Clinical trial NCT04343651
Conditions: Coronavirus Disease 2019
Keywords: COVID-19
Sponsor: CytoDyn, Inc.
Start date: 2020-04-01; Completion date: 2021-09-20
Enrollment: 86 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a Phase 2, two-arm, randomized, double blind, placebo controlled multicenter study to evaluate the safety and efficacy of leronlimab (PRO 140) in patients with mild-to-moderate symptoms of respiratory illness caused by coronavirus 2019 infection.

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

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

A total of 75 subjects will be randomized 2:1 in this study.

Arms: arm 1: The placebo comparator consists of the formulation buffer for leronlimab, i.e., the placebo is the same as the active arm without leronimab. The placebo is presented in the same container closure at the same fill volume as the active (nominal 1mL fill volume). The formulation buffer contains histidine, glycine, sodium chloride, sorbitol, polysorbate 20 and sterile water for injections. arm 2: Each vial of active contains 175mg of leronlimab at a concentration of 175mg/ml (nominal 1mL fill volume) in formulation buffer containing histidine, glycine, sodium chloride, sorbitol, polysorbate 20 and sterile water for injections.
Interventions: intervention 1: Placebo intervention 2: Leronlimab (700mg)
Intervention descriptions: intervention 1: Placebo intervention 2: Leronlimab (PRO) 140 is a humanized IgG4, monoclonal antibody (mAb) to the C-C chemokine receptor type 5 (CCR5)

Protocol documents:
Prot_000.pdf: 
CONFIDENTIAL 
 
  
 
Page 1 of 91 
 
 
 
A Phase 2, Randomized, Double Blind, Placebo Controlled Study to Evaluate 
the Efficacy and Safety of Leronlimab for Mild to Moderate Coronavirus 
Disease 2019 (COVID-19) 
 
Protocol Number: 
CD10_COVID-19 
Version: 
5.0 
Date: 
30-Mar-2020 
 
 
 
Sponsor: 
CytoDyn, Inc. 
1111 Main Street, Suite 660 
Vancouver, Washington 98660 
(360) 980-8524-Work 
(360) 980-8549-Fax 
www.cytodyn.com 
 
 
 
 
Confidentiality Statement 
 
This document is a confidential communication of CytoDyn, Inc. It is provided for the conduct 
of a clinical research study. The information contained in this document is confidential and, 
except to the extent necessary to obtain informed consent or IEC/IRB approval, cannot be 
disclosed unless required by governmental regulation. Persons to whom any portion of the 
contents of this document is disclosed must be informed that the information is confidential and 
may not be further disclosed by them. 


 
 
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PROTOCOL APPROVAL PAGE 
 
 
 
 
Protocol Number:  
CD10_COVID-19 
 
Version: 
 
5.0 
 
Date: 
 
30-Mar-2020 
 
We, the undersigned, have reviewed this protocol and agree that it contains all relevant 
information required to meet FDA, GCP and all applicable regulatory guidelines and statutes. 


 
 
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INVESTIGATOR’S SIGNATURE PAGE 
 
 
 
Protocol Number:  
CD10_COVID-19 
 
Version: 
 
5.0 
 
Date: 
 
30-Mar-2020 
 
I have read the protocol specified above and agree to participate in and comply with the 
procedures, as outlined herein for the conduct of this clinical trial. I also agree to comply with 
US Food and Drug Administration (FDA) 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 
 
 
 


 
 
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SPONSOR INFORMATION 
Sponsor Office: 
CytoDyn, Inc. 
 
 
 
 
 
1111 Main Street, Suite 660 
 
 
 
 
 
Vancouver, Washington 98660 
 
 
 
 
 
(360) 980-8524-Work 
 
 
 
 
 
(360) 980-8549-Fax 
 
 
 
 
 
www.cytodyn.com 
 


 
 
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PROTOCOL SYNOPSIS 
Name of Sponsor/Company:  
CytoDyn, Inc. 
Name of Study Product:  
Leronlimab (PRO 140)  
Protocol Number:   
CD10_COVID-19 
Indication:   
Coronavirus Disease 2019 (COVID-19) 
Title of Study: 
A Randomized, Double Blind, Placebo Controlled Study to Evaluate the Efficacy and Safety of 
Leronlimab for Mild to Moderate Coronavirus Disease 2019 (COVID-19) 
Study Center: Up to 10 centers in the United States. Centers must have the capability of implementing 
appropriate infection-control measures to prevent infection of study staff and others who share the 
clinical site space.  
Planned Number of Subjects:  
75 subjects  
Study Development Phase:  
Phase 2 
Indication for Use: Leronlimab is indicated for treatment of adult patients with mild-to-moderate 
symptoms of respiratory illness caused by Coronavirus disease 2019 (COVID-19). 
Objective:  
The purpose of this study is to assess the safety and efficacy of leronlimab (PRO 140) administered as weekly 
subcutaneous injection in subjects with COVID-19. 
Study Outcomes (Endpoints): 
Primary Outcome (Endpoint) Measure: 
 
Clinical Improvement as assessed by change in total symptom score (for fever, myalgia, dyspnea and 
cough) 
Note: The total score per patient ranges from 0 to 12 points. Each symptom is graded from 0 to 3. 
[0=none, 1=mild, 2=moderate, and 3=severe].  
Secondary Outcome (Endpoints) Measures: 
1. Time to clinical resolution (TTCR) 
Time to clinical resolution (TTCR), defined as the time from initiation of study treatment until 
resolution of clinical symptoms (fever, myalgia, dyspnea and cough). 
2. Change from baseline in National Early Warning Score 2 (NEWS2) at Days 3, 7, and 14.  
This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental 
oxygen, temperature, systolic blood pressure, heart rate, level of consciousness). 
3. Change from baseline in pulse oxygen saturation (SpO2) at Days 3, 7, and 14 


 
 
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Name of Sponsor/Company:  
CytoDyn, Inc. 
Name of Study Product:  
Leronlimab (PRO 140)  
Protocol Number:   
CD10_COVID-19 
Indication:   
Coronavirus Disease 2019 (COVID-19) 
4. Change from baseline in the patient’s health status on a 7-category ordinal scale at Days 3, 7, and 14. 
A 7-category ordinal scale of patient health status ranges from: 1) Death; 2) Hospitalized, on invasive 
mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-
invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) 
Hospitalized, not requiring supplemental oxygen; 6) Not hospitalized, limitation on activities; 7) Not 
hospitalized, no limitations on activities. 
5. Incidence and duration (days) of hospitalization 
6. Incidence and duration (days) of mechanical ventilation supply  
7. Incidence and duration (days) of oxygen use 
8. Mortality rate at Day 14 
9. Time to return to normal activity 
Exploratory Outcome (Endpoints) Measures: 
1. Change in size of lesion area by chest radiograph or CT 
2. Change from baseline in serum cytokine and chemokine levels at Days 3, 7, and 14  
3. Change from baseline in CCR5 receptor occupancy levels for Tregs and macrophages at Days 3, 7, 
and 14 
4. Change from baseline in CD3+, CD4+ and CD8+ T cell count at Days 3, 7, and 14 
Safety Measures: 
1. Incidence of treatment-related adverse events (TEAEs)  
2. Incidence and severity of treatment-emergent adverse events (TEAEs) 
3. Incidence of  serious adverse events (SAEs) 
4. Incidence of TEAEs and SAEs leading to discontinuation of study medication.  
5. Changes in blood chemistry, hematology and coagulation parameter results 
6. Changes in vital signs including temperature, pulse, respiratory rate, systolic and diastolic blood 
pressure 
7. Changes in physical examination results 
8. Changes in electrocardiogram (ECG) results 
Trial Design:  
This is a Phase 2, two-arm, randomized, double blind, placebo controlled multicenter study to evaluate the 
safety and efficacy of leronlimab (PRO 140) in patients with mild-to-moderate symptoms of respiratory illness 
caused by coronavirus 2019 infection. Patients will be randomized to receive weekly doses of 700 mg 
leronlimab (PRO 140), or placebo. Leronlimab (PRO 140) and placebo will be administered via subcutaneous 


 
 
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Name of Sponsor/Company:  
CytoDyn, Inc. 
Name of Study Product:  
Leronlimab (PRO 140)  
Protocol Number:   
CD10_COVID-19 
Indication:   
Coronavirus Disease 2019 (COVID-19) 
injection.  
The study will have three phases: Screening Period, Treatment Period, and Follow-Up Period. 
Screening Period (up to 1 week):  
Screening assessments will commence at Visit 1 (V1) after obtaining signed informed consent, and will 
include review of medical and medication history, eligibility evaluation, physical examination, vital signs, 
Clinical Symptom Score assessment, pulse oxygen saturation, National Early Warning Score 2 (NEWS2) 
assessment, electrocardiogram (ECG), nasopharyngeal swab sample collection, chest radiograph or CT (if 
clinically indicated), ordinal scale assessment, and laboratory sample collection for routine serum biochemical, 
hematologic, coagulation, urinalysis, and serum/urine pregnancy (if applicable). These assessments must be 
conducted within 7 days of the First Treatment Visit (V2).  
All subjects who fail to meet eligibility criteria are considered screen failures, and are exited from the study 
without further evaluation. 
Treatment Period (2 weeks ± allowed windows):  
The schedule of visits during Treatment Period is as follows:  
 
Visit 2 (V2) [first treatment]: Within 1 week of the Screening Visit 
 
Visit 3 (V3): 3 (±1) day after V2 
 
Visit 4 (V4) [second treatment]: 7 (±1) days after V2 
 
Visit 5 (V5) / End of Treatment (EOT) Visit: 7 (±1) days after V4.  
Subjects who meet the eligibility criteria will have completed the following evaluations and assessments at V2 
prior to treatment: review of any changes in medical and medication history, physical examination, vital signs, 
Clinical Symptom Score assessment, pulse oxygen saturation, National Early Warning Score 2 (NEWS2) 
assessment, nasopharyngeal swab sample collection, health status assessment on an ordinal scale, baseline 
assessment for the requirement of: Mechanical Ventilation, Oxygen, and Hospital Stay, and blood sample 
collection for CD3+, CD4+ and CD8+ T cell count, CCR5 receptor occupancy for Treg and macrophages, 
serum cytokine and chemokine levels, and CCR5 gene polymorphisms. If Visit 2 (V2) takes place on the same 
day as the Screening Visit (V1), scheduled assessments performed under screening (V1) do not need to be 
repeated at V2. 
Study 
Drug 
Dosage 
Form 
IP 
concentration 
Dosing Frequency and Amount 
Route of 
Administration 
PRO 140 
(700 mg) 
Parenteral 
solution 
175 mg/mL 
2 injections of PRO 140 (2 X 2 mL/inj.) 
per week on opposite sides of abdomen 
SC injection 
Placebo 
Parenteral 
solution 
0 mg/mL 
2 injections of placebo (2 X 2 mL/inj.) 
per week on opposite sides of abdomen 
SC injection 


 
 
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Name of Sponsor/Company:  
CytoDyn, Inc. 
Name of Study Product:  
Leronlimab (PRO 140)  
Protocol Number:   
CD10_COVID-19 
Indication:   
Coronavirus Disease 2019 (COVID-19) 
At V2, subjects will be randomized to receive leronlimab (PRO 140) or placebo which will be administered 
subcutaneously weekly at Visit 2 (Day 0) and Visit 4 (Day 7) by a qualified medical professional at clinic or 
subject’s home.  
The following assessments will be performed at V3, V4, and V5/EOT: physical examination, vital signs, 
Clinical Symptom Score assessment, pulse oxygen saturation, National Early Warning Score 2 (NEWS2) 
assessment, nasopharyngeal swab sample collection, health status assessment on an ordinal scale, assessment 
for the requirement of: Mechanical Ventilation, Oxygen, and Hospital Stay, and laboratory sample collection 
for routine serum biochemical, hematologic, coagulation, urinalysis, CD3+, CD4+ and CD8+ T cell count, 
CCR5 receptor occupancy for Treg and macrophage, serum cytokine and chemokine levels, and CCR5 gene 
polymorphisms. 
Additionally, chest radiograph or CT (if clinically indicated), mortality assessment and ECG will be performed 
at V5/EOT visit. Adverse events and medications will be monitored throughout the study. 
Follow Up Period (2 and 4 weeks after EOT± allowed windows) 
Follow-up visits will be performed at 2 weeks (V6) and 4 weeks (V7) after the End of Treatment (EOT) visit. 
The following assessments will be performed at V6 and V7 visit: review of adverse events and concomitant 
medications, physical examination, vital signs, nasopharyngeal swab sample collection, mortality status, and 
blood collection for routine serum biochemical, hematologic, coagulation and urine laboratory assessments 
(V7 only). 
Note: During visits conducted at the study clinic, subjects and site personnel will use appropriate protective 
gear (e.g., masks, gloves) to prevent the spread of the infection. If possible, scheduled visits can be conducted 
by a visiting nurse (or trained site staff) at the subject’s home to mitigate the risk of spreading COVID-19.  
During visits conducted at the subject’s home, the visiting nurse (or trained site staff) will administer study 
drug (if applicable), monitor subjects for safety, perform blood draw, and all other assessments related to study 
outcomes measures. 
Duration of Treatment:  
 
Screening Period (Screening to Baseline): Up to 7 days (1 Week) 
 
Treatment Period: 14 Days (2 weeks) 
 
Follow-Up Period: 28 Days (4 weeks) 
Total Study Duration: 7 Weeks 
Inclusion Criteria:  
1. Male or female adult ≥ 18 years of age at time of enrollment. 


 
 
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Name of Sponsor/Company:  
CytoDyn, Inc. 
Name of Study Product:  
Leronlimab (PRO 140)  
Protocol Number:   
CD10_COVID-19 
Indication:   
Coronavirus Disease 2019 (COVID-19) 
2. Subjects with mild-to-moderate symptoms of respiratory illness caused by coronavirus 2019 infection 
as defined below: 
Mild (uncomplicated) Illness: 
- 
Diagnosed with COVID-19 by a standardized RT-PCR assay AND 
- 
Mild symptoms, such as fever, rhinorrhea, mild cough, sore throat, malaise, headache, muscle 
pain, or malaise, but with no shortness of breath AND 
- 
No signs of a more serious lower airway disease AND 
- 
RR<20, HR <90, oxygen saturation (pulse oximetry) > 93% on room air 
Moderate Illness: 
- 
Diagnosed with COVID-19 by a standardized RT-PCR assay AND 
- 
In addition to symptoms above, more significant lower respiratory symptoms, including 
shortness of breath (at rest or with exertion) OR 
- 
Signs of moderate pneumonia, including RR ≥ 20 but <30, HR ≥ 90 but less than 125, oxygen 
saturation (pulse oximetry) > 93% on room air AND 
- 
If available, lung infiltrates based on X-ray or CT scan < 50% present 
3. Clinically normal resting 12-lead ECG at Screening Visit or, if abnormal, considered not clinically 
significant by the Principal Investigator. 
4. Subject (or legally authorized representative) provides written informed consent prior to initiation of 
any study procedures. 
5. Understands and agrees to comply with planned study procedures. 
6. Women of childbearing potential must agree to use at least one medically accepted method of 
contraception (e.g., barrier contraceptives [condom, or diaphragm with a spermicidal gel], hormonal 
contraceptives [implants, injectables, combination oral contraceptives, transdermal patches, or 
contraceptive rings], or intrauterine devices) for the duration of the study. 
Exclusion Criteria: 
1. Subjects showing signs of acute respiratory distress syndrome (ARDS) or respiratory failure 
necessitating mechanical ventilation at the time of screening; 
2. History of severe chronic respiratory disease and requirement for long-term oxygen therapy; 
3. Subjects showing signs of clinical jaundice at the time of screening; 


 
 
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Name of Sponsor/Company:  
CytoDyn, Inc. 
Name of Study Product:  
Leronlimab (PRO 140)  
Protocol Number:   
CD10_COVID-19 
Indication:   
Coronavirus Disease 2019 (COVID-19) 
4. History of moderate and severe liver disease (Child-Pugh score >12); 
5. Subjects requiring Renal Replacement Therapy (RRT) at the time of screening; 
6. History of severe chronic kidney disease or requiring dialysis; 
7. Any uncontrolled active systemic infection requiring admission to an intensive care unit (ICU); 
Note: Subjects infected with chronic hepatitis B virus or hepatitis C virus will be eligible for the study 
if they have no signs of hepatic decompensation.  
Note: Subjects infected with HIV-1 will be eligible for the study with undetectable viral load and are 
on a stable ART regimen. Investigators are required to review the subjects’ medical records to 
confirm HIV-1 RNA suppression within the previous 3 months. 
Note: Empirical antibiotic treatment for secondary bacterial infections is allowed during the course of 
study.  
8. Patients with malignant tumor, or other serious systemic diseases; 
9. Patients who are participating in other clinical trials; 
10. Patients who have a history of allergic reactions attributed to compounds of similar chemical or 
biologic composition to leronlimab (PRO 140) are not eligible; and 
11. Inability to provide informed consent or to comply with test requirements 
Statistical Considerations:   
Sample Size Determination and Rationale 
A total of 75 subjects will be randomized 2:1 in this study. The sample size is based on clinical judgment. No 
statistical power calculation is used to establish the sample size for this proof-of-concept study. 
Analysis Populations 
The Modified Intent-to-Treat (mITT) population is defined as the set of subjects who have received at least 
one dose of leronlimab (PRO 140) or placebo. This population will be used for the analysis of efficacy 
parameters or measurements. 
The Per Protocol (PP) population is defined as the set of subjects who meet the Evaluable Population 
requirements and were not associated with any major protocol violations. This population will be identified 
before the database lock.  
The Safety Population will include all subjects who have received one dose of leronlimab (PRO 140) or 
placebo. This population will be used for the analysis of safety parameters or measurements. 


 
 
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Name of Sponsor/Company:  
CytoDyn, Inc. 
Name of Study Product:  
Leronlimab (PRO 140)  
Protocol Number:   
CD10_COVID-19 
Indication:   
Coronavirus Disease 2019 (COVID-19) 
Analysis Methods 
Descriptive statistics (n, mean, standard deviation, median, minimum, and maximum) will be calculated for 
continuous variables. Frequencies and percentages will be presented for categorical variables. 


