of study eligibility: the study doctor will evaluate you to determine if you are still 
eligible to take part in the study. 
• Review of any changes to your medical condition and medications: you will be asked to report 
any changes in your medical status and medications, or new medications taken since the last 
visit. 
• Physical examination: The study doctor will conduct a physical exam. 
• Vital Signs and weight measurements: Your sitting blood pressure, heart rate, breathing rate and 
body temperature will be assessed. These measurements will be taken in the sitting position 
after you have rested for at least 5 minutes. Your weight will also be measured at this visit. 
• Electrocardiogram: You will have an electrocardiogram (ECG) which is a routine test that 
records the heart’s electrical activity. 
• Laboratory assessments: You will have blood and urine tests for routine laboratory evaluations. 
The blood test will also include collecting samples for pharmacokinetics, immunogenicity and 
inflammatory biomarkers, monocyte/T cell CCR5 biomarker analysis and other assessment 
tests for NASH. The blood test will require taking approximately 30 mL (approximately one 
ounce) of blood from your arm.  
• If you are a female of childbearing potential, a urine pregnancy test will also be performed. If 
found to be pregnant, your participation in the study will be terminated 


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• Randomization: If you are enrolled in Part 1 of the study (Randomized Phase), you will be 
randomly assigned (by chance) to one of the two study treatment groups. The study treatment 
assignment will be in a 1:1 ratio to one of the following:  
− Leronlimab (PRO 140), 700mg; Or 
− Placebo  
 
Neither you nor the study doctor will know which one you will receive. This information can be 
made available in case of an emergency. You will be asked to report any symptoms that you 
experienced. 
 
Randomization is not applicable if you are enrolled in Part 2 of the study and the study 
treatment will be leronlimab (PRO 140), 350 mg. You will be asked to report any symptoms 
that you experienced 
 
Once all of the above assessments have been completed, you will receive your treatment injections 
of Leronlimab (PRO 140) or placebo. If you are enrolled in Part 1 (Randomized Phase), you will 
either receive 700 mg of Leronlimab (PRO 140) or placebo which will be given as two shots of 2 
mL each, under your skin on opposite sides of the abdomen at the clinic. If you are enrolled in Part 
2 (Non-Randomized, open-label), you will receive Leronlimab (PRO 140), 350mg which will be 
given as one shot of 2 mL, under your skin in your abdomen area. 
 
Note: Subjects with low body fat may experience discomfort with 2 mL shots. In such cases, the 
study treatment (Leronlimab (PRO 140) or placebo) can be injected at different areas other than 
abdomen as per discretion of the study doctor. 
 
After receiving the injection, the study doctor will perform the following procedures: 
 
• Review of any adverse events (bad side effects): The study doctor will ask you for any 
unfavorable signs or symptoms.  
• Assess reaction to the study drug: You will be observed at approximately 30 minutes after 
completing study drug administration and asked for any unfavorable signs or symptoms. Your 
doctor will assess the injection site for any pain, tenderness, etc. 
• Vital Signs: Your sitting blood pressure, heart rate, breathing rate and body temperature will be 
assessed within 15 minutes after receiving the injection. 
 
This visit will take about 4-5 hours of your time. 
 
Treatment Visit 2 (T2) to Treatment Visit 13 (T13): 
 
The following procedures will be performed every week at clinic at T2 to T13 and also at End of 
Treatment Visit, or Early Termination Visit (if applicable) (Unless stated otherwise): 
 
• Review of any adverse events (bad side effects): The study doctor will ask you for any 
unfavorable signs or symptoms.  


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• Review of any changes to your medical condition and medications: you will be asked to report 
any changes in your medical status and medications, or new medications taken since the last 
visit. 
• Vital Signs and weight measurement: Your sitting blood pressure, heart rate, breathing rate and 
body temperature will be assessed before you receive your injection. Your weight will be 
measured at T2, T6, T10 and at End of Treatment Visit (or Early Termination Visit, if 
applicable). 
• Physical examination: Your study doctor will conduct a physical exam based on any symptoms 
that you experienced, every 4 weeks at T2, T6, T10, and also at Early Termination Visit, if 
applicable. A complete physical exam will be performed at End of Treatment Visit. 
• Study drug administration: If you are enrolled in Part 1 (Randomized Phase), you will receive 
your treatment injection of Leronlimab (PRO 140) 700 mg, or placebo every week from T2 to 
T13. If you are enrolled in Part 2 (Non-Randomized, open-label), you will receive Leronlimab 
(PRO 140), 350mg every week from T2 to T13. 
• Assess pain: You will be asked to assess the pain at your injection site every week from T2 to 
T13 and also at End of Treatment Visit. 
• Assess reaction to the study drug: You will be observed at approximately 30 minutes after 
completing study drug administration and asked for any unfavorable signs or symptoms. Your 
doctor will assess the injection site for any pain, tenderness, etc. 
• Laboratory assessments: Urine and blood samples will be taken every 4 weeks at T2, T6, T10, 
and also at End of Treatment Visit (or Early Termination Visit, if applicable), unless stated 
otherwise. The blood sample will be collected for complete blood count, blood chemistry, 
pharmacokinetics, immunogenicity and inflammatory biomarkers, monocyte/T cell CCR5 
biomarker analysis and other tests for NASH. The blood test will require taking approximately 
30 mL (approximately one Ounce) of blood from your arm.  
• If you are a female of childbearing potential, a urine pregnancy test will also be performed at 
T6, T10, and at End of Treatment Visit (or Early Termination Visit, if applicable). If found to 
be pregnant your participation in the study will be terminated. 
• Electrocardiogram: You will have an electrocardiogram (ECG) which is a routine test that 
records the heart’s electrical activity every 4 weeks at T2, T6, T10, and also at End of 
Treatment Visit (or Early Termination Visit, if applicable). 
• Based on the tests on your liver function, you MAY be asked to come to clinic more than once 
a week for the following assessments per your study doctor’s discretion: 
− Blood test for chemistry 
− Some other tests for assessment of possible other liver disease 
− Liver biopsy or consulting 
− Consultations from Gastroenterology or hepatology doctors 
• Liver MRI: A liver MRI (an imaging exam – to check your liver) will be performed at End of 
Treatment Visit (or Early Termination Visit, if applicable). 
 
Note: If you stop the study early for any reason, the investigator will ask you to perform the 
assessment of Early Termination Visit at clinic. 
 


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Treatment Visits 3, 4, 5, 7, 8, 9, 11, 12 and 13 will take about 1 hour of your time. 
 
Treatment Visits 2, 6, 10 and End of Treatment Visit (or Early Termination Visit, if applicable) will 
each take about 3-4 hours of your time. 
 
Follow-Up Period: 
 
All participants will be followed up Twenty-eight (28) days after the End of Treatment Visit (or 
Early Termination Visit, if applicable), and will be asked at the clinic for performing the following 
procedures: 
 
• Review of any changes to your medical condition and medications: you will be asked to report 
any changes in your medical status and medications, or new medications taken since the last 
visit. 
• Physical examination: The study doctor will conduct a physical exam based on any symptoms 
that you experienced.  
• Vital Signs: Your sitting blood pressure, heart rate, breathing rate and body temperature will be 
assessed within 15 minutes after receiving the injection. 
• Laboratory assessments: You will have blood tests for routine laboratory evaluations. The 
blood test will also include collecting samples for blood chemistry, pharmacokinetics, 
immunogenicity and inflammatory biomarkers, monocyte/T cell CCR5 biomarker analysis and 
other tests for NASH. The blood test will require taking approximately 30 mL (approximately 
one ounce) of blood from your arm.  
Note: If you have already completed the EOT and follow-up visits, you will be asked to come 
to the clinic at a later time and a blood sample will be taken for monocyte/T cell CCR5 
biomarker analysis during this unscheduled visit. This blood test will require taking 
approximately 10 mL of blood from your arm. 
• Review of any adverse events (bad side effects): The study doctor will ask you for any 
unfavorable signs or symptoms you have experienced since last visit.  
 
How long will I be in this research study? 
 
You will be in this research study for around 22 weeks (including screening period, treatment 
period and follow-up period) if 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. 
• A decision is made to close the study. 
• Or for other unforeseen reasons that make it necessary to stop your participation in the 
research study 


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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. In a research study, all the risks or side effects may not be known before 
you start the study. You need to tell your doctor or a member of the study team immediately if 
you experience any side effects. 
 
You and your caregiver will be instructed by the study doctor to recognize the signs and symptoms 
of potential liver injury and report these symptoms immediately to the study center. Some of these 
symptoms include abdominal pain, nausea, vomiting, loss of appetite, dark yellow urine, yellow 
eyes or skin, or persistent fatigue. 
 
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 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 Leronlimab: 
 
• Reactions at the site of the injection such as: 
o Bruising 
o Redness of the skin 
o Fluid leakage 
o Itching 
o Rash 
• Headache 
• Diarrhea 
• Fatigue 
 
All of these side effects occurred in less than 2% of subjects. 
 
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 


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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. 
• Studies on Leronlimab (PRO 140) to determine its capability to cause harm to an unborn child 
have not been performed. Therefore, if you are pregnant or think you might be, you will not be 
allowed to participate in this study. If you are a woman of childbearing potential, you will be 
tested for pregnancy at the beginning and end 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. 
 


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ICF, Version 7.0, 14-Jun-2021 
[PI Full Name] 
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 two effective methods of birth control throughout the course 
of this study and for six (6) months after the last day of treatment. Let your doctor know 
immediately if you become pregnant. 
 
If you 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. 
 
ECG/EEG 
 
You may have skin irritation from the contacts used. 
 
Fibroscan 
 
Risks include discomfort from gel or pressure from hand piece. 
 
MRI 
 
You may experience feelings of claustrophobia or anxiety.  If you have metallic objects, there may be injury 
of tissue around the metallic objects and movement of the metallic object if not attached to bone.  
 
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. 
 
Will I be paid to take part in this research 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. 
 
[You will not be paid for participating in this study]. 
 
OR 
 
Patients will receive $[site specific details] 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.] 


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[PI Full Name] 
 
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 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 study that is 
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 person in 
charge of this research study as soon as possible. The research doctor’s name and phone number 
are listed in this consent form. 
 
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 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. 
 
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. 
 
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. 


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Jul 07, 2021 
 
ICF, Version 7.0, 14-Jun-2021 
[PI Full Name] 
 
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 Amarex Clinical Research, 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) and other foreign regulatory 
bodies may review study results and subject records to check that the study is being conducted 
correctly. 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. 
 
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. 
 
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 plan 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 late 2020. Once the study is 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. 
 
The biological materials (e.g. blood, urine) collected during this research study, might be stored and 
used for future research studies without asking you to sign an additional informed consent form. 


CytoDyn,Inc./ Protocol Number CDI-NASH-01 
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ICF, Version 7.0, 14-Jun-2021 
[PI Full Name] 
 
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. 
 
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. 
 
Early Termination: 
 
Your participation in this study may be stopped at any time by the study doctor, the sponsor 
(CytoDyn, Inc), the FDA, and/or the IRB without your consent for any of the following reasons: 
 
• If it is in your best interest; 
• If you do not consent to continue in the study after being told of changes in the research that 
may affect you; 
• If you do not follow research directions; 
• If you experience any serious side effects to the study drug; 
• If lost to follow-up; 
• Administrative reasons; 
• If you are found to be pregnant; 
• Or other reason as per study plan. 
 


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ICF, Version 7.0, 14-Jun-2021 
[PI Full Name] 
Whom do I contact if I have questions about the research study?  
 
If you have any questions, concerns, or complaints about the study or problems relating to your 
participation in this study, please contact: 
 
 
[Site Specific – PI and CRC Contact Details] 
 
If, at any time, you feel you have experienced a research-related injury or a reaction to the study 
drug, contact your study doctor: 
 
 
[Site Specific – PI Contact Details] (24 hours) 
 
If you have questions about your rights as a research subject or if you have questions, input 
concerns or complaints about the research, you may contact: 
 
WCG IRB at 855-818-2289 or researchquestions@wcgirb.com 
IRB is a group of people who perform independent review of research. 
 
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. 
 


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ICF, Version 7.0, 14-Jun-2021 
[PI Full Name] 
If you choose to participate in this study, please read the following and sign and date where 
indicated. 
 
PARTICIPANT STATEMENT OF 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. 
 
 
 
 
Printed Name of Participant 
 
 
 
 
 
 
 
 
Participant’s Signature 
Date 
Time 
 


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ICF, Version 7.0, 14-Jun-2021 
[PI Full Name] 
STATEMENT OF PERSON CONDUCTING INFORMED CONSENT DISCUSSION 
 
I, the undersigned, certify that to the best of my knowledge that subject named above 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 the study subject’s satisfaction. I confirm that 
the study subject freely and voluntarily gave consent to participate in this research study 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 and answered the subject’s questions. The subject 
appeared to have understood the information and was able to answer the following questions 
correctly: 
 
1. What is the purpose of this study? 
2. If you decide to be in the study, what will you be asked to do? 
3. What is the possible benefit of participating in this study? 
4. What are the possible risks of participating in this study? 
5. If you decide not to participate in this study, what options do you have? 
6. Will participating in this study cost you anything? If so, what will you have to pay for? 
7. Do you have to be in this study? 
8. 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  
 


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ICF, Version 7.0, 14-Jun-2021 
[PI Full Name] 
---------------------------- Use this witness section only if applicable ------------------------- 
 
If this consent form is read to the subject because the subject 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. The subject freely consented to be in the 
research study. 
 
 
 
 
 
 
Signature of Impartial Witness 
Date 
 
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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ICF, Version 7.0, 14-Jun-2021 
[PI Full Name] 
AUTHORIZATION TO USE AND DISCLOSE PROTECTED HEALTH 
INFORMATION 
 
While you are participating in this research study, the study doctor and his/her 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/she 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). 
 
Under a United States federal law called the “Privacy Rule” or Health Insurance 
Portability and Accountability Act of 1996 (HIPAA), no one’s PHI that is gathered 
and obtained during research can be used to conduct the research or be given to 
anyone for research purposes without one’s permission. Because of this rule, you 
may not participate in this study unless you give your permission to use and disclose 
your PHI. 
 
By signing and dating this consent form, you are giving permission for the study 
doctor and his/her study staff, along with the sponsor (CytoDyn, Inc.), Amarex 
Clinical Research (the Contract Research Organization) and the Regulatory 
authorities such as the U.S. Food and Drug Administration (FDA) and Institutional 
Review Boards (IRB) 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. 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 being 
conducted. These representatives will review your PHI to make sure the information 
is correct. The IRB may also have access to your PHI to meet its oversight 
responsibilities. These disclosures help to make sure that all information related to 
the research is available to those who need it. 
 


CytoDyn,Inc./ Protocol Number CDI-NASH-01 
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ICF, Version 7.0, 14-Jun-2021 
[PI Full Name] 
Your identity will remain confidential, except for the disclosures described above 
and detailed specifically in the consent page, and 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 those 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. 
 
Your HIPAA Authorization will expire 50 years from the date you sign and date it 
unless you revoke (cancel or withdraw) it sooner. 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 (tests) and reports for this research. 
 
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 for them to use or 
disclose your protected health information. If you cancel this authorization, you will 
not be allowed to continue in this study. 
 
Subjects will receive a signed and dated copy of this document. 
 
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. 
 
 
 
 
Printed Name of participant (Study Subject) 
 
 
 
 
 
 
 
 
Participant’ Signature 
Date 
Time 
 

Prot_000.pdf: 
CONFIDENTIAL 
Page 1 of 96 
 
 
 
 
 
A Phase II, Multi-center, Two-Part (Part 1: Randomized, Double-Blind, Placebo- 
Controlled with Leronlimab 700mg and placebo; and Part 2: Open-label, Single Arm with 
Leronlimab 350mg), Three-Arm, Dose-Ranging Study of the Safety and Efficacy of 
Leronlimab (PRO 140) in Adult Patients with Nonalcoholic Steatohepatitis (NASH) 
 
 
 
 
Protocol Number: 
CDI-NASH-01 
Final Version: 
7.0 
Date: 
14-Jun-2021 
 
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 # CDI-NASH-01 
Final Version 7.0 
Date: 14-Jun-2021 
CONFIDENTIAL 
Page 2 of 96 
 
 
 
PROTOCOL APPROVAL PAGE 
 
 
Protocol Number: 
CDI-NASH-01 
Final Version: 
7.0 
Date: 
14-Jun-2021 
 
 
 
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 # CDI-NASH-01 
Final Version 7.0 
Date: 14-Jun-2021 
CONFIDENTIAL 
Page 3 of 96 
 
 
 
INVESTIGATOR’S SIGNATURE PAGE 
 
 
Protocol Number: 
CDI-NASH-01 
Final Version: 
7.0 
Date: 
14-Jun-2021 
 
 
 
 
 
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) 
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 # CDI-NASH-01 
Final Version 7.0 
Date: 14-Jun-2021 
CONFIDENTIAL 
Page 4 of 96 
 
 
 
SPONSOR INFORMATION 
CytoDyn, Inc. 
 
1111 Main Street, Suite 660 
Vancouver, Washington 98660 
(360) 980-8524-Work 
(360) 980-8549-Fax 
www.cytodyn.com 
 
 
 
 
 
 
 
 
 
 






Protocol # CDI-NASH-01 
Final Version 7.0 
Date: 14-Jun-2021 
CONFIDENTIAL 
Page 7 of 96 
 
 
 
mg dose) will be weekly administered subcutaneously (SC) by a licensed healthcare professional at the clinic 
sites. 
 Part 1: randomized, double-blind, placebo-controlled, two-arm (up to 60 subjects) 
 
Leronlimab (PRO 140 700 mg) or Placebo SC weekly injection for 13 weeks 
 Part 2: non-randomized, open-label, single-arm (up to 30 subjects) 
 
Leronlimab (PRO 140 350 mg) SC weekly injection for 13 weeks 
This study consists of screening, treatment, and follow-up periods. 
Screening Period (Up to 4 weeks): 
Screening assessments will commence after obtaining signed Informed Consent Form (ICF), and review of 
medical history, demographic information, baseline disease characteristics, eligibility evaluation, physical 
examination, vital signs, height and weight, prior and concomitant medications, electrocardiogram (ECG), 
Liver MRI, FibroScan (or equivalent non-invasive imaging test), FibroTest, routine serum biochemistry 
including liver function test, hematology, HIV and hepatitis serology panel, urinalysis, serum pregnancy (if 
applicable). These assessments must be conducted within 28 days of the first treatment visit. Subjects who 
fail to meet eligibility criteria will be considered screen failures and exit the study without any further 
evaluations. 
Treatment Period (Up to 14 Weeks): 
In the Part 1 of the study, subjects who meet all eligibility criteria, as per data gathered from Screening Visit, 
will be randomized 1:1 to one of the two study arms to receive Leronlimab 700 mg (Group A), or placebo 
(Group B) during the treatment period. 
 