 
 
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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 .........................................................................21 
1.1. Statement of Intent ..............................................................................................................21 
1.2. Background of the Disease ..................................................................................................21 
1.3. Leronlimab (PRO 140) ........................................................................................................21 
1.4. Summary of Prior Pre-Clinical and Clinical Studies ...........................................................22 
1.4.1. 
Pre-Clinical Studies with PRO 140 ...................................................................22 
1.4.2. 
Clinical Studies with PRO 140 ..........................................................................22 
1.5. Treatment Rationale for this Study .....................................................................................32 
1.5.1. 
Study Rationale .................................................................................................32 
1.5.2. 
Rationale for Dose Selection and Treatment Duration .....................................34 
1.6. Risks / Benefits Assessment ................................................................................................36 
2. STUDY OBJECTIVES ..........................................................................................................38 
3. STUDY DESIGN ....................................................................................................................39 
3.1. Study Center ........................................................................................................................40 
3.2. Study Population .................................................................................................................40 
3.3. Eligibility Criteria ................................................................................................................40 
3.3.1. 
Inclusion Criteria ...............................................................................................40 
3.3.2. 
Exclusion Criteria ..............................................................................................41 
4. STUDY SCHEDULE .............................................................................................................42 
4.1. Screening Phase ...................................................................................................................47 
4.1.1. 
Screening Visit (V1) ..........................................................................................47 
4.2. Treatment Phase ..................................................................................................................48 


 
 
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4.2.1. 
Visit 2 (V2) ........................................................................................................48 
4.2.2. 
Visits 3 and 4, (V3 and V4) ...............................................................................49 
4.2.3. 
End of Treatment – EOT (V5) ..........................................................................50 
4.3. Follow-Up Phase .................................................................................................................51 
4.3.1. 
Visits 6 and 7 (V6 and V7) ................................................................................51 
4.4. Unscheduled Visits ..............................................................................................................51 
5. SUBJECT COMPLETION, WITHDRAWAL AND CRITERIA FOR STOPPING THE 
STUDY ....................................................................................................................................53 
5.1. Subject Completion .............................................................................................................53 
5.2. Early Stopping Rules ...........................................................................................................53 
5.3. Removal of Subjects from Study Treatment and/or Study as a Whole ...............................53 
5.4. Data Collected from Withdrawn Subjects ...........................................................................54 
5.5. Screen Failures ....................................................................................................................54 
6. STUDY TREATMENT .........................................................................................................55 
6.1. Leronlimab (PRO 140) ........................................................................................................55 
6.1.1. 
Leronlimab (PRO 140) - Packaging and Labeling ............................................56 
6.1.2. 
Leronlimab (PRO 140) - Storage and Handling ................................................57 
6.1.3. 
Leronlimab (PRO 140) - Administration ..........................................................57 
6.1.4. 
Leronlimab (PRO 140) - Post Injection Monitoring .........................................58 
6.1.5. 
Leronlimab (PRO 140) - Toxicity Management ...............................................58 
6.1.6. 
Leronlimab (PRO 140) - Disposition ................................................................59 
6.1.7. 
Leronlimab (PRO 140) - Accountability ...........................................................59 
7. DESCRIPTION OF PROTOCOL ASSESSMENTS AND PROCEDURES ...................60 
7.1. Informed Consent ................................................................................................................60 
7.2. Assessment of Eligibility .....................................................................................................60 
7.2.1. 
Re-screening ......................................................................................................60 
7.3. Demographic Information ...................................................................................................60 
7.4. Medical History ...................................................................................................................61 
7.5. Physical Examination ..........................................................................................................62 
7.6. Vital Signs, Height and Weight ...........................................................................................62 


 
 
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7.7. Concomitant Medications ....................................................................................................63 
7.7.1. 
Excluded Medications .......................................................................................63 
7.7.2. 
Allowable Medications and Therapies ..............................................................63 
7.8. Clinical Laboratory Assessments ........................................................................................64 
7.9. Study Treatment Application ..............................................................................................65 
7.10. Clinical Symptom Score Assessment ..................................................................................65 
7.11. Pulse Oxygen Saturation (SpO2) ........................................................................................65 
7.12. National Early Warning Score 2 Assessment ......................................................................65 
7.13. 12-Lead Electrocardiogram .................................................................................................65 
7.14. Nasopharyngeal Swab Sample Collection ..........................................................................65 
7.15. Chest Radiograph or Computed Tomography Scan ............................................................66 
7.16. Ordinal Scale Assessment ...................................................................................................66 
7.17. Requirement of Mechanical Ventilation, Oxygen, and Hospital Stay ................................66 
7.18. Randomization .....................................................................................................................66 
8. STATISTICAL ANALYSIS .................................................................................................67 
8.1. Treatment Groups ................................................................................................................67 
8.2. Description of Study Outcomes (Endpoints) .......................................................................67 
8.2.1. 
Primary Outcome (Endpoints) Measures ..........................................................67 
8.2.2. 
Secondary Outcome (Endpoints) Measures ......................................................67 
8.2.3. 
Exploratory Outcome (Endpoints) Measures ....................................................68 
8.2.4. 
Safety Measures ................................................................................................68 
8.3. Sample Size Determination and Rationale ..........................................................................68 
8.4. Randomization .....................................................................................................................69 
8.5. Blinding ...............................................................................................................................69 
8.6. Stratification ........................................................................................................................69 
8.7. Interim Analysis ..................................................................................................................69 
8.8. General Statistical Considerations .......................................................................................69 


 
 
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8.8.1. 
Analysis Populations .........................................................................................69 
8.8.2. 
Covariates ..........................................................................................................70 
8.8.3. 
Missing Data......................................................................................................70 
8.9. Analysis Methods ................................................................................................................70 
8.9.1. 
Subject Disposition............................................................................................70 
8.9.2. 
Demographic and Baseline Characteristics .......................................................70 
8.9.3. 
Study Outcome Assessment ..............................................................................70 
9. ADVERSE EVENTS (DEFINITIONS AND REPORTING) ............................................73 
9.1. Adverse event (AE) .............................................................................................................73 
9.2. Reporting of Adverse Events ..............................................................................................73 
9.2.1. 
Impact on Study Treatment ...............................................................................73 
9.2.2. 
CTCAE Grade (Intensity) Assessment..............................................................73 
9.2.3. 
Causality Assessment ........................................................................................74 
9.2.4. 
Treatment Given as a Result of the Event .........................................................75 
9.2.5. 
Outcome Assessment ........................................................................................75 
9.3. Serious Adverse Events .......................................................................................................75 
9.4. Reporting of Serious Adverse Events (SAE) ......................................................................76 
9.5. SAE Follow-Up ...................................................................................................................76 
9.6. Expected/anticipated events ................................................................................................77 
10. DIRECT ACCESS TO SOURCE DATA/DOCUMENTATION ......................................78 
11. QUALITY CONTROL AND QUALITY ASSURANCE ...................................................79 
11.1. Monitoring Requirements ....................................................................................................79 
11.2. Acceptability of Case Report Forms (CRFs) ......................................................................79 
11.3. Modification of Protocol .....................................................................................................79 
11.4. Reporting Protocol Deviations ............................................................................................80 
11.4.1. 
Major Protocol Deviation or Violation .............................................................80 
11.4.2. 
Minor Protocol Deviation or Violation .............................................................80 
12. ETHICS AND REGULATORY REQUIREMENTS .........................................................82 
12.1. Institutional Review Board/Independent Ethics Committee (IRB/IEC) .............................82 
12.2. Investigator’s Responsibilities ............................................................................................82 


 
 
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12.3. Subject Informed Consent Requirements ............................................................................83 
13. DATA HANDLING AND RECORD KEEPING ................................................................84 
13.1. Recording and Collection of Data .......................................................................................84 
13.2. Clinical Data Management ..................................................................................................84 
13.3. Archiving .............................................................................................................................85 
14. PUBLICATION PLAN .........................................................................................................86 
15. REFERENCES .......................................................................................................................87 
16. APPENDIX .............................................................................................................................89 
16.1. Appendix 1: National Early Warning Score 2 (NEWS2) ....................................................89 
16.2. Appendix 2: Common Terminology Criteria for Adverse Events v5.03 ............................91 


 
 
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LIST OF TABLES 
Table 1-1: 
List of Completed Clinical Studies with Leronlimab (PRO 140) ...........................29 
Table 1-2: 
List of Ongoing Clinical Studies with Leronlimab (PRO 140) ...............................31 
Table 1-3: 
Immunologic Status - Post Leronlimab Therapy in COVID-19 Patients ................32 
Table 1-4: 
Cytokine Levels - Post Leronlimab Therapy in COVID-19 Patients ......................33 
Table 4-1: 
Treatment Groups ....................................................................................................42 
Table 4-2: 
Schedule of Assessments .........................................................................................44 
Table 6-1: 
Treatment Administration Summary .......................................................................55 
Table 6-2: 
Investigational Product - Leronlimab (PRO 140) ...................................................55 
Table 6-3: 
Leronlimab (PRO 140) - Management for Injection Site Reactions .......................58 
Table 6-4: 
Leronlimab (PRO 140) - Management for all Other Potential Toxicities 
(Attributable to Leronlimab) ...................................................................................59 
Table 7-1: 
Lab Parameters ........................................................................................................64 
Table 9-1: 
CTCAE v5.0 General Guidelines ............................................................................74 
 


 
 
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LIST OF FIGURES 
Figure 1-1: 
Dose-response curve for inhibition of CC-chemokine-induced calcium mobilization 
by PRO 140 .............................................................................................................35 
Figure 3-1: 
Study Schematic ......................................................................................................39 
Figure 6-1: 
Investigational Product - Vial Label .......................................................................56 
Figure 6-2: 
Investigational Product - Syringe Label ..................................................................56 
Figure 6-3: 
Investigational Product - Kit Label .........................................................................57 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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


 
 
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Abbreviation 
Term 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization 
IEC 
Independent Ethics Committee 
IND 
Investigational New Drug 
IP 
Investigational Product 
IRB 
Institutional Review Board 
ISR 
Injection Site Reaction 
ITT 
Intent to Treat 
IV 
Intravenous 
LAR 
Legally Authorized Representative 
LTF 
Lost to Follow-Up 
MedDRA 
Medical Dictionary for Regulatory Activities  
mg 
Milligram 
MTD 
Maximum Tolerated Dose 
NEWS 
National Early Warning Score 2 
OBT 
Optimized Background Therapy 
PD 
Pharmacodynamic 
PK 
Pharmacokinetic 
PI 
Principal Investigator 
SAE 
Serious Adverse Event 
SARS-CoV-2 
Severe Acute Respiratory Syndrome Coronavirus 2 
SC 
Subcutaneous 
SOP 
Standard Operating Procedure 
SpO2 
Peripheral Capillary Oxygen Saturation 
SV 
Screening Visit 
TEAE 
Treatment Emergent Adverse Event 
TNBC 
Triple Negative Breast Cancer 
Treg 
T regulatory cell 
TV 
Treatment Visit 
V 
Visit 
VL 
Viral Load 


 
 
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1 INTRODUCTION AND BACKGROUND 
1.1. 
STATEMENT OF INTENT 
The design, conduct and reporting of this study shall be conducted in compliance with the 
protocol, International Conference on Harmonization/Good Clinical Practice (ICH/GCP), and all 
appropriate regulatory requirements. Investigator(s) participating in this study will have 
documented training in GCP. Independent monitoring of the trial will be accomplished utilizing a 
Contract Research Organization (CRO). 
1.2. 
BACKGROUND OF THE DISEASE 
Coronavirus disease 2019 (COVID-19) is a respiratory illness that can spread from person to 
person. The infectious agent that causes COVID-19 is a novel Coronavirus, named ‘SARS-CoV-
2’, was first identified during a recent outbreak in December 2019, in Wuhan, China. Patients 
with COVID-19 have had mild to severe respiratory illness with symptoms of fever, cough, and 
shortness of breath along with non-specific symptoms including myalgia and fatigue. Some 
patients were more likely to develop a severe respiratory illness similar to severe acute respiratory 
syndrome (SARS), or even die from the disease.  
Current standard of care treatment includes oxygen therapy. There is no specific antiviral 
treatment recommended for COVID-19 by Centers for Disease Control and Prevention (CDC). 
People with COVID-19 should receive supportive care to help relieve symptoms. For severe 
cases, treatment should include care to support vital organ functions. 
The aim of this study is to test efficacy and safety of leronlimab (PRO140) for treatment of adult 
patients with mild-to-moderate symptoms of respiratory illness caused by ‘SARS-CoV-2’ 
coronavirus infection. 
1.3. 
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. 
Leronlimab (PRO 140) has been shown to bind to the N terminus (Nt) and the extracellular loop 2 
(ECL2) domain of the CCR5 cell surface receptor that HIV-1 uses to gain entry to a cell. 
Leronlimab (PRO 140) (binding to CCR5 blocks viral entry by interfering with the final phase of 
viral binding to the cell surface prior to fusion of the viral and cell membranes. Leronlimab (PRO 
140) has been administered intravenously or subcutaneously to more than 750 healthy and HIV-1 
infected individuals in Phase I/II/III studies. The drug has been well tolerated following 
intravenous administration of single doses of 0.5 to 10 mg/kg or up to 700 mg weekly doses as 


 
 
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subcutaneous (SC) injection. Overall, 324 subjects have been exposed to leronlimab (PRO 140) 
350 mg SC weekly dose with the longest duration of exposure lasting 4 years. Similarly, more than 
250 and 150 subjects have been exposed to leronlimab (PRO 140) 525 mg and 700 mg SC weekly 
dose, respectively. 
1.4. 
SUMMARY OF PRIOR PRE-CLINICAL AND CLINICAL STUDIES 
1.4.1. Pre-Clinical Studies with PRO 140 
In vitro and in vivo preclinical studies have been conducted to determine the pharmacokinetic, 
immunogenicity, and toxicity profiles of leronlimab (PRO 140) following IV and SC 
administration. Several acute and chronic toxicity studies have been conducted to support the 
clinical development plan.  
Acute toxicity of leronlimab (PRO 140) was evaluated in New Zealand rabbits, following IV 
administration of 5 or 15 mg/kg. Chronic toxicity was evaluated in cynomolgus monkeys 
following biweekly administration of IV doses up to 10 mg/kg for six months and biweekly 
administration of various SC doses up to 50 mg/kg for 24 weeks. The drug was generally well 
tolerated. Biweekly administration of IV doses up to 10 mg/kg for six months resulted in 
minimum to mild lymphoid hyperplasia in assorted lymph nodes and spleen, which was 
considered an expected immune response to a foreign protein. Biweekly administration of SC 
doses up to 50 mg/kg for 24 weeks resulted in minimum injection-site reactions (minimal, 
multifocal, mononuclear cell infiltrates in the subcutis), which were considered due to an 
inflammatory response to the injected antigen. Monkeys tolerated treatment with leronlimab 
(PRO 140) for 24 weeks without evidence of local or systemic toxicity. Leronlimab (PRO 140) 
caused no mortality, cageside observations, in-life injection-site observations, or gross pathologic 
findings. Chronic treatment with leronlimab (PRO 140) did not affect body weight, food 
consumption, hematology, clinical chemistry or coagulation parameters. 
Both IV and SC administration resulted in elimination half-lives of approximately 200 hours, and 
overall exposure increased with increasing doses. Following SC administration of leronlimab 
(PRO 140) in monkeys, the maximal concentration (Cmax) was achieved within 56 hours and 
bioavailability for leronlimab (PRO 140) after SC dosing was approximately 70%. 
1.4.2. Clinical Studies with PRO 140 
Current human experience with leronlimab (PRO 140) consists of nine completed and six ongoing 
clinical trials, mostly on healthy subjects or HIV-1 positive subjects. These studies are 
summarized in Table 1-1 and Table 1-2. In all clinical trials, the majority of adverse events (AEs) 
have been mild or moderate. No dose-limiting toxicities or patterns of drug-related toxicities were 
observed. Antiviral activity was potent, rapid, prolonged, dose-dependent, and highly significant. 
1.4.2.1. 
PRO 140 1101 Study 


 
 
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For the first-in-human trial, PRO 140 1101, the drug was administered IV at 0.1, 0.5, 2.0, or 5.0 
mg/kg to healthy subjects and was generally well tolerated, non-immunogenic, and without 
clinically relevant toxicity. Treatment Emergent Adverse Events (TEAEs) did not increase with 
rising PRO 140 dose levels. Seventy-five percent (75%) of subjects reported TEAEs, most of 
which were deemed unrelated to study treatment by the investigator. 
1.4.2.2. 
PRO 140 1102 Study 
For PRO 140 1102, the majority of AEs, other than injection-site reactions, were considered mild 
and possibly related to drug administration. The majority of injection-site reactions were 
considered mild, self-resolving, and definitely related to drug administration. PRO 140 derived 
from Chinese Hamster Ovary (CHO) cells and administered at 100 mg/mL was generally well 
tolerated in healthy, normal volunteers. Overall, PRO 140 administered SC using Autoject® 2 
appeared better tolerated than manual injection. 
1.4.2.3. 
PRO 140 1103 Study  
In PRO 140-1103, administration of PRO 140 at 350 mg using Autoject® 2 appeared well 
tolerated. Manual injections, on the other hand, were associated with a greater number of AEs. 
There did not appear, however, to be any substantial difference in subject perception of pain or 
discomfort related to site of drug administration. No anti-PRO 140 antibodies were detected in 
any subjects in this study. There was a tendency of higher exposure associated with SC 
administration of PRO 140 at 350 mg in the abdomen and the thigh. A higher number of AEs 
were associated with injections in the arm. Based on these observations, thigh and abdominal 
administration of PRO 140 were preferred over arm injection. 
1.4.2.4. 
PRO 140 1302 Study 
The initial proof-of-concept study was a randomized, double-blind, placebo-controlled study in 
subjects with early-stage, asymptomatic HIV infection, only R5 HIV-1 detectable, and no 
antiretroviral therapy for 12 weeks [Jacobson, 2008]. Subjects (n=39) were randomized to receive 
a single IV injection of placebo or PRO 140 at doses of 0.5, 2, or 5 mg/kg. Subjects were 
monitored for antiviral effects, safety, and PRO 140 pharmacokinetics (PK) for 58 days.  
PRO 140 demonstrated potent, rapid, prolonged, and dose-dependent antiviral activity. 
Intravenous PRO 140 was generally well tolerated. No drug-related serious events or dose-
limiting toxicity was observed [Jacobson, 2008]. The most common adverse events (headache, 
lymphadenopathy, diarrhea, and fatigue) were observed at similar frequencies across the placebo 
and PRO 140 dose groups. There was no significant effect on QTc intervals or other 
electrocardiographic parameters, and there were no remarkably laboratory findings. 
1.4.2.5. 
PRO 140 2301 Study 


 
 
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PRO 140 2301 was a multi-center, randomized, double-blind, placebo-controlled, parallel group 
study in 30 male and female adult subjects infected with HIV-1 [Jacobson, 2010]. Subjects were 
randomized to one of three groups (N=10/group), each receiving one of three treatments: (i) a 
single IV dose of 5 mg/kg by 30-minute IV infusion; (ii) a single IV dose of 10 mg/kg by 30-
minute IV infusion; (iii) a single placebo dose by 30-minute IV infusion. The objective of the 
study was to assess and characterize the PK and PD of PRO 140 administered by IV infusion, 
assess efficacy at a new dosage level, and safety and tolerability of single doses of PRO 140. 
All PRO 140-treated subjects had more than 10-fold reduction in viral loads [Jacobson, 2010]. 
Both the 5 mg/kg and 10 mg/kg doses have shown favorable tolerability and no dose-limiting 
toxicity has been observed. High levels of receptor occupancy (>85% reduction in the number of 
cells detected) were observed for 29 days after treatment with both 5 and 10 mg/kg doses.  
1.4.2.6. 
PRO 140 2101 Study 
A subcutaneous (SC) form of PRO 140 was tested in HIV-infected subjects. The trial was a 
randomized, double-blind, placebo-controlled study in subjects (n=44) with early-stage, 
asymptomatic HIV infection, only R5 HIV-1 detectable, and no antiretroviral therapy for 12 
weeks [Thompson, 2009]. Placebo (n=10) and three PRO 140 doses were examined: 162 mg 
weekly for three weeks (n=11), 324 mg weekly for three weeks (n=11), and 324 mg biweekly 
(every other week) for two doses (n=12). Subjects were followed for 44 days after the final dose.  
Potent, dose-dependent and highly statistically significant antiviral activity was observed. The 
trial established the first antiviral proof of concept for a long-acting, self-administrable drug for 
HIV-1 infection [Thompson, 2009]. 
Subcutaneous PRO 140 was generally well tolerated both locally and systemically. There was no 
obvious dose-related pattern of toxicity. The most common adverse events (diarrhea, headache, 
lymphadenopathy and hypertension) were mild to moderate and self-resolving. These events are 
common in HIV infection and were reported with similar frequencies in the placebo and PRO 140 
treatment groups. Administration-site reactions were mild, transient, and observed in a fraction of 
subjects.  
1.4.2.7. 
PRO 140_CD01 Study 
PRO 140_CD01 study (open-label, 43 subjects, multi-center) evaluated the efficacy, safety, and 
tolerability of PRO 140 monotherapy (350 mg subcutaneous injection weekly for up to 12 weeks) 
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.  


 
 
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Forty-three (43) subjects (M/F: 37/3) with median age of 54.5 years (26-72) and median CD4 T-
cell count of 604.5 cells/mm3 (365-1240) were enrolled in the CD01 study. Overall, twenty-two 
out of 40 (55%) enrolled subjects completed 12 weeks of PRO140 monotherapy without 
experiencing virologic failure. Virologic failure was defined as two consecutive HIV-1 RNA 
levels of ≥ 400 copies/mL separated by at least 3 days. Of the 43 enrolled subjects, 3 subjects 
were found to have Dual/Mixed (D/M) tropism [1 at baseline and 2 at the time of virologic 
failure] and 37 subjects were found to have exclusive CCR5-tropic virus. A letter of amendment 
was filed to increase the planned number of subjects from 40 to 43 subjects to compensate for the 
3 Dual/Mixed subjects enrolled in the study. 
All virologic failure subjects who had available lab data in both studies achieved viral suppression 
to < 400 HIV-1 RNA copies/mL, as well as viral suppression to ‘Non Detectable’ or < 50 HIV-1 
RNA copies/mL after re-initiation of ART.  
The by-subject analysis of PhenoSense® Entry Assay data for PRO140, maraviroc, and 
AMD3100 shows no significant changes in the post-treatment IC50 and IC90 values were noted 
when compared with baseline values in virologic failure and non-virologic failure groups of 
subjects. As the aggregate analysis shows for initial 40 subjects, the subjects who experienced 
virologic failure had higher IC90 value for PR0140 at baseline compared to subjects without 
virologic failure. The mean IC90 for subjects who experienced virologic failure was higher (10.84 
µg/mL) than the IC90 for subjects without virologic failure (6.70 µg/mL) in the CD01 study 
(p=0.0115).  
Anti-PRO140 antibodies were not identified in any post-treatment sample and data derived from 
the CD01 study further supports the favorable PRO140 PK profile data generated from both pre-
clinical as well as prior Phase 1/2 clinical trials. 
Safety data were analyzed for all 43 enrolled subjects. One (1) of 43 subjects experienced an SAE 
that was deemed not related to the study drug by the Principal Investigator. Twenty-eight (28) of 
43 subjects (67%) experienced one or more adverse events (AEs) after receiving at least one dose 
of PRO140. The most commonly occurring AEs were infections and infestation conditions which 
were reported by 14 of 43 (32.5%) subjects. The majority of the reported AEs (62/87; 71.2%) 
were deemed either unlikely or not related to study treatment by the Investigator. Similarly, the 
majority of the reported AEs (70/87; 80.4%) were deemed mild in nature.  
1.4.2.8. 
PRO 140 CD01 Extension Study 
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-
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completed the first 12 weeks of CD01 study without experiencing virologic failure. As with the 
CD01 study, virologic failure was defined as two consecutive HIV-1 RNA levels of ≥ 400 
copies/mL separated by at least 3 days. Consenting patients may remain on PRO 140 
monotherapy until PRO 140 receives marketing approval or IND is withdrawn by Sponsor.  
A total of 17 subjects participated in the CD01-Extension study of which one subject was 
considered not eligible as subject experienced virologic failure prior to first extension treatment. 
Sixteen (16) eligible subjects (M/F: 14/2) with median age of 54.9 years (26-68) and median CD4 
T-cell count of 593 cells/mm3 (365-1059) were enrolled in an extension study. One patient 
discontinued at week 37 (with viral load of <40 copies/mL) due to relocation. Two subjects were 
withdrawn due to non-treatment related SAEs at week 140 and 149, respectively. One subject was 
withdrawn due to re-starting their ART at week 99. Two subjects withdrew consent at week 81 
and 139, respectively. Five (5) subjects experienced virologic failure (VF) (two consecutive viral 
load of ≥400 copies/mL). The mean time to virologic failure was 329 days (106-691).  
Five (5) subjects are currently receiving weekly 350 mg PRO140 SC monotherapy and have 
completed more than three years of treatment (176 - 198 weeks). Overall, 12 subjects completed 
at least one year of treatment and 9 subjects completed at least two years of treatment in this study 
PRO140 was generally well tolerated, and no drug-related SAEs were observed.  
This clinical study is currently ongoing. 
1.4.2.9. 
PRO 140_CD02 Study 
PRO 140_CD02 study (double blind, placebo controlled, 52 subjects, multi-center) seeks to 
evaluate the efficacy, safety, and tolerability of PRO 140 in combination with either existing ART 
(failing regimen) or Optimized Background Therapy (OBT) in patients infected with HIV-1. The 
study population includes 52 adult patients with a documented history of genotypic or phenotypic 
resistance to ART drugs within two or more drug classes who demonstrate evidence of HIV-1 
replication despite ongoing antiretroviral therapy and have limited treatment options. The options 
may be limited as a result of drug antiviral class cross-resistance, documented treatment 
intolerance, documented objective assessments such as renal or hepatic insufficiency (e.g. high 
creatinine at baseline, limiting treatment options due to potential for toxicity), past adverse 
reactions such as 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. 


 
 
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In Part 2 of double-blind treatment period, subjects will continue treatment with PRO 140 in 
combination with OBT within the 24-week open-label period.  
Fifty-two subjects with a mean age of 52.4 years, 73.1% male, 48.1% non-white and mean 
duration of HIV-1 infection of 20.4 years were randomized 1:1 to the PRO 140 SC or placebo 
arm. Subjects had been previously exposed to an average of 11 ART drugs and had documented 
resistance to >9 ART drugs. Mean baseline VL and CD4 cell count were 21,104 c/mL and 297.8 
c/mm3, respectively. The primary efficacy endpoint- the proportion of patients with ≥0.5 log10 
reduction in HIV-1 VL from baseline at the end of the 1-week double-blind, randomized, 
placebo-controlled treatment period- was met (16/25 vs 6/26 [p-value <0.0032, ITT population]). 
Forty seven (47) of 52 patients have completed the 25-week study. Approximately 81% of 
patients completing 25-weeks of PRO 140 SC treatment demonstrated HIV-1 VL <50 c/mL and 
92% had HIV-1 VL <400 c/mL. Continued access to PRO 140 SC was provided through a 
rollover study and 40 patients entered the extension protocol after completing the CD02 study. 
PRO 140 SC was generally well tolerated. No drug-related SAEs or treatment discontinuations 
were reported in the study. 
This clinical study is completed. 
1.4.2.10. 
PRO 140_CD02 Extension Study 
PRO 140_CD02 Extension study (open label, 40 subjects, multi-center) seeks to evaluate the long 
term efficacy, safety and tolerability of PRO 140 weekly injection in combination with Optimized 
Background Therapy (OBT) in patients infected with HIV-1. The study population includes 40 
treatment-experienced HIV-infected adult patients with CCR5-tropic virus who successfully 
completed PRO 140_CD02 study and continue to demonstrate HIV-1 viral suppression. 
This clinical study is currently ongoing. 
1.4.2.11. 
PRO 140_CD03 HIV Study 
PRO 140_CD03 HIV (open-label, 350 subjects, multi-center) is a three part study enrolling 
virally suppressed HIV-1 patients with CCR5-tropic HIV-1 receiving combination antiretroviral 
(cART) therapy. Patients received weekly doses of PRO 140 on single-agent maintenance therapy 
following one week of overlap of the existing cART regimen that is then discontinued. In part 1, 
156 participants received 350 mg PRO 140 SC in a single-arm design. In part 2, 147 participants 
received 350 or 525 mg PRO 140 SC in a 1:1 ratio as randomized controlled, two-arm study. In 
an ongoing part 3, 51 participants have been randomized to receive 525 or 700 mg PRO 140 SC 
in a 1:1 ratio.  
Despite reaching the enrollment target of 350 subjects for the PRO140_CD03 HIV study, the 
enrollment is ongoing as the goal of enrolling 20 subjects for the CNS sub-study have not 


 
 
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achieved. As a result, sites that are currently participating in the CNS sub-study are permitted to 
continue enrollment in the CD03 HIV study. 
Of the 354 patients enrolled, median age was 51 yrs (21-77) with the majority reported as male 
(79%) and 37% were non-white. A total of 27 subjects have been randomized to 700 mg dose. In 
addition, another 18 subjects have been exposed to 700 mg dose after rescuing from the lower 
doses (350 mg or 525mg). On average, participants were diagnosed with HIV-1 infection for 16.8 
yrs and were on cART regimen for 14.8 yrs. The frequency and severity of injection site reactions 
were comparable between the three dose groups (350, 525 and 700mg) and the incidence or 
severity of injection site reactions was not increased in patients receiving higher doses. Overall, 
PRO 140 SC was generally well tolerated at all dose levels in this study. 
This clinical study is currently ongoing. 
1.4.2.12. 
PRO 140_CD03 HIV Extension Study 
PRO 140_CD03 study (open-label, 350 subjects, multi-center) seeks to evaluate the long term 
efficacy, safety and tolerability of PRO 140 SC as long-acting single-agent maintenance therapy 
in virologically suppressed subjects with CCR5-tropic HIV-1 infection. The study population 
includes up to 300 treatment-experienced HIV-infected adult patients who successfully completed 
PRO 140_CD03 HIV study and continue to demonstrate HIV-1 viral suppression. 
This clinical study is currently ongoing. 
1.4.2.13. 
PRO 140_CD06 Study 
PRO 140_CD06 study (double-blind, 80 subjects, single-center) seeks to evaluate the evaluate 
comparability of PRO 140 formulation Batch Lot # 3-FIN-3143 versus formulation Batch Lot# 3-
FIN-2618 as a one-time subcutaneous (SC) injection in healthy subjects under non-fasting 
conditions.  
1.4.2.14. 
PRO 140_CD07 Study 
CD07_TNBC study (open-label, two-part [Phase Ib: Up to 18 subjects; Phase II: 30 Subjects], 
multi-center) seeks to evaluate the efficacy, safety, tolerability and maximum tolerate dose 
(MTD) of leronlimab (PRO 140) when combined with carboplatin in patients with CCR5+ 
metastatic triple-negative breast cancer (mTNBC). 
The study population includes patients with CCR5-positive, locally advanced or metastatic triple-
negative breast cancer (mTNBC) who are naïve to chemotherapy in metastatic setting but have 
been exposed to anthracyclines and taxane in neoadjuvant and adjuvant settings (first-line). 
This clinical study is currently ongoing. 
1.4.2.15. 
 CD08_mCRC Study 


 
 
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CD08_mCRC study (open-label, 30 subjects, multi-center) seeks to evaluate the effect on overall 
response rate (ORR) of Leronlimab (PRO 140) when combined with Regorafenib in patients with 
CCR5+, Microsatellite Stable (MSS), Metastatic Colorectal Cancer (mCRC).  
The study population includes patients with CCR5+, Microsatellite Stable (MSS), metastatic 
Colorectal Cancer (mCRC) who have been previously treated with fluoropyrimidine-, oxaliplatin- 
and irinotecan-based chemotherapy, an antiVEGF therapy, and, if RAS wild type, an anti-EGFR 
therapy.  
1.4.2.16. 
CD07_Compassionate Use 
CD07_Compassionate Use study (open-label, two-part, multi-center) seeks to evaluate the 
efficacy, safety, and tolerability of leronlimab (PRO 140) when combined Treatment of 
Physician’s Choice in the treatment of patients with CCR5+ Metastatic Triple Negative Breast 
Cancer (mTNBC). The study population includes patients with CCR5-positive, locally advanced 
or metastatic triple-negative breast cancer (mTNBC). 
This clinical study is currently ongoing. 
Table 1-1: 
List of Completed Clinical Studies with Leronlimab (PRO 140) 
Protocol 
Number 
Phase 
No. of 
Subjects 
(Planned/ 
Analyzed) 
Doses 
Subject 
Population 
Comments 
PRO 140 
1101 
1 
20/20 
Single 0.1, 0.5, 
2.0, or 5.0 mg/kg 
Healthy 
Generally well tolerated; non-immunogenic; 
dose-dependent coating of CCR5; significant 
coating of CCR5 over placebo at 0.5, 2, and 5 
mg/kg 
PRO 140 
1102 
1 
20/20 
Either two or 
three doses 
totaling 200 or 
350 mg 
respectively 
Healthy 
Generally well tolerated; drug derived from 
CHO cells well tolerated also; SC 
administration by Autoject® 2 better tolerated 
than manual injection 
PRO 140 
1103 
1 
15/14 
Two doses, each 
of 350 mg 
Healthy 
More AEs associated with arm injection; trend 
of lower exposure in arm injections; thigh and 
abdominal administration preferred 
PRO 140 
1302 
1b 
40/39 
Single 0.5, 2.0, 
or 5.0 mg/kg 
HIV-1 
positive 
Generally well tolerated; antiviral suppression 
maintained for approx. 10 days with higher 
doses; favorable tolerability and potent, dose-
dependent antiviral activity provide proof-of-
concept 


 
 
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Protocol 
Number 
Phase 
No. of 
Subjects 
(Planned/ 
Analyzed) 
Doses 
Subject 
Population 
Comments 
PRO 140 
2301 
2a 
30/31 
Single 5.0 or 
10.0 mg/kg 
HIV-1 
positive 
Generally well tolerated with no dose-limiting 
toxicities; potent antiviral suppression 
maintained for approx. 20 days when 
administered IV at 5 or 10 mg/kg. No dose-
limiting toxicities at 10 mg/kg. 
PRO 140 
2101 
2a 
40/44 
Three doses of 
162 or 324 mg 
each 
HIV-1 
positive 
Generally well tolerated, no drug-related 
SAEs or dose-limiting toxicity; antiviral 
activity was statistically significant; two-fold 
exposure at higher dose; single dose 
demonstrated favorable tolerability, and 
potent, long-acting, dose-dependent antiviral 
activity. 
PRO 140 
CD01 
2b 
43/43 
350 mg SC 
weekly dose for 
12 weeks of 
monotherapy 
(total treatment 
duration 14 
weeks) 
HIV-1 
positive 
Generally well tolerated, no drug-related 
SAEs or dose-limiting toxicity; Open-label 
administration of PRO 140 demonstrated 
favorable tolerability, and potent, long-acting, 
antiviral activity. 
PRO 140 
CD02 
2b/3 
50/52 
350 mg SC 
weekly dose of 
PRO 140 or 
placebo along 
with existing 
ART for 1 week 
then PRO 140 
along with 
optimized 
background 
therapy for 24 
weeks (total 
treatment 
duration 25 
weeks) 
HIV-1 
positive, 
treatment-
experienced 
This study is completed pending database 
lock. 
PRO 140 
CD06 
PK 
80/79 
Single dose PK 
study with 350 
mg SC dose 
Healthy 
This clinical study is completed. 
 
 


 
 
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Table 1-2: 
List of Ongoing Clinical Studies with Leronlimab (PRO 140) 
Protocol 
Number 
Phase 
No. of 
Subjects 
(Planned/ To 
be analyzed) 
Doses 
Subject 
Population 
Comments 
PRO 140 
CD_01-
Extension 
2b 
17/16 
350 mg SC weekly dose (as 
monotherapy)  
HIV-1 
positive, 
treatment 
experienced 
This clinical study is 
currently ongoing. 
PRO 140 
CD02 
Extension 
2b/3 
50/40 
350 mg SC weekly dose in 
combination with Optimized 
Background Therapy (OBT) 
HIV-1 
positive, 
treatment 
experienced 
This clinical study is 
currently ongoing. 
PRO 140 
CD03 
2 
350/TBD 
350 or 525 or 700 mg SC weekly 
dose for 46 weeks of 
monotherapy (total treatment 
duration 48 weeks) 
HIV-1 
positive, 
treatment-
experienced 
This clinical study is 
currently ongoing. 
PRO 140 
CD03 
Extension 
2 
350/TBD 
350 or 525 or 700 mg SC weekly 
dose (as monotherapy) 
HIV-1 
positive, 
treatment 
experienced 
This clinical study is 
currently ongoing. 
PRO 140 
CD07 
1a/2b 
Phase Ib: Up 
to 18 subjects   
Phase II: 30 
Subjects 
350 or 525 or 700 mg SC weekly 
dose (as monotherapy) 
Triple negative 
breast cancer 
This clinical study is 
currently ongoing. 
CD08_mC
RC 
2 
30/TBD 
700 mg SC weekly dose in 
combination with Regorafenib 
CCR5+, 
Microsatellite 
Stable (MSS), 
Metastatic 
Colorectal 
Cancer 
(mCRC). 
 This clinical study is 
pending start-up. 
CD07_Co
mpassiona
te Use 
Comp
. Use 
30/TBD 
350  mg SC weekly dose (as 
monotherapy) 
Triple negative 
breast cancer 
This clinical study is 
currently ongoing. 
 
 


 
 
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1.5. 
TREATMENT RATIONALE FOR THIS STUDY 
1.5.1. Study Rationale 
Chemokines regulate inflammation, leukocyte trafficking, and immune cell differentiation. The 
role of chemokines in tissue-specific homing of lymphocyte subsets and in trafficking of 
inflammatory cells has been well studied. Chemokines and chemokine receptors play a critical 
role in the recruitment, activation, and coordination of leukocytes in pathophysiology of lung 
inflammation. The acute respiratory distress syndrome (ARDS) results from the accumulation of 
neutrophils within the pulmonary circulation and alveolar spaces via well-studied adhesion 
molecule-dependent and independent pathways [Doerschuk, 2000]. A published study 
demonstrated a crucial role for C-C chemokine receptor 5 (CCR5) in the accelerated recruitment 
of memory CD8(+) T cells to the lung airways during virus challenge [Kohlmeier, 2008]. This is 
consistent with our preliminary data showing very low CD8% and increased CD4/CD8 ratio both 
of which are improved at Day 3 after first dose of leronlimab (PRO 140) 700 mg in patients with 
severe COVID-19 infection treated under individual patient, emergency use INDs. 
Table 1-3: 
Immunologic Status - Post Leronlimab Therapy in COVID-19 Patients 
Test 
Patient: WS 
  
Patient: IW 
56 yr/Male 
  
74 yr/Female 
Day 0 
Day 3 
  
Day 0 
Day 3 
(18-Mar-20) 
(21-Mar-20) 
  
(18-Mar-20) 
(21-Mar-20) 
CD4% 
52.1% 
30.3% 
28% 
30.2% 
CD8% 
16.5% 
19.1% 
  
7% 
13.1% 
CD4/CD8 
3.15 
1.6 
  
4 
2.3 
CCR5 RO – T cells 
0 
69% 
  
0 
54% 
CCR5 RO – Macrophage 
0 
83% 
0 
63% 
CCR5 RO – Treg 
0 
61% 
  
0 
94% 
RO=receptor occupancy 
 
Test 
Patient: WSa 
  
Patient: KM 
54 yr/Male 
  
74 yr/Male 
Day 0 
Day 3 
  
Day 0 
Day 3 
(20-Mar-20) 
(23-Mar-20) 
  
(21-Mar-20) 
(24-Mar-20) 
CD4% 
32.1% 
38.9% 
23.58% 
18.96% 
CD8% 
5% 
9.6% 
  
5.45% 
7.15% 
CD4/CD8 
6.42 
4 
  
4.33% 
2.65% 
CCR5 RO – T cells 
0 
81% 
  
0 
52% 
CCR5 RO – Macrophage 
0 
72% 
0 
55% 
CCR5 RO – Treg 
0 
89% 
  
0 
87% 
RO=receptor occupancy 


 
 
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Additionally, serum levels of pro-inflammatory cytokines such as interleukin (IL)-6 and tumor 
necrosis factor (TNF)-α showed substantial reduction at Day 3 after first dose of leronlimab (PRO 
140) 700 mg in patients with severe COVID-19 infection treated under the individual patient, 
emergency use INDs. 
Table 1-4: 
Cytokine Levels - Post Leronlimab Therapy in COVID-19 Patients 
Test 
  
Patient: WS 
  
Patient: IW 
  
56 yr/Male 
  
74 yr/Female 
  
Day 0 
Day 3 
  
Day 0 
Day 3 
Bead ID 
(18-Mar-20) 
(21-Mar-20) 
  
(18-Mar-20) 
(21-Mar-20) 
IL-5 
A4 
<3 
<3 
<3.4 
<3.4 
IL-13 
A5 
<7 
<7 
  
<7.6 
<7.6 
IL-2 
A6 
<0.8 
<0.8 
<0.9 
<0.9 
IL-6 
A7 
161 
78 
  
1000.1 
344.2 
IL-10 
A10 
13.3 
2.6 
<1.9 
7.7 
IL-9 
A8 
6 
5.6 
  
<2.2 
<2.2 
IFN-γ 
B2 
<5.8 
<5.8 
<5.8 
6.9 
TNF-α 
B3 
19.5 
8.5 
  
8.48 
<8.2 
IL-17A 
B4 
0.8 
<0.5 
<0.5 
<0.5 
IL-17F 
B5 
10.5 
4.19 
  
<2.1 
<2.1 
IL-4 
B6 
<4.8 
<4.8 
<4.8 
<4.8 
IL-21 
B7 
51.3 
25.5 
  
<19.8 
<19.8 
IL-22 
B9 
49.4 
13.9 
<0.8 
10.9 
All values in pg/mL; All samples performed in duplicate 
Test 
  
Patient: WSa 
  
Patient: KM 
  
54 yr/Male 
  
74 yr/Male 
  
Day 0 
Day 3 
  
Day 0 
Day 3 
Bead ID 
(20-Mar-20) 
(23-Mar-20) 
  