PRO 140 (700mg) SC weekly injection (Group A) 
 
Placebo (0 mg) SC weekly injection (Group B) 
Study treatments for each group (Leronlimab 700 mg or placebo) will be subcutaneously administered every 
week by a licensed healthcare professional at the study site for 13 weeks. The End of Treatment (EOT) visit 
(or early withdrawal visit in case of patients withdrawn prematurely from the study) will happen 1 week 
after receiving the last study treatment. 
In the non-randomized, single-arm, open-label phase (Part 2) of the study, leronlimab (PRO 140 350 mg 
dose) will be weekly administered subcutaneously (SC) by a licensed healthcare professional at the clinic 
sites for 13 weeks. 
Follow-Up Period: 
A Follow-Up visit will be conducted 28 (± 3) days after the End of Treatment (EOT) or Early Termination 
(ET) Visit. 
Duration of Treatment: 
 
Screening Period: Up to 4 weeks 
 
Treatment Period: Up to 14 weeks 
 
Follow-Up Period: Up to 4 weeks after End of Treatment (EOT) or Early Termination (ET) Visit 










Protocol # CDI-NASH-01 
Final Version 7.0 
Date: 14-Jun-2021 
CONFIDENTIAL 
Page 12 of 96 
 
 
 
TABLE OF CONTENTS 
PROTOCOL SYNOPSIS ............................................................................................................... 5 
TABLE OF CONTENTS ............................................................................................................. 12 
List of Tables ................................................................................................................................. 17 
List of Figures ................................................................................................................................ 18 
List of Abbreviations ..................................................................................................................... 19 
1 INTRODUCTION AND BACKGROUND .......................................................................... 23 
1.1 
Statement of Intent ............................................................................................................... 23 
1.2 
Background of the Disease .................................................................................................. 23 
Inflammatory response in nonalcoholic steatohepatitis (NASH) ......................................... 23 
1.3 
Study Treatment ................................................................................................................... 24 
Leronlimab (PRO 140) ........................................................................................................ 24 
1.4 
Pre-Clinical Studies of Leronlimab (PRO 140) ................................................................... 24 
Non-Clinical Studies with Leronlimab (PRO 140) on NASH ............................................. 25 
1.5 
Clinical Studies with Leronlimab (PRO 140) ...................................................................... 25 
PRO 140 1101 Study ........................................................................................................... 25 
PRO 140 1102 Study ........................................................................................................... 26 
PRO 140 1103 Study ........................................................................................................... 26 
PRO 140 1302 Study ........................................................................................................... 26 
PRO 140 2301 Study ........................................................................................................... 26 
PRO 140 2101 Study ........................................................................................................... 27 
PRO 140_CD01 Study ......................................................................................................... 27 
PRO 140_CD01 Extension Study ........................................................................................ 28 
PRO 140_CD02 Study ......................................................................................................... 29 
PRO 140_CD06 Study ......................................................................................................... 30 
PRO 140_CD02 Extension Study ........................................................................................ 30 
PRO 140_CD03 HIV Study ................................................................................................. 30 
PRO 140_CD03 HIV Extension Study ................................................................................ 31 
CD07_TNBC Study ............................................................................................................. 31 
CD08_mCRC Study ............................................................................................................ 31 
1.6 
Dose Section Rationale ........................................................................................................ 34 


Protocol # CDI-NASH-01 
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CONFIDENTIAL 
Page 13 of 96 
 
 
1.7 
Risks / Benefits Assessment ............................................................................................... 36 
Risks/Discomfort to Subjects and Precautions to Minimize Risk ....................................... 36 
Intended Benefit for Subjects .............................................................................................. 37 
2 STUDY OBJECTIVES ......................................................................................................... 38 
2.1 
Primary Objective ............................................................................................................... 38 
2.2 
Secondary Objective: .......................................................................................................... 38 
3 STUDY DESIGN ................................................................................................................... 39 
3.1 
Study Centers ...................................................................................................................... 39 
3.2 
Study Population ................................................................................................................. 39 
3.3 
Eligibility Criteria ............................................................................................................... 41 
Inclusion Criteria ................................................................................................................ 41 
Exclusion Criteria ............................................................................................................... 42 
4 STUDY SCHEDULE ............................................................................................................ 45 
4.1 
Screening Period ................................................................................................................. 50 
Screening Visit ................................................................................................................... 50 
4.2 
Treatment Period ................................................................................................................ 51 
Treatment Visit 1 (T1) ........................................................................................................ 52 
Treatment Visit 2 (T2) to Treatment Visit 13 (T13) ........................................................... 53 
End of Treatment (EOT) Visit ............................................................................................ 54 
Early Termination (ET) Visit .............................................................................................. 55 
4.3 
Follow-Up Period ............................................................................................................... 55 
4.4 
Unscheduled Visits ............................................................................................................. 56 
5 SUBJECT COMPLETION, WITHDRAWAL AND CRITERIA FOR STOPPING THE 
STUDY ................................................................................................................................... 57 
5.1 
Subject Withdrawal ............................................................................................................. 57 
5.2 
Subject Replacement ........................................................................................................... 59 
5.3 
Data Collected from Withdrawn Subjects .......................................................................... 59 
5.4 
Screen Failures .................................................................................................................... 59 
5.5 
Clinical Trial Stopping Criteria .......................................................................................... 60 
6 STUDY TREATMENT ......................................................................................................... 61 
6.1 
Investigational Product ....................................................................................................... 61 


Protocol # CDI-NASH-01 
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Date: 14-Jun-2021 
CONFIDENTIAL 
Page 14 of 96 
 
 
Leronlimab (PRO 140) ........................................................................................................ 61 
Placebo 
61 
6.2 
Leronlimab (PRO 140) - Packaging and Labeling .............................................................. 62 
6.3 
Leronlimab (PRO 140) - Storage and Handling .................................................................. 63 
6.4 
Investigational Product Administration ................................................................................. 63 
Post Injection Monitoring .................................................................................................... 64 
Dose Modifications .............................................................................................................. 64 
6.5 
Investigational Product Disposition ...................................................................................... 65 
6.6 
Investigational Product Accountability ................................................................................. 65 
7 DESCRIPTION OF PROTOCOL ASSESSMENTS AND PROCEDURES ..................... 66 
7.1 
Informed Consent ................................................................................................................ 66 
7.2 
Assessment of Eligibility ..................................................................................................... 66 
Re-screening ........................................................................................................................ 66 
7.3 
Demographic Information and Baseline Disease Characteristics ........................................ 66 
7.4 
Medical History ................................................................................................................... 67 
7.5 
Concomitant Medication ...................................................................................................... 68 
Permitted Medications ......................................................................................................... 68 
Prohibited Medications ........................................................................................................ 68 
7.6 
Vital Signs, Height and Weight ........................................................................................... 69 
7.7 
Physical Examination .......................................................................................................... 69 
7.8 
Electrocardiogram (ECG) .................................................................................................... 70 
7.9 
Clinical Laboratory Assessments ......................................................................................... 70 
Sample Collection Guidelines ............................................................................................. 73 
Sample Processing, Storage, and Shipment ......................................................................... 73 
7.10 Study Treatment Application ............................................................................................... 73 
7.11 Post-Injection Evaluation and Injection Site Reaction Assessment ..................................... 73 
7.12 Pain Severity Assessment .................................................................................................... 73 
7.13 Fibroscan .............................................................................................................................. 74 
7.14 Liver MRI (MultiScan) ........................................................................................................ 74 
8 STATISTICAL ANALYSIS .................................................................................................. 75 


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8.1 
Treatment Groups ................................................................................................................ 75 
8.2 
Study Outcome Measures ..................................................................................................... 75 
Primary Efficacy Outcome Measure .................................................................................... 75 
Secondary Efficacy Outcome Measures: ............................................................................. 75 
Exploratory Outcome Measures .......................................................................................... 75 
8.3 
Sample Size Determination and Rationale .......................................................................... 76 
8.4 
Randomization ..................................................................................................................... 76 
8.5 
Blinding ............................................................................................................................... 76 
8.6 
Interim Analysis ................................................................................................................... 76 
8.7 
General Statistical Considerations ........................................................................................ 76 
Analysis Populations ............................................................................................................ 77 
Intent-to-Treat Population ..................................................................................................... 77 
Per Protocol Population ....................................................................................................... 77 
Safety Population ................................................................................................................. 77 
Covariates 77 
Missing Data ........................................................................................................................ 77 
8.8 
Analysis Methods ................................................................................................................ 77 
Subject Disposition .............................................................................................................. 78 
Demographic and Baseline Disease Characteristics ............................................................ 78 
Study Analyses .................................................................................................................... 78 
Efficacy Analysis ................................................................................................................. 78 
Safety Analyses ................................................................................................................... 78 
9 ADVERSE EVENTS (DEFINITIONS AND REPORTING) .............................................. 80 
9.1 
Adverse event (AE) ............................................................................................................. 80 
9.2 
Reporting and Follow-Up of Adverse Events ...................................................................... 80 
Impact on Study Treatment .................................................................................................. 80 
CTCAE Grade (Intensity) Assessment ................................................................................. 81 
Causality Assessment .......................................................................................................... 81 
Treatment Given as a Result of the Event ........................................................................... 82 
Outcome Assessment ........................................................................................................... 82 
Injection-site reactions ......................................................................................................... 82 
9.3 
Serious Adverse Events ....................................................................................................... 82 


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9.4 
Reporting of Serious Adverse Events .................................................................................. 83 
9.5 
SAE Follow-Up ................................................................................................................... 83 
9.5.1. 
Regulatory Reporting Requirements for SAEs .................................................. 84 
9.6 
Pregnancy Reporting ............................................................................................................ 84 
10 DIRECT ACCESS TO SOURCE DATA/DOCUMENTATION ........................................ 85 
11 QUALITY CONTROL AND QUALITY ASSURANCE .................................................... 86 
11.1 Monitoring Requirements .................................................................................................... 86 
11.2 Acceptability of Case Report Forms (CRFs) ....................................................................... 86 
11.3 Modification of Protocol ...................................................................................................... 86 
11.4 Reporting Protocol Deviations ............................................................................................. 87 
Major Protocol Deviation or Violation ................................................................................ 87 
Minor Protocol Deviation or Violation ................................................................................ 87 
12 ETHICS AND REGULATORY REQUIREMENTS .......................................................... 89 
12.1 Institutional Review Board/Independent Ethics Committee (IRB/IEC) .............................. 89 
12.2 Investigator’s Responsibilities ............................................................................................. 89 
12.3 Subject Informed Consent Requirements ............................................................................ 90 
13 DATA HANDLING AND RECORD KEEPING ................................................................. 91 
13.1 Recording and Collection of Data ....................................................................................... 91 
13.2 Clinical Data Management .................................................................................................. 91 
13.3 Archiving ............................................................................................................................. 92 
14 PUBLICATION PLAN .......................................................................................................... 93 
15 REFERENCES ....................................................................................................................... 94 
16 APPENDIX ............................................................................................................................. 95 
16.1 Appendix 1: Acceptable Methods of Contraception ........................................................... 95 
16.2 Appendix 2: Common Terminology Criteria for Adverse Events v5.0 ............................... 96 


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LIST OF TABLES 
Table 1-1: 
List of Completed Clinical Studies with Leronlimab (PRO 140) ........................... 32 
Table 1-2: 
List of Ongoing Clinical Studies with Leronlimab (PRO 140) ............................... 33 
Table 4-1: 
Treatment Groups ................................................................................................... 45 
Table 4-2: 
Schedule of Assessments ........................................................................................ 47 
Table 6-1: 
Treatment Administration Summary ...................................................................... 61 
Table 6-2: 
Part 1: Investigational Product - Leronlimab (PRO 140) or Placebo ...................... 62 
Table 6-3: 
Part 2: Investigational Product - Leronlimab (PRO 140) ........................................ 62 
Table 6-4: 
Leronlimab (PRO 140) Dose Modification and Management for Injection Site 
Reactions ................................................................................................................. 65 
Table 7-1: 
Central Lab Parameters ........................................................................................... 72 
Table 9-1: 
CTCAE v5.0 General Guidelines ........................................................................... 81 


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LIST OF FIGURES 
Figure 3-1: 
Study Design Schematic .......................................................................................... 40 
Figure 6-1: 
Investigational Product - Vial Label ........................................................................ 63 
Figure 6-2: 
Investigational Product - Kit Label .......................................................................... 63 
Figure 7-1: 
11-Point Numeric Pain Rating Scale ....................................................................... 73 


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LIST OF ABBREVIATIONS 
 
Abbreviation 
Term 
ADA 
Anti-Drug Antibodies 
AE 
Adverse Event 
AASLD 
American Association for the Study of Liver disease 
ALP 
Alkaline Phosphatase 
ALT 
Alanine Aminotransferase 
ANCOVA 
Analysis of Covariance 
ART 
Antireteroviral therapy 
AST 
Aspartate Aminotransferase 
BUN 
Blood Urea Nitrogen 
BMI 
Body Mass Index 
BLM 
Baseline Measurement 
CAP 
Controlled Attenuation Parameter 
CBC 
Complete Blood Count 
CBR 
Clinical Benefit Rate 
CCL5 
C-C Chemokine Ligand Type-5 (RANTES) 
CCR5 
C-C Chemokine Receptor Type-5 
CFR 
Code of Federal Regulations 
CHO 
Chinese Hamster Ovary 
CK 
Creatine Kinase 
CK-18 
Cmax 
Cytokeratin 18 
Maximal Concentration 
CNS 
Central Nervous System 
CRA 
Clinical Research Associate 
CRF 
Case Report Form 
CRO 
cT1 
CTCAE 
Contract Research Organization 
Corrected T1 
Common Terminology Criteria for Adverse Events 
CVD 
Cardiovascular Disease 
D/M 
Dual/Mixed 
DILI 
Drug- Induced Liver Injury 
ECG 
Electrocardiogram 
ECL2 
ExtraCellular Loop 2 


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Abbreviation 
Term 
eCRF 
Electronic Case Report Form 
EASL 
European Association for the Study of the Liver 
eGFR 
Estimated Glomerular Filtration Rate 
EGFR 
Epidermal Growth Factor Receptor 
ELF Score 
Enhanced Liver Fibrosis Score 
EOT 
End of Treatment 
ET 
Early Termination 
F1-F4 
Fibrosis (Stage) 
FDA 
U.S. Food and Drug Administration 
Flu-Mist 
Influenza Vaccine 
FOCBP 
Females of Child-bearing Potential 
GCP 
Good Clinical Practice 
GGT 
Gamma-Glutamyltransferase 
GMP 
Good Manufacturing Practice 
GVHD 
Graft versus Host Disease 
HAV 
Hepatitis A Virus 
HbA1c 
Hemoglobin A1c 
HBsAg 
Hepatitis B Virus Surface Antigen 
HCC 
Hepatocellular Carcinoma 
HCV 
Hepatitis C Virus 
HEENT 
Head, Ears, Eyes, Nose, and Throat 
HEV 
Hepatitis E Virus 
HIPAA 
Health Insurance Portability and Accountability Act 
HIV-1 
Human Immunodeficiency Virus Type 1 
HSC 
Hepatic Stellate Cells 
IA 
Interim Analysis 
ICF 
Informed Consent Form 
ICH 
International Council for Harmonisation 
IEC 
Independent Ethics Committee 
IHC 
Immunohistochemistry assay 


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Abbreviation 
Term 
IND 
INR 
Investigational New Drug 
International Normalized Ratio 
IP 
Investigational Product 
IRB 
Institutional Review Board 
ISR 
Injection Site Reactions 
ITT 
Intent-to-Treat 
IV 
KC 
Intravenous 
Kupffer cell 
kPa 
kilopascals 
LDL 
Low Density Lipoprotein 
LTF 
Lost to Follow-up 
mAb 
Monoclonal Antibody 
mCRC 
Metastatic Colorectal Cancer 
MedDRA 
Medical Dictionary for Regulatory Activities 
M/F 
MRI 
Male/Female 
Magnetic Resonance Imaging 
MSS 
Microsatellite Stable 
MTD 
Maximum Tolerated Dose 
mTNBC 
Metastatic Triple-Negative Breast Cancer 
NAFLD 
NASH 
Nonalcoholic Fatty Liver Disease 
Nonalcoholic Steatohepatitis 
NOAEL 
No Observed Adverse Effect Level 
NCS 
Not Clinically Significant 
Nt 
N terminus 
OBT 
Optimized Background Therapy 
OELF Score 
Original European Liver Fibrosis Panel Score 
ORR 
Overall Response Rate 
OTC 
Over the Counter 
PD 
Pharmacodynamics 
PDFF 
Proton derived fat fraction 
PI 
Principal Investigator 
PK 
Pharmacokinetics 


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Abbreviation 
Term 
PP 
Per Protocol 
PT 
Preferred Term 
QTc 
QT interval corrected for heart rate 
RNA 
Ribonucleic Acid 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SC 
Subcutaneous 
SOC 
System Organ Class 
SOP 
T3 
T4 
Standard Operating Measures 
Triiodothyronine 
Thyroxine 
TBL 
Total Bilirubin 
T2DM 
Type 2 Diabetes Mellitus 
TEAE 
TSH 
Treatment Emergent Adverse Event 
Thyroid-Stimulating Hormone 
ULN 
Upper Limit Normal 
US 
United States 
USP 
United States Pharmacopeia 
VEGF 
Vascular Endothelial Growth Factor 
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 Council for Harmonisation/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 
Nonalcoholic steatohepatitis (NASH) is a chronic liver disease characterized histologically by the 
presence of hepatic inflammation and cell injury (hepatocellular ballooning) due to hepatic fat 
accumulation (steatosis) equal or superior to 5% of hepatocytes. NASH develops in the absence of 
excessive alcohol consumption but is linked to unhealthy eating habits and lack of physical activity. 
It is often referred to as metabolic disease of the liver (Naga Chalasani, 2018). NASH can progress 
to high-burden conditions such as cirrhosis, end stage liver disease and Hepatocellular Carcinoma 
(HCC) (Manca Povsic, 2019). It is predicted that NASH will become the leading cause of liver 
transplantation by 2020 in the United States. It is the most common form of chronic liver disease, 
affecting about one-quarter of the population in the United States. An estimated 3-7% of the adult 
population develop NASH, of which approximately 15-20% progress to advanced fibrosis or 
cirrhosis (Zobair M. Younossi, 2018). Despite its very high burden, there are currently no approved 
pharmacological therapies for NASH. Available therapies focus solely on treating NASH 
comorbidities, such as obesity, Type 2 Diabetes Mellitus (T2DM) and Cardiovascular Disease 
(CVD), while NASH management options focus on lifestyle changes, based on diet and exercise, 
and control of the associated comorbidities. Lifestyle changes have demonstrated greatest benefit in 
improving steatosis and mild fibrosis; however, as patients with advanced fibrosis due to NASH are 
at a significantly higher risk of liver-related mortality, pharmacological treatments are urgently 
needed. 
Inflammatory response in nonalcoholic steatohepatitis (NASH) 
In NASH, liver homeostasis is impaired due to an accumulation of toxic lipids. Certain gut bacteria- 
derived products can also penetrate in the liver, where they activate immune responses. This 
contributes to local inflammation of hepatic tissue. This pathological environment provokes 
hepatocytes damage and leads to a state called ballooning. Steatosis, inflammation and ballooning 
are the three lesions that define NASH histologically. 
The inflammatory response to hepatocyte injury plays a key role in hepatic fibrogenesis and involves 
recruitment of inflammatory cells to the site of injury. Recruitment of extra-hepatic inflammatory 


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cells to the site of hepatic injury is largely mediated by interactions between chemokines and their 
receptors. Monocytes, Kupffer cells (KCs) and Hepatic Stellate Cells (HSCs) can express C-C 
chemokine receptor types 5 (CCR5) on their surface. Evidence implicates CCR5 and their ligands 
including C-C chemokine ligand type 5 (CCL5) in the pathogenesis of liver fibrosis following liver 
injury. 
It has also been shown that patients with chronic liver disease show high levels of CCR5 and CCL5, 
thus showing the role of CCR5 and its ligands in liver fibrosis. Numerous studies of NASH with 
other CCR5 agents have shown anti-inflammatory and anti-fibrotic effects (Lefebvre E, 2016). For 
that reason, CCR5 has become an attractive target for developing new antifibrotic therapies (Zobair 
M. Younossi, 2018). 
 
1.3 
STUDY TREATMENT 
 
Leronlimab (PRO 140) 
Leronlimab (PRO 140) is a humanized IgG4, Monoclonal Antibody (mAb) to the C-C chemokine 
receptor type 5 (CCR5), under development as a therapy for Human Immunodeficiency Virus 
(HIV) infection and other indications including triple negative breast cancer, colorectal cancer and 
Graft versus Host Disease (GVHD). 
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 administration of single doses of 0.5 to 10 mg/kg or up to 700 mg weekly 
doses as Subcutaneous (SC) injection. Overall, more than 300 subjects have been exposed to 
Leronlimab (PRO 140) 350 mg SC weekly dose with the longest duration of exposure lasting more 
than 5 years. Similarly, more than 250 and 150 subjects have been exposed to Leronlimab (PRO 140) 
525 mg and 700 mg SC weekly dose, respectively. To date, the longest exposure to PRO 140 525 mg 
and 700mg SC weekly dose is more than 2 years and 48 weeks, respectively. Considering its anti-CCR5 
activity and per the pre-clinical studies conducted, Leronlimab (PRO 140) is being developed as a 
potential therapy for liver fibrosis and inflammation conditions, including NASH. 
 
1.4 
PRE-CLINICAL STUDIES OF LERONLIMAB (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 Intravenous (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 


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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%. 
Non-Clinical Studies with Leronlimab (PRO 140) on NASH 
An in vivo study was conducted to determine the anti-fibrotic activity of PRO 140 humanized 
monoclonal antibody against CCR5 in mouse xenograft models of NASH (Study No.20127293). 
The objective of this study was to assess the effect of PRO 140 on NASH in mice when given by 
intraperitoneal injection bi-weekly for 4 weeks. 
Reduction in liver fibrosis was observed when 2mg PRO 140 was administered via intraperitoneal 
injection twice weekly for 4 weeks 
 
1.5 
CLINICAL STUDIES WITH LERONLIMAB (PRO 140) 
Current human experience with Leronlimab (PRO 140) consists of ten 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. 
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. 


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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. 
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 was associated with injections in 
the arm. Based on these observations, thigh and abdominal administration of PRO 140 were 
preferred over arm injection. 
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 
groups. There was no significant effect on QTc intervals or other electrocardiographic parameters, 
and there were no remarkably laboratory findings. 
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 Pharmacokinetics (PK) and Pharmacodynamics (PD) of PRO 140 


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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. 
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. 
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) 
for the maintenance of viral suppression following substitution of antiretroviral therapy in HIV-1 
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 PRO 140 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 


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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 Antiretroviral Therapy (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 PRO 140 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-PRO 140 antibodies were not identified in any post-treatment sample and data derived from 
the CD01 study further supports the favorable PRO 140 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 a Serious 
Adverse Event (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 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. 
PRO 140_CD01 Extension Study 
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 Investigational New Drug (IND) application 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. 


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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. 
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 
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 Viral Load (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 


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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. 
PRO 140_CD06 Study 
PRO 140_CD06 study (double-blind, 80 subjects, single-center) seeks to evaluate the 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. This clinical 
study is completed. 
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 continues to demonstrate HIV-1 viral suppression. 
This clinical study is currently ongoing. 
 
PRO 140_CD03 HIV Study 
PRO 140_CD03 HIV (open-label, 566 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 
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, 263 participants have been randomized to receive 525 or 700 mg PRO 140 SC in a 
1:1 ratio. 
Of the 566 patients enrolled, median age was 52 yrs (21-81) with the majority reported as male 
(78%) and 38% were non-white. A total of 132 subjects have been randomized to 700 mg dose. In 
addition, another 71 subjects have been exposed to 700mg dose after rescuing from the lower doses 
(350 mg or 525mg). On average, participants were diagnosed with HIV-1 infection for 
approximately 17 yrs and were on cART regimen for approximately15 yrs. The frequency and 
severity of injection site reactions were comparable between the three dose groups (350, 525 and 


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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. 
 
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. 
 
CD07_TNBC 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 Tolerated Dose 
(MTD) 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. 
 
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+, MSS, mCRC who have been previously 
treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-Vascular 
Endothelial Growth Factor (VEGF) therapy, and, if RAS wild type, an anti- Epidermal Growth 
Factor Receptor (EGFR) therapy. 








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Leronlimab 700mg Exposure Summary in Clinical Trials 
 
 
Duration of 
Treatment 
Approximate Number of 
Subjects Received 700mg 
dose of Leronlimab 
CD10_COVID-19 
A Randomized, Double Blind, Placebo Controlled Study to 
Evaluate the Efficacy and Safety of Leronlimab for Mild to 
Moderate Coronavirus Disease 2019 (COVID-19) 
2 Weeks 
56 
CD12_COVID-19 
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) 
2 Weeks 
130 
PRO 140_CD03 
A Multicenter Study to Assess the Clinical Safety and Treatment 
Strategy of Using PRO 140 SC as Long-Acting Single-Agent 
Maintenance Therapy for 48 Weeks in Virologically Suppressed 
Subjects with CCR5-tropic HIV-1 infection 
Up to 48 Weeks 
132 
+ 
79 (Rescue dose) 
PRO 140_CD03 extension 
An Extension Protocol for Virologically Suppressed Subjects 
Who Successfully Completed PRO140_CD03 Study 
Up to 100+ 
Weeks 
29 
Total Number of Subjects receiving Leronlimab 700mg dose: 
426 
The safety profile of Leronlimab (PRO 140) has been extensively evaluated in clinical trials of 
HIV-positive patients. Data accumulated for PRO 140 suggest a favorable profile in terms of safety 
in humans and efficacy against HIV-1 infection. 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 administration of single doses of 0.5 to 10 
mg/kg or up to 700 mg weekly doses as SC injection. Overall, more than 250 subjects have been 
exposed to PRO 140 525 mg SC weekly dose with the longest duration of exposure lasting >2 years. 
Similarly, more than 150 subjects have been exposed to PRO 140 700 mg SC weekly dose, 
respectively. To date, the longest exposure to PRO 140 700 mg SC weekly dose is 48 weeks. 
Subjects treated with 525 mg and 700 mg Leronlimab (PRO 140) have not experienced any SAEs 
related to Leronlimab (PRO 140). The majority of AEs have been mild in severity. In addition, 
there have been no presented patterns of drug-related toxicities observed during treatment with 525 
mg and 700 mg Leronlimab (PRO 140). The most common AEs have been injection site reactions, 
the majority which have been mild and considered as self-resolving. Considering the favorable 
safety profile of PRO 140 to date, this study is meant to further evaluate safety and potential efficacy 
of Leronlimab (PRO 140 at 700 mg) compared to placebo in adult patients with NASH. 


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We anticipate a manageable safety profile with Leronlimab (PRO 140) therapy since: 1) 
Leronlimab (PRO 140) is not metabolized by the liver, and therefore may have the potential for a 
better tolerability profile than many of the existing small-molecule therapies; 2) Unlike small 
molecules, monoclonal antibodies are too large to be filtered by the kidneys and are not eliminated 
in the urine, except in pathologic conditions. If low molecular weight antibody fragments are 
filtered, they are usually reabsorbed and metabolized in the proximal tubule of the nephron. 
Considering the results of studies on CCR5 blocker we believe, CCR5 inhibition may provide us 
with a new strategy for the treatment of NASH. 
 
1.7 
RISKS / BENEFITS ASSESSMENT 
 
Risks/Discomfort to Subjects and Precautions to Minimize Risk 
 
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), infusion of proteins always carries with it the 
theoretical risk for anaphylactic shock. Accordingly, whenever Leronlimab (PRO 140) is 
administered to subjects, there should be available and in place the procedures required to manage 
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 are unknown at this time; 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 


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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. 
 
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 co-receptor 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 from chemotherapy and therefore, 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. 
Intended Benefit for Subjects 
This study provides an opportunity for subjects with NASH to have once weekly SC treatment with 
Leronlimab (PRO 140). Subjects participating in the present study will contribute to the 
development of a drug which has the potential to become a treatment option for them and others in 
the future. 


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2 
STUDY OBJECTIVES 
 
2.1 
PRIMARY OBJECTIVE: 
 The Primary objective of this study is to assess the efficacy of Leronlimab (PRO 140) in 
improving liver function in adult patients diagnosed with NASH compared to placebo 
 
2.2 
SECONDARY OBJECTIVE: 
 The Secondary objective of this study is to assess the safety and tolerability of 
Leronlimab (PRO 140) in adult patients diagnosed with NASH compared to placebo 


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3 
STUDY DESIGN 
 
This is a phase II, multi-center, two-part study (Part 1: randomized, double-blind, placebo- 
controlled, two-arm with 60 patients; Part 2: non-randomized, single-arm, open-label with 30 
patients) designed to evaluate the safety and efficacy of leronlimab (PRO 140) SC in patients with 
NASH for 13 weeks. In Part 1 of the study, leronlimab (PRO 140 at 700 mg dose) or placebo will 
be weekly administered subcutaneously by a licensed healthcare professional at the clinic sites. 
A single arm, non-randomized, open-label phase (Part 2) is added to the protocol after completion 
of enrollment in the Randomized Phase (Part 1) of the study. In Part 2 of the study, leronlimab (PRO 
140 350 mg dose) will be weekly administered subcutaneously (SC) by a licensed healthcare 
professional at the clinic sites. 
 Part 1: randomized, double-blind, placebo-controlled, two-arm (up to 60 subjects) 
 Leronlimab (PRO 140 700 mg) or Placebo SC weekly injection for 13 weeks 
 Part 2: non-randomized, open-label, single-arm (up to 30 subjects) 
 Leronlimab (PRO 140 350 mg) SC weekly injection for 13 weeks 
This study consists of screening, treatment, and follow-up periods. 
The study flow diagram is presented in Figure 3-1. 
 
3.1 
STUDY CENTERS 
Up to 20 centers in the United States (US). 
 
3.2 
STUDY POPULATION 
For this study, adult patients with NASH will be enrolled. This will be a multicenter trial with up to 
90 subjects. 
Eligibility will be evaluated by the study team according to the following criteria. Eligibility waivers 
are not permitted. Subjects must meet all of the inclusion and none of the exclusion criteria to be 
enrolled in the study. 


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Figure 3-1: 
Study Design Schematic 
 
 


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3.3 
ELIGIBILITY CRITERIA 
 
Inclusion Criteria 
Subjects are required to meet ALL of the following criteria for enrollment into the study: 
1. Subject is a male or female between 18 to 75 years of age inclusive. 
2. Evidence of nonalcoholic steatohepatitis (NASH) based on one of the following criteria: 
 Criteria 1: Histologically-confirmed diagnosis of NASH on a liver biopsy, or 
 Criteria 2: FibroScan or Shearwave US during screening (or within 6 months before 
screening) shows kPa ≥7 but <14 and CAP ≥260. 
3. Subject shows presence of hepatic fat fraction as defined by ≥ 8% on MRI-PDFF and cT1 
≥ 800 ms at Screening. 
4. Has had a stable body weight (±5%) within 6 months prior to Screening. 
5. Body Mass Index (BMI) ≥ 28 kg/m2 at Screening 
6. Has clinically normal resting 12-lead ECG at Screening Visit or, if abnormal, considered 
not clinically significant by the Principal Investigator. 
7. Laboratory Screening results as indicated below: 
a. AST:ALT Ratio ≤ 1, if AST or ALT value is > ULN 
b. Screening Liver enzymes (AST, ALT, and ALK PHOS) < 5 x ULN. 
c. Total Bilirubin ≤ 1.3 mg/dL (except if Gilbert’s Disease) 
d. Platelet count ≥ 150,000/mm3 
e. International normalized ratio (INR) < 1.3 
f. Estimated Glomerular Filtration Rate (eGFR) ≥ 60/mL/min 
g. Glycosylated hemoglobin (HbA1c) < 9%. 
h. TSH within normal reference range. 
Note: Any subject with a non-clinically significant TSH value outside of the normal range 
may be enrolled if their T3 and free T4 values are within the normal range. 
8. Subjects with pre-diabetes or type 2 diabetes will be allowed to participate if the following 
criteria is met: 
 Subjects who are taking anti-diabetic medications should be on a stable dose for a period 
of at least 3 months prior to Screening and do not anticipate clinically significant dose 
adjustments during the course of study. 


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  Subjects must be on a stable diet/lifestyle regimen for at least 3 months prior to 
screening and do not anticipate a clinically significant change during the course of study. 
9. Subjects who are taking Vitamin E should be on a stable dose of Vitamin E (if ≥ 400 IU) 
for a period of at least 4 weeks prior to Screening and do not anticipate dose adjustments 
for the duration of the study. 
10. Both male and female patients and their partners of childbearing potential must agree to use 
two medically accepted methods of contraception (e.g., barrier contraceptives [male 
condom, female condom, or diaphragm with a spermicidal gel], hormonal contraceptives 
[implants, injectables, combination oral contraceptives, transdermal patches, or 
contraceptive rings], or one of the following methods of birth control (intrauterine devices, 
tubal sterilization or vasectomy) or must practice complete abstinence from intercourse of 
reproductive potential from study entry to 6 months after the last day of treatment (excluding 
women who are not of childbearing potential and men who have been sterilized). 
11. Females of child-bearing potential must have a negative serum pregnancy test at Screening 
Visit and negative urine pregnancy test prior to receiving the first dose of study drug; and 
Male participants must agree to use contraception and refrain from donating sperm for at 
least 90 days after the last dose of study intervention. 
12. Subject is willing and able to give informed consent prior to any study specific procedures 
being performed. 
13. Subject is willing and able to comply with scheduled visits, drug administration plan, 
laboratory tests, other study procedures and study restrictions. 
 
 
Exclusion Criteria 
Subjects meeting ANY of the following criteria will be excluded from enrollment: 
1. Any concurrent clinically significant liver disease with an etiology other than NASH 
including autoimmune hepatitis, alcoholic hepatitis, hypoxic/ischemic hepatopathy, and 
biliary tract disease. 
2. History of alcohol consumption greater than 21/units/week (for males) and 14/units/week 
(for females) within the last 2 years prior to screening. 
Note: Use of online unit calculator for alcohol consumption is recommended (e.g., 
https://alcoholchange.org.uk/alcohol-facts/interactive-tools/unit-calculator) 
3. Any drug-induced steatohepatitis secondary to amiodarone, corticosteroids, estrogens, 
methotrexate, tetracycline, or other medications known to cause hepatic steatosis. 
4. Undergone major surgery, including liver surgery, within 6 months prior to screening. 


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5. Prior or pending liver transplantation. 
6. History or presence of cirrhosis or stage 4 fibrosis in historical liver biopsy and/or hepatic 
decompensation including ascites, hepatic encephalopathy or variceal bleeding. 
7. Active hepatitis B (defined as having a positive hepatitis B surface antigen [HBsAg] test), 
hepatitis C (defined as having a positive Anti-HCV test with detectable reflex HCV RNA; 
Note: Subject with positive Anti-HCV test and with undetectable HCV RNA would not be 
excluded), acute hepatitis A (defined as subjects with serum positive for hepatitis A IgM 
(HAV) antibody) or acute hepatitis E (defined as having anti-HEV IgM antibody). 
8. Any active infection requiring systemic therapy at the time of screening, which is considered 
clinically significant per the Investigator. 
9. Positive test for human immunodeficiency virus (HIV) or HIV infection. 
10. History of bleeding diathesis within 6 months of screening. 
11. Any malignancy within the past 5 years, excluding successfully treated basal cell carcinoma 
or squamous cell carcinoma without evidence of metastases. 
12. Seizure disorder requiring ongoing antiseizure therapy or with any condition that, in the 
judgment of the investigator, is likely to increase the risk of seizure (e.g. CNS malignancy) 
13. Clinically significant active cardiac disease which would interfere with study conduct or 
study results interpretation per the PI. 
14. Any known psychiatric or substance abuse disorders that would interfere with cooperation 
with the requirements of the trial. 
15. Prior therapy with Leronlimab or any other CCR5 antagonist (e.g. maraviroc) within 6 
months prior to screening. 
16. History of severe allergic, anaphylactic, or other hypersensitivity reactions to humanized 
monoclonal antibodies. 
17. Any condition requiring continuous systemic treatment with immunosuppressive (such as 
corticosteroids) or immunomodulatory medications. 
Note: Inhaled or topical steroids of up to 5 mg daily prednisone equivalent dose are 
permitted in the absence of active autoimmune disease. 
18. History of administration of a live, attenuated vaccine within four weeks prior to start of 
PRO 140 treatment or anticipation that such a live attenuated vaccine will be required during 
the remainder of the study. 
Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and 
are allowed; however intranasal influenza vaccines (e.g., Flu-Mist ®) are live attenuated 


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vaccines, and are not allowed. 
19. Currently participating in an investigational study or received an investigational drug within 
28 days or 5 half-lives (whichever is longer) prior to study drug administration. 




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Subjects who complete the treatment period will continue to End of Treatment (EOT) Visit 
assessments at week 14 and enter the Follow-up Phase of the study. Subjects who meet any criteria 
for discontinuation of study treatment as specified in Section 5.1 of the protocol, will undergo Early 
Termination (ET) Visit assessments 7 days after the last injection and enter the Follow-up Phase of 
the study. 
Follow-Up Period: Follow-up visit will be conducted 28 (± 3) days after the End of Treatment 
(EOT) or Early Termination (ET) Visit. 






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Other: Fasting blood Glucose , Serum HbA1C, Thyroid profile 
Note: Screening laboratory testing can be repeated once during the 28-day screening window based on the Investigator’s clinical judgement). 
[12] 
Urine samples will be tested for pH, appearance, color, specific gravity, turbidity, ketones, bilirubin, occult blood, glucose, protein, nitrites, urobilinogen, and 
leukocyte esterases. Microscopic examination of urine sediment will be performed if there are abnormalities in macroscopic urinalysis results. Microscopic urine 
tests include bacteria, cast, crystals, epithelial cells, RBC and WBC. 
[13] 
Only performed on women of childbearing potential 
[14] 
Blood sample collected at T1 (prior to first dose of PRO 140), pre-dose at T2, T6, T10, and at EOT (or ET) and Follow-up visit 
[15] 
Randomization via WebView CTMS system only applicable for Part 1 of the study 
[16] 
Leronlimab (PRO 140) or placebo is administered as subcutaneous injection in the abdomen weekly. In Part 1 of the study, a total of 700 mg dose of leronlimab 
(PRO 140) or placebo will be delivered as two injections of 2 mL. In the Part 2 of the study, a total dose of 350 mg dose of leronlimab (PRO 140) will be 
delivered as one injection of 2 mL. 
[17] 
Injection Site Reaction Assessment as assessed by Investigator (or designee) at the clinic . 
[18] 
Subject-perceived injection site pain (average pain since last treatment) will be assessed using 11-point Numeric Rating Scale from 0 to 10 prior to each study 
treatment administration. “0” meaning “no pain” and “10” meaning “worst possible” pain. 
[19] 
AE and CM evaluations to be conducted at each clinic visit applicable 
[20] 
Subjects discontinuing the study at any time for any reason (early termination-ET) should complete the procedures listed AND the follow-up visit 
[21] 
In case subjects have already completed their EOT/ET and FU visits, site should use the Unscheduled Visit option to collect blood sample for Monocyte/T Cell 
CCR5 analysis. 


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4.1 
SCREENING PERIOD 
 
Screening Visit 
The subject will sign and date the Informed Consent Form (ICF) and Health Insurance Portability 
and Accountability Act (HIPAA) authorization (according to site policy and practices) prior to any 
study-related procedures. A unique identification number (screening number) will be assigned to 
each subject who has provided written informed consent. The screening number will incorporate a 
three-digit Study Center number (101, 102, etc.) and a three-digit numeric ID assigned in successive 
order of consenting to screening procedures after signing the ICF at each center, beginning with 001 
at each site (e.g. 101-001 or 102-001, etc.). 
 