(21-Mar-20) 
(24-Mar-20) 
IL-5 
A4 
9.9 
<3.4 
<3.4 
6.1 
IL-13 
A5 
17.8 
9.7 
  
<7.6 
<7.6 
IL-2 
A6 
15.1 
1.9 
<0.9 
<0.9 
IL-6 
A7 
351.7 
242.2 
  
124.2 
84.4 
IL-10 
A10 
35.8 
14.8 
<1.9 
3.7 
IL-9 
A8 
15.7 
14.8 
  
<2.2 
8.1 
IFN-γ 
B2 
10.6 
<5.8 
<5.8 
<5.8 
TNF-α 
B3 
22.6 
<8.2 
  
<8.2 
<8.2 
IL-17A 
B4 
3.5 
<0.5 
<0.5 
<0.5 
IL-17F 
B5 
8.1 
30.6 
  
<2.1 
<2.1 
IL-4 
B6 
7.3 
<4.8 
<4.8 
<4.8 
IL-21 
B7 
<19.8 
66.3 
  
<19.8 
<19.8 
IL-22 
B9 
17.9 
<0.8 
<0.8 
4.2 
All values in pg/mL; All samples performed in duplicate 


 
 
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The migration of macrophages and release of pro-inflammatory cytokines (cytokine storm) led to 
acute respiratory distress syndrome (ARDS) in lungs. Mice with genetic deficiency of CC-
chemokine receptor (CCR) type 5, displayed reduced lung damage [Russkanmp-2020]. Moreover, 
treatment with a CCR5 antagonist, maraviroc, was protective against experimental acute lung 
injury/acute respiratory distress syndrome in the animal model [Russkanmp-2020].  
The changes in the cytokine milieu influence CCR5 expression and may explain emergence of 
tropism-specific strains facilitating coronavirus transmission and disease progression similar to 
HIV transmission [Patterson 1999]. Chen et al. study on BALB/c mice showed that depletion of 
CD4+ T cells resulted in an enhanced immune-mediated interstitial pneumonitis and delayed 
clearance of SARS-CoV from the lungs, which was associated with reduced neutralizing antibody 
and cytokine production and reduced pulmonary recruitment of lymphocytes [Chen-2010]. 
Leronlimab (PRO 140) is a humanized IgG4,  monoclonal antibody (mAb) specific for the type 
5 C-C chemokine receptor (CCR5). Leronlimab (PRO 140) inhibits migration of Tregs into areas 
of inflammation which can inhibit the innate immune response against pathogens and most 
importantly, the migration of macrophages [Glass 2001] and release of pro-inflammatory 
cytokines in lungs. CCR5 engagement of macrophages changes them into effector cells rather 
than mediators of inflammation. In addition, the role of CCR5 antagonists in helping the innate 
immune response which is critical for infections the body has not been introduced to before (e.g. 
COVID-19), is discussed in Halama et al (2016). 
The ARDS has known to be one of the main reasons for mortalities in patients with COVID-19. 
CytoDyn believes that leronlimab, CCR5 antagonist, is a potential therapeutics in inhibiting pro-
inflammatory cytokines (cytokine storm) responses as observed in ARDS and thus could be 
useful in treatment of COVID-2019. 
1.5.2. Rationale for Dose Selection and Treatment Duration 
Leronlimab (PRO 140) is currently under development for the indication of HIV, Graft versus 
host disease (GVHD), metastatic triple negative breast cancer (mTNBC), and metastatic 
colorectal cancer (mCRC).  
The safety profile of leronlimab (PRO 140) has been extensively evaluated in clinical trials. PRO 
140 has been administered intravenously or subcutaneously to more than 750 healthy and HIV-1 
infected individuals thus far, in Phase I/II/III studies. The drug has been well tolerated following 
intravenous administration of single doses of 0.5 to 10 mg/kg or up to 700 mg weekly doses as 
subcutaneous (SC) injection. Overall, 324 subjects have been exposed to PRO 140 350 mg SC 
weekly dose with the longest duration of exposure lasting 4 years. Similarly, more than 250 and 
150 subjects have been exposed to PRO 140 525 mg and 700 mg SC weekly dose, respectively. 
Available safety data from 131 subjects that received 700 mg dose in the ongoing PRO 
140_CD03 study shows that less than 10% of subjects reported AEs considered definitely related 


 
 
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to study treatment. All of these AEs were injection site reactions and considered to be mild or 
moderate in severity.  
By severity, three subjects (2.3%, 3/131) reported AEs that were considered severe and two 
subjects (1.5%, 2/131) reported events that were deemed to be life-threatening. No events were 
considered related to the study treatment.  
Serious adverse events (SAEs) were reported for six subjects (4.6%, 6/131). None of SAEs were 
considered related to the study treatment.  
Additionally, there have been four patients with severe COVID-19 infection treated with 700 mg 
leronlimab (PRO 140) under individual patient, emergency use INDs. The current data from these 
patients are provided in the Investigational Brochure (IB).  
Leronlimab (PRO 140) 700mg will be administered once weekly for two weeks only in this study 
as most patients with mild to moderate COVID-19 disease fully recovery within 2 weeks of 
developing initial symptoms. 
While leronlimab showed weak activity relative to the positive control (2D7, an anti-CCR5 
antibody) in Study 300-TD-018, the IC50 values were: 59.1 µg/mL for RANTES, 21.2 µg/mL for 
MIP-1α and 39.6 µg/mL for MIP-1β. The modeled Cmax* for the proposed 700 mg weekly dose 
is 267.2 µg/mL which is 4.5-12.6-fold higher than the IC50 values for these cytokines. In 
addition, at leronlimab concentrations greater than 75 µg/ml for RANTES and greater than 100 
µg/ml for MIP-1α and MIP-1β, inhibition of 80% or more was seen for these cytokines 
(Appendix, Figure 2 of Study 300-TD-018). Therefore, leronlimab is anticipated to inhibit these 
cytokines following the 700 mg once weekly dose regimen. 
Figure 1-1: 
Dose-response curve for inhibition of CC-chemokine-induced calcium 
mobilization by PRO 140 
 
 
*The human Cmax was modeled for a dose of 700 mg once weekly in a 70 kg human subject. An interspecies 
population pharmacokinetic model was fit to available monkey and adult human data (concentration-time). 


 
 
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Simulations were carried out to identify leronlimab serum concentration-time profiles (approximate to adults 
receiving 700 mg SC once weekly). 
Leronlimab’s role in the binding and signaling of chemokines MIP-1α(CCL3), MIP-1β(CCL4), 
and RANTES (CCL5) will be further evaluated in the Phase 2 study. In addition, Cytokine and 
Chemokine Panel will include assessment of sCD40L, EGF, Eotaxin (CCL11), FGF-2, Flt-3 
ligand, Fractalkine, G-CSF, GM-CSF, GRO alpha (CXCL1), IFN-alpha2, IFN-gamma, IL-1 
alpha, IL-1 beta, IL-1RA, IL-2, IL-2R, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8 (CXCL8), IL-9, IL-10, 
IL-12 (p40/p70) IL-13, IL-15, IL-17A, IL-17E/IL-25, IL-17F, IL-18, IL-22, IL-27, IP-10 
(CXCL10), MCP-1 (CCL2), MCP-3, M-CSF, MDC (CCL22), MIG (CXCL9), MIP-1 alpha  
(CCL3), MIP-1 beta (CCL4), PDGF-AA, PDGF-AB/BB, RANTES (CCL5), TGF-alpha, TNF-
alpha, TNF-beta, and VEGF-A. 
1.6. 
RISKS / BENEFITS ASSESSMENT 
Allergic Reaction 
Leronlimab (PRO 140) belongs to the monoclonal antibody class of drugs. Monoclonal 
antibodies are sometimes associated with allergic reactions or flu-like reactions (such as fever, 
chills, and aches) or injection-site reactions. These events are usually of short duration if they 
occur at all. Severe allergic reactions, however, can be life-threatening. Although anaphylaxis 
has not been observed in prior trials of leronlimab (PRO 140), the protein infusion always 
carries theoretical risk for anaphylactic shock. Accordingly, whenever leronlimab (PRO 140) is 
administered to subjects, procedures should be available and in place to manage the occurrence 
of anaphylactic shock. 
Immune Response 
People who take leronlimab (PRO 140) or other monoclonal antibodies can also develop an 
immune response to leronlimab (PRO 140) that may affect their ability to receive monoclonal 
antibodies, or to benefit from diagnosis or therapy with a monoclonal antibody in the future. 
Pregnancy 
Risks to unborn babies exposed to leronlimab (PRO 140) are unknown at this time; thus 
pregnant females will be excluded from this study. Females of childbearing potential must have 
a negative pregnancy test prior to enrollment. Both male and female patients and their partners 
of childbearing potential must agree to use appropriate birth control methods throughout the 
study duration (excluding women who are not of childbearing potential and men who have been 
sterilized).  
Venipuncture 


 
 
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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, DSMB and the 
investigators will be alerted to risks of West Nile infections. Furthermore, this has not been 
established to be a risk with maraviroc, the other FDA-approved anti-CCR5 drug already. 
Collectively, the experience with both IV and SC, simulation modeling and the recent 
confirmation that a higher concentration of leronlimab (PRO 140) synthesized using a highly 
efficient CHO cell line can be conveniently and safely administered has resulted in the design of 
the current study. 
 
 
 
 
 
 
 
 
 


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


 
 
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3. 
STUDY DESIGN  
This study is a Phase 2, two arm, randomized, double blind, placebo controlled study to evaluate 
the safety and efficacy of leronlimab (PRO 140) in patients with mild-to-moderate symptoms of 
respiratory illness caused by Coronavirus disease 2019 (COVID-19). Patients will be randomized 
2:1 to receive leronlimab (PRO 140) or placebo. Subjects will receive weekly 700 mg leronlimab 
(PRO 140) or placebo via subcutaneous injection for two weeks. The study will enroll 30 
subjects. The study flow diagram is presented in Figure 3-1. 
Figure 3-1: 
Study Schematic 
Screening Visit 
Visit 1 (V1)
SCREENING 
PERIOD
TREATMENT PERIOD
V2-V5 Visits
FOLLOW-UP PERIOD
V6 to V7 Visits
No
Yes
Does 
Subject Meet 
Inclusion/Exclusion 
Criteria?
Screen 
Failure
Informed 
Consent
Up to 4 Weeks
Up to 2 Weeks
4 Weeks
Visit 2 (V2)
Day 0
Wi hin 7 Days of Screening Visit
Visit 3 (V3)
Day 3
3 (±1) days after V2
Visit 4 (V4)
Day 7
7 (±1) days after V2
Visit 5 (V5) / EOT
Day 14
7 (±1) days after V4
End of Study
Visit 6 (V6)
(14 ± 3 Days after EOT Visit)
Visit 7 (V7)
(28 days ±3 Days after EOT Visit)
First Leronlimab dose
Second Leronlimab dose
 


 
 
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3.1. 
STUDY CENTER 
Up to 10 study centers in the United States (US). Centers must have the capability of 
implementing appropriate infection-control measures to prevent infection of study staff and others 
who share the clinical site space. 
3.2. 
STUDY POPULATION 
The target population for this study is adult subjects with mild-to-moderate symptoms of 
respiratory illness caused by coronavirus disease 2019 (COVID-19). 
3.3. 
ELIGIBILITY CRITERIA 
3.3.1. Inclusion Criteria 
Potential subjects are required to meet all of the following criteria for enrollment into the study: 
1. Male or female adults ≥ 18 years of age at time of enrollment; 
2. Subjects with mild-to-moderate symptoms of respiratory illness caused by coronavirus 
2019 infection; 
Mild (uncomplicated) Illness: 
- Diagnosed with COVID-19 by a standardized RT-PCR assay AND 
- Mild symptoms, such as fever, rhinorrhea, mild cough, sore throat, malaise, 
headache, muscle pain, or malaise, but with no shortness of breath AND 
- No signs of a more serious lower airway disease AND 
- RR<20, HR <90, oxygen saturation (pulse oximetry) > 93% on room air 
Moderate Illness: 
- Diagnosed with COVID-19 by a standardized RT-PCR assay AND 
- In addition to symptoms above, more significant lower respiratory symptoms, 
including shortness of breath (at rest or with exertion) OR 
- Signs of moderate pneumonia, including RR ≥ 20 but <30, HR ≥ 90 but less than 
125, oxygen saturation (pulse oximetry) > 93% on room air AND 
- If available, lung infiltrates based on X-ray or CT scan < 50% present 
3. Clinically normal resting 12-lead ECG at Screening Visit or, if abnormal, considered not 
clinically significant by the Principal Investigator; 
4. Subject (or legally authorized representative) provides written informed consent prior to 
initiation of any study procedures;  


 
 
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5. Understands and agrees to comply with planned study procedures; and 
6. Women of childbearing potential must agree to use at least  medically accepted method of 
contraception (e.g., barrier contraceptives [condom, or diaphragm with a spermicidal gel], 
hormonal contraceptives [implants, injectables, combination oral contraceptives, 
transdermal patches, or contraceptive rings], or intrauterine devices) for the duration of the 
study. 
3.3.2. Exclusion Criteria 
Potential subjects meeting any of the following criteria will be excluded from enrollment: 
1. Subjects showing signs of acute respiratory distress syndrome (ARDS) or respiratory 
failure necessitating mechanical ventilation at the time of screening; 
2. History of severe chronic respiratory disease and requirement for long-term oxygen 
therapy; 
3. Subjects showing signs of clinical jaundice at the time of screening; 
4. History of moderate and severe liver disease (Child-Pugh score >12); 
5. Subjects requiring Renal Replacement Therapy (RRT) at the time of screening; 
6. History of severe chronic kidney disease or requiring dialysis; 
7. Any uncontrolled active systemic infection requiring admission to an intensive care unit 
(ICU)  
Note: Subjects infected with chronic hepatitis B virus or hepatitis C virus will be eligible 
for the study if they have no signs of hepatic decompensation.  
Note: Subjects infected with HIV-1 will be eligible for the study with undetectable viral 
load and are on a stable ART regimen. Investigators are required to review the subjects’ 
medical records to confirm HIV-1 RNA suppression within the previous 3 months.  
Note: Empirical antibiotic treatment for secondary bacterial infections is allowed during 
the course of study. 
8. Patients with malignant tumor, or other serious systemic diseases; 
9. Patients who are participating in other clinical trials; 
10. Patients who have a history of allergic reactions attributed to compounds of similar 
chemical or biologic composition to leronlimab (PRO 140) are not eligible; and 
11. Inability to provide informed consent or to comply with test requirements. 


 
 
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4. 
STUDY SCHEDULE 
The study will have three phases: Screening Period, Treatment Period, and Follow-Up Period. 
The study Schedule of Assessments in presented in Table 4-2. 
Screening Period (up to 1 week):  
Screening assessments will commence at Visit 1 (V1) after obtaining signed informed consent, 
and will include review of medical and medication history, eligibility evaluation, physical 
examination, vital signs, Clinical Symptom Score assessment, pulse oxygen saturation, National 
Early Warning Score 2 (NEWS2) assessment, electrocardiogram (ECG), nasopharyngeal swab 
sample collection, chest radiograph or CT (if clinically indicated), ordinal scale assessment, and 
laboratory sample collection for routine serum biochemical, hematologic, coagulation, urinalysis, 
and serum/urine pregnancy (if applicable). These assessments must be conducted within 7 days of 
the First Treatment Visit (V2).  
All subjects who fail to meet eligibility criteria are considered screen failures, and are exited from 
the study without further evaluation. 
Treatment Period (2 weeks ± allowed windows):  
The schedule of visits during Treatment Period is as follows:  
- Visit 2 (V2) [first treatment]: Within 1 week of the Screening Visit 
- Visit 3 (V3): 3 (±1) day after V2 
- Visit 4 (V4) [second treatment]: 7 (±1) days after V2 
- Visit 5 (V5) / End of Treatment (EOT) Visit: 7 (±1) days after V4.  
Subjects who meet the eligibility criteria will have completed the following evaluations and 
assessments at V2 prior to treatment: review of any changes in medical and medication history, 
physical examination, vital signs, Clinical Symptom Score assessment, pulse oxygen saturation, 
National Early Warning Score 2 (NEWS2) assessment, nasopharyngeal swab sample collection, 
health status assessment on an ordinal scale, baseline assessment for the requirement of: 
mechanical ventilation, oxygen, and hospital stay, and blood sample collection for CD3+, CD4+ 
and CD8+ T cell count, CCR5 receptor occupancy for Treg and macrophages, serum cytokine and 
chemokine levels, and CCR5 gene polymorphisms. If Visit 2 (V2) takes place on the same day as 
the Screening Visit (V1), scheduled assessments performed under screening (V1) do not need to 
be repeated at V2. 
Table 4-1: 
Treatment Groups 
Study 
Drug 
Dosage 
Form 
IP 
concentration 
Dosing Frequency and Amount 
Route of 
Administration 
PRO 140 
(700 mg) 
Parenteral 
solution 
175 mg/mL 
2 injections of PRO 140 (2 X 2 mL/inj.) 
per week on opposite sides of abdomen 
SC injection 


 
 
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Placebo 
Parenteral 
solution 
0 mg/mL 
2 injections of placebo (2 X 2 mL/inj.) 
per week on opposite sides of abdomen 
SC injection 
At V2, subjects will be randomized to receive leronlimab (PRO 140) or placebo which will be 
administered subcutaneously weekly at Visit 2 (Day 0) and Visit 4 (Day 7) by a qualified medical 
professional at clinic or at subject’s home.  
The following assessments will be performed at V3, V4, and V5/EOT: physical examination, vital 
signs, Clinical Symptom Score assessment, pulse oxygen saturation, NEWS2 assessment, 
nasopharyngeal swab sample collection, health status assessment on an ordinal scale, assessment 
for the requirement of: mechanical ventilation, oxygen, and hospital stay, and laboratory sample 
collection for routine serum biochemical, hematologic, coagulation, urinalysis, CD3+, CD4+ and 
CD8+ T cell count, CCR5 receptor occupancy for Treg and macrophage, serum cytokine and 
chemokine levels, and CCR5 gene polymorphisms. 
Additionally, a chest radiograph or CT (if clinically indicated), mortality assessment, and ECG 
will be performed at V7/EOT visit. Adverse events and medications will be monitored throughout 
the study. 
Follow Up Period (2 and 4 weeks after EOT± allowed windows) 
Follow-up visits will be performed at 2 weeks (V6) and 4 weeks (V7) after the End of Treatment 
(EOT) visit. The following assessments will be performed at V6 and V7 visit: review of adverse 
events and concomitant medications, physical examination, vital signs, mortality status, and blood 
collection for routine serum biochemical, hematologic, coagulation and urine laboratory 
assessments (V7 only). 
Note: During visits conducted at the study clinic, subjects and site personnel will use appropriate 
protective gear (e.g., masks, gloves) to prevent the spread of the infection. If possible, scheduled 
study visits can be conducted by a visiting nurse (or trained site staff) at the subject’s home to 
mitigate the risk of spreading COVID-19.  
During visits conducted at the subject’s home, the visiting nurse (or trained site staff) will 
administer study drug (if applicable), monitor subjects for safety, perform blood draw, and all 
other assessments related to study outcomes measures. All procedures (except chest radiograph or 
CT scan) listed under the schedule of assessments can be performed by visiting nurse at visits 
taking place in the subject’s home.  