XXX 
- 
YYY 
Subject Screening #: 
 
 
XXX=Study Center  
YYY=Subject Numeric ID 
 
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 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 if they are found to meet all inclusion and no exclusion criteria when re- 
screened. 
Once the Screening ICF has been signed, screening procedures and information will be obtained to 
confirm subject eligibility including: 
 Demographic information and baseline disease characteristics (see Section 7.3), 
 Medical history (see Section 7.4), 
 Prior and concomitant medications assessment (see Section 7.5), 
 Vital Signs (see Section 7.6), 
 Body Weight & Height measurements (see Section 7.6), 
 Physical examination (see Section 7.7), 
 12-lead Electrocardiogram (see Section 7.8) 
 FibroScan (or equivalent non-invasive imaging test) (see Section 7.13) 
 Collection of lab specimens (see Section 7.9) for 
o Complete blood count 
o Biochemistry 


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o Serum pregnancy test, for female subjects of childbearing potential 
o Urine sample for urinalysis parameters 
o FibroTest 
o HBS Ag, HCV Ab and HCV RNA (if required), HIV Ab, HAV IgM antibody, and 
HEV Ab 
 Liver MRI (see section 7.14) 
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 PERIOD 
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 exit 
the study without further evaluation 
The maximum sample size for this study is 90 subjects that will be followed by treatment according 
to the schedule described above. 
In Part 1 of the study, eligible subjects will be randomized to 1:1 to one of the two study arms to 
receive Leronlimab (PRO 140) 700 mg (Group A), or placebo (Group B) as two subcutaneous 
injections, given once per week (± 1 day) for up to 13 weeks during the treatment period. 
 PRO 140 700mg SC weekly injection (Group A) 
 Placebo 0 mg SC weekly injection (Group B) 
The study treatment (PRO 140 700 mg or placebo SC injections) will be administered by a licensed 
healthcare professional once a week at the study site. 
In Part 2 of the study, eligible subjects will be enrolled to receive leronlimab (PRO 140) 350 mg as 
one injection, given once per week (± 1 day) for up to 13 weeks during the treatment period. 
 PRO 140 350mg SC weekly injection 


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The study treatment (PRO 140 350 mg SC injection) will be administered by a licensed healthcare 
professional once a week at the study site. 
Treatment Visit 1 (T1) 
The following assessments will be performed at the first treatment visit, unless otherwise specified: 
Pre-Treatment 
 Confirmation of eligibility criteria by reviewing test results and other criteria assessments 
performed at Screening Visit (see Section 7.2) 
 Vital Signs and body weight measurement (see Section 7.6), 
 Physical examination (see section 7.7), 
 12-lead Electrocardiogram (see Section 7.8) 
 Change in concomitant medications (see Section 7.5), 
 Any changes in medical history since Screening Visit (see Section 7.4), 
 Randomization only applicable for Part 1 of the study (see Section 8.4) 
 Collection of lab specimens (see Section 7.9) for 
o Complete blood count 
o Biochemistry 
o Urine pregnancy test, for female subjects of childbearing potential 
o Urine sample for urinalysis parameters 
o FibroTest 
o Anti-Drug Antibodies (ADA) to PRO 140 
o PK evaluations 
o Serum pro-inflammatory cytokine/chemokine evaluations 
o Monocyte/T cell CCR5 biomarker assay 
Administration of study treatment [PRO 140 or placebo] 
PRO 140 or placebo is administered as subcutaneous injection in the abdomen weekly. In part 1 of 
the study, a total of 700 mg (175 mg/mL) or placebo is delivered as two injections of 2 mL on 
opposite sides of the abdomen. In Part 2 of the study, a dose of 350 mg of leronlimab (PRO 140) 
(175 mg/mL) will be delivered as one injection of 2 mL and administered subcutaneously in the 
abdomen. 


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Note: All study treatments (PRO 140 or placebo) must be administered by a licensed healthcare 
professional. 
Post-Treatment 
 Injection Site Reaction Assessment (see Section 7.11) 
 Assessment of Adverse Events (AE) ( see Section 9.1) 
 Vital Signs (see Section 7.6) will be assessed within 15 minutes of study treatment 
administration. 
After treatment administration, subjects who meet any criteria for discontinuation of study 
treatment as specified in Section 5.1 of the protocol, will undergo End of Treatment (EOT) Visit 
assessments and enter the Follow-up Phase of the study. 
Treatment Visit 2 (T2) to Treatment Visit 13 (T13) 
The following assessments will be performed at each visit, unless otherwise specified: 
 Assess for any AEs (see Section 9.1) 
 Concomitant medications assessment (see Section 7.5) 
 Vital Signs and body weight measurement (see Section 7.6) (weight only on visits T2, T6, 
T10 ) 
 Symptom-directed physical examination at clinic visits (see Section 7.7) (only on visits T2, 
T6, T10) 
 12-lead Electrocardiogram (see Section 7.8) (only on visits T2, T6, T10) 
 Collection of lab specimens at T2 , T6, T10 (see Section 7.9 ) for: 
o Complete blood count 
o Biochemistry 
o Urine sample for urinalysis parameters 
o Urine pregnancy test, for female subjects of childbearing potential (T6 and T10 
only) 
o FibroTest 
o Anti-Drug Antibodies (ADA) to PRO 140 
o PK assessment 
o Serum pro-inflammatory cytokine/chemokine evaluations 
o Monocyte/T cell CCR5 biomarker assay 


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 Leronlimab (PRO 140) Administration (see Section 6.4) 
 Injection Site Reaction Assessment (see Section 7.11) 
 Subject-perceived Injection Site Pain Assessment (see Section 7.12) 
Note: Subject-perceived injection site pain will be assessed using 11-point Numeric Pain Rating 
Scale from 0 to 10 prior to study treatment administration assessing average pain at injection site 
since last treatment. “0” meaning “no pain” and “10” meaning “worst possible pain”. 
End of Treatment (EOT) Visit 
Subjects who complete the treatment period will undergo End of Treatment (EOT) Visit. The 
following assessments will be performed for the subjects: 
 Assess for any Adverse Events (see Section 9.1) 
 Changes in Concomitant medications (see Section 7.5), 
 Physical examination (see Section 7.7), 
 Vital Signs and body weight measurement (see Section 7.6), 
 Subject-perceived Injection Site Pain Assessment (see Section 7.12), 
 12-lead Electrocardiogram (see section 7.8), 
 Liver MRI (see section 7.14) 
 Collection of Blood Specimens (see section 0) for: 
o Complete Blood Count 
o Biochemistry 
o FibroTest 
o Anti-Drug Antibodies (ADA) to PRO 140 
o PK assessment 
o Serum pro-inflammatory cytokine/chemokine evaluations 
o Monocyte/T cell CCR5 biomarker assay 
Note: In case subjects have already completed their EOT/ET and FU visits, site should 
use the Unscheduled Visit option to collect blood sample for Monocyte/T Cell CCR5 
analysis. 
 
 Urine pregnancy test, for female subjects of childbearing potential. 
 Urine sample for urinalysis parameters 


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Early Termination (ET) Visit 
Subjects who meet any criteria for discontinuation of study treatment as specified in Section 5.1 of 
the protocol, will undergo Early Termination (ET) Visit. 
The following assessments will be performed: 
 Assess for any Adverse Events (see Section 9.1) 
 Changes in Concomitant medications (see Section 7.5), 
 Symptom-directed physical examination (see Section 7.7), 
 Vital Signs and body weight measurement (see Section 7.6), 
 12-lead Electrocardiogram (see section 7.8), 
 Liver MRI (see section 7.14) 
 Collection of Blood Specimens (see section 0) for: 
o Complete Blood Count 
o Biochemistry 
o FibroTest 
o Anti-Drug Antibodies (ADA) to PRO 140 
o PK assessment 
o Serum pro-inflammatory cytokine/chemokine evaluations 
o Monocyte/T cell CCR5 biomarker assay 
 Urine pregnancy test, for female subjects of childbearing potential. 
 Urine sample for urinalysis parameters 
 
4.3 
FOLLOW-UP PERIOD 
Follow- up visit will be conducted 28 (± 3) days after the End of Treatment (EOT) or Early 
Termination (ET) Visit. All subjects will be followed for biochemistry lab assessment, anti-drug 
antibodies (ADA) to PRO 140, PK assessment, serum pro-inflammatory assessment, blood sample 
for Monocyte/T cell CCR5 biomarker assay vital signs, symptom-directed physical exam, adverse 
events, and concomitant medications assessment. 
Subjects who discontinue treatment for unacceptable adverse event(s) will be followed until 
resolution or stabilization of the adverse event (i.e. the grade is not changing). 


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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. 
Any hospitalization or ER visits in between the scheduled visits should be promptly notified to the 
site staff. 


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5 SUBJECT COMPLETION, WITHDRAWAL AND CRITERIA FOR 
STOPPING THE STUDY 
A subject who has completed the 14-week treatment period and 4-week follow-up period will be 
considered as having completed the study. 
 
5.1 
SUBJECT WITHDRAWAL 
A subject who enters the Treatment Phase but does not complete the study, as defined in this section, 
is considered to have prematurely withdrawn (early terminated) from the Study. 
All subjects have the right to withdraw at any point during treatment without prejudice to future 
care. It will be documented whether or not each subject completed the clinical study. If for any 
subject, study treatment or observations were discontinued, the reason(s) will be recorded. 
Subjects WILL be withdrawn from the study, in consultation with the Medical Monitor and the 
Investigator, if any of the following are met: 
 A subject is significantly non-compliant with the requirements of the protocol. 
 The Investigator determines that it is in the best interest of the subject. 
 Subject chooses to withdraw or is withdrawn due to an adverse event 
 A subject becomes pregnant 
Note: The pregnancy will be followed to term for safety follow-up. Relevant safety information 
collected after the study has completed will be reported as supplemental information. 
 Discontinuation of study by Sponsor 
 Subject becomes lost to follow-up (LTF) 
 Subject experiences unacceptable toxicity 
 Subject voluntarily withdraws from treatment (follow-up permitted) 
 Subject withdraws consent (no follow-up permitted) 
Discontinuation of study treatment for the individual subject MAY occur if, in consultation with the 
Medical Monitor and the Investigator, any of the following are met: 
 A subject is treated with a prohibited medication. 
 Diabetic subjects with an increased HbA1C results of >9% or experiencing significant 
changes in glucose control requiring modification to the dosage or regimen of antidiabetic 
medication 
 Major protocol violation (Section 0) 


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 Subjects who have two occurrences of a Grade 2 or higher allergic/hypersensitivity reaction 
directly related to the study drug that lead to permanent discontinuation of study drug. 
 Subjects experiencing grade 3 or higher AE (per CTCAE v5.0) that is possibly or probably 
related to the study drug OR grade 4 or higher AE regardless of attribution to the study drug. 
 Subjects considered to potentially have Drug-Induced Liver Injury (DILI) as described 
below. 
Drug- induced liver Injury (DILI) 
If subjects with abnormal baseline liver indices develop elevations of AST or ALT >2x baseline or 
Total Bilirubin (TBL) >1.5x baseline values during the study, the tests will be repeated within 48- 
72 hours. If there are persistent elevations (AST or ALT>2x baseline or TBL >1.5 baseline values) 
upon repeat testing, then close observation of the subjects per below should be implemented and 
discontinuation of the study treatment will be considered as per Section 5.1. During the close 
observation period, liver enzyme and serum bilirubin tests will need to be repeated two or three times 
weekly. Frequency of retesting can decrease to once a week or less if abnormalities stabilize or the 
study treatment has been discontinued and the subject is asymptomatic. 
Additionally, further gastroenterology or hepatology consultations and/or liver biopsy can be 
considered per Investigator’s discretion. 
If patient is unable to come to clinic for blood draw during the close observation period, laboratory 
testing can be performed locally, and the results should be promptly communicated to the 
investigator site. A decision to discontinue or temporarily interrupt the study drug will be considered 
based on factors that include how much higher than baseline the ALT and AST are relative to the 
upper limit of normal (ULN) and how much the AST and ALT levels have increased relative to 
baseline, in addition to whether there is a concomitant elevation of bilirubin or INR. The study 
treatment will be discontinued or temporarily interrupted under the following conditions: 
 If Baseline Measurements (BLM) were <2x ULN, The study treatment should be 
discontinued if ALT or AST increases to >5x BLM 
 If BLM was 2x ULN but <5x ULN, The study treatment will be discontinued if ALT or AST 
increases to 3x BLM 
 If BLM was 5x ULN, The study treatment will be discontinued if ALT or AST increases to 
>2x BLM 
 If ALT or AST increases >2x BLM and the increase is accompanied by a concomitant 
increase in TB to >2x BLM or the INR concomitantly increases by 0.2, The study treatment 
will be discontinued 


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 If any subject presents with signs or symptoms of fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, fever, rash, and or eosinophilia (>5%), the study treatment 
should be discontinued 
Note: For the purpose of the assessment of drug-induced liver injury (DILI), Baseline Measurements 
(BLM) for lab values (such as AST, ALT, total Bilirubin) refers to the average (mean) value of 
Screening Visit (SV) and T1 Visit. If liver function tests are repeated during Screening Phase, the 
average (mean) value of all Screening Visit tests and T1 Visit will be used to calculate the Baseline 
Measurements. 
All data normally collected at the scheduled EOT Visit should be recorded at the time of premature 
discontinuation. 
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 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. 
 
5.2 
SUBJECT REPLACEMENT 
Subject replacement is not applicable in this study. 
 
5.3 
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 Sections 9.2 and 9.4 must be followed. 
 
5.4 
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, 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 


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screenings) and may be enrolled if they are found to meet all inclusion and no exclusion criteria at 
the subsequent screening visit. 
 
5.5 
CLINICAL TRIAL STOPPING CRITERIA 
The clinical trial should be halted if any of the following occurs: 
 Three patients develop the same Grade 3 AE attributed to the study drug per CTCAE v5.0 
OR 
 Two patients develop any Grade 4 AE attributed to study drug per CTCAE v5.0 
OR 
 One patient develops a grade 5 AE attributed to study drug per CTCAE v5.0 






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Protocol: CDI-NASH-01 
Site No.  
 
Kit No. N01-XXXX 
Subject No.  
 
Kit contains 2 single-use vials of PRO 140 2mL at 175 mg/mL solution for 
subcutaneous injection 
USE AS PER STUDY PROTOCOL 
Store at 2oC to 8oC 
Caution: New Drug – Limited by Federal (or United States) Law to 
Investigational Use 
CytoDyn Inc., Vancouver, WA, USA 
Below are representative samples of the Investigational Product, FDP individual vial (Figure 6-1), 
and kit label ( 
Figure 6-2) designated for use in this clinical protocol. Each kit contains two labeled vials. 
Figure 6-1: 
Investigational Product - Vial Label 
 
 
Protocol: CDI-NASH-01 
Kit No. N01-XXXX 
Subject No.  
 
Single use vial of PRO 140 2 mL at 175 mg/mL solution for 
subcutaneous injection 
Store at 2oC to 8oC 
Caution: New Drug – Limited by Federal (or United States) 
Law to Investigational Use 
CytoDyn Inc., Vancouver, WA, USA 
Protocol: CDI-NASH-01 
Kit No. N01-XXXX 
Subject No.  
 
Single use vial of PRO 140 2 mL at 175 mg/mL solution for 
subcutaneous injection 
Store at 2oC to 8oC 
Caution: New Drug – Limited by Federal (or United States) 
Law to Investigational Use 
CytoDyn Inc., Vancouver, WA, USA 
 
Figure 6-2: 
Investigational Product - Kit Label 
 
 
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. 
 
6.3 
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. An unblinded study 
Clinical Research Associate (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. 
 
6.4 
INVESTIGATIONAL PRODUCT ADMINISTRATION 


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Guidelines for dose preparation can be found in the pharmacy manual. 
Leronlimab (PRO 140) 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. In Part 1 of the 
study, each of two syringes is filled to deliver 2.0 mL of study drug. Equivalent volumes of PRO 
140 or placebo will be administered subcutaneously on opposite sides of the abdomen. 
In Part 2 of the study, one syringe is filled to deliver 2.0 mL of study drug. Leronlimab (PRO 140) 
will be administered subcutaneously in the abdomen. 
A 20-guage needle should be used to remove PRO 140 or placebo from vial and a 25-guage needle 
is used for administration to subjects. 
Note: After the leronlimab or placebo solution is drawn into the syringe, it can be stored at 
 room temperature (20°C to 25°C, 68°F to 77°F) for up to 2 hours, or 
 refrigerated (2°C to 8°C, 36°F to 46°F) for up to 4 hours. 
IP should be administered slowly over 15 seconds per mL. 
Following each SC delivery of drug, careful examination will be made to assess the appearance of 
any study drug Injection Site Reactions (ISRs) as per CTCAE v5.0. 
In Part 1 of the study, all doses of study drug will be prepared by either the unblinded credentialed 
pharmacist or qualified medical professional and will be provided to a blinded licensed healthcare 
professional at clinic site to be administered as SC injection. The blinding aspect is not applicable 
for the Part 2 of the study. 
All Leronlimab (PRO 140) SC weekly injections must be administered at clinic by a healthcare 
professional. 
Note: It is preferred that the same injection site be used throughout the study. At the same time, it 
is not recommended to inject the study drug into areas where skin shows signs of a previous 
injection site reaction. It is advised to change the injection site if any previous injection site reaction 
remains unresolved. 
Post Injection Monitoring 
Subject will be observed at approximately 30 minutes post-injection or longer, if necessary, for 
injection site reaction as per CTCAE v5.0. 
In addition, the tolerability of repeated subcutaneous administration of PRO 140 is evaluated based 
on assessment of subject-perceived injection site pain using 11-point Numeric Pain Rating Scale. 
Dose Modifications 




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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 for pre-screening and screening 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 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’ continued eligibility for the study as per the Inclusion and 
Exclusion criteria, during the Screening Period. The eligibility criteria are described in Section 0 
(Inclusion Criteria) and Section 0 (Exclusion Criteria). In the event that the subject is not suitable 
or eligible for the study, the subject will be considered “screen failure”. 
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 AND BASELINE DISEASE CHARACTERISTICS 
In this study the demographic information will include: 
 Dates of ICF signature 
 Date of birth 
 Gender 


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 Race (American Indian/Alaskan Native, Asian, Black/African American, Native 
Hawaiian/Pacific Islander, Caucasian, or other) 
 Ethnicity (Hispanic/Latino or Not Hispanic/Latino) 
In addition, the following baseline disease characteristics will be collected: 
 Disease diagnosis date 
 
Medications used for the indication 
 Previous histological procedures, if available for the indication: 
o Date of the most recent procedure 
o Stage of liver fibrosis per the most recent procedure 
o Any indication for cirrhosis per the most recent procedure 
o Stage of steatosis per the most recent procedure 
 
7.4 
MEDICAL HISTORY 
A complete review of the subject’s past medical history (including prior and concurrent liver 
disease and cirrhosis), past surgeries, current therapies (medications and non-medications), and 
history of exposure to environmental chemical agents will be undertaken by the Investigator to 
check that all inclusion and no exclusion criteria have been met. 
Events that emerge prior to the first treatment (T1) 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: 
 
 Cardiovascular 
 Lymphatic 
 Respiratory 
 Hematologic 
 Gastrointestinal 
 Immunologic 
 Renal 
 Dermatologic 
 Hepatic 
 Psychiatric 
 Neurological 
 Genitourinary 
 Endocrine 
 Other 
 
For each relevant history, the following will be documented: 


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 Disease/disorder/condition 
 Date of diagnosis 
 History status (resolved or ongoing). 
 
7.5 
CONCOMITANT MEDICATION 
All concomitant medication administered or taken by the subject beginning 6 month 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) including all prescription, over-the-counter 
(OTC), herbal supplements, and IV medications and fluids. If changes occur during the trial period, 
documentation of drug dosage, frequency, route, and date may also be included on the CRF. 
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). 
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 dates (if medication/therapy is not ongoing). 
Permitted Medications 
All treatments that the investigator considers necessary for a subject’s welfare may be administered 
at the discretion of the investigator in keeping with the community standards of medical care. 
Prohibited Medications 
Subjects are prohibited from receiving the following therapies during the Screening and Treatment 
Period of this trial: 
 Use of radiation or cytotoxic chemotherapy, immunosuppressants and immunomodulating 
agents (e.g., interleukins, interferons) 
 Use of any non-FDA approved/investigational therapy 


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 Use of hepatotoxic medications such as antiarrhythmic drugs e.g., Amiodarone, Dronedarone 
 Clinically significant dose adjustments of the existing T2DM medication regimen or 
initiation of new anti-diabetic medications for the duration of the study. 
 
7.6 
VITAL SIGNS, HEIGHT AND WEIGHT 
The following will be collected: 
 Vital signs: 
o Seated blood pressure (taken after the subject has been seated for at least 5 minutes) 
o Pulse 
o Temperature (oral or tympanic) 
o Respiratory Rate 
 Height (only at the Screening Visit) 
 Weight 
 BMI (derived from the height and weight measurements). 
 
7.7 
PHYSICAL EXAMINATION 
The physical examination will include routine examinations for the following: 
 Head, Ears, Eyes, Nose, Throat (HEENT) 
 Abnormalities of the extremities 
 Neurologic abnormalities 
 Heart/cardiovascular abnormalities 
 Musculoskeletal abnormalities 
 Dermatologic abnormalities 
 Any other body system for which an abnormality is noted and which, in the opinion of the 
Investigator, is relevant to the safety of the subject or could impact safety or efficacy results 
for the subject; i.e., the abnormality is clinically significant. 
Each abnormality will be recorded and the Investigator will record an assessment of its clinical 
significance. 
The complete physical examination will be conducted at the Screening Visit (SV), T1 (Pre- 
treatment) and End of Treatment (EOT) Visit. Only symptom-directed physical examination will 


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be performed at treatment visits T2, T6, T10 and at unscheduled visits within the Treatment period 
and also at Early Termination (ET) Visit and Follow-up Visit. 
 
7.8 
ELECTROCARDIOGRAM (ECG) 
A resting supine 12-lead ECG will be conducted at Screening Visit (SV), T1 (Pre-treatment), T2, 
T6, T10, EOT/ET visits. 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. 
 
7.9 
CLINICAL LABORATORY ASSESSMENTS 
Blood samples will be collected for analysis of the following parameters: 
 Hematology (Complete Blood Count) will be performed at SV, T1 (prior to first dose), T2, 
T6, T10, EOT/ET visits. 
 Biochemistry will be performed at SV, T1 (prior to first dose), T2, T6, T10, EOT/ET and 
FU visits. 
Note: Screening laboratory test can be repeated once during the 28-day screening window 
based on the Investigator’s clinical judgement). 
 Serum pro-inflammatory biomarkers including IL-1 alpha, IL-1 beta, IL-6, RANTES 
(CCL5), TNF-alpha, TNF-beta, CRP will be performed at T1 (prior to first dose), T2 (pre- 
dose), T6 (pre-dose), T10 (pre-dose), EOT/ET and FU visits. 
 FibroTest (requires fasting for 12 hours or more) combines 5 standard biomarkers (gamma- 
glutamyltransferase, total bilirubin, alpha-2-macroglobulin, apolipoprotein A1, and 
haptoglobin). The Acti-Test adds a marker for inflammatory activity (alanine 
aminotransferase: ALT). FibroTest will be performed at SV, T1 (prior to first dose), T2, 
T6, T10, EOT/ET visits. 
 Serology tests including HBs Ag, HCV Ab and HCV RNA (only performed if HCV Ab is 
positive), HIV Ab, Hepatitis A and Hepatitis E Abs will be performed at SV. 
 Anti-Drug antibodies (ADA) to PRO 140 at T1 (prior to first dose), T2 (pre-dose), T6 (pre- 
dose), T10 (pre-dose), EOT/ET and FU visits. 
 PK assessment at T1 (prior to first dose), T2 (pre-dose), T6 (pre-dose), T10 (pre-dose), 
EOT/ET and FU visits. 


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 Serum pregnancy test (for female subjects of childbearing potential) at SV. 
 Monocyte/T cell CCR5 biomarker assay at T1 (prior to first dose), T2 (pre-dose), T6 (pre- 
dose), T10 (pre-dose), EOT/ET and FU visits. 
Note: In case subjects have already completed their EOT/ET and FU visits, site should use 
the Unscheduled Visit option to collect blood sample for Monocyte/T Cell CCR5 analysis. 
 
Urine samples will be collected for analysis of the following parameters: 
 Urine pregnancy at T1 (prior to first dose), T6, T10, EOT/ET visits. 
Note: A urine sample will be collected from female subjects of childbearing potential. This 
test will be performed at the study site using a commercially available kit. 
 Urine analysis testing at SV, T1 (prior to first dose), T2, T6, T10, EOT/ET visits. 
Urine samples will be tested for color, appearance, specific gravity, pH, protein, glucose, occult 
blood, ketones, leukocyte esterases, nitrites, bilirubin, urobilinogen. Microscopic examination of 
urine sediment will be performed if there are abnormalities in macroscopic urinalysis results. 
Microscopic urine tests include bacteria, cast, crystals, epithelial cells, RBC and WBC. 
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. In order to make the 
determination of clinical significance the testing may be needed to be repeated as per Investigator’s 
judgement. Validated, quality-controlled laboratory data will be transferred to the main database 
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Total Bilirubin 
0.2-0.9 mg/dl 
Direct Bilirubin 
0.0 – 0.2 mg/dl 
SGOT (AST) 
15-41 IU/L 
SGPT (ALT) 
M: 17-63 IU/L; F: 14-54 IU/L 
Alkaline Phosphatase (ALP) 
34-104 IU/L 
 
Sample Collection Guidelines 
Please refer to laboratory manual for more details 
 
Sample Processing, Storage, and Shipment 
Please refer to laboratory manual for more details 
 
7.10 STUDY TREATMENT APPLICATION 
Refer to Section 0 for details. 
 
7.11 POST-INJECTION EVALUATION AND INJECTION SITE REACTION ASSESSMENT 
At each treatment visit, an injection site reaction assessment will be made for the current and 
previous injection sites. Injection site reaction assessments are recorded by the Investigator starting 
after the first injection is given. Subject will be observed at approximately 30 minutes post-injection 
or longer if necessary for injection site reaction as per CTCAE v5.0. Refer to Sections 0 for more 
details. 
 
7.12 PAIN SEVERITY ASSESSMENT 
Tolerability of repeated subcutaneous administration of Leronlimab (PRO 140) is evaluated based 
on assessment of subject-perceived injection site pain using 11-point Numeric Pain Rating Scale. 
Before each study treatment administration (T2 to T13, and at EOT), subjects will be asked to 
evaluate the pain intensity over the past week at the site of injection administration based on 11- 
point Numeric Rating Scale from 0 to 10. “0” meaning “no pain” and “10” meaning “worst possible 
pain”. 
Figure 7-1: 
11-Point Numeric Pain Rating Scale 
 


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7.13 FIBROSCAN 
Fibroscan ultrasound measures both liver fibrosis (scarring) and steatosis (fatty change). FibroScan 
steatosis (Controlled Attenuation Parameter (CAP)) score and fibrosis score will be evaluated for 
eligibility in this study. 
 
7.14 LIVER MRI (MULTISCAN) 
Liver MRI (MultiScan) is a non-invasive diagnostic technology for evaluating liver diseases using 
multiparametric MRI to non-invasively quantify liver tissue. Combining the information from 
multiple parametric maps provides a comprehensive analysis of liver tissue, which can be used to 
aid the diagnosis of liver disorders. 
The Magnetic Resonance Imaging–derived Proton Density Fat Fraction (MRI-PDFF) is a novel 
imaging-based biomarker that allows fat mapping of the entire liver. 
Corrected T1 (cT1) is also an MRI-based diagnostic imaging biomarker of the liver. cT1 is intended 
to be used as a proxy for inflammation and fibrosis. 
In this study, Liver MRI will be performed to evaluate MRI-derived biomarkers such as PDFF and 
cT1 at SV and EOT/ET visits. 


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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 
 
In Part 1 of the study, all eligible subjects will be randomized to receive PRO 140 as a 700mg 
subcutaneous injection or placebo weekly for up to 13 weeks. 
In Part 2 of the study, all eligible subjects will receive PRO 140 as a 350 mg subcutaneous injection 
weekly for up to 13 weeks. 
 
8.2 
STUDY OUTCOME MEASURES 
 
Primary Efficacy Outcome Measure: 
 Change from baseline in hepatic fat fraction assessed by magnetic resonance imaging- 
derived proton density fat fraction (MRI-PDFF) at week 14 
 Secondary Efficacy Outcome Measures: 
 Change from baseline in fibro-inflammatory activity as assessed by cT1 (corrected T1) 
assessed by multiparametric magnetic resonance imaging (MRI) of liver at week 14 
Note: cT1 measured in milliseconds (ms) is a quantitative metric for assessing a composite 
of liver inflammation and fibrosis 
 Change from baseline in liver fibrosis using FibroTest at week 14 
 Change from baseline in hepatic inflammatory activity using FibroTest at week 14 
 Change from baseline in serum pro-inflammatory biomarkers assessments 
 Change from baseline in Gamma-glutamyltransferase (GGT) at week 14 
 Change from baseline in CK-18 level at week 14 
 Change from baseline in Leronlimab (PRO 140) PK assessments 
Exploratory Outcome Measures: 
 Change from baseline in Alanine transaminase (ALT) at week 14 
 Change from baseline in Aspartate transaminase (AST) at week 14 


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 Change from baseline in total bilirubin at week 14 
 Change from baseline in triglycerides at week 14 
 Change from baseline in Low Density Lipoprotein (LDL) at week 14 
 To explore Monocyte/T cell CCR5 biomarkers that may predict activity of leronlimab. 
 
8.3 
SAMPLE SIZE DETERMINATION AND RATIONALE 
 
The sample size of 90 total subjects [60 subjects (30 subjects per arm) for the Randomized Phase 
and up to 30 subjects for the non-randomized, open-label phase] is selected on the basis of clinical 
judgment and not based on statistical power calculation. The number of subjects is deemed adequate 
to provide clinically meaningful descriptive results consistent with study objectives. 
 
8.4 
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 the T1 Visit prior to IP administration. 
The randomization will be central and will use 1:1 ratio of Treatment groups A and B: 
 PRO 140 700mg SC weekly injection (Group A) 
 Placebo 0 mg SC weekly injection (Group B) 
Note: Randomization is not applicable for the open-label, single-arm portion (Part 2) of the study. 
 
8.5 
BLINDING 
All subjects, Investigators and their 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. 
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). 
Note: Blinding is not applicable for the open-label, single-arm portion (Part 2) of the study. 
 
8.6 
INTERIM ANALYSIS 
No interim analysis (IA) will be performed for efficacy. 
 
8.7 
GENERAL STATISTICAL CONSIDERATIONS 


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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 by treatment group for continuous 
variables. Frequencies and percentages will be presented by treatment group for categorical 
variables. 
Analysis Populations 
Intent-to-Treat Population 
The Intent-to-Treat (ITT) population is defined as the set of subjects who have received at least 
one dose of study treatment (Leronlimab (PRO 140) or placebo) and have at least one post-baseline 
efficacy assessment. The ITT population will be used as the primary analysis population. 
Per Protocol Population 
The Per Protocol (PP) population is defined as the set of subjects who meet the ITT population 
requirements, were not associated with any major protocol violations and have at least 80% of 
compliance with study treatment. This population will be identified before the database lock. 
The PP analysis of primary and secondary endpoints will be considered supportive. 
 
Safety Population 
The Safety Population will include all subjects who have received one dose of study treatment 
(Leronlimab (PRO 140) or placebo). This population will be used for the analysis of safety 
parameters. 
Covariates 
For efficacy analyses, the baseline values will be used as covariates in the analysis models. Other 
important prognostic factors will be specified in the SAP for the study. 
Missing Data 
All data will be used as observed, and no imputations will be made for any missing data point for 
early phase study. 
 
8.8 
ANALYSIS METHODS 
A 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. All inferential 
statistical analysis will be based on a two-sided test with a Type I error rate of 0.05. 
All the efficacy analyses presented here will be conducted using both the ITT and PP populations. 
All safety analyses will be conducted using the Safety population. Continuous data summaries will 


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include number of observations, mean, standard deviation, median, and minimum and maximum 
values. Categorical data summaries will include frequency counts and percentages. 
Subject Disposition 
The disposition of all subjects who sign an ICF will be provided. The numbers of subjects screened, 
randomized, received treatment, completed, and discontinued during the study, as well as the 
reasons for all post-enrollment discontinuations will be listed and/or summarized by treatment 
group. 
Demographic and Baseline Disease Characteristics 
Demographics and baseline disease characteristics including medical history, prior and concomitant 
medications/therapies will be listed and/or summarized by treatment group using appropriate 
descriptive statistics. 
Study Analyses 
Efficacy Analysis 
Analysis of the efficacy endpoints will be conducted according to below methods: 
o If the Normality assumption is met, Analysis of Covariance (ANCOVA) or Mixed 
Model using the covariates in the model. 
o If the Normality assumption is not met, a non-parametric method or a rank – 
ANCOVA analysis will be used. 
Safety Analyses 
Safety will be assessed by close monitoring and timely assessment of adverse events (AEs), 
laboratory parameters (blood tests, urinalysis), vital signs (blood pressure, heart rate), subject’s 
medical condition (physical examination including weight). Tolerability of repeated subcutaneous 
administration of Leronlimab (PRO 140) as assessed by study participants (using 11-point Numeric 
Pain Rating Scale) and by investigator-evaluation of injection site reactions. 
 
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 treatment group, System Organ Class, 
and preferred term. The following TEAE summaries will be provided: 
 by PT in descending order of frequency 
 by SOC and PT 
 by SOC, PT, and severity 


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 by SOC, PT, and relationship to study drug 
 
Clinical Laboratory Data 
All laboratory values will be listed. Laboratory measurements will also be summarized as 
continuous variable and presented by treatment group and time point. 
 
Physical Examination 
All physical examination findings will be listed and/or summarized. 
 
Vital Signs 
All vital sign findings will be listed and summarized. 
Electrocardiograms (ECGs) 
All ECG findings will be listed and summarized. 
Tolerability 
Pain severity assessment (using 11-point Numeric Pain Rating Scale) and injection site reactions 
will be listed and summarized. 


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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 subject 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 abnormalities in visit 
evaluations, physical examination findings or laboratory results that the investigator believes are 
clinically significant 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 be 
not be recorded as an AE. 
 
9.2 
REPORTING AND FOLLOW-UP OF ADVERSE EVENTS 
Report initiation for all AEs and serious adverse events (SAEs), (see Section 9.3), will begin at the 
time of the first treatment and continue up to the final study visit. All events will be followed to 
resolution or until 30 days after 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 0), the CTCAE grade (intensity) of the event (see Section 0), the 
causality of the event (see Section 0), whether treatment was given as a result of the event (see 
Section 0), and the outcome of the event (see Section 0). 
Impact on Study Treatment 
The impact the event had on the study treatment will be assessed as either: dose increased, dose not 
changed, dose reduced, drug interrupted, drug withdrawn, unknown, and not applicable. The “not 
applicable” assessment will be used only when the subject is no longer in the treatment period of 
the protocol or died. 




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4. Probably – The event follows a reasonable temporal sequence from the study biologic or 
control, abates upon discontinuation of the study drug or control, or cannot be reasonably 
explained by known characteristics of the patient’s clinical state. 
5. Definitely – The event follows a reasonable temporal sequence from the study biologic or 
control, abates upon discontinuation and cannot be explained by known characteristics of 
the patient’s clinical state. 
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). 
Outcome Assessment 
The outcome of the event will be assessed as either: fatal, not recovered/not resolved, 
recovered/resolved, recovered/resolved with sequalae, recovering/resolving, and 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 
Injection-site reactions 
Injection-site reactions thought to be directly related to the injection are considered to be AEs of 
special interest, and will be assessed as per CTCAE v5.0. 
For subjects who develop Grade 1 or Grade 2 events, therapy will be continued as per protocol. If 
a subject chooses to discontinue study treatment, the site should notify the protocol team leadership, 
and encourage the subject to complete any remaining study visits until the toxicity resolves. 
For subjects who develop Grade 3 events following study drug injection, the subject should be 
reevaluated closely until the AE returns to Grade 1 or less, at which time study treatment may be 
reintroduced at the discretion of the site investigator. If the same Grade 3 AE recurs following the 
next administration of study drug, study treatment must be permanently discontinued. Subjects 
experiencing Grade 3 AEs requiring permanent discontinuation of study treatment should be 
followed closely for resolution of the AE to Grade 1 or less and the team leadership must be notified. 
For Grade 4 events permanently discontinue therapy. 
 
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) 


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 Requires subject hospitalization or prolongs existing hospitalization 
 Results in persistent or significant disability/incapacity 
 Is a congenital anomaly/birth defect 
 Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered a serious adverse device effect when, based upon appropriate 
medical judgment, they may jeopardize the 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 
The Investigator is required to report all SAEs that occur during the time period specified in 
Section 9.2. Once the Investigator becomes aware of an SAE, he/she must report the SAE to 
 Safety and Pharmacovigilance Department within 24 hours: 
 
 
 
 
A written SAE report must include a full description of the event as described in Section 9.2 and 
must follow within 24 hours from the time the Investigator first learned of the event. The
 
Medical Monitor may request additional supporting documentation as it becomes available, such 
as lab reports, electrocardiogram (ECG) reports, discharge summary, hospital notes, etc, if 
applicable. 
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 


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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. 
9.5.1. Regulatory Reporting Requirements for SAEs 
The investigator, or responsible person per local requirements, must comply with the applicable local 
regulatory requirements related to the reports of SAEs to regulatory authorities and the Institutional 
Review Board (IRB)/ Institutional Ethics Committee (IEC). 
The Sponsor is responsible for the ongoing evaluation of the study drug. Any adverse experience 
associated with the use of the study drug that is both serious and unexpected must be reported. In 
accordance with the US Code of Federal Regulations, Title 21 CFR Part 312.32, and the ICH 
Guidelines for Clinical Safety Data Management Definitions and Standards for Expedited Reporting, 
the Sponsor must submit written documentation in the form of an Investigational New Drug (IND) 
Safety Report or suspected unexpected serious adverse reaction (SUSAR) reports, respectively. All 
events qualifying as IND Safety Reports/SUSARs will be reported to the IRB/IECs, and 
Investigators will be provided by the drug safety group for regulatory authorities. IND Safety 
Reports/SUSARs are required to be reported within 7 calendar days for life-threatening events and 
those resulting in death or 15 calendar days for all others. These timeframes begin with the first 
notification of the IND Safety Reports/SUSARs to the drug safety group from the Investigator. 
The Sponsor should submit to the regulatory authority all safety updates and periodic reports, as 
required by applicable regulatory requirements. 
 