 
 
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Table 4-2: 
Schedule of Assessments 
Procedure/Assessments 
Screening 
Visit 
Treatment Phase 
Follow-Up 
Visit 
V1 
V2 [16] 
V3 
V4 
V5 (EOT) 
V6 
V7 
(Pre-Rx) 
(Post-Rx) 
Day 
 
Day 0 
Day 3 
Day 7 
Day 14 
Day 28 
Day 42 
Window Period 
 
Within 7 days of the Screening 
Visit 
3(±1) days after 
V2 
7(±1) days after 
V2 
7(±1) days after 
V4 
14(±3) days 
after EOT Visit 
28(±3) days 
after EOT Visit 
Informed Consent [1] 
X 
 
 
 
 
 
 
 
Eligibility Evaluation [2] 
X 
 
 
 
 
 
 
 
Subject Demographics  
X 
 
 
 
 
 
 
 
Medical History [3] 
X 
 
 
 
 
 
 
 
Physical Examination 
X 
X 
 
X[4] 
X[4] 
X 
X[4] 
X [4] 
Vital Signs [5] 
X 
X 
X 
X 
X 
X 
X 
X 
Clinical Symptom Score Assessment [6] 
X 
X 
 
X 
X 
X 
 
 
Pulse oxygen saturation (SpO2) 
X 
X 
 
X 
X 
X 
 
 
National Early Warning Score 2 (NEWS2) Assessment[7] 
X 
X 
 
X 
X 
X 
 
 
ECG 
X 
 
 
 
 
X 
 
 
Laboratory tests:  
 
 
 
 
 
 
 
 
Complete Blood Count [8] 
X 
 
 
X 
X 
X 
 
X 
Biochemistry [9] 
X 
 
 
X 
X 
X 
 
X 
Coagulation Indices [10] 
X 
 
 
X 
X 
X 
 
X 
Serum/Urine Pregnancy Test [11] 
X 
 
 
 
 
X 
 
 
Urinalysis [12] 
X 
 
 
X 
X 
X 
 
X 
CD3+, CD4+ and CD8+ T cell count 
 
X 
 
X 
X 
X 
 
 
CCR5 receptor occupancy for Treg and macrophage  
 
X 
 
X 
X 
X 
 
 


 
 
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Procedure/Assessments 
Screening 
Visit 
Treatment Phase 
Follow-Up 
Visit 
V1 
V2 [16] 
V3 
V4 
V5 (EOT) 
V6 
V7 
(Pre-Rx) 
(Post-Rx) 
Day 
 
Day 0 
Day 3 
Day 7 
Day 14 
Day 28 
Day 42 
Window Period 
 
Within 7 days of the Screening 
Visit 
3(±1) days after 
V2 
7(±1) days after 
V2 
7(±1) days after 
V4 
14(±3) days 
after EOT Visit 
28(±3) days 
after EOT Visit 
Serum cytokine and chemokine levels 
 
X 
 
X 
X 
X 
 
 
CCR5 Gene Polymorphisms [13] 
 
X 
 
X 
X 
X 
 
 
Nasopharyngeal Swab Sample Collection [14] 
X 
X 
 
X 
X 
X 
X 
X 
Chest radiograph or CT (if clinically indicated) [15] 
X 
 
 
 
 
X 
 
 
Ordinal Scale Assessment 
X 
X 
 
X 
X 
X 
 
 
Randomization [17] 
 
X 
 
 
 
 
 
 
PRO 140 (700 mg) or Placebo Administration 
 
 
X 
 
X 
 
 
 
Assessment for the requirement of: Mechanical Ventilation, 
Oxygen, and Hospital Stay 
X 
X 
 
X 
X 
X 
 
 
Mortality Status 
 
 
 
 
 
X 
X 
X 
Concomitant Medications 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse Events 
 
 
X 
X 
X 
X 
X 
X 
[1] Informed consent must be obtained prior to patient participation in any protocol-related activities that are not part of routine care. 
[2] Initial evaluation of patient eligibility will be performed by Investigator. 
[3] Medical history and current therapies (medications and non-medications). 
[4] Symptom-directed physical examination 
[5] Post treatment vital signs will be recorded at V2, V4, V5 (EOT) and will include blood pressure, heart rate, respiration rate, and temperature. 
[6] Clinical Improvement will be assessed based on symptom score for fever, myalgia, dyspnea and cough. Each symptom is graded from 0 to 3. [0=none, 1=mild, 
2=moderate, and 3=severe].The total score per patient ranges from 0 to 12 points. Clinical Improvement will be assessed daily while subject is hospitalized and will 
continue to be assessed on the scheduled treatment visits and at EOT after the subject is discharged from the hospital. 
[7] National Early Warning Score 2 (NEWS2) Assessment is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, 
systolic blood pressure, heart rate, level of consciousness) 
[8] Hemoglobin, Hematocrit (HCT), Red Blood Cells (RBC), White Blood Cells (WBC) with total and differential count, Absolute Neutrophil Count (ANC) and platelets. 
[9] Biochemistry  


 
 
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Hepatic function indicators: total bilirubin, alkaline phosphatase, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total protein, albumin Lactate 
dehydrogenase (LDH) 
Renal function indicators: creatinine clearance, eGFR 
Electrolytes: sodium, potassium, chloride, calcium and bicarbonate 
Other: glucose (random), cholesterol (total), Creatine kinase, C-reactive protein 
[10] Prothrombin time (PT) and International Normalized Ratio (INR) 
[11] ONLY performed on women of childbearing potential. 
[12] Urine samples will be tested for color, appearance, specific gravity, pH, protein, glucose, occult blood, ketones, leukocyte esterase, nitrite, bilirubin, urobilinogen, and 
microscopic examination of urine sediment. 
[13] Blood samples collected for receptor occupancy testing will also be used for CCR5 gene polymorphism for PRO 140 susceptibility.  
[14] Swabs will be used for quantitative virologic testing. Samples are to be stored at -70°C. 
[15] Chest radiograph or CT will be performed if clinically indicated by the treating physician. 
[16] If Visit 2 (V2) takes place on the same day as the Screening Visit (V1), scheduled assessments performed under screening (V1) do not need to be repeated at V2. 
[17] Randomization via WebView CTMS system 


 
 
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4.1. 
SCREENING PHASE 
The subject (or Legally Acceptable Representative (LAR)) will sign and date the informed 
consent form (ICF) and Health Insurance Portability Accountability Act (HIPAA) authorization 
(according to site policy and practices) prior to any study-related procedures. All study centers 
will be instructed to maintain the study-specific screening and enrollment logs at their sites. If a 
subject initially fails to meet inclusion/exclusion criteria and is later reconsidered for 
participation, the subject will be re-consented and assigned a new unique identification number at 
the time of re-screening. Subjects who fail their first screening attempt may be re-screened a 
maximum of once and may be enrolled if they are found to meet all inclusion and no exclusion 
criteria when re-screened. 
4.1.1. Screening Visit (V1) 
After the ICF has been signed, screening procedures and information will be obtained to confirm 
subject eligibility, including: 
 Demographic information (see Section 7.3); 
 A detailed medical history (see Section 7.4); 
 Physical examination (see Section 7.5); 
 Vital signs (see Section 7.6), 
 Clinical symptom score assessment (see Section 7.10); 
 Pulse oxygen saturation (SpO2) (see Section 7.11); 
 National Early Warning Score 2 (NEWS2) assessment (see Section 7.12); 
 12-lead electrocardiogram (see Section 7.13); 
 Collection of blood specimens (see Section 7.8) for 
o Complete blood count; 
o Biochemistry; 
o Coagulation indices; 
o Serum/urine pregnancy test, for female subjects of childbearing potential; and 
o Urine sample for urinalysis parameters. 
 Nasopharyngeal Swab Sample Collection (See Section 7.14) 
 Chest radiograph or computer tomography (CT) scan (if clinically indicated) (See Section 
7.15); 


 
 
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 Ordinal scale assessment (see Section 7.16); 
 Assessment for the requirement of mechanical ventilation, oxygen, and hospital stay (see 
Section 7.17); and 
 Prior medications assessment (see Section 7.7). 
All screening information will be fully documented in the subject’s medical records (i.e., source 
documents).  
 For consented subjects who do not meet eligibility criteria, a Screen Failure Case Report 
Form (CRF) will be completed. The Screen Failure CRF will contain the following 
details: the subject identification number, the date of ICF signature, demographic 
information (see Section 7.3), and the reason for screen failure. No additional information 
will be required for subjects who fail screening.  
 For consented subjects who meet eligibility criteria, all required screening information 
will be transcribed onto the appropriate page of the CRF. 
4.2. 
TREATMENT PHASE 
Subjects who meet all eligibility criteria, as per data gathered from Screening Period are to be 
treated. All subjects who fail to meet eligibility criteria will be considered screen failure and will 
exit the study without further evaluation 
4.2.1. Visit 2 (V2) 
The following assessments will be performed at the first treatment visit prior to the first treatment 
administration. If Visit 2 (V2) takes place on the same day as the Screening Visit (V1), scheduled 
assessments performed under screening (V1) do not need to be repeated at V2. 
 Physical examination (see Section 7.5); 
 Vital Signs (see Section 7.6), 
 Clinical symptom score assessment (see Section 7.10); 
 Pulse oxygen saturation (SpO2) (see Section 7.11); 
 National Early Warning Score 2 (NEWS2) Assessment (see Section 7.12); 
 Collection of blood specimens (see Section 7.8) for 
o CD3+, CD4+ and CD8+ T cell count; 
o CCR5 receptor occupancy for Treg and macrophage;  
o Serum cytokine and chemokine levels; and 


 
 
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o CCR5 Gene Polymorphisms. 
 Nasopharyngeal Swab Sample Collection (See Section 7.14) 
 Ordinal scale assessment (see Section 7.16); 
 Assessment for the requirement of mechanical ventilation, oxygen, and hospital stay (see 
Section 7.17); and 
 Prior medications assessment (see Section 7.7). 
Subjects will be randomized 2:1 via WebView CTMS system to Leronlimab (PRO 140) or 
Placebo (see Section 7.18). 
 Leronlimab (PRO 140) 700 mg or 
 Placebo 
Leronlimab (PRO 140) or placebo will be administered subcutaneously to all subjects at a weekly 
dose of 700 mg. After receiving the first leronlimab (PRO 140) dose, the following assessments 
will be performed: 
 Vital signs (see Section 7.6), 
 Concomitant medications assessment (see Section 7.7),  
 Review of adverse events (see Section 9) 
4.2.2. Visits 3 and 4, (V3 and V4) 
The following assessments will be performed during the remaining visits during the treatment 
period: 
 Physical examination (see Section 7.5); 
 Vital Signs (see Section 7.6), 
 Clinical symptom score assessment (see Section 7.10); 
 Pulse oxygen saturation (SpO2) (see Section 7.11); 
 National Early Warning Score 2 (NEWS2) Assessment (see Section 7.12); 
 Collection of blood specimens (see Section 7.8) for 
o Complete blood count; 
o Biochemistry; 
o Coagulation indices; 
o Urine sample for urinalysis parameters; 


 
 
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o CD3+, CD4+ and CD8+ T cell count; 
o CCR5 receptor occupancy for Treg and macrophage;  
o Serum cytokine and chemokine levels; and 
o CCR5 Gene Polymorphisms 
 Nasopharyngeal Swab Sample Collection (See Section 7.14) 
 Ordinal scale assessment (see Section 7.16); 
 Leronlimab (PRO 140) or Placebo Administration – V4 only (see Section 6.1.3); 
 Assessment for the requirement of mechanical ventilation, oxygen, and hospital stay (see 
Section 7.17); 
 Prior medications assessment (see Section 7.7); and 
 Review of adverse events (see Section 9). 
4.2.3. End of Treatment – EOT (V5) 
The last visit during the treatment phase will be considered at the End of Treatment (EOT) visit. 
The assessments performed at this visit will include: 
 Physical examination (see Section 7.5); 
 Vital Signs (see Section 7.6), 
 Clinical symptom score assessment (see Section 7.10); 
 Pulse oxygen saturation (SpO2) (see Section 7.11); 
 National Early Warning Score 2 (NEWS2) Assessment (see Section 7.12); 
 12-lead electrocardiogram (see Section 7.13); 
 Collection of blood specimens (see Section 7.8) for 
o Complete blood count; 
o Biochemistry; 
o Coagulation indices; 
o Serum/urine pregnancy test, for female subjects of childbearing potential; 
o Urine sample for urinalysis parameters; 
o CD3+, CD4+ and CD8+ T cell count; 
o CCR5 receptor occupancy for Treg and macrophage;  


 
 
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o Serum cytokine and chemokine levels; and 
o CCR5 Gene Polymorphisms. 
 Nasopharyngeal Swab Sample Collection (See Section 7.14) 
 Chest radiograph or computer tomography (CT) scan (if clinically indicated); 
 Ordinal scale assessment (see Section 7.16); 
 Assessment for the requirement of mechanical ventilation, oxygen, and hospital stay (see 
Section 7.17); 
 Review of mortality status; 
 Prior medications assessment (see Section 7.7); and 
 Review of adverse events (see Section 9). 
4.3. 
FOLLOW-UP PHASE 
The first visit of the follow-up phase is scheduled 14(±3) days after EOT Visit. Two follow-up 
visits are included in the follow-up phase.  
4.3.1. Visits 6 and 7 (V6 and V7) 
The assessments performed at these visits will include: 
 Physical examination (see Section 7.5); 
 Vital Signs (see Section 7.6), 
 Collection of blood specimens  at Visit 9 only (see Section 7.8) for 
o Complete blood count; 
o Biochemistry; 
o Coagulation indices; and 
o Urine sample for urinalysis parameters. 
 Nasopharyngeal Swab Sample Collection (See Section 7.14) 
 Review of mortality status; 
 Prior medications assessment (see Section 7.7); and 
 Review of adverse events (see Section 9). 
4.4. 
UNSCHEDULED VISITS 


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


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


 
 
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 Treating physician determines that continuation on the study would not be in the subject’s 
best interest 
 Subject becomes pregnant 
 Subject becomes lost to follow-up (LTF) 
 Subject will be withdrawn from the study if 2 consecutive injections of study drug are 
missed 
 Subject manifesting Grade 4 or Grade 3 toxicity attributable to the Leronlimab (PRO 140) 
If a subject fails to return for the scheduled study visit or is discontinued from the study, an 
attempt will be made to determine the reason(s). If the subject is unreachable by telephone, a 
registered letter will be sent to the subject requesting that he/she contact the clinic.  
All patients with an ongoing SAE or AE attributable (definitely, probably, or possibly related) to 
the study treatment at the Post-Study (Follow-up) Visit (scheduled or premature) must be 
followed until the event is resolved (with or without sequelae) or deemed stable. 
5.4. 
DATA COLLECTED FROM WITHDRAWN SUBJECTS 
Every attempt should be made to collect follow-up information. The reason for withdrawal from 
the study will be recorded in the source documents and on the appropriate page of the CRF. 
Before a subject is identified as lost-to-follow up, the site should make all reasonable efforts to 
contact the subject. These attempts must be documented and should include at a minimum one 
phone call and one certified letter.  
In the event that a subject is withdrawn from the study at any time due to an adverse event or 
SAE, the procedures stated in Section 9 (Safety) must be followed. 
5.5. 
SCREEN FAILURES 
A subject who signed a consent form, but did not meet the inclusion/exclusion criteria is 
classified as a screen failure. Subject number, demographics and reason for screen failure will be 
recorded. 
In the event that a subject initially fails to meet inclusion/exclusion criteria and is later 
reconsidered for participation, the subject will be re-consented and assigned a new screening 
number at the time of re-screening. Subjects who fail their first screening attempt may be re-
screened again (i.e., up to two screenings) and may be enrolled if they are found to meet all 
inclusion and no exclusion criteria at the subsequent screening visit. 




 
 
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Note: Patients with low body fat percentages may find subcutaneous injections uncomfortable. In 
such cases, leronlimab (PRO 140) 700 mg can be injected as four 175mg/ml injections and/or 
subcutaneous injections can be placed at different areas other than abdomen as per discretion of 
the Investigator. 
6.1.1. Leronlimab (PRO 140) - Packaging and Labeling 
Study drug will be prepared by Ajinomoto Althea, Inc. and will be packaged, labeled, and shipped 
by Sherpa Clinical Packaging, LLC. 
The contents of each vial are described in Section 6.1. Leronlimab (PRO 140) kits will be labeled 
with information such as: study protocol #; fill volume; concentration; storage condition; a “use 
as per study protocol” statement; a cautionary statement; sponsor’s name and address; and the kit 
number. 
Below are representative samples of the Investigational Product, finished drug product (FDP) 
individual vial (Figure 6-1), syringe label (Figure 6-2), and kit labels (Figure 6-3) designated for 
use in this clinical protocol. Each kit contains two labeled vials and two syringe labels.  
Figure 6-1: 
Investigational Product - Vial Label 
Protocol: CD10_COVID-19               Kit No. xxx 
Subject No. _________        
Single use 3 mL vial contains 1.4 mL of PRO 140 (175 
mg/mL) or placebo solution for subcutaneous injection 
Store at 2oC to 8oC (36oF to 46oF) 
USE AS PER STUDY PROTOCOL 
Caution: New Drug – Limited by Federal (or United States) 
Law to Investigational Use 
CytoDyn Inc., Vancouver, WA, USA 
Protocol: CD10_COVID-19                    Kit No. xxx 
Subject No. _________        
Single use 3 mL vial contains 1.4 mL of PRO 140 (175 
mg/mL) or placebo solution for subcutaneous injection 
Store at 2oC to 8oC (36oF to 46oF) 
USE AS PER STUDY PROTOCOL 
Caution: New Drug – Limited by Federal (or United States) 
Law to Investigational Use 
CytoDyn Inc., Vancouver, WA, USA 
 
Figure 6-2: 
Investigational Product - Syringe Label 
Protocol: CD10_COVID-19                  Contents of Kit No. xxx 
This syringe contains 2 mL PRO 140 (175 mg/mL) or placebo solution for 
subcutaneous injection 
USE AS PER STUDY PROTOCOL 
Caution: New Drug – Limited by Federal (or United States) Law to 
Investigational Use 


 
 
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CytoDyn Inc., Vancouver, WA, USA 
 
Figure 6-3: 
Investigational Product - Kit Label 
Protocol: CD10_COVID-19                            Kit No. xxx 
Site No. ____________              Subject No. ________________   
This kit contains 4 single-use vials 
Each 3 mL vial contains 1.4 mL of PRO 140 (175 mg/mL) or placebo solution for 
subcutaneous injection 
Store at 2oC to 8oC (36oF to 46oF) 
USE AS PER STUDY PROTOCOL 
Caution: New Drug – Limited by Federal (or United States) Law to Investigational 
Use 
CytoDyn Inc., Vancouver, WA, USA 
The pharmacy manual provides the criteria regarding vial acceptance or rejection, as well as 
instructions for the preparation of the IP syringes to be used to administer drug.  
6.1.2. Leronlimab (PRO 140) - Storage and Handling 
Study drug will be shipped at 2°C to 8°C (refrigerated [36°F to 46°F]) to the investigator’s site. 
Upon receipt at the site, the responsible site staff or pharmacist should verify the integrity of the 
vials. Study drug should be stored at 2°C to 8°C (refrigerated [36°F to 46°F]). The contents of the 
vial should appear as a clear to opalescent, colorless to yellow solution; fine translucent particles 
may be present. This is normal.  
The investigator must maintain an accurate record of the shipment, storage, and dispensing of the 
study drug in a drug accountability log. An accurate record including the date and amount of 
study drug dispensed to each subject must be available for inspection at any time. A study CRA 
assigned to monitor the investigational site will review these documents once study drug has been 
received by the investigational site. Study drug will be accounted for on an ongoing basis during 
the study. 
6.1.3. Leronlimab (PRO 140) - Administration 
Guidelines for dose preparation can be found in the pharmacy manual. 


 
 
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Leronlimab (PRO 140) or placebo will be provided to the administering personnel in single-use 
syringes prepared from vials of study drug stored at 2-8°C at the site pharmacy prior to use. Each 
of two syringes is filled to deliver 2 mL of study drug.  
Equivalent volumes of PRO 140 will be administered subcutaneously on opposite sides of the 
abdomen.  
A 20-guage needle should be used to remove PRO 140 from vial and a 25-guage needle is used 
for administration to subjects. 
IP should be administered slowly over 15 seconds per mL. Leronlimab (PRO 140) should not be 
kept in syringe for longer than 60 minutes. 
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. 
Leronlimab (PRO 140) will be administered as SC injection by a qualified medical professional at 
the study clinic or at the subject’s home.  
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. 
6.1.4. Leronlimab (PRO 140) - 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. 
6.1.5. Leronlimab (PRO 140) - Toxicity Management 
Refer to Table 6-3 and Table 6-4 below. Recovery to acceptable levels must occur to allow 
leronlimab (PRO 140) continuation. 
Table 6-3: 
Leronlimab (PRO 140) - Management for Injection Site Reactions 
CTCAE Grade 
Treatment Modifications 
Grade 1 
No dose adjustment is required. 
Grade 2 
First Occurrence: No dose adjustment is required. 
Second Occurrence of the same event: Closely follow-up for 
resolution of the AE to Grade ≤ 1 
Grade 3 
Withhold treatment until symptoms resolve to:  
• Grade 1 or less  
Grade 4 
Study treatment will be permanently discontinued  


 
 
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Table 6-4: 
Leronlimab (PRO 140) - Management for all Other Potential Toxicities 
(Attributable to Leronlimab) 
CTCAE Grade 
(attributable to leronlimab) 
Treatment Modifications 
Grade 1 
No dose adjustment is required. 
Grade 2 
Withhold treatment until symptoms resolve to:  
• Grade 1 or less or baseline; 
Grade 3 
Study treatment will be permanently discontinued 
Grade 4 
Study treatment will be permanently discontinued  
6.1.6. Leronlimab (PRO 140) - Disposition 
All drug supplies are to be used only for this protocol and not for any other purpose. The 
investigator must not destroy any drug labels or any partially used or unused drug supply until 
instructed by the Sponsor. At the conclusion of the study and as appropriate during the course of 
the study, the investigator will return all used and unused drug containers and drug labels to the 
drug distributor as directed by the Sponsor. A copy of the completed drug disposition form will be 
sent to CytoDyn, Inc. or to its designee. 
6.1.7. Leronlimab (PRO 140) - Accountability 
Study drug must be used in accordance with this protocol and only under the direction of the 
responsible investigator. The investigational site must maintain complete and accurate records 
showing receipt and disposition of all study drug, including master records listing the date of 
receipt, the number and nature of medication units received, and a dispensing record which 
includes each quantity dispensed, identification of the staff member/subject to whom dispensed, 
the date of dispensing, the intended study participant, and the identification of the preparer. All 
used and unused study kits will be retained by the investigational site until drug accountability 
can be confirmed by study CRA during the monitoring visits. Instructions will be provided by 
Sponsor regarding final disposition of all study drugs in compliance with applicable regulations. 


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


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


 
 
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Note: For COVID-19 diagnosis, the number of days between the onset of symptoms and the 
initiation of treatment for each subject will be documented.  
7.5. 
PHYSICAL EXAMINATION 
The physical examination will include routine examinations for the following: 
 Constitutional/General Appearance 
 Head, Ears, Eyes, Nose, Throat (HEENT) 
 Neurologic  
 Cardiovascular 
 Musculoskeletal and Extremities 
 Dermatologic 
 Respiratory  
 Gastrointestinal 
 Genitourinary  
 Lymphatic 
 Psychiatric  
Each abnormality will be recorded and the Investigator will record an assessment of its clinical 
significance.  
7.6. 
VITAL SIGNS, HEIGHT AND WEIGHT 
The following will be collected:  
o Systolic Blood Pressure  
o Diastolic Blood Pressure 
o Heart Rate 
o Temperature 
o Respiratory Rate  
 Height  
 Weight 
 Body Mass Index  


 
 
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7.7. 
CONCOMITANT MEDICATIONS 
All medications and therapies administered or taken by the subject beginning 30 days prior to 
Screening Visit and throughout the study will be recorded in the source documents and on the 
appropriate page of the Case Report Form (CRF). Additionally, all other investigational and off-
label therapies for COVID-19 will be recorded. Subjects must be questioned at each study visit 
concerning any new medications or changes in current medications including over-the-counter 
medication and topical medication. 
For each medication and non-study treatment, the following will be documented: 
 Medication/treatment name (generic name may be used if trade name is unknown) 
 Dose, unit, and frequency of dosing (individual dosages, not total daily dose).  
o Note: Each new dose of medication should be recorded as a separate entry, with 
the exception of medications that are given on a sliding scale. For these, it is 
acceptable to enter the range of the dosage, including the start and stop dates for 
which the specified dosage range was used. 
 Route of dosing  
 Indication for use 
 The start date  
 The stop date (if medication/therapy is not ongoing).  
7.7.1. Excluded Medications 
The following medications are prohibited: 
 The use of immunosuppressive medications are prohibited with the following exceptions: 
o Intranasal, inhaled, topical steroids, or local steroid injections 
o Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of 
prednisone or its equivalent 
Note: Organ transplant patients will be allowed to continue baseline immunosuppressive 
therapy during the course of study.  
 Other CCR5 antagonists 
 Other investigational products 
7.7.2. Allowable Medications and Therapies 
Patients with underlying chronic viral illnesses will be allowed to receive antiviral therapy. 


 
 
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7.8. 
CLINICAL LABORATORY ASSESSMENTS 
Blood samples will be collected for analysis of the following parameters described in Table 7-1. 
 Biochemistry and Complete Blood Count (CBC): At Screening (V1), V3, V4, V5 (EOT),  
and V7.  
 Serum/urine pregnancy test (for female subjects of childbearing potential): At Screening 
(V1) 
All laboratory reports will be reviewed by the Investigator. Abnormal results that are considered 
by the Investigator to be clinically significant will be recorded as adverse events. If in the 
Investigator judgment, in order to make the determination of clinical significance the testing may 
be needed to be repeated. Validated, quality-controlled laboratory data will be transferred to the 
main database for analyses. 
Table 7-1: 
Lab Parameters 
CBC Parameters 
Biochemistry Parameters 
Urinalysis 
Hemoglobin (g/dL) 
Hematocrit (%) 
RBC/Erythrocytes (10^12/L) 
WBC/Leukocytes (10^6/L) 
Absolute Neutrophil Count (10^6/L) 
Platelets (10^9/L) 
Differential WBC: 
- 
Neutrophils (%) 
- 
Lymphocytes (%) 
- 
Monocytes (%) 
- 
Eosinophils (%) 
- 
Basophils (%)  
Liver Function Tests 
Total bilirubin (mg/dL) 
Alkaline Phosphatase (ALP) (U/L) 
Aspartate Aminotransferase (AST) 
(or SGOT) (U/L) 
Alanine Aminotransferase (ALT) 
(or SGPT) (U/L) 
Total Protein (g/dL) 
Albumin (g/dL) 
Lactate Dehydrogenase (U/L) 
Renal Function Tests 
Creatinine clearance,  
eGFR 
Electrolytes 
Sodium (mEq/L) 
Potassium (mEq/L) 
Chloride (mEq/L) 
Calcium (mg/dL) 
Bicarbonate (mEq/L) 
Other: 
Glucose, Random (mg/dL) 
Cholesterol, Total (mg/dL) 
Creatine kinase,  
C-reactive protein 
Coagulation Parameters 
pH  
Specimen Appearance  
Color  
Specific Gravity 
Ketones  
Bilirubin  
Occult Blood  
Glucose 
Protein 
Nitrite 
Urobilinogen (mg/dL) 
Leukocyte Esterase 
Leukocytes(/HPF) 
Miscellaneous 
Cytokine and Chemokine Panel 
Serum pregnancy test 
Urine pregnancy test 
(for female subjects of childbearing 
potential) 
CD3+, CD4+ and CD8+ T cell 
count 
CCR5 receptor occupancy for Treg 
and macrophage 
CCR5 Gene Polymorphisms 
sCD40L, EGF, Eotaxin (CCL11), 
FGF-2, Flt-3 ligand, Fractalkine, G-
CSF, GM-CSF, GRO alpha (CXCL1), 
IFN-alpha2, IFN-gamma, IL-1 alpha, 
IL-1 beta, IL-1RA, IL-2, IL-2R, IL-3, 
IL-4, IL-5, IL-6, IL-7, IL-8 (CXCL8), 
IL-9, IL-10, IL-12 (p40/p70) IL-13, IL-
15, IL-17A, IL-17E/IL-25, IL-17F, IL-
18, IL-22, IL-27, IP-10 (CXCL10), 
MCP-1 (CCL2), MCP-3, M-CSF, 
MDC (CCL22), MIG (CXCL9), MIP-


 
 
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Prothrombin time (PT) 
International Normalized Ratio 
(INR)  
1 alpha  (CCL3), MIP-1 beta (CCL4), 
PDGF-AA, PDGF-AB/BB, RANTES 
(CCL5), TGF-alpha, TNF-alpha, TNF-
beta, VEGF-A. 
7.9. 
STUDY TREATMENT APPLICATION 
Refer to Section 6.1.3 for details. 
7.10. CLINICAL SYMPTOM SCORE ASSESSMENT 
Clinical Improvement will be assessed based on symptom score for fever, myalgia, dyspnea and 
cough. Each symptom is graded from 0 to 3. [0=none, 1=mild, 2=moderate, and 3=severe]. 
The total score per patient ranges from 0 to 12 points. Clinical Improvement will be assessed 
daily while subject is hospitalized and will continue to be assessed on the scheduled treatment 
visits and at EOT after the subject is discharged from the hospital. 
7.11. PULSE OXYGEN SATURATION (SPO2) 
Pulse Oxygen Saturation (SPO2) will be measured at Screening and at V2 (pre-dose), V3, V4, 
and V5 (EOT).   
7.12. NATIONAL EARLY WARNING SCORE 2 ASSESSMENT 
The National Early Warning Score 2 (NEWS2) Assessment is based on 7 clinical parameters 
(respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood 
pressure, heart rate, level of consciousness). See Appendix 16.1. 
7.13. 12-LEAD ELECTROCARDIOGRAM 
A resting supine 12-lead ECG will be conducted at the Screening Visit (V1) and Visit 5 (End of 
Treatment). A 12-lead ECG will be repeated during the study only if clinically indicated and at 
the discretion of the treating physician. The results will be evaluated by the Investigator. The 
following parameters will be recorded: ventricular rate (beats per minute), PR interval (msec), 
QRS interval (msec), QT interval (msec), and QTc interval (msec). Additionally, the Investigator 
will record the overall results of the ECG reading as either normal or abnormal, and as either not 
clinically significant or clinically significant. If abnormalities are observed, each will be recorded.  
7.14. NASOPHARYNGEAL SWAB SAMPLE COLLECTION 
Nasopharyngeal swabs will be used for quantitative virologic testing. The subject will be 
followed and samples will be collected for the entire duration of the study.  


 
 
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Samples are to be stored at -70°C. 
7.15. CHEST RADIOGRAPH OR COMPUTED TOMOGRAPHY SCAN 
If clinically indicated by the treating physician, a chest radiograph or CT scan will be performed 
at Screening Visit (V1) and V5 (EOT) 
7.16. ORDINAL SCALE ASSESSMENT 
Subject clinical status will be assessed using a 7-category ordinal scale. The scale ranges from:  
(1) Death;  
(2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation 
(ECMO);  
(3) Hospitalized, on non-invasive ventilation or high flow oxygen devices;  
(4) Hospitalized, requiring supplemental oxygen;  
(5) Hospitalized, not requiring supplemental oxygen;  
(6) Not hospitalized, limitation on activities;  
(7) Not hospitalized, no limitations on activities. 
7.17. REQUIREMENT OF MECHANICAL VENTILATION, OXYGEN, AND HOSPITAL STAY 
The incidence and duration, in days, of mechanical ventilation, oxygen, and hospital stay will be 
assessed at Screening (V1) and V3, V4, and V5 (EOT). 
7.18. RANDOMIZATION 
Subjects who are eligible to participate in the trial will be randomized to one of the treatment 
groups via IWRS (Interactive Web Based Randomization System) at Visit 2 prior to IP 
administration. The randomization will be central and will use mixed block size of 3 and 6 with a 
2:1 ratio of Active Treatment to Control Treatment to ensure even distribution of Active and 
Control subjects.  
 
 


 
 
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8. 
STATISTICAL ANALYSIS  
This section presents general information about statistical considerations and concepts and a brief 
discussion on analysis methodology, as well as some data conventions. Detailed descriptions of 
the statistical analysis methods and data conventions that will be used in this study will be in a 
separate document; i.e., the Statistical Analysis Plan (SAP). 
8.1. 
TREATMENT GROUPS 
There will be two treatment groups in the study:  
 700 mg Leronlimab (PRO 140) 
 Placebo 
8.2. 
DESCRIPTION OF STUDY OUTCOMES (ENDPOINTS) 
8.2.1. Primary Outcome (Endpoints) Measures 
The primary outcome (endpoint) measure is: 
 
Clinical Improvement as assessed by change in total symptom score (for fever, myalgia, 
dyspnea and cough) 
Note: The total score per patient ranges from 0 to 12 points. Each symptom is graded 
from 0 to 3. [0=none, 1=mild, 2=moderate, and 3=severe].  
8.2.2. Secondary Outcome (Endpoints) Measures 
The secondary outcome (endpoints) measures for the study are: 
1. Time to clinical resolution (TTCR) 
Time to clinical resolution (TTCR), defined as the time from initiation of study treatment 
until resolution of clinical symptoms (fever, myalgia, dyspnea and cough). 
2. Change from baseline in National Early Warning Score 2 (NEWS2) at Days 3, 7, and 14.  
This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any 
supplemental oxygen, temperature, systolic blood pressure, heart rate, level of 
consciousness). 
3. Change from baseline in pulse oxygen saturation (SpO2) at Days 3, 7, and 14 
4. Change from baseline in the patient’s health status on a 7-category ordinal scale at Days 3, 
7, and 14 
A 7-category ordinal scale of patient health status ranges from: 1) Death; 2) Hospitalized, 
on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) 


 
 
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Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, 
requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen; 6) 
Not hospitalized, limitation on activities; 7) Not hospitalized, no limitations on activities. 
5. Incidence and duration (days) of hospitalization 
6. Incidence and duration (days) of mechanical ventilation supply  
7. Incidence and duration (days) of oxygen use 
8. Mortality rate at Day 14 
9. Time to return to normal activity 
8.2.3. Exploratory Outcome (Endpoints) Measures 
1. Change in size of lesion area by chest radiograph or CT 
2. Change from baseline in serum cytokine and chemokine levels at Days 3, 7, and 14 
3. Change from baseline in CCR5 receptor occupancy levels for Tregs and macrophages at 
Days 3, 7, and 14 
4. Change from baseline in CD3+, CD4+ and CD8+ T cell count at Days 3, 7, and 14 
8.2.4. Safety Measures 
Safety will be assessed using: 
 Incidence of treatment-related adverse events (TEAEs) Incidence and severity of 
treatment-emergent adverse events (TEAEs) 
 Incidence of  serious adverse events (SAEs) 
 Incidence of TEAEs and SAEs leading to discontinuation of study medication.  
 Changes in blood chemistry, hematology and coagulation parameter results 
 Changes in vital signs including temperature, pulse, respiratory rate, systolic and diastolic 
blood pressure 
 Changes in physical examination results 
 Changes in electrocardiogram (ECG) results 
8.3. 
SAMPLE SIZE DETERMINATION AND RATIONALE 
A total of 75 subjects will be enrolled in this study. The sample size is based on clinical judgment. 
No statistical power calculation is used to establish the sample size for this proof-of-concept 
study. 


 
 
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8.4. 
RANDOMIZATION 
An individual, independent of the clinical trial team, will develop the randomization schedules. 
The actual randomization assignment will be made through an Interactive Web Based Response 
System (IWRS) called WebView®. Subjects who have provided written informed consent and 
have met all the inclusion criteria and none of the exclusion criteria will be randomized to one of 
the treatment groups. 
8.5. 
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 Amarex Information Technology department will be unblinded to treatment. As noted above, 
the Amarex 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).  
8.6. 
STRATIFICATION 
Randomization will be stratified by baseline total symptom score (i.e., using categories ≤4, >4)), 
and also by age (i.e., using categories <60, ≥60). 
8.7. 
INTERIM ANALYSIS 
No Interim Analysis (IA) will be performed for efficacy  
8.8. 
GENERAL STATISTICAL CONSIDERATIONS 
All collected study data will be presented in subject data listings. Statistical analyses will be 
performed using SAS® for Windows, version 9.4 or later. Descriptive statistics (n, mean, standard 
deviation, median, minimum and maximum) will be presented for continuous variables. 
Frequencies and percentages will be presented for categorical variables. 
8.8.1. Analysis Populations 
8.8.1.1. 
Intent-to-Treat Population 
The Modified Intent-to-Treat (mITT) population is defined as the set of subjects who have 
received at least one dose of leronlimab (PRO 140) or placebo. This population will be used for 
the analysis of efficacy parameters or measurements. 
8.8.1.2. 
PP Population 


 
 
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The Per Protocol (PP) population is defined as the set of subjects who meet the Evaluable 
Population requirements and were not associated with any major protocol violations. This 
population will be identified before the database lock.  
8.8.1.3. 
Safety Population 
The Safety Population will include all subjects who have received one dose of leronlimab (PRO 
140) or placebo. This population will be used for the analysis of safety parameters or 
measurements. 
8.8.2. Covariates 
There is no planned inferential statistics and there will be no covariates for this study. 
Stratification factors will be included in the analysis model. 
8.8.3. Missing Data 
Every effort will be made to obtain required data at each scheduled evaluation from all subjects 
who have been randomized to minimize missing data. However, in the event when there is 
missing data the following imputation methods will be used. 
For efficacy evaluations, multiple imputation methods will be used to handle missing data. This 
imputation method is a robust method to impute missing measurements.  The imputation will be 
carried out in SAS version 9.4 or later using PROC MI. Each imputation model will include the 
stratification factor as a covariate in the model.  The details of multiple imputation will be 
included in the statistical analysis plan.  
8.9. 
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. 
8.9.1. Subject Disposition 
The disposition of all subjects who signed an ICF will be provided. The number of subjects 
screened, screen failed, received at least one treatment, completed, and discontinued during the 
study, as well as the reasons for all discontinuations will be summarized. Disposition and reason 
for study discontinuation will also be provided as a by-subject listing. 
8.9.2. Demographic and Baseline Characteristics 
Demographics and baseline characteristics including medical history, prior and concomitant 
medications/therapies will be summarized using appropriate descriptive statistics. 
8.9.3. Study Outcome Assessment 
Efficacy Summaries  


 
 
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The evaluable population will be the primary analysis population for the analysis of the efficacy 
outcome measures of the study. All the primary and secondary outcome measures will be 
analyzed according to the variable type:  
 Continuous data summaries will include:  
o Number of observations, mean, standard deviation, median, and minimum and 
maximum values.   
o Analysis of Covariance (ANCOVA) adjusted for the stratification factors for 
inferential statistics.  
 Categorical data summaries will include: 
o Frequency counts and percentages.  
o Logit model will be used for inferential statistics using the stratification factors. 
Safety Summaries  
8.9.3.1. 
Adverse Events 
Adverse events will be coded using the most recent version of Medical Dictionary for Regulatory 
Activities (MedDRA). Treatment Emergent AE’s (TEAE) are defined as events with an onset on 
or after the first treatment. TEAEs will be summarized by System Organ Class and preferred term 
by treatment group. The following TEAE summaries will be provided: 
 Overall (i.e., regardless of severity or relationship to treatment); 
 By intensity  (mild, moderate, severe, life threatening or death); 
 By causality (definitely, probably, possibly, remotely or unrelated); 
 By impact on study treatment (dose increased, dose not changed, dose rate reduced, dose 
reduced, drug interrupted, drug withdrawn, not applicable, or unknown). 
In addition, separate summaries of serious adverse events, and adverse events resulting in 
discontinuation of study treatment will be presented. 
8.9.3.2. 
Clinical Laboratory Data 
All laboratory values will be listed. Laboratory measurements will also be summarized by 
treatment group and presented by time point. 
8.9.3.3. 
ECG 
All ECG values will be listed. ECG measurements will also be summarized by treatment group 
and presented by time point. 
8.9.3.4. 
Vital Signs 
All vital sign findings will be listed and/or summarized by treatment group. 


 
 
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8.9.3.5. 
Physical Examination 
All physical examination findings will be listed and/or summarized by treatment group. 