9.6 
PREGNANCY REPORTING 
Pregnancies detected during the study must be reported to Medical Monitor within the same 
timelines as an SAE using the appropriate form. The outcome of a pregnancy should be followed up 
carefully and any abnormal outcome of the mother and/or child should be reported. The investigator 
must report any pregnancy that occurs in a study subject. Any female subject who becomes pregnant 
during the study will be discontinued from investigational product and will be followed for 
pregnancy outcome. 


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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, 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 


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2. When the modification does not involve the subject’s participation in the trial. 
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. 
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. 
 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 


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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: 
 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 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. 
 
12.1 INSTITUTIONAL REVIEW BOARD/INDEPENDENT ETHICS COMMITTEE (IRB/IEC) 
The Principal Investigator (PI) at the 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. 
 
12.2 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. 
 
12.3 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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13 DATA HANDLING AND RECORD KEEPING 
 
13.1 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. 
 
13.2 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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13.3 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 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 
 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. 
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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14 PUBLICATION PLAN 
 
All information supplied by CytoDyn 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, shall not be disclosed to others without the written consent 
of CytoDyn, 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. 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 multi-center trial or 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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Page 94 of 96 
 
 
15 REFERENCES 
 
Cichoż-Lach, H., Celiński, K., Prozorow-Król, B., Swatek, J., Słomka, M., & Lach, T. (2012). The 
BARD score and the NAFLD fibrosis score in the assessment of advanced liver fibrosis in 
nonalcoholic fatty liver disease. Med Sci Monit, 18(12), CR735–CR740. 
Jacobson JM, Saag MS, Thompson MA, Fischl MA, Liporace R, Reichman RC, Redfield RR, 
Fichtenbaum CJ, Zingman BS, Patel MC, Murga JD. Antiviral activity of single-dose PRO 140, a 
CCR5 monoclonal antibody, in HIV-infected adults. Journal of Infectious Diseases. 2008 Nov 
1;198(9):1345-52. 
 
Jack X. Q. Pang. Liver Stiffness by Transient Elastography Predicts Liver-Related Complications 
and Mortality in Patients with Chronic Liver Disease. PLoS One, 2014; 9(4). 
Manca Povsic, L. O. A structured literature review of interventions used in the management of 
nonalcoholic steatohepatitis (NASH). Pharmacol Res Perspect, 2019; 7(3), e00485. 
Naga Chalasani, Z. Y. The Diagnosis and Management of Nonalcoholic Fatty Liver 
Disease:Practice Guidance From the American Association for the Study of Liver Diseases. 
HEPATOLOGY, 2018; 67(1) 
Lefebvre E, M. G. Antifibrotic Effects of the Dual CCR2/CCR5 Antagonist Cenicriviroc in 
Animal Models of Liver and Kidney Fibrosis. 2016; 11(6), e0158156 
Suleiman J, Zingman BS, Diaz RS, Ramalho Madruga JV, DeJesus E, Slim J, Mak C, Lee E, 
McCarthy MC, Dunkle LM, Walmsley S. Vicriviroc in combination therapy with an optimized 
regimen for treatment-experienced subjects: 48-week results of the VICTOR-E1 phase 2 trial. The 
Journal of infectious diseases. 2010 Feb 15;201(4):590-9. 
Thompson M, Lalezari J, Saag M, Jacobson J, Zingman B, Stambler N, D'Ambrosio P, Maddon P, 
Olson W, Morris S. Weekly and biweekly subcutaneous PRO 140 demonstrates potent, sustained 
antiviral activity. In16th Conference on Retroviruses and Opportunistic Infections 2009 Feb 8 (pp. 
8-11). 
US Food and Drug Administration. Noncirrhotic Nonalcoholic Steatohepatitis With Liver 
Fibrosis:Developing Drugs for Treatment Guidance for Industry. December 2018. 37256dft.docx 
Zobair M. Younossi, F. The epidemiology of nonalcoholic steatohepatitis. Clin Liver Dis 
(Hoboken), 2018; 11(4), 92–94. 


Protocol # CDI-NASH-01 
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Page 95 of 96 
 
 
16 APPENDIX 
 
16.1 APPENDIX 1: 
ACCEPTABLE METHODS OF CONTRACEPTION 
 
 
 
Barrier Methods 
Intrauterine Device Methods 
Hormonal Methods 
 Male condom plus 
spermicide 
 Cap plus spermicide 
 Diaphragm plus 
spermicide 
 Copper T 
 Progesterone T 
 Levonorgestrel-releasing 
 Implants 
 Hormone shot or 
injection 
 Combined pill 
 Minipill 
 Patch 
NOTE: choice of contraception should be discussed with primary treating physician to discuss 
the risks and benefits of different modalities of contraception. 


Protocol # CDI-NASH-01 
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Page 96 of 96 
 
 
 
16.2 APPENDIX 2: 
COMMON TERMINOLOGY CRITERIA FOR ADVERSE EVENTS V5.0 
 
 
For complete detailed information please refer to the link below: 
https://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/CTCAE_v5_Quick_Re 
ference_8.5x11.pdf 

SAP_001.pdf: 
 
STATISTICAL ANALYSIS PLAN (SAP) 
 
CD1-NASH-01 
 
 
Protocol No. 
CD1-NASH-01 
Revision No. 
Rev. 00 
Effective Date: 
17-Dec-2021 
 
CONFIDENTIAL 
 
 
Page 1 of 30 
 
STATISTICAL ANALYSIS PLAN (SAP) 
FOR PROTOCOL CD1-NASH-01 
Sponsor 
CytoDyn, Inc.  
1111 Main Street, Suite 660  
Vancouver, Washington 98660 
Protocol Number: 
CDI-NASH-01 
Protocol Title: 
A Phase II, Multi-center, Two-Part (Part 1: Randomized, Double-Blind, 
Placebo-Controlled with Leronlimab 700mg and placebo; and Part 2: 
Open-label, Single Arm with Leronlimab 350mg), Three-Arm, Dose-
Ranging Study of the Safety and Efficacy of Leronlimab (PRO 140) in 
Adult Patients with Nonalcoholic Steatohepatitis (NASH) 
Clinical Protocol 
Version/Date: 
Version 7 / 14-Jun-2021 
SAP Author: 
Approved by: 
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 
 
 


 
STATISTICAL ANALYSIS PLAN (SAP) 
 
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Protocol No. 
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Revision No. 
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Effective Date: 
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Page 2 of 30 
 
TABLE OF CONTENTS 
 
Glossary of abbreviations ......................................................................................................... 4 
1 
INTRODUCTION .......................................................................................................... 5 
2 
PROTOCOL DESIGN AND OBJECTIVES ................................................................... 5 
2.1 
Study Objectives .................................................................................................... 5 
2.2 
Study Design ......................................................................................................... 5 
2.3 
Study Duration ....................................................................................................... 7 
2.4 
Study Centers ........................................................................................................ 7 
2.5 
Study Target Population ........................................................................................ 8 
2.6 
Study Treatments .................................................................................................. 9 
2.7 
Randomization ....................................................................................................... 9 
2.8 
Blinding .................................................................................................................. 9 
2.9 
Protocol Deviations .............................................................................................. 10 
2.9.1 
Major Protocol Deviations ............................................................................... 10 
3 
STUDY ENDPOINTS .................................................................................................. 10 
3.1 
Primary Endpoint ................................................................................................. 10 
3.2 
Secondary Endpoints ........................................................................................... 10 
3.3 
Exploratory Endpoints .......................................................................................... 11 
3.4 
Safety Endpoints .................................................................................................. 11 
4 
SAMPLE SIZE ............................................................................................................ 12 
5 
INTERIM ANALYSIS .................................................................................................. 12 
6 
Primary hypothesis to be tested ................................................................................. 12 
7 
ANALYSIS SETS ........................................................................................................ 12 
7.1 
Full Analysis Set .................................................................................................. 12 
7.2 
Per Protocol Set ................................................................................................... 12 
7.3 
Safety Analysis Set .............................................................................................. 13 
8 
Data Handling Conventions ........................................................................................ 13 
8.1.1 
Data entry errors and potential outliers ........................................................... 13 
8.1.2 
Missing data .................................................................................................... 13 
8.1.3 
Partial dates .................................................................................................... 13 
8.1.4 
Derived data .................................................................................................... 14 
8.1.5 
Analysis Data for Regulatory Submission ....................................................... 15 
9 
STATISTICAL METHODS .......................................................................................... 15 
9.1 
GENERAL STATISTICAL CONSIDERATIONS ................................................... 15 
9.1.1 
Mock Table Shells ........................................................................................... 15 
9.1.2 
Covariates ....................................................................................................... 15 
9.1.3 
Protocol Deviations ......................................................................................... 15 
9.1.4 
Analysis sets ................................................................................................... 15 
9.1.5 
Subject Disposition and Withdrawals .............................................................. 16 
9.1.6 
Demographic and Baseline Disease Characteristics ...................................... 16 
9.1.7 
Alcohol Consumption and Related Variables .................................................. 17 
9.1.8 
Medical History ................................................................................................ 18 
9.1.9 
Concomitant Medications ................................................................................ 18 
9.2 
Analysis of efficacy data ...................................................................................... 19 
9.2.1 
Analysis of Primary Efficacy Endpoint ............................................................. 19 
9.2.2 
Analysis of Secondary Endpoints .................................................................... 20 
9.2.3 
Analysis of Exploratory Outcome Measures ................................................... 20 
9.2.4 
Analysis of CCR5 Biomarkers that may Predict Activity of Leronlimab ........... 21 
9.3 
Analysis of Safety Data ........................................................................................ 22 


 
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9.3.1 
Extent of Exposure .......................................................................................... 22 
9.3.2 
Adverse Events ............................................................................................... 22 
9.3.3 
Clinical Laboratory Assessments .................................................................... 25 
9.3.4 
Physical Examination ...................................................................................... 26 
9.3.5 
Vital Signs ....................................................................................................... 26 
9.3.6 
Electrocardiogram (ECG) ................................................................................ 27 
9.3.7 
Tolerability ....................................................................................................... 27 
10 
CHANGES IN SAP COMPARED TO STUDY PROTOCOL ....................................... 28 
10.1 
Addition of Exploratory Outcome Measures ........................................................ 28 
11 
DATA HANDLING AND RECORD KEEPING ............................................................ 28 
11.1 
Recording and Collection of Data ........................................................................ 28 
11.2 
Clinical Data Management ................................................................................... 29 
11.3 
Data Transfer to Sponsor .................................................................................... 29 
12 
REFERENCES ........................................................................................................... 29 
 
 


 
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GLOSSARY OF ABBREVIATIONS 
 
AE 
Adverse event 
BMI 
Body Mass Index 
CAT 
Categorical 
CCR5 
C-C chemokine receptor type 5 
CI 
Confidence Interval 
CONT 
Continuous 
CRO 
Clinical Research Organization 
cT1 
Corrected T1 
eCRF 
Electronic Case Report Form 
EOT 
End of treatment 
ET 
Early termination 
FAS 
Full Analysis Set 
FU 
Follow-Up 
LTFU 
Lost to follow-up 
MRI 
Magnetic Resonance Imaging 
N 
Number 
NASH 
Nonalcoholic steatohepatitis 
PDFF 
Proton Density Fat Fraction 
PP 
Per Protocol Set 
PT 
Preferred Term 
SAP 
Statistical Analysis Plan 
SC 
Subcutaneous 
SOC 
System Organ Class 
TEAE 
Treatment Emergent Adverse Event 
 


 
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1 INTRODUCTION 
This Statistical Analysis Plan describes the planned analyses and reporting for the clinical 
trial protocol CDI-NASH-01 version 7.0 dated June 14, 2021 sponsored by CytoDyn Inc. The 
main objective of this plan is to provide details pertaining to statistical methodology, data 
conventions, and processes used for the analysis of data from this trial. 
 
This Statistical Analysis Plan provides sufficient detail to meet the regulatory and statistical 
profesional guidelines [1-6].  
2 PROTOCOL DESIGN AND OBJECTIVES 
2.1 Study Objectives 
Primary Objective: 
 
• 
The Primary objective of this study is to assess the efficacy of Leronlimab (PRO 140) 
in improving liver function in adult patients diagnosed with NASH compared to 
placebo 
 
Secondary Objective: 
 
• 
The Secondary objective of this study is to assess the safety and tolerability of 
Leronlimab (PRO 140) in adult patients diagnosed with NASH compared to placebo 
2.2 Study Design 
This is a phase II, multi-center, two-part study. 
 
• 
Part 1. Randomized, double-blind, placebo-controlled, two-arm with 60 patients 
designed to evaluate the safety, tolerability, and efficacy of leronlimab (PRO 140 
700mg dose) or placebo weekly administered subcutaneously (SC) in patients with 
NASH for 13 weeks. 
• 
Part 2. Non-randomized, single-arm, open-label with 30 patients designed to evaluate 
the safety, tolerability, and efficacy of leronlimab (PRO 140 350mg dose) weekly 
administered subcutaneously (SC) in patients with NASH for 13 weeks SC in patients 
with NASH for 13 weeks  
 
For Part 1 of the study leronlimab 700mg group will be compared to placebo. 
For Part 2 of the study leronlimab 350mg group will be compared to placebo from Part 1. 
 
The study schematic is presented in Figure 2.1 and Figure 2.2 
 
 


 
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Figure 2.1: Study Schematic 
 
 
 
 




 
STATISTICAL ANALYSIS PLAN (SAP) 
 
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2.5 Study Target Population 
Adult patients with NASH who meet the eligibility criteria will be enrolled. 
 
 


 
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2.6 Study Treatments 
In Part 1 of study leronlimab 700mg or placebo will be subcutaneously administered 
every week by a licensed healthcare professional at the study site for 13 weeks. 
 
Part 1 
Treatment Groups 
 
 
 
 
STUDY 
DRUG 
DOSE 
ROUTE 
SCHEDULE 
Leronlimab 
 
700mg  
SC  
Start on Day 1 and every week thereafter  
Placebo  
N/A  
SC  
Start on Day 1 and every week thereafter  
 
In Part 2 of the study, the non-randomized, single-arm, open-label phase, leronlimab 350mg 
dose) will be administered subcutaneously (SC) weekly for 13 weeks. 
 
Part 2 
Treatment Groups 
 
 
 
 
STUDY 
DRUG 
DOSE 
ROUTE SCHEDULE 
Leronlimab 
  
350 mg  
SC  
Start on Day 1 and every week thereafter  
2.7 Randomization 
Part 1: 
 
Subjects who are eligible to participate in the trial will be randomized 1:1 to one of the 
treatment groups via IWRS (Interactive Web Based Randomization System) at the Visit prior 
to IP administration. The randomization will be central and will use 1:1 ratio of Treatment 
groups 
 
• 
Leronlimab 700mg SC weekly injection  
• 
Placebo 0mg SC weekly injection 
 
Part 2: 
 
Randomization is not applicable for the open-label, single-arm portion (Part 2) of the study. 
2.8 Blinding 
All subjects, investigators and their staff, and all Sponsor/CRO personnel involved in the 
management of the study will be blinded to treatment assignments. 
 
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). 
 
Note: Blinding is not applicable for the open-label, single-arm portion (Part 2) of the study. 


 
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2.9 Protocol Deviations 
The protocol deviations will be classified as minor and major deviations before unblinding. 
2.9.1 Major Protocol Deviations 
The following deviations will be considered as major protocol deviation: and will result in 
exclusion from PP analysis set: 
 
• 
Dietary noncompliance clinically significant as deemed per investigator 
• 
Noncompliance with amount of alcohol use as stipulated in exclusion criteria during 
the study 
• 
Poor diabetic control with consistent elevated fasting blood glucose >=200 
• 
Noncompliance with diabetic and or lipid lowering medications clinically significant as 
deemed per investigator 
• 
Use of Hepatotoxic medications clinically significant as deemed per investigator: 
including but not limited to: Isoniazid, glucocorticoids- prednisone, NSAIDS, 
Paracetamol, Ketoconazole, Hydralazine, Iproniazid.  
• 
Missing 2 consecutive doses of IP or less than 80% cumulative compliance 
• 
Not meeting inclusion or exclusion criteria 
• 
Early termination before 14-week evaluation period 
• 
T1 labs meeting exclusion criteria including but not limited to HbA1C >9, abnormal 
TSH and panel, autoimmune disorder with associated hepatitis.  Elevations of CRP at 
T1 should be considered as potential autoimmune etiology until proven otherwise if 
workup was not performed prior to screening. 
3 STUDY ENDPOINTS 
3.1 Primary Endpoint 
The primary endpoint for Part 1 of the study is: 
 
Change from baseline in hepatic fat fraction assessed by magnetic resonance imaging-derived 
proton density fat fraction (MRI-PDFF) at week 14. 
3.2 Secondary Endpoints 
The secondary endpoints for Part 1 of the study are 
 
• 
Change from baseline in fibro-inflammatory activity as assessed by cT1 (corrected 
T1) assessed by multiparametric magnetic resonance imaging (MRI) of liver at week 
14 (Note: cT1 measured in milliseconds is a quantitative metric for assessing a 
composite of liver inflammation and fibrosis) fibrosis).  
• 
Change from baseline in liver fibrosis using FibroTest at week 14  
• 
Change from baseline in hepatic inflammatory activity using FibroTest at week 14  
• 
Change from baseline in serum pro-inflammatory biomarkers assessments  
• 
Change from baseline in Gamma-glutamyltransferase (GGT) at week 14  
• 
Change from baseline in Cytokeratin 18 (CK-18) level at week 14  
• 
Change from baseline in Leronlimab (PRO 140) PK assessments  


 
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The secondary endpoints for Part 2 of the study are: 
 
• 
Change from baseline in fibro-inflammatory activity as assessed by cT1 (corrected 
T1) assessed by multiparametric magnetic resonance imaging (MRI) of liver at week 
14 (Note: cT1 measured in milliseconds is a quantitative metric for assessing a 
composite of liver inflammation and fibrosis) compared to part 1 placebo 
• 
Change from baseline in liver fibrosis using FibroTest at week 14 compared to Part 1 
placebo 
• 
Change from baseline in hepatic inflammatory activity using FibroTest at week 14 
compared to Part 1 placebo 
• 
Change from baseline in serum pro-inflammatory biomarkers assessments compared 
to Part 1 placebo 
• 
Change from baseline in Gamma-glutamyltransferase (GGT) at week 14 compared to 
Part 1 placebo 
• 
Change from baseline in Cytokeratin 18 (CK-18) level at week 14 compared to Part 1 
placebo 
• 
Change from baseline in Leronlimab (PRO 140) PK assessments compared to Part 1 
placebo 
3.3 Exploratory Endpoints 
The exploratory endpoints for Part 1 of the study are 
 
• 
The fibrosis scores categorized by degree of liver fibrosis as per cT1 value: 
 
Mild 800-850 cT1 
 
Moderate 851-999 cT1 
 
Mild-Moderate 800-999 cT1 
 
Severe >=1000 cT1 
• 
Change from baseline in Alanine transaminase (ALT) at week 14  
• 
Change from baseline in Aspartate transaminase (AST) at week 14  
• 
Change from baseline in total bilirubin at week 14  
• 
Change from baseline in triglycerides at week 14  
• 
Change from baseline in Low Density Lipoprotein (LDL) at week 14  
• 
Change from baseline in High Density Lipoprotein (HDL) at week 14  
• 
To explore Monocyte/T cell CCR5 biomarkers that may predict activity of leronlimab.  
3.4 Safety Endpoints 
Safety endpoints of the study are: 
 
• 
Adverse events (AEs) 
• 
Laboratory parameters (blood tests, urinalysis) 
• 
Vital signs (blood pressure, heart rate) 
• 
Subject’s medical condition (physical examination including weight) 
• 
Tolerability of repeated subcutaneous administration of Leronlimab (PRO 140) will 
assessed by 
• 
Subject rated 11-point Numeric Pain Rating Scale 
• 
Investigator-evaluation of injection site reactions. 


 
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4 SAMPLE SIZE 
The sample size of 90 total subjects [60 subjects (30 subjects per arm) for the Randomized 
Phase and up to 30 subjects for the non-randomized, open-label phase] is based on clinical 
judgment. The number of subjects is deemed adequate to provide clinically meaningful 
descriptive results consistent with study objectives. 
5 INTERIM ANALYSIS 
No interim analysis (IA) will be performed. 
6 PRIMARY HYPOTHESIS TO BE TESTED 
The null hypothesis of no between treatment group difference in mean change from baseline 
to Week 14 in Proton Density Fat Fraction (MRI-PDFF) will be tested against the alternate 
hypothesis of a non-zero difference. 
7 ANALYSIS SETS 
7.1 Full Analysis Set 
Full anaysis set (FAS) will be the set of subjects which is as complete as possible and as 
close as possible to the intention-to-treat ideal of including all randomized subjects. The FAS 
is defined as the set of subjects who  
 
• 
Receive at least one dose of study treatment  
• 
Have at least one post-baseline efficacy assessment 
• 
Subjects who fail to satisfy an entry criterion may be excluded from FAS only under 
the following circumstances: The entry criterion was measured prior to randomization, 
the detection of the relevant eligibility violations was made completely objectively, all 
subjects receive equal scrutiny for eligibility violations and all detected violations of 
the particular entry criterion are excluded. 
 
The FAS will be used as the primary analysis set. 
 
The randomized treatment will be used for primary efficacy analysis.  
7.2 Per Protocol Set 
The PP set will be used as the supportive analysis set.  
 
The Per Protocol (PP) population is defined as the set of subjects who meet the intention to 
treat requirements, were not associated with any major protocol violations and have at least 
80% compliance with study treatment. This population will be identified before the database 
lock. 
 
Per protocol set (PP) will be subset of the subjects in the full analysis set who were not 
associated with any major protocol violations and have at least 80% compliance with study 


 
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treatment. Subjects will be excluded from the PP if a major protocol deviation occurred. The 
criteria for major protocol deviations are listed in Section entitled Protocol Deviations.  
 
The actual treatment will be used for the Per Protocol efficacy analysis.  
 
7.3 Safety Analysis Set 
The Safety Analysis set will comprise all subjects who have received one dose of study 
treatment. This analysis set will be used for the analysis of safety variables. 
 
Actual treatment received will be used for safety analysis in event of a major protocol 
deviation. 
8 DATA HANDLING CONVENTIONS 
8.1.1 Data entry errors and potential outliers 
Patients may have potential outliers for particular observations. Potential outliers based on 
correct values will be included in the analysis. However, sensitivity analyses excluding 
outliers may be calculated to evaluate the influence of such extreme values. Values found to 
be incorrect due to data entry error will be excluded from all analyses as missing values. 
Incidence of incorrect values and potential outliers may be listed and summarized per 
treatment arm. If assumptions or data structure do not allow planned analyses, analyses will 
be updated appropriately. 
8.1.2 Missing data 
Subjects may have missing specific data points for a variety of causes. In general, data may 
be missing due to a missed visit, non-evaluability of a specific clinical measurement at its 
planned clinical visit or a subject’s early withdrawal from study. All data will be used as 
observed, and no imputations will be made for any missing data point. 
8.1.3 Partial dates 
Partially incomplete dates will be imputed for dates related to events and follow up 
information. Dates with missing months or years will not be imputed. Derived data from these 
dates will be calculated using only the information that is available. 
 
Imputation will be done as described in the following table: 
 
 
MISSING 
IMPUTE 
DURATION  
CALCULATION 
Date 
Day 
15 
Duration will be presented in days and is 
calculated as the difference between date1 and 
date2 
Date 
Month 
NONE 
Duration will be presented in years and is 
calculated as the difference between year1 and 
year2. 
Example: Duration of NASH diagnosis 
 


 
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8.1.4 Derived data 
 
BMI : Body Mass Index is the weight in kilograms divided by the square of height in meters 
 
BMI category: Based upon the calculated value of BMI, patients will be categorized into the 
subcategories  
 
• 
Underweight : <18.5 
• 
Healthy weight : 18.5 – 24.9 
• 
Overweight : 25.0 – 29.9 
• 
Low risk obesity : 30.0 – 34.9 
• 
Moderate risk obesity : 35.0 – 39.9 
• 
High risk obesity : >=40.0 
 
Heart rate: the measurements will be categorized as 
• 
Slow: <60 beats per minute 
• 
Normal : 60-100 beats per minute 
• 
Fast :>100 beats per minute 
 
Blood pressure: To evaluate blood pressure results of systolic and diastolic measurements 
are combined to denote hypertension 
 
• 
Hypertension: Systolic>=140 and Diastolic>=90 
• 
No hypertension : All other combinations 
 
Duration of NASH diagnosis: Time period in years between date of initial NASH diagnosis 
and randomization date in the study 
 
Grade change from baseline to week 14 in CT1 by degree of fibrosis 
• 
In patients with CT1 800-849 msec mild 
• 
In patients with CT1 850-999 msec moderate 
• 
In patients with CT1 ≥ 1000 msec severe 
 
End of Treatment (EOT): Subjects who complete the treatment period of 13 weeks have 
reached their End of Treatment.  
 
Early Termination (ET): Subjects who meet any criteria for discontinuation of study treatment, 
as specified in Section 5.1 of the protocol, will undergo Early Termination (ET).  
 
Medications: 
• 
Concomitant medications will be coded using WHO dictionary and associated with 
ATC levels 1 and 2: 
 
Adverse Events:  
• 
Treatment Emergent AE’s (TEAE) are defined as events with an onset on or after the 
first treatment.  


 
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• 
System Organ Class (SOC) and preferred terms (PT) will be associated with each 
adverse event using most recent version of Medical Dictionary for Regulatory 
Activities (MedDRA).  
8.1.5 Analysis Data for Regulatory Submission 
Data collected during this study as well as the derived data will be formatted to meet the SDTM 
(Study Data Tabulation Model) and the Analysis Data Model (ADaM) standards of Clinical Data 
Interchange Standards Consortium (CDISC). A standard Define.doc file that describes the data 
attributes will be provided, 
9 STATISTICAL METHODS 
9.1 GENERAL STATISTICAL CONSIDERATIONS 
All statistical summaries and analyses will be performed using SAS® for Windows, version 
9.4 or later. 
 
Collected study data will be presented in subject data listings.  
 
For continuous variables descriptive statistics (n, mean, standard deviation, median, 
minimum and maximum) will be presented by treatment group.  
 
For categorical variables data summaries by treatment group will include frequency counts 
and percentages. 
 
Formal treatment group comparisons will be made at the nominal two-sided 0.05 level of 
significance using the FAS and PP analysis sets.  The 95% confidence intervals and p-
values for comparing treatment groups will be computed. 
 
9.1.1 Mock Table Shells 
A separate document will be created that describes the format of the statistical Listings and 
Tables (i.e. mock table shells) 
9.1.2 Covariates 
For efficacy analyses the baseline values will be used as a covariate. 
 
9.1.3 Protocol Deviations 
Subject listing of major protocol deviations by treatment group will be provided. 
9.1.4 Analysis sets 
The number of subjects in each analysis set will be computed for each part of the study and 
treatment group and overall. 
 
Number of Subjects in Analysis Set 
 


 
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PART 1 
PART 2 
 
PLACEBO LERONLIMAB 
700 MG 
OVERALL 
LERONLIMAB 
350 MG 
 
Full Analysis set (FAS) 
n 
n 
n 
n 
 
Per protocol set (PP) 
n 
n 
n 
n 
 
Safety analysis set  
n 
n 
n 
n 
 
 
9.1.5 Subject Disposition and Withdrawals 
The disposition of all subjects who sign an ICF will be provided. The numbers of subjects 
screened, randomized, received treatment, completed study, terminated early, and reasons 
fortermination will be listed and/or summarized by treatment group.  
 
Summary of Subject Disposition 
 
 
PART 1 
PART 2 
PLACEBO 
N (%) 
LERONLIMAB 
700 MG 
N (%) 
LERONLIMAB 
350 MG 
N (%) 
Assessed for screening 
n (xx) 
n (xx) 
n (xx) 
     Eligible at screening  
n (xx) 
n (xx) 
n (xx) 
     Ineligible at screening 
n (xx) 
n (xx) 
n (xx) 
Eligible and randomised 
n (xx) 
n (xx) 
n (xx) 
     Received randomized therapy 
n (xx) 
n (xx) 
n (xx) 
     Not received randomized therapy 
n (xx) 
n (xx) 
n (xx) 
End of Treatment 
n (xx) 
n (xx) 
n (xx) 
Early Termination 
n (xx) 
n (xx) 
n (xx) 
     ET – LTFU 
n (xx) 
n (xx) 
n (xx) 
     ET- PATIENT WISH 
n (xx) 
n (xx) 
n (xx) 
     ET – AE 
n (xx) 
n (xx) 
n (xx) 
     ET - Other 
n (xx) 
n (xx) 
n (xx) 
9.1.6 Demographic and Baseline Disease Characteristics 
Demographics and baseline disease characteristics medical history, prior and concomitant 
medications/therapies will be summarized by treatment group  
 
The following variables will be summarized descriptively using frequency counts and/or 
summary statistics n, mean, sd, median, min and max, as appropriate: 
 
VARIABLE 
TYPE 
PRESENTATION 
Age 
CONT 
In years 
Gender 
CAT 
Male vs Female 
Racial categories 
CAT 
Non-Hispanic 
Caucasian 
Hispanic 
Black/African American 
Asian 
Natives 
Other 


 
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BMI 
CONT 
Continuous  
BMI category 
CAT 
Underweight : <18.5 
Healthy weight : 18.5 – 24.9 
Overweight : 25.0 – 29.9 
Low risk obesity : 30.0 – 34.9 
Moderate risk obesity : 35.0 – 39.9 
High risk obesity : >=40.0 
Blood pressure 
CAT 
Hypertension: Systolic>=140 and Diastolic>=90 
No hypertension : All other combinations 
Heart rate 
CAT 
Slow : <60 beats per minute 
Normal : 60-100 beats per minute 
Fast :>100 beats per minute 
 
 
 
Alcohol consumption 
CAT 
Never/Current/Former 
Duration NASH diagnosis 
CONT 
Duration in years 
Nash medication 
CAT 
None/unknown/yes 
Stage Liver Fibrosis 
histology 
CAT 
F0/F1/F2/F3/F4/Unknown 
Stage Steatosis histology 
CAT 
S0/S1/S2/S3 
Stage Steatosis CAP US  
CAT 
S1 238-260 
S2 260-290 
S3 >290 
Stage Fibrosis US  
CAT 
F0-F1 2-7 
F2       7.5 -10 
F3       10 – 14 
F4       >14 
cT1 
CONT 
 
PDFF 
CONT 
 
Co-morbidities 
CAT 
Yes/No  
Number of co-morbidities 
CAT 
0-5  
5-10 
10-15 
15-20 
20-25 
>25 
Concomitant medication 
CAT 
Yes/No  
Number of concomitant 
medications 
CAT 
0-5 
5-10 
>10 
 
9.1.7 Alcohol Consumption and Related Variables 
For the patient population entering the study alcohol consumption variables will be 
summarized as follows: 
 
Summary of Alcohol Consumption and Related Variables 
 
PART 1 
PART 2 


 
STATISTICAL ANALYSIS PLAN (SAP) 
 
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ALCOHOL 
CONSUMPTION 
PLACEBO 
(N=NN) 
LERONLIMAB 700 
MG 
(N=NN) 
LERONLIMAB 350 
MG 
(N=NN) 
Never 
n (xx%) 
n (xx%) 
n (xx%) 
Current 
n (xx%) 
n (xx%) 
n (xx%) 
Former 
n (xx%) 
n (xx%) 
n (xx%) 
 
 
 
 
9.1.8 Medical History 
Medical history of the subjects will be listed and summarized by treatment group. 
 
Summary of Medical History 
N (%) 
 
 
 
 
 
PART 1 
PART 2 
 
PLACEBO 
(N=NN) 
LERONLIMAB 700 
MG 
(N=NN) 
LERONLIMAB 350 
MG 
(N=NN) 
 
n (xx%) 
n (xx%) 
n (xx%) 
 
n (xx%) 
n (xx%) 
n (xx%) 
 
n (xx%) 
n (xx%) 
n (xx%) 
 
9.1.9 Concomitant Medications 
Concomitant medications will be coded using WHO dictionary. Concomitant medications will 
be listed and summarized by treatment group and ATC levels 1 and 2: 
 
Concomitant Medications 
N (%) 
 
 
PART 1 
PART 2 
PLACEBO 
(N=NN) 
LERONLIMAB 
700 MG 
(N=NN) 
LERONLIMAB 
350 MG 
(N=NN) 
Anatomic Group 
 
 
 
  Therapeutic subgroup 
 
 
 
    Preferred Drug Name 
 
 
 
 
 
 
 
Alimentary Tract and 
Metabolism 
 
 
 
  Drugs For Acid Related 
Disorders 
 
 
 
   OMEPRAZOLE 
n (xx) 
n (xx) 
n (xx) 
   RANITIDINE 
n (xx) 
n (xx) 
n (xx) 
 
 
 
 


 
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9.2 Analysis of efficacy data 
Data for each part of the study will be analysed separately. For Part 1 of the study leronlimab 
700mg group will be compared to placebo. For Part 2 of the study leronlimab 350mg group will 
be compared to placebo from Part 1. 
 
9.2.1 Analysis of Primary Efficacy Endpoint  
The null hypothesis of no between treatment group difference in mean change from baseline 
in hepatic fat fraction assessed by magnetic resonance imaging-derived proton density fat 
fraction (MRI-PDFF) at week 14 against alternate hypothesis of a non-zero treatment-
difference will be tested at 0.05 level of significance. 
 
A preliminary assessment of normality will be performed using Shapiro-Wilks test at the 5% 
significance level. 
 
If departure from normality is not concluded a normality-based parametric test of the null 
hypothesis will be performed using ANCOVA with baseline as a continuous covariate and 
treatment group as a categorical covariate. The point estimate of the mean (SD) along with 
corresponding 95% confidence interval will be presented.  The baseline adjusted estimates of 
the treatment means and treatment difference along with 95% confidence interval and the two-
sided p-values will be presented.  
 
Otherwise, the null hpothsis will be tested using the two-sample Wilcoxon Rank Sum test and 
the Hodges-Lehmann estimate of location shift along with the corresponding 95% confidence 
intervals will be reported. 
 
Even if the parametric analysis is deemed appropriate, the non-parametric analyses will be 
performed to assess the robustness of the conclusions based on ANCOVA.  
 
Summary of MRI-PDFF 
Method: ANCOVA 
 
 
PART 1 
 
 
LERONLIMAB 
DIFFERENCE 
 
 
PLACEBO 
(N=NN) 
700MG 
(N=NN) 
95%CI 
(Lower-Upper) 
P-VALUE 
[1] 
Number. of Subjects 
nn 
nn 
 
 
 
 
 
 
 
Baseline 
xx.x (xx.x) 
xx.x (xx.x) 
 
 
Week 14 
xx.x (xx.x) 
xx.x (xx.x) 
 
 
Change at WK14 
xx.x (xx.x) 
xx.x (xx.x) 
 
 
Baseline Adjusted Change at 
WK14 
xx.x (xx.x) 
xx.x (xx.x) 
xx.xxx (xx.x) 
(xx.xxx-xx.xxx) 
0.xxx 
[1] p-value computed using ANCOVA accounting for treatment and baseline as covariates. 
 
*Programming note1: Create similar tables for Method=Non-parametric, change headers and 
footers accordingly.  
*Programminmg note 2: Repeat these tables for Part 2.   


 
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9.2.2 Analysis of Secondary Endpoints 
 
The secondary efficacy endpoints will be analyzed as follows:  
Analysis of Change from Baseline in Fibro-Inflammatory Activity 
Change from baseline in fibro-inflammatory activity as assessed by cT1 (corrected T1) 
assessed by multiparametric magnetic resonance imaging (MRI) of liver at week 14 will be 
summarized. The secondary endpoints including change from baseline in cT1, will be 
assessed in a manner like the assessment of the primary endpoint. 
Analysis of Fibro-Inflammatory Activity Categories 
Frequencies will be computed for cT1 grade categories (Mild: 1 ≥ 800-850) Moderate: (851-
999, Severe: (≥ 1000) and treatment. The treatment groups will be compared using Cochran-
Mantel Haenszel chi-square (CMH) test. 
 
Summary of Fibro-Inflammatory Activity Grades Based on cT1 Scores 
n (%) 
 
PART 1* 
 
PLACEBO 
(N=XX) 
LERONLIMAB 700 
MG 
(N=XX) 
P-VALUE 
[1] 
 
 
 
 
Mild (1 ≥ 800-850) 
n (xx) 
n (xx) 
 
Moderate (851-999) 
n (xx) 
n (xx) 
0.xxx 
Severe (≥ 1000) 
n (xx) 
n (xx) 
 
[1] p-value computed using CMH chi-square test. 
 
*Programming note: Repeat summary table for Part 2 
 
Analysis of Other Continuous Secondary Endpoints 
Change from baseline to Week 14 in the continuous secondary endpoints will be analyzed 
using methods like the one used for the primary endpoint. 
 
• 
liver fibrosis using FibroTest at week 14  
• 
hepatic inflammatory activity using FibroTest at week 14  
• 
serum pro-inflammatory biomarkers assessments  
• 
Gamma-glutamyltransferase (GGT) at week 14  
• 
Cytokeratin 18 (CK-18) level at week 14  
• 
Leronlimab (PRO 140) PK assessments 
9.2.3 Analysis of Exploratory Outcome Measures 
The exploratory efficacy endpoints are: 
 
Alanine transaminase (ALT) at week 14  
Aspartate transaminase (AST) at week 14  
Total bilirubin at week 14  
Triglycerides at week 14  


 
STATISTICAL ANALYSIS PLAN (SAP) 
 
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Density Lipoprotein (LDL) at week 14  
 
Analysis of Continouos Exploratory Endpoints 
Change from baseline to Week 14 in the continuous exploratory endpoints will be analyzed 
using methods like the one used for the primary endpoint. 
 