 
 
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9. 
ADVERSE EVENTS (DEFINITIONS AND REPORTING)  
The Investigator is responsible for the detection and documentation of events meeting the criteria 
and definition of an AE or SAE, as provided in this protocol. During the study when there is a 
safety evaluation, the Investigator or site staff will be responsible for detecting, documenting and 
reporting AEs and SAEs as detailed in this Section of the protocol.  
9.1. 
ADVERSE EVENT (AE)  
An adverse event (AE) is defined as any unfavorable or unintended sign, symptom, or disease that 
occurs or is reported by the patient to have occurred, or a worsening of a pre-existing condition. 
An adverse event may or may not be related to the study treatment.  
AEs will be elicited through direct questioning and subject reports. Any abnormality in physical 
examination findings or laboratory results that the investigator believes is clinically significant 
(CS) to the research subject and that occurred after initiation of the first study treatment will be 
reported as AEs. Abnormal findings that are NOT clinically significant should not be recorded as 
an AE. 
9.2. 
REPORTING OF ADVERSE EVENTS 
Report initiation for all AEs and SAEs will begin at the time of the first treatment visit and 
continue until the end of final study visit.  All events will be followed to resolution or until the 
subject completes the study. A final assessment of outcome will be made at that time.  
All AEs must be recorded in the subject’s medical records and on the CRF. AEs will be reported 
using customary medical terminology along with the following information: the onset and end 
dates,  whether the event is considered to be a SAE (see Section 9.3), the impact the event had on 
study treatment (see Section 9.2.1), the Common Terminology Criteria for Adverse Events 
(CTCAE) grade (intensity) of the event (see Section 9.2.2), the causality of the event (see Section 
9.2.3), whether treatment was given as a result of the event (see Section 9.2.4), and the outcome 
of the event (see Section 9.2.5) 
9.2.1. Impact on Study Treatment 
The impact the event had on the study treatment will be assessed as either: dose increased, dose 
not changed, dose rate reduced, dose reduced, drug interrupted, drug withdrawn, not applicable, 
or unknown. The “not applicable” assessment will be used only when the subject is no longer in 
the Treatment Phase of the protocol. 
9.2.2. CTCAE Grade (Intensity) Assessment 
The guidelines outlined in CTCAE v5.0 will be used for assessing the intensity of the event (See 
Appendix 16.2). The general guidelines for assessing the AE grade appear below. Full guidelines 


 
 
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may be obtained at 
https://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/CTCAE_v5_Quick_Re
ference_8.5x11.pdf 
Table 9-1: 
CTCAE v5.0 General Guidelines 
Grade 
Description 
Grade 1 
Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated. 
Grade 2 
Moderate; minimal, local or noninvasive intervention indicated; limiting age-
appropriate instrumental activities of daily living (ADL)*. 
Grade 3 
Severe or medically significant but not immediately life-threatening; hospitalization 
or prolongation of hospitalization indicated; disabling; limiting self care ADL†. 
Grade 4 
Life-threatening consequences; urgent intervention indicated. 
Grade 5 
Death related to AE. 
*Instrumental ADL refer to preparing meals, shopping for groceries or clothes, using the telephone, managing money, etc. 
†Self care ADL refer to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not bedridden. 
 
-Common Terminology Criteria for Adverse Events (CTCAE), v5.0: November 27, 2017 
9.2.3. Causality Assessment 
AEs will be assigned a relationship (causality) to the study treatment. The Investigator will be 
responsible for determining the relationship between an AE and the study treatment. The type of 
event, organ system affected, and timing of onset of the event will be factors in assessing the 
likelihood that an AE is related to the study treatment. Relationship of AEs to study treatment will 
be classified as follows: 
1. Definitely related: This category applies to those AEs that the Investigator feels are 
incontrovertibly related to the study treatment. An AE may be assigned an attribution of 
definitely related if or when it meets all of the following criteria: (1) it follows a reasonable 
temporal sequence from administration of the study treatment; (2) it could not be reasonably 
explained by the known characteristics of the subject’s clinical state, environmental or toxic 
factors, or other modes of therapy administered to the subject; (3) it follows a known response 
pattern to treatment with the study treatment. 
2. Probably related: This category applies to those AEs which, after careful medical 
consideration at the time they are evaluated, are felt with a high degree of certainty to be 
related to the study treatment. An AE may be considered probable if or when (must have 
three): (1) it follows a reasonable temporal sequence from administration of the study 
treatment. (2) It could not readily have been produced by subject’s clinical state, 
environmental or toxic factors, or other therapies administered to the subject. (3) Disappears 
or is decreased upon discontinuation of the study treatment. (4) It follows a known response 
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3. Possibly related: This category applies to those AEs which, after careful medical 
consideration at the time they are evaluated, are judged unlikely but cannot be ruled out with 
certainty to the study treatment. An AE may be considered possible if or when (must have 
two): (1) it follows a reasonable temporal sequence from administration of the study 
treatment. (2) It could not readily have been produced by subject’s clinical state, 
environmental or toxic factors, or other therapies administered to the subject. (3) Disappears 
or is decreased upon discontinuation of the study treatment. (4) It follows a known response 
pattern to treatment with the study treatment.  
4. Remotely related: In general this category can be considered applicable to those AEs which, 
after careful medical consideration at the time they are evaluated, are judged likely to be 
unrelated to the study treatment. An AE may be considered unlikely if or when (must have 
two): (1) it does not follow a reasonable temporal sequence from administration of the study 
treatment. (2) It could not readily have been produced by subject’s clinical state, 
environmental or toxic factors, or other therapies administered to the subject. (3) Disappears 
or is decreased upon discontinuation of the study treatment. (4) It does not follow a known 
response pattern to treatment with the study treatment.  
5. Unrelated: This category applies to those AEs which, after careful consideration at the time 
they are evaluated, are clearly and incontrovertibly due to extraneous causes (disease, 
environment, etc.) and determined with certainty to have no relationship to the study 
treatment.  
9.2.4. Treatment Given as a Result of the Event 
The event impact in terms of treatment provided will be as either: none, medication administered, 
non-drug therapy administered, surgery performed, hospitalization, or other (with a specification). 
9.2.5. Outcome Assessment 
The outcome of the event will be assessed as either: fatal, not recovered/not resolved, 
recovered/resolved, recovered/resolved with sequelae, recovering/resolving, or unknown. Only 
one AE per subject is allowed to have an outcome assessment as “death.” If there are multiple 
causes of death for a given subject, only the primary cause of death will have an outcome of 
death.  
9.3. 
SERIOUS ADVERSE EVENTS 
A SAE is defined as any AE that: 
 Results in death 
 Is life threatening (the subject is at immediate risk of dying from the adverse experience) 
 Requires subject’s hospitalization or prolongs existing hospitalization 
 Results in persistent or significant disability/incapacity 


 
 
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 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 effect when, based upon appropriate 
medical judgment, they may jeopardize the subject or subject and may require medical or 
surgical intervention to prevent one of the outcomes listed in this definition. 
9.4. 
REPORTING OF SERIOUS ADVERSE EVENTS (SAE)  
The Investigator is required to report all SAEs that occur during the time period specified in 
Section 9.2.2. Once the Investigator becomes aware of an SAE, he/she must report the SAE to 
Medical Monitor within 24 hours. 
 
 
 
 
 
 
 
 
 
The Medical Monitor may request additional supporting documentation as it becomes available, 
such as lab reports, ECG reports, discharge summary, hospital notes, etc, if applicable. Additional 
follow-up information as it becomes available must be reported to the Medical Monitor. 
The Investigator is also responsible for reporting all SAEs to the appropriate Institutional Review 
Board (IRB) in accordance with local laws and regulations. The Investigator is responsible for 
maintaining documentation in the study file that indicates the IRB has been properly notified.  
Study participants should be instructed to notify the investigator and discontinue investigational 
product immediately if they become pregnant at any time during the study or if they become 
pregnant within 30 days of last investigational product dose. A participant whose partner has 
become pregnant or suspects she is pregnant during the study must report the information to the 
investigator. The Investigator is required to report any notification of pregnancy to CytoDyn, 
Inc/designated CRO promptly. The participants should receive appropriate monitoring and care 
until the conclusion of the pregnancy. Any complication experienced through the end of the 
pregnancy should be considered as an adverse event (AE), and should be recorded, and if it meets  
the seriousness criteria, it must be reported to CytoDyn, Inc/designated CRO promptly. Pregnancy 
outcomes will be reported in the clinical study report. 
9.5. 
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 


 
 
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stabilizes at a level acceptable to the investigator (i.e., recovery, return to baseline status, no 
further improvement expected, or death). 
For each SAE indicated as an unresolved event on the initial report, regardless of whether the 
subject completed the study or withdrew, the site should submit a follow-up report with updated 
information. 
9.6. 
EXPECTED/ANTICIPATED EVENTS 
Refer to Investigator Brochure for the expected/anticipated events. 
 


 
 
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10. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTATION 
Subjects will be identified on eCRFs by a unique subject identification number and on source 
documents by name and date of birth. No personal identifier will be used in any publication or 
communication used to support this research study. The subject identification number will be 
used if it becomes necessary to identify data specific to a single subject.  
The local IRB, FDA, 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: 


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


 
 
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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 each site will provide the Institutional Review 
Board/Independent Ethics Committee (IRB/IEC) with all appropriate materials as required by 
their IRB/IEC, including but not limited to the clinical study protocol, informed consent form, and 
any advertising materials. The study will not be initiated until the IRB/IEC provides written 
approval of the aforementioned documents and until approval documents have been obtained by 
the Principal Investigator and Sponsor or Sponsor designee. The Investigator will not participate 
in the decision. If the Investigator is an IRB or IEC member, documentation must be provided 
indicating recusal from the approval process. Appropriate reports on the progress of this study by 
the Principal Investigator will be made to the IRB/IEC as required by local and applicable 
government regulations and in agreement with policy established by the Sponsor. The 
Investigator is required to maintain an accurate and complete record of all written correspondence 
to and received from the IRB/IEC, and must agree to share all such documents and reports with 
the Sponsor. 
No changes from the final approved protocol will be initiated without the IRB/IEC’s prior written 
approval or favorable opinion of a written amendment, except when necessary to eliminate 
immediate hazards to the subjects or when the modification does not involve the subject’s 
participation in the trial.  
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 
 Completed quality of life questionnaire 
 Other documents pertaining to the conduct of the study 
These documents must be maintained and kept on file by the Investigator so that the conduct of 
the study can be fully documented and monitored. 
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, Inc. in connection with this study and not previously 
published, is considered confidential information. This information includes, but is not 
limited to, the Investigator’s Brochure, clinical protocol, case report forms and other scientific 
data. Any data collected during the study are also considered confidential. This confidential 
information shall remain the sole property of CytoDyn, Inc., shall not be disclosed to others 
without the written consent of CytoDyn, Inc., and shall not be used except in the performance of 
this study. 
It is understood by the Investigator that the Sponsor will use the information collected in this 
clinical trial in connection with the development of CytoDyn, Inc.. Therefore, this information 
may be disclosed as required to other Investigators or appropriate regulatory authorities. By 
agreeing to participate in this clinical trial, the Investigator understands that he/she has an 
obligation to provide the Sponsor with complete test results and all data developed during this 
trial. 
Publication and Disclosure: The site and Investigator agree to submit any proposed manuscript, 
presentation or other public disclosure regarding the study to Sponsor for review at least thirty 
(30) days prior to submitting such proposed manuscript to a publisher or delivering or making 
such presentation or other public disclosure to any third party. Within thirty (30) days of its 
receipt, Sponsor shall advise the site and/or Investigator, as the case may be, in writing of any 
information contained therein that is confidential information (other than research results included 
in a proposed manuscript) or that may impair Sponsor’s ability to obtain patent protection. 
Sponsor shall have the right to require the site and/or Investigator, as applicable, to remove 
specifically identified confidential information (but may not require removal of research results 
from a proposed manuscript) and/or to delay the proposed submission or delivery of the proposed 
manuscript or presentation, or other public disclosure, for an additional sixty (60) days to enable 
Sponsor to seek patent protection. The site and Investigator shall not publish, publicly disclose, 
present or discuss any results of or information pertaining to the site’s and Investigator’s activities 
prior to completion of the trial, even if the study is terminated before its completion and the final 
clinical study report is signed off, or with respect to any endpoints or analyses other than those 
specified in this protocol. 


 
 
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15. 
REFERENCES 
Center for Disease Control (CDC) (2020, March 3). Coronavirus Disease 2019 (COVID-19) 
Situation Summary Retrieved March 5, 2020, from https://www.cdc.gov/coronavirus/2019-
ncov/summary.html 
Chen, J., Lau, Y. F., Lamirande, E. W., Paddock, C. D., Bartlett, J. H., Zaki, S. R., & Subbarao, 
K. (2010). Cellular immune responses to severe acute respiratory syndrome coronavirus (SARS-
CoV) infection in senescent BALB/c mice: CD4+ T cells are important in control of SARS-CoV 
infection. Journal of virology, 84(3), 1289-1301. 
Doerschuk, C. M., Tasaka, S., & Wang, Q. (2000). CD11/CD18-dependent and-independent 
neutrophil emigration in the lungs: how do neutrophils know which route to take?. American 
journal of respiratory cell and molecular biology, 23(2), 133-136. 
Glass, W. G., Liu, M. T., Kuziel, W. A., & Lane, T. E. (2001). Reduced macrophage infiltration 
and demyelination in mice lacking the chemokine receptor CCR5 following infection with a 
neurotropic coronavirus. Virology, 288(1), 8-17. 
Halama N, Zoernig I, Berthel A, Kahlert C, Klupp F, Suarez-Carmona M, Suetterlin T, Brand K, 
Krauss J, Lasitschka F, Lerchl T. Tumoral immune cell exploitation in colorectal cancer 
metastases can be targeted effectively by anti-CCR5 therapy in cancer patients. Cancer cell. 2016 
Apr 11;29(4):587-601. 
Jacobson, J. M., Lalezari, J. P., Thompson, M. A., Fichtenbaum, C. J., Saag, M. S., Zingman, B. 
S., ... & Maddon, P. J. (2010). Phase 2a study of the CCR5 monoclonal antibody PRO 140 
administered intravenously to HIV-infected adults. Antimicrobial agents and chemotherapy, 
54(10), 4137-4142. 
Jacobson, J. M., Saag, M. S., Thompson, M. A., Fischl, M. A., Liporace, R., Reichman, R. C., ... 
& Murga, J. D. (2008). Antiviral activity of single-dose PRO 140, a CCR5 monoclonal antibody, 
in HIV-infected adults. Journal of Infectious Diseases, 198(9), 1345-1352. 
Kohlmeier, J. E., Miller, S. C., Smith, J., Lu, B., Gerard, C., Cookenham, T., ... & Woodland, D. 
L. (2008). The chemokine receptor CCR5 plays a key role in the early memory CD8+ T cell 
response to respiratory virus infections. Immunity, 29(1), 101-113. 
Patterson, B. K., Czerniewski, M., Andersson, J., Sullivan, Y., Su, F., Jiyamapa, D., ... & Landay, 
A. (1999). Regulation of CCR5 and CXCR4 expression by type 1 and type 2 cytokines: CCR5 
expression is downregulated by IL-10 in CD4-positive lymphocytes. Clinical Immunology, 91(3), 
254-262. 
Russkamp, N. F., Ruemmler, R., Roewe, J., Moore, B. B., Ward, P. A., & Bosmann, M. (2015). 
Experimental design of complement component 5a-induced acute lung injury (C5a-ALI): a role of 


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






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

SAP_001.pdf: 
 
STATISTICAL ANALYSIS PLAN 
FOR PROTOCOL CD10_COVID-19 
 
 
Sponsor: 
 
CytoDyn, Inc. 
1111 Main Street, Suite 660 
Vancouver, Washington 
98660 
(360) 980-8524-Work 
(360) 980-8549-Fax 
www.cytodyn.com 
Protocol Number: 
CD10_COVID-19 
Protocol Title: 
A Randomized, Double Blind, Placebo Controlled Study to 
Evaluate the Efficacy and Safety of Leronlimab for Mild to 
Moderate Coronavirus Disease 2019 (COVID-19) 
Protocol Version / Date: 
Version 5.0 / 30 Mar 2020 
 
 
Plan Version: 
SAP - Final Version 1.0 
Plan Date: 
26 Apr 2020 
 
 
 
 
 
 
 
--- confidential--- 


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Protocol Number: 
CD10_COVID-19 
Protocol Version: 
Version 5.0 
Protocol Name: 
A Randomized, Double Blind, Placebo Controlled Study to 
Evaluate the Efficacy and Safety of Leronlimab for Mild to 
Moderate Coronavirus Disease 2019 (COVID-19) 
Sponsor: 
CytoDyn, Inc. 
1111 Main Street, Suite 660 
Vancouver, Washington 98660 
Prepared by: 
Amarex Clinical Research 
20201 Century Boulevard 
Germantown, Maryland 20874 
SAP Version: 
Final Version 1.0 
SAP Date: 
26 Apr 2020 
 
 
 
 
I have read and approve the Statistical Analysis Plan specified above and agree with its 
content: 
 
 


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TABLE OF CONTENTS 
 
Section 
Page 
LIST OF ABBREVIATIONS ............................................................................................................ 5 
1. 
INTRODUCTION ........................................................................................................................... 7 
2. 
PROTOCOL DESIGN AND OBJECTIVES................................................................................. 7 
2.1 
Study Objectives ................................................................................................................. 7 
2.2 
Design Overview ................................................................................................................. 8 
2.3 
Study Treatments ............................................................................................................... 13 
2.4 
RANDOMIZATION ............................................................................................................... 13 
2.5 
STRATIFICATION ................................................................................................................ 13 
2.6 
BLINDING ........................................................................................................................... 14 
2.7 
Time to UNBLINDING ..................................................................................................................................... 14 
2.7.1 
Emergency Unblinding ....................................................................................... 14 
2.7.2 
Final Analysis ..................................................................................................... 14 
3. 
STUDY OUTCOME MEASURES (ENDPOINTS) .................................................................... 15 
3.1 
Primary Outcome (Endpoints) Measures ........................................................................... 15 
3.2 
Secondary Outcome (Endpoints) Measures ....................................................................... 15 
3.3 
Exploratory Outcome (Endpoints) Measures ..................................................................... 16 
3.4 
Safety Measures ................................................................................................................ 16 
4. 
SAMPLE SIZE DETERMINATION AND RATIONALE ........................................................ 16 
5. 
INTERIM ANALYSIS .................................................................................................................. 16 
6. 
PRIMARY HYPOTHESIS TO BE TESTED .............................................................................. 17 
7. 
ANALYSIS POPULATIONS ....................................................................................................... 17 
7.1 
Intent-to-Treat Population ................................................................................................. 17 
7.2 
PP Population .................................................................................................................... 17 
7.3 
Safety Population .............................................................................................................. 17 
8. 
DATA CONVENTION AND RELATED DEFINITIONS ......................................................... 18 
8.1 
Baseline Definition ............................................................................................................ 18 
8.2 
Duplicate Data ................................................................................................................... 18 
8.3 
Handling of Missing Data ................................................................................................. 18 
8.3.1 
Multiple Imputation for Continuous variables ..................................................... 18 
8.3.2 
Multiple Imputation for Categorical variables ..................................................... 18 
8.4 
Multiple Comparisons and Type I Error Rate Multiplicity adjustments ............................ 19 
8.5 
Subgroups ......................................................................................................................... 19 
8.6 
Standard Calculations ........................................................................................................ 19 
8.6.1 
Age...................................................................................................................... 19 
8.6.2 
Body Mass Index (BMI) ..................................................................................... 19 
8.6.3 
Change from Baseline ......................................................................................... 20 
8.6.4 
Time to Any Event .............................................................................................. 20 
9. 
STATISTICAL METHODS ......................................................................................................... 20 
9.1 
Summarizing and Tabulating the Collected Data .............................................................. 20 
9.1.1 
Subject Disposition and Withdrawals.................................................................. 20 
9.1.2 
Protocol Deviations ............................................................................................. 20 


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9.1.3 
Demographics and Baseline Characteristics ........................................................ 21 
9.1.4 
Prior and Concomitant Medications .................................................................... 21 
9.1.5 
Treatment Exposure ............................................................................................ 21 
9.2 
Analysis of Efficacy Data .................................................................................................. 21 
9.2.1 
Primary Efficacy Outcome (Endpoint) Measure ................................................. 21 
9.2.2 
Secondary Efficacy Outcome (Endpoint) Measure ............................................. 22 
9.2.3 
Exploratory Outcome Measures (Endpoints) ...................................................... 24 
9.3 
Analysis of Safety Data ..................................................................................................... 24 
9.3.1 
Adverse Events .................................................................................................... 24 
9.3.2 
Clinical Laboratory Evaluations .......................................................................... 24 
9.3.3 
Vital Signs .......................................................................................................... 25 
9.3.4 
Electrocardiogram (ECGs) .................................................................................. 25 
9.3.5 
Physical Examination .......................................................................................... 26 
10. 
APPENDIX – PLANNED TLG .................................................................................................... 27 
10.1 
Planned by-subject listings ................................................................................................ 27 
10.2 
Planned Summary Tables .................................................................................................. 28 
11. 
VERSION HISTORY ................................................................................................................... 29 
12. 
REFERENCES .............................................................................................................................. 30 


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LIST OF ABBREVIATIONS 
 
Abbreviation 
Term 
AE 
Adverse Event 
ALT 
Alanine Transaminase 
ARDS 
Acute Respiratory Distress Syndrome 
AST 
Aspartate Aminotransferase 
BUN 
Blood Urea Nitrogen 
CCR5 
C-C chemokine receptor type 5 
CD 
Cluster of Differentiation 
CFR 
Code of Federal Regulations 
COVID-19 
Coronavirus Disease 2019 
CRF 
Case Report Form 
CRO 
Contract Research Organization 
CS 
Clinically Significant 
CTCAE 
Common Terminology Criteria for Adverse Events 
eCRF 
Electronic Case Report Form 
CV 
Curriculum Vitae 
ECG 
Electrocardiogram 
ECMO 
Extracorporeal Membrane Oxygenation 
EOT 
End of Treatment 
FDA 
U.S. Food and Drug Administration 
FDP 
Finished Drug Product 
GCP 
Good Clinical Practice 
GFR 
Glomerular Filtration Rate 
GMP 
Good Manufacturing Practice 
HEENT 
Head, Ears, Eyes, Nose, and Throat 
HIPAA 
Health Insurance Portability Accountability Act 
IA 
Interim Analysis 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization 
IEC 
Independent Ethics Committee 
IND 
Investigational New Drug 
IP 
Investigational Product 
IRB 
Institutional Review Board 
LAR 
Legally Authorized Representative 
LTF 
Lost to Follow-Up 
MedDRA 
Medical Dictionary for Regulatory Activities 
mg 
Milligram 
mITT 
Modified Intent-to-Treat 


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Abbreviation 
Term 
NEWS 
National Early Warning Score 2 
PI 
Principal Investigator 
SAE 
Serious Adverse Event 
SC 
Subcutaneous 
SOP 
Standard Operating Procedure 
SpO2 
Peripheral Capillary Oxygen Saturation 
SV 
Screening Visit 
TEAE 
Treatment Emergent Adverse Event 
Treg 
T regulatory cell 
V 
Visit 


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1. 
INTRODUCTION 
This Statistical Analysis Plan describes the planned analyses and reporting for the clinical trial 
protocol CD10_COVID-19, sponsored by CytoDyn Inc. The reader of this Statistical Analysis Plan 
(SAP) is encouraged to review the complete protocol and amendments as this plan contains only a 
limited overview of protocol information. 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. 
The format and content of this Statistical Analysis Plan are structured to provide sufficient detail to 
meet the requirements specified by the International Conference on Harmonization (ICH) E9: 
Guidance on Statistical Principles in Clinical Trials. All work planned and presented in this 
Statistical Analysis Plan will follow the ethical guidelines published by the American Statistical 
Association (ASA). 
The following documents and references [1-6], were reviewed in preparation of this Statistical 
Analysis Plan: 
• Protocol Version 5.0 / 30 Mar 2020 
 
• US Federal Register, Department of Health and Human Services, FDA, Guidance on Statistical 
Principles for Clinical Trials (1998) 
• ASA Ethical Guidelines for Statistical Practice (2016) 
 
• The Royal Statistical Society: Code of Conduct (2014) 
 
• ICH Guidance on the Structure and Content of Clinical Study Reports (ICH E3(R1), 2013) 
 
• ICH Guidance on the Statistical Principles for Clinical Trials (ICH E9(R1), 2017) 
 
2. 
PROTOCOL DESIGN AND OBJECTIVES 
2.1 Study Objectives 
 
The purpose of this study is to assess the safety and efficacy of leronlimab (PRO 140) administered 
as weekly subcutaneous injection in subjects with COVID-19. 




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The study will have three phases: Screening Period, Treatment Period, and Follow-Up Period. The 
study Schedule of Assessments in presented in Table 2-1. 
Screening Period (up to 1 week): 
Screening assessments will commence at Visit 1 (V1) after obtaining signed informed consent, and 
will include review of medical and medication history, eligibility evaluation, physical examination, 
vital signs, Clinical Symptom Score assessment, pulse oxygen saturation, National Early Warning 
Score 2 (NEWS2) assessment, electrocardiogram (ECG), nasopharyngeal swab sample collection, 
chest radiograph or CT (if clinically indicated), ordinal scale assessment, and laboratory sample 
collection for routine serum biochemical, hematologic, coagulation, urinalysis, and serum/urine 
pregnancy (if applicable). These assessments must be conducted within 7 days of the First 
Treatment Visit (V2). 
All subjects who fail to meet eligibility criteria are considered screen failures, and are exited from 
the study without further evaluation. 
Treatment Period (2 weeks ± allowed windows): 
The schedule of visits during Treatment Period is as follows: 
• Visit 2 (V2) [first treatment]: Within 1 week of the Screening Visit 
• Visit 3 (V3): 3 (±1) day after V2 
• Visit 4 (V4) [second treatment]: 7 (±1) days after V2 
• Visit 5 (V5) / End of Treatment (EOT) Visit: 7 (±1) days after V4. 
Subjects who meet the eligibility criteria will have completed the following evaluations and 
assessments at V2 prior to treatment: review of any changes in medical and medication history, 
physical examination, vital signs, Clinical Symptom Score assessment, pulse oxygen saturation, 
National Early Warning Score 2 (NEWS2) assessment, nasopharyngeal swab sample collection, 
health status assessment on an ordinal scale, baseline assessment for the requirement of: 
Mechanical Ventilation, Oxygen, and Hospital Stay, and blood sample collection for CD3+, CD4+ 
and CD8+ T cell count, CCR5 receptor occupancy for Treg and macrophages, serum cytokine and 
chemokine levels, and CCR5 gene polymorphisms. If Visit 2 (V2) takes place on the same day as 
the Screening Visit (V1), scheduled assessments performed under screening (V1) do not need to be 
repeated at V2. 
At V2, subjects will be randomized to receive leronlimab (PRO 140) or placebo which will be 


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administered subcutaneously weekly at Visit 2 (Day 0) and Visit 4 (Day 7) by a qualified medical 
professional at clinic or subject’s home. 
The following assessments will be performed at V3, V4, and V5/EOT: physical examination, vital 
signs, Clinical Symptom Score assessment, pulse oxygen saturation, National Early Warning Score 
2 (NEWS2) assessment, nasopharyngeal swab sample collection, health status assessment on an 
ordinal scale, assessment for the requirement of: Mechanical Ventilation, Oxygen, and Hospital 
Stay, and laboratory sample collection for routine serum biochemical, hematologic, coagulation, 
urinalysis, CD3+, CD4+ and CD8+ T cell count, CCR5 receptor occupancy for Treg and 
macrophage, serum cytokine and chemokine levels, and CCR5 gene polymorphisms. 
Additionally, chest radiograph or CT (if clinically indicated), mortality assessment and ECG will be 
performed at V5/EOT visit. Adverse events and medications will be monitored throughout the 
study. 
Follow Up Period (2 and 4 weeks after EOT± allowed windows) 
Follow-up visits will be performed at 2 weeks (V6) and 4 weeks (V7) after the End of Treatment 
(EOT) visit. The following assessments will be performed at V6 and V7 visit: review of adverse 
events and concomitant medications, physical examination, vital signs, nasopharyngeal swab 
sample collection, mortality status, and blood collection for routine serum biochemical, 
hematologic, coagulation and urine laboratory assessments (V7 only). 
Note: During visits conducted at the study clinic, subjects and site personnel will use appropriate 
protective gear (e.g., masks, gloves) to prevent the spread of the infection. If possible, scheduled 
visits can be conducted by a visiting nurse (or trained site staff) at the subject’s home to mitigate the 
risk of spreading COVID-19. 
During visits conducted at the subject’s home, the visiting nurse (or trained site staff) will 
administer study drug (if applicable), monitor subjects for safety, perform blood draw, and all other 
assessments related to study outcomes measures. 








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2.6 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). 
The process for emergency unblinding will be outlined in details in the Randomization Plan. In 
addition, any subject that is unblinded for any reason will be identified and discussed in the final 
clinical study report. 
 
2.7 Time to UNBLINDING 
2.7.1 Emergency Unblinding 
Breaking the blind prematurely will be allowed only if the subject’s well-being requires knowledge 
of the subject’s treatment allocation. Every attempt will be made to maintain the blind throughout 
the study. 
In the event of an urgent safety issue where the randomized treatment of a subject is necessary to 
manage and treat the affected study subject (e.g., unblinding subjects because of SAEs that meet 
“expedited criteria” and requires reporting to FDA), the Investigator will contact the Medical 
Monitor. The Medical Monitor, in consultation with sponsor, will make a decision to unblind. If the 
decision has been made to unblind, a prompt written notification will be provided to the 
Investigator. The reason for unblinding must be recorded; however the investigator must not record 
the subject’s treatment assignment in study documentation and must not reveal the subject’s 
treatment assignment to the clinical monitor. 
If reporting of an adverse event is to be performed unblinded as per regulatory authority guidelines, 
study-unrelated personnel will unblind the individual subject’s treatment group and will perform the 
unblinded reporting. No treatment group information would be shared with study personnel. 
2.7.2 Final Analysis 
Treatment unblinding and release of the randomization codes of the investigational product 
assignments for the study will occur immediately following database lock when all randomized 


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subjects have completed the study or discontinued from the study and after all clinical data have 
been received and data inconsistencies have been resolved. 
 
3. 
STUDY OUTCOME MEASURES (ENDPOINTS) 
3.1 Primary Outcome (Endpoints) Measures 
The primary outcome (endpoint) measure is: 
• 
Clinical Improvement as assessed by change in total symptom score (for fever, myalgia, 
dyspnea and cough) 
Note: The total score per patient ranges from 0 to 12 points. Each symptom is graded from 
0 to 3. [0=none, 1=mild, 2=moderate, and 3=severe]. 
3.2 Secondary Outcome (Endpoints) Measures 
The secondary efficacy outcome (endpoints) for the study are: 
1. Time to clinical resolution (TTCR) 
Time to clinical resolution (TTCR), defined as the time from initiation of study treatment 
until resolution of clinical symptoms (fever, myalgia, dyspnea and cough). 
2. Change from baseline in National Early Warning Score 2 (NEWS2) at Days 3, 7, and 14. 
This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any 
supplemental oxygen, temperature, systolic blood pressure, heart rate, level of 
consciousness). 
3. Change from baseline in pulse oxygen saturation (SpO2) at Days 3, 7, and 14 
4. Change from baseline in the patient’s health status on a 7-category ordinal scale at Days 3, 
7, and 14 
A 7-category ordinal scale of patient health status ranges from: 1) Death; 2) Hospitalized, 
on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) 
Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, 
requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen; 6) Not 
hospitalized, limitation on activities; 7) Not hospitalized, no limitations on activities. 


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5. Incidence and duration (days) of hospitalization 
6. Incidence and duration (days) of mechanical ventilation supply 
7. Incidence and duration (days) of oxygen use 
8. Mortality rate at Day 14 
9. Time to return to normal activity 
3.3 Exploratory Outcome (Endpoints) Measures 
1. Change in size of lesion area by chest radiograph or CT 
2. Change from baseline in serum cytokine and chemokine levels at Days 3, 7, and 14 
3. Change from baseline in CCR5 receptor occupancy levels for Tregs and macrophages at 
Days 3, 7, and 14 
4. Change from baseline in CD3+, CD4+ and CD8+ T cell count at Days 3, 7, and 14 
3.4 Safety Measures 
Safety will be assessed using: 
• Incidence of treatment-related adverse events (TEAEs) Incidence and severity of treatment- 
emergent adverse events (TEAEs) 
• Incidence of serious adverse events (SAEs) 
• Incidence of TEAEs and SAEs leading to discontinuation of study medication. 
• Changes in blood chemistry, hematology and coagulation parameter results 
• Changes in vital signs including temperature, pulse, respiratory rate, systolic and diastolic 
blood pressure 
• Changes in physical examination results 
• Changes in electrocardiogram (ECG) results 
 
4. 
SAMPLE SIZE DETERMINATION AND RATIONALE 
 
This is a randomized study with two treatment groups. The subjects will be randomized to the 
treatment groups (leronlimab or placebo) in a 2:1 ratio. 
A total of 75 subjects will be enrolled in this study. The sample size is based on clinical judgment. 
No statistical power calculation is used to establish the sample size for this proof-of-concept study. 
 
5. INTERIM ANALYSIS 
No Interim Analysis (IA) will be performed for efficacy 


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6. 
PRIMARY HYPOTHESIS TO BE TESTED 
This clinical trial is designed to primarily test the hypothesis that leronlimab provides a Clinical 
Improvement as assessed by change in total symptom score (for fever, myalgia, dyspnea and 
cough). Hence, the statistical inference will be done on µleronlimab (i.e., mean change from baseline 
in total symptom score for the subjects in the leronlimab group) vs. µControl (i.e., mean change from 
baseline in total symptom score for the subjects in the Placebo group); that is the following 
hypothesis will be examined: 
H0: µleronlimab = µControl 
H1: µleronlimab ≠ µControl 
 
7. ANALYSIS POPULATIONS 
 
7.1 Intent-to-Treat Population 
The Modified Intent-to-Treat (mITT) population is defined as the set of subjects who have 
received at least one dose of leronlimab (PRO 140) or placebo. This population will be used for the 
analysis of efficacy parameters or measurements. 
 
7.2 PP Population 
The Per Protocol (PP) population is defined as the set of subjects who meet the Evaluable 
Population requirements and were not associated with any major protocol violations. This 
population will be identified before the database lock. 
 
7.3 Safety Population 
The Safety Population will include all subjects who have received one dose of leronlimab (PRO 
140) or placebo. This population will be used for the analysis of safety parameters or 
measurements. 


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8. 
DATA CONVENTION AND RELATED DEFINITIONS 
8.1 Baseline Definition 
 
For all parameters, baseline will be defined as the last available value prior to randomization. 
 
8.2 Duplicate Data 
 
For unplanned duplicate data within a protocol-specified visit, the last measured value will be used 
for the analysis. If it is not possible to identify the “last measured value” the average of the 
duplicate values will be used. 
No data will be excluded. All collected data will be listed. 
 
8.3 Handling of Missing Data 
 
Every effort will be made to obtain required data at each scheduled evaluation from all subjects 
who have been randomized to minimize missing data. However, in the event when there is missing 
data the following imputation methods will be used. 
For efficacy evaluations, multiple imputation methods will be used to handle missing data. This 
imputation method is a robust method to impute missing measurements. The method for imputing 
variables is available in SAS PROC MI for both monotone and arbitrary missing data patterns and 
will be implemented with the PREDICT MEAN MATCHING option. Each imputation model will 
include the stratification factor as a covariate in the model. The multiple imputation is used for 
subjects that have some baseline and post-baseline data, i.e., if a subject is missing all pre and post 
baseline data, no data will be imputed. 
8.3.1 Multiple Imputation for Continuous variables 
If the missing data point is continuous in nature with monotone pattern, predictive mean 
matching (PMM) method will be used in the model. 
If the missing data point is continuous in nature with arbitrary pattern, a fully conditional 
specification (FCS) using the predictive mean matching (PMM) method with joint distribution for 
all variables will be used. 
8.3.2 Multiple Imputation for Categorical variables 
If the data point is categorical in nature with monotone pattern, logistic method will be used in the 
model. 


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Age (years) = integer of[(date of informed consent – date of birth)/ 365.25] 
If the data point is categorical in nature with arbitrary pattern, a fully conditional specification 
(FCS) using logistic regression approach with joint distribution for all variables will be used. 
8.4 Multiple Comparisons and Type I Error Rate Multiplicity adjustments 
 
For the primary endpoint only one hypothesis will be tested, hence there is no adjustment for Type I 
error rate. 
For the secondary endpoints, the hierarchical test procedure, with fixed sequence approach will be 
used to protect the trial-wise error rate. Please see Section 9.2.2 for the order of the secondary 
endpoints. 
8.5 Subgroups 
 
As several factors are considered to be related to treatment, subgroup analyses will be performed to 
evaluate whether the treatment effects are consistent across different subgroups. These factors 
include: 
−  Baseline total symptom score <=4 
−  Baseline total symptom score>4 
−   Age < 60 
−   Age >= 60 
 
In addition, subgroup analyses will be performed to evaluate whether the treatment effects are 
consistent without and with use of any off-label COVID-19 treatments including 
hydroxychloroquine, chloroquine or azithromycin at baseline. 
 
8.6 Standard Calculations 
8.6.1 Age 
Age will be calculated as the number of completed years between the date of informed consent and 
the subject’s birth date. 
 
8.6.2 Body Mass Index (BMI) 
BMI will be calculated using height (in cm) and weight (in kg) according to the formula noted 
below. 
 
BMI (kg/m2) = weight (kg) / [[height (cm)/100]2] 


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Time to Event (days) = 
(Date of Event – Date of randomization) + 1 
8.6.3 Change from Baseline 
For any of the effectiveness measurements change from baseline will be calculated using the 
formula noted below. 
 
8.6.4 Time to Any Event 
The number of days from the randomization date to any event will be calculated as follows. 
 
 
 
9. STATISTICAL METHODS 
All data collected during this study will be presented in subject data listings. All statistical analyses 
will be performed using SAS® for Windows, version 9.4 or later. 
9.1 Summarizing and Tabulating the Collected Data 
 
All data collected will be summarized according to the variable type: 
• Continuous data summaries will include number of observations, mean, standard 
deviation, median, and minimum and maximum values. 
• Categorical data summaries will include frequency counts and percentages. 
 
9.1.1 Subject Disposition and Withdrawals 
The disposition of all subjects who sign an ICF will be provided. The number of subjects screened, 
screen failure, randomized, received at least one treatment, completed, and discontinued during the 
study, as well as the reasons for all post treatment discontinuations will be summarized. Disposition 
and reason for study discontinuation will also be provided as a by-subject listing. 
9.1.2 Protocol Deviations 
Protocol deviations will be identified and classified as minor or major before un-blinding. 
Protocol deviations for all randomized subjects will be listed as by-subject listing and major 
deviations will be summarized descriptively according to the following categories: 
• Did not meet Inclusion/Exclusion criteria but entered into study 
 
• Developed withdrawal criteria during the study but not withdrawn 
Change from baseline = 
Post Baseline Measurement – Baseline Measurement 


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• Received excluded concomitant medication 
 
• Study treatment dosing deviation 
 
9.1.3 Demographics and Baseline Characteristics 
Demographics and baseline characteristics (i.e., Age, Race, Gender etc.) will be summarized using 
appropriate descriptive statistics. 
Medical history of the subjects will also be summarized and also provided as a by-subject listing. 
 
9.1.4 Prior and Concomitant Medications 
Prior and concomitant medications will be summarized for the Safety population. All prior and 
concomitant medications recorded in the eCRFs will be coded to generic term and all matching 
Anatomic Therapeutic Classification (ATC) codes using WHO Drug Summaries will be prepared 
using the coded terms. All prior and concomitant medications recorded in the eCRFs will also be 
listed. 
9.1.5 Treatment Exposure 
All data from administration of study drug will be listed and summarized. 
 
9.2 Analysis of Efficacy Data 
 
The primary analysis will be conducted on the mITT population. The PP population will be used as 
a supportive analysis if there is at least 5% difference between the numbers of subjects in the two 
populations. All statistical tests for efficacy will be two-sided tests, with α=0.05 
 
9.2.1 Primary Efficacy Outcome (Endpoint) Measure 
 
The primary endpoint for the study is clinical Improvement as assessed by change in total symptom 
score (for fever, myalgia, dyspnea and cough). 
The estimated difference in change in total symptom score along with 95% confidence interval and 
p-value will be calculated using ANCOVA adjusting for stratification factors in the model. 


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9.2.2 Secondary Efficacy Outcome (Endpoint) Measure 
 
9.2.2.1 Time to clinical resolution (TTCR) 
 
Time to clinical resolution will be compared between the treatment