9.2.4 Analysis of CCR5 Biomarkers that may Predict Activity of Leronlimab 
To examine if monocyte/T cell CCR5 biomarker is predictive of leronlimab activity, the 
statistical significance of biomarker and treatment group interaction group will be assessed.  
The change from baseline to Week 14 in MRI-PDFF (and cT1) will be regressed on 
biomarker and treatment group and their interaction as covariables.  The p-values for these 
effects will be presented: 
 
Summary of Biomarker as a Predictive Factor 
PART 1* 
 
 
p-value 
** 
Bio- 
marker 
Treat- 
ment 
Inter- 
action 
Pro-inflammatory Biomarkers 
0.xxx 
0.xxx 
0.xxx 
IL-1 alpha 
0.xxx 
0.xxx 
0.xxx 
IL-1 beta 
0.xxx 
0.xxx 
0.xxx 
IL-6 
0.xxx 
0.xxx 
0.xxx 
RANTES (CCL5) 
0.xxx 
0.xxx 
0.xxx 
TNF-alpha 
0.xxx 
0.xxx 
0.xxx 
TNF-beta 
0.xxx 
0.xxx 
0.xxx 
CRP 
0.xxx 
0.xxx 
0.xxx 
 
 
 
 
Fibro Test 
 
 
 
Gamma-glutamyltransferase 
0.xxx 
0.xxx 
0.xxx 
Total bilirubin 
0.xxx 
0.xxx 
0.xxx 
Alpha-2-macroglobulin 
0.xxx 
0.xxx 
0.xxx 
Apolipoprotein A1 
0.xxx 
0.xxx 
0.xxx 
Haptoglobin. 
0.xxx 
0.xxx 
0.xxx 
ALT 
0.xxx 
0.xxx 
0.xxx 
 
 
 
 
Liver Function Tests / NASH Markers 
0.xxx 
0.xxx 
0.xxx 
Total Bilirubin 
0.xxx 
0.xxx 
0.xxx 
Direct Bilirubin 
0.xxx 
0.xxx 
0.xxx 
Alkaline Phosphatase (ALP) 
0.xxx 
0.xxx 
0.xxx 
Alanine Aminotransferase (ALT) (or SGPT) 
0.xxx 
0.xxx 
0.xxx 
Aspartate Aminotransferase (AST) (or SGOT) 
0.xxx 
0.xxx 
0.xxx 
Prothrombin Time (PT) 
0.xxx 
0.xxx 
0.xxx 
International Normalized Ratio (INR) 
0.xxx 
0.xxx 
0.xxx 
Albumin 
0.xxx 
0.xxx 
0.xxx 
Total Protein 
0.xxx 
0.xxx 
0.xxx 
Triglycerides 
0.xxx 
0.xxx 
0.xxx 
Cholesterol (Low density lipoprotein) 
0.xxx 
0.xxx 
0.xxx 
Cholesterol (High density lipoprotein) 
0.xxx 
0.xxx 
0.xxx 


 
STATISTICAL ANALYSIS PLAN (SAP) 
 
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Effective Date: 
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Creatine kinase 
0.xxx 
0.xxx 
0.xxx 
Gamma-glutamyltransferase (GGT) 
0.xxx 
0.xxx 
0.xxx 
Serum CK-18 
0.xxx 
0.xxx 
0.xxx 
 
*Programming Note 1: Repeat for Part 2 using Plaebo from Part 1 in the statistical model 
**Programming Note2: Please adjust the list according to the actual lab data. 
9.3 Analysis of Safety Data 
9.3.1 Extent of Exposure 
The duration of exposure will be categorized as 0-2 weeks,2-4 weeks, 4-8 weeks, 8-12 weeks, 
and >12 weeks. Actual categories will be specified at the time of reporting to adequately 
summarize the extent of exposure. The number and percentage of subjects in each category 
will be summarized using number (%) of subjects by treatment group and category. 
 
Summary of Extent of Exposure 
N (%) 
 
DURATION 
(WEEKS) 
PLACEBO 
LERONLIMAB 
700MG 
LERONLIMAB  
350MG 
 
xx (xx%) 
xx (xx%) 
xx (xx%) 
0-2 
xx (xx%) 
xx (xx%) 
xx (xx%) 
2-4 
xx (xx%) 
xx (xx%) 
xx (xx%) 
4-8 
xx (xx%) 
xx (xx%) 
xx (xx%) 
8-12 
xx (xx%) 
xx (xx%) 
xx (xx%) 
>12 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 
xx (xx%) 
xx (xx%) 
xx (xx%) 
9.3.2 Adverse Events 
Since in each part of this study, surveillance of adverse events (AE) will begin from the time 
the subject receives study treatment until the end of the study, all AEs in this study are 
considered treatment-emergent AEs (TEAEs). The TEAEs verbatim text recorded in the data 
base will be coded to associate MedDRA System Organ Classes (SOCs) and preferred term 
(PT). 
 
TEAEs will be listed and summarized as follows. 
 
Listing of Subject Numbers for Adverse Events 
 
SYSTEM ORGAN 
CLASS 
    Preferred Term 
TREATMENT 
NO. 
WITH 
EVENT 
SUBJECT NUMBERS 
 
 
 
 
 
 
 
 
SOC1 
 
 
 
    Preferred term a 
Placebo 
3 
xxx, xxx, xxx 
 
Leronlimab 
700 mg  
2 
xxx, xxx 


 
STATISTICAL ANALYSIS PLAN (SAP) 
 
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Leronlimab 
350 mg  
1 
xxx 
 
 
 
 
    Preferred term b 
Placebo 
3 
xxx, xxx, xxx 
 
Leronlimab 
700 mg  
2 
xxx, xxx 
 
Leronlimab 
350 mg  
1 
xxx 
 
 
Listing of Relationship of Adverse Event SOCs, and Verbatim Text 
 
SYSTEM ORGAN CLASS 
PREFFERED TERM 
VERBATIM TEXT 
 
 
 
     SOC1 
xxxxxx 
xxxxxxx 
 
xxxxxxx  xxxxxx  xxxx 
xxxxxx xxxxxxxxx 
 
 
 
    SOC 2 
xxxxxx 
xxxxxxx 
 
xxxxxxx  xxxxxx  xxxx 
xxxxxx xxxxxxxxx 
 
xxxxxx 
xxxxxxx 
 
Adverse Event Subject Listings 
 
Subject listings of adverse events will be sorted by treatment, subject number, SOC and PT 
will be provided and will display the following variables: 
 
• 
Treatment group 
• 
Subject Number 
• 
System Organ Class (SOC) 
• 
Preferred Term (PT) 
• 
CTCAE Intensity Grade Assessment (1-5) 
• 
Relationship to study treatment (Causality: Unrelated, Unlikely, Possibly, probably, 
Definitely)  
• 
Treatment given to treat the event 
• 
Outcome (fatal, not recovered/not resolved, recovered/resolved, recovered/resolved 
with sequalae, recovering/resolving, and unknown),  
• 
Seriousness (Y/N) 
• 
Impact (dose increased, dose not changed, dose reduced, drug interrupted, drug 
withdrawn, unknown, and not applicable) 
 
Following subject listings will be produced: 
 
• 
Subject listing of all adverse events 
• 
Subject listing of fatal adverse events 
• 
Subject llisting of non-fatal adverse events 
• 
Subject listing of adverse events of special interest (injection site reaction)  
• 
Subject listing of serious adverse events 
• 
Subject listing of adverse events leading to withdrawal 
 
Subject Listing of All Adverse Events* 


 
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Effective Date: 
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Treatment: Placebo* 
Subject Age 
Sex 
Race 
Weight 
Preferred term/ 
Verbatim text 
Outcome/ 
Onset 
date/ 
Resolution 
date 
Time 
since 
1st 
dose/ 
Time 
since 
last 
dose 
Intensity/ 
Seriousness/ 
Withdrawal 
Action 
taken/ 
Relationship 
to Study 
drug 
xxx 
xxxx/ 
xxx/ 
xxxx/ 
xxxx 
 
xxxxxxxxx/ 
xxxxxxxxx 
 
xxx/ 
xxx/ 
xxxxx 
xxxxx 
xxxxx 
xxxxx/ 
xxxx/ 
xxxx 
xxxxx/ 
xxxxxxx 
xxx 
xxxx/ 
xxx/ 
xxxx/ 
xxxx 
 
xxxxxxxxx/ 
xxxxxxxxx 
xxx/ 
xxx/ 
xxxxx 
xxxxx 
xxxxx 
xxxxx/ 
xxxx/ 
xxxx 
xxxxx/ 
xxxxxxx 
*Programming note: Repeat for fatal, non-fatal, events of special interest, serious and 
adverse events leading to withdrawal 
 
Adverse Event Summaries 
 
For the purposes of summarizing the TEAEs, the adverse event summaries will be sorted by 
MedDRA System Organ Classes (SOCs), in descending order from the SOC with the highest 
total incidence (i.e., summed across all treatment groups) for any adverse event within the 
class to the SOC with the lowest total incidence. Within each level, adverse events will be 
presented in descending order from the adverse event with the highest total incidence to the 
lowest total incidence. If the total incidence for any two or more adverse events is equal, the 
events will be presented in alphabetical order. Levels will not be presented if no adverse 
events occur within the level. 
 
The following TEAE summaries will be provided:  
 
• 
Summary of all adverse events 
• 
Summary of drug-related adverse events 
• 
Summary of serious adverse events 
• 
Summary of adverse events leading to withdrawal 
 
Summary of All Adverse Events* 
 
 
PART 1 
PART 2 
PLACEBO 
(N=X) 
LERONLIMAB 
700 MG 
(N=XX) 
LERONLIMAB 
350MG 
(N=XX) 
ANY EVENT 
n (xx%) 
n (xx%) 
n (xx%) 
  SOC 
n (xx%) 
n (xx%) 
n (xx%) 
    Any event 
n (xx%) 
n (xx%) 
n (xx%) 
    PT 1 
n (xx%) 
n (xx%) 
n (xx%) 
    PT 2 
n (xx%) 
n (xx%) 
n (xx%) 
 
 
 
 


 
STATISTICAL ANALYSIS PLAN (SAP) 
 
CD1-NASH-01 
 
 
Protocol No. 
CD1-NASH-01 
Revision No. 
Rev. 00 
Effective Date: 
17-Dec-2021 
 
CONFIDENTIAL 
 
 
Page 25 of 30 
 
*Programming note: Repeat for drug-related, serious and events leading to withdrawal. 
 
9.3.3 Clinical Laboratory Assessments 
All laboratory values Including Height, Weight and BMI will be listed. These variables will also 
be summarized as continuous variable and presented by treatment group and time point. 
For the purpose of this study, the below baseline (normal) values/reference range for the 
liver function panel be flagged: 
 
Total Bilirubin  
0.2-0.9 mg/dl  
Direct Bilirubin 
0.0 – 0.2 mg/dl  
SGOT (AST)  
15-41 IU/L  
SGPT (ALT)  
M: 17-63 IU/L; F: 14-54 IU/L  
Alkaline Phosphatase (ALP) 
34-104 IU/L 
 
Subject listing of Clinical Laboratory Data: 
 
Part 1, Treatment: Placebo 
Subject Age 
Sex 
Race 
Weight 
Lab test (Units) 
Visit 
Value 
Normal 
range 
Flag 
xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Normal range flag: H=above range, L=below range.   
 
Subject Listing of Height, Weight, and BMI 
 
 
Treat- 
ment 
Investi- 
gator 
Subject 
Visit 
Height 
Weight 
BMI 
 
 
 
 
 
 
 
 
Part 1 Placebo 
 
 
 
 
 
 
 
Leronlimab 700 
mg 
 
 
 
 
 
 
Part 2 
Leronlimab 350 mg 
 
 
 
 
 
 
 
 
The clinical laboratories at every assessed time point and changes from baseline will be 
summarised using the minimum set of summary statistics n, mean, SD, Median, Min and 
Max 
 
Summary of Laboratory Data 
 
Laboratory: xxxxx* 
 
Treatment 
N 
Visit 
n 
Mean 
SD 
Median Min 
Max 
 
 
 
 
 
 
 
 
 
 
Part 1 
Placebo 
 
 
 
 
 
 
 
 
 
Leronlimab 
700 mg 
 
 
 
 
 
 
 
 


 
STATISTICAL ANALYSIS PLAN (SAP) 
 
CD1-NASH-01 
 
 
Protocol No. 
CD1-NASH-01 
Revision No. 
Rev. 00 
Effective Date: 
17-Dec-2021 
 
CONFIDENTIAL 
 
 
Page 26 of 30 
 
Part 2 
Leronlimab 
350 mg 
 
 
 
 
 
 
 
 
*Programming note: Repeat for all labs 
9.3.4 Physical Examination 
Subject-listing of abnormalities noted during physical examination including Weight will be 
presented. 
 
Listing of Abnormalities in Physical Examination 
 
 
TREAT- 
MENT 
INVESTI- 
GATOR 
SUBJECT 
VISIT 
ABNORMALITY 
 
 
 
 
 
 
Part 1 
Placebo 
 
 
 
 
 
Leronlimab 700 
mg 
 
 
 
 
Part 2 
Leronlimab 350 
mg 
 
 
 
 
 
9.3.5 Vital Signs 
Subject-listing of  vital signs will be presented. 
 
Subject Listing of Vital Signs 
 
 
 
 
 
Treatment 
 
 
 
Inv. 
 
 
 
Subj. 
 
Age(y)/ 
Sex/ 
Race 
 
 
 
Visit 
 
 
Systolic BP 
(mmHg) 
 
 
Diastolic BP 
(mmHg) 
 
 
Vital Sign 3 
(units) 
 
 
 
 
 
 
 
 
 
Part 1 Placebo 
xx 
xx 
23/ 
xx 
  xx H 
   xx L 
   x H 
 
 
 
 
Male/ 
xx 
   xx 
   xx 
   xx H 
 
 
 
 
White 
xx 
  xx 
   xx H 
   xx  
 
 
 
 
 
 
 
 
 
 
The vital signs at every assessed time point and changes from baseline will be summarised 
using the minimum set of summary statistics n, mean, SD, Median, min and max. 
 
Summary of Systolic BP (mmHg)* 
 
 
Treatment 
N 
Visit n 
Mean SD 
Median Min 
Max 
 
 
 
 
 
 
 
 
 
 
Part 1 
Placebo 
 
 
 
 
 
 
 
 
 
Leronlimab 700 
mg 
 
 
 
 
 
 
 
 
Part 2 
Leronlimab 350 
mg 
 
 
 
 
 
 
 
 
*Programming note:  Repeat for Diastolic BP (mmHG) and Heart Rate 


 
STATISTICAL ANALYSIS PLAN (SAP) 
 
CD1-NASH-01 
 
 
Protocol No. 
CD1-NASH-01 
Revision No. 
Rev. 00 
Effective Date: 
17-Dec-2021 
 
CONFIDENTIAL 
 
 
Page 27 of 30 
 
9.3.6 Electrocardiogram (ECG) 
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. 
Subject-listing of  ECG values will be presented. 
 
The ECG at each assessed time point and changes from baseline will be summarised using 
the minimum set of summary statistics n, mean, SD, Median, Minimum and maximum 
 
Summary of Ventricular rate (beats per minute) 
 
 
Treatment 
N 
Visit 
n 
Mean 
SD 
Median Min 
Max 
 
 
 
 
 
 
 
 
 
 
Part 1 
Placebo 
 
 
 
 
 
 
 
 
 
Leronlimab 
700 mg 
 
 
 
 
 
 
 
 
Part 2 
Leronlimab 
350 mg 
 
 
 
 
 
 
 
 
*Programming note: Repeat for PR interval (msec) QRS interval (msec), QT interval 
(msec), and QTc interval (msec). 
 
Summary of Overall Result of 12-Lead ECG 
 
TREAT-
MENT 
VISIT 
NORMAL 
ABNORMAL 
CLINICALLY 
NOT 
SIGNIFICANT 
CLINICALLY 
SIGNIFICANT 
 
 
 
 
 
 
 
Part 1 
Placebo 
xx 
xx (xx) 
xx (xx) 
xx (xx) 
xx (xx) 
 
Leronlimab 
700 mg 
xx 
xx (xx) 
xx (xx) 
xx (xx) 
xx (xx) 
Part 2 
Leronlimab 
350 mg 
xx 
xx (xx) 
xx (xx) 
xx (xx) 
xx (xx) 
 
9.3.7 Tolerability 
Tolerability of repeated injections will be assessed by 
 
• 
Subject rated 11-point Numeric Pain Rating Scale (0=None to 10=Worse) 
• 
Investigator-evaluation of injection site reactions 
 
Subject Injection Site Pain Rating Score 
 
A subject lising of pain score will be presented.  
 
The frequencies of subject rated pain score will be computed 
 


 
STATISTICAL ANALYSIS PLAN (SAP) 
 
CD1-NASH-01 
 
 
Protocol No. 
CD1-NASH-01 
Revision No. 
Rev. 00 
Effective Date: 
17-Dec-2021 
 
CONFIDENTIAL 
 
 
Page 28 of 30 
 
Summary of Inject Site Pain Score 
N (%) 
 
Placebo 
Leronlimab 700 mg 
Leronlimab 350 mg 
 
(N=nn) 
(N=nn) 
(N=nn) 
Severity[1] 
 
 
 
0-5 
xx (%) 
xx (%) 
xx (%) 
6-7 
xx (%) 
xx (%) 
xx (%) 
8-10 
xx (%) 
xx (%) 
xx (%) 
[1] 0=None to 10=Worse. 
 
Investigator evaluation of Injection Site Reactions 
The injection site reactions are reported as part of the TEAEs. For each subject with an 
injection site reaction, subject profiles will be produced that summarize corresponding adverse 
event data along with demographic variables, dose of study drug, duration of exposure, drug 
discontinuation, CRP and eosinophil levels and medications used to treat the injection site 
reaction 
10 CHANGES IN SAP COMPARED TO STUDY PROTOCOL 
10.1 Addition of Exploratory Outcome Measures 
 
After finalization of the protocol, following outcome measures were added to the list of 
exploratory outcome measurements. 
 
Efficacy outcome parameters by a CCR5 Haplotype biomarker : 
• 
Change from baseline in hepatic fat fraction assessed by magnetic resonance 
imaging-derived proton density fat fraction (MRI-PDFF) at week 14 by CCR5 
Haplotype biomarker  
• 
Change from baseline in fibro-inflammatory activity as assessed by cT1 (corrected 
T1) assessed by multiparametric magnetic resonance imaging (MRI) of liver at week 
14 by CCR5 Haplotype biomarker 
Efficacy outcome parameters by a CCR5 calcium flux biomarker : 
• 
Change from baseline in hepatic fat fraction assessed by magnetic resonance 
imaging-derived proton density fat fraction (MRI-PDFF) at week 14 by CCR5 calcium 
flux biomarker 
• 
Change from baseline in fibro-inflammatory activity as assessed by cT1 (corrected 
T1) assessed by multiparametric magnetic resonance imaging (MRI) of liver at week 
14 by CCR5 calcium flux biomarker 
11 DATA HANDLING AND RECORD KEEPING  
11.1 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.  


 
STATISTICAL ANALYSIS PLAN (SAP) 
 
CD1-NASH-01 
 
 
Protocol No. 
CD1-NASH-01 
Revision No. 
Rev. 00 
Effective Date: 
17-Dec-2021 
 
CONFIDENTIAL 
 
 
Page 29 of 30 
 
 
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.  
11.2 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. 
11.3 Data Transfer to Sponsor 
All data formatted to meet the SDTM (Study Data Tabulation Model) standard of Clinical 
Data Interchange Standards Consortium (CDISC) along with a Define.doc file that lists 
attributes of data variables will be transferred to the sponsor. 
12 REFERENCES 
• 
ASA. Ethical Guidelines for Statistical Practice. Prepared by the Committee on 
Professional Ethics, April, 2016. 
• 
The Royal Statistical Society: Code of Conduct (2014). 
• 
E8 General Considerations for Clinical Trials, ICH Guidance, Federal Register, 1997. 
• 
E9 Statistical Principles for Clinical Trials, ICH Guideline, Federal Register, 1998 
• 
E9 (R1) Statistical Principles for Clinical Trials, ICH Guideline, Federal Register, 1998 


 
STATISTICAL ANALYSIS PLAN (SAP) 
 
CD1-NASH-01 
 
 
Protocol No. 
CD1-NASH-01 
Revision No. 
Rev. 00 
Effective Date: 
17-Dec-2021 
 
CONFIDENTIAL 
 
 
Page 30 of 30 
 
• 
Guideline for the Format and Content of the Clinical and Statistical Section of an 
Application, 2017. 
• 
Guideline for Industry: Structure and Content of Clinical Study Reports (ICH E3), July 
1996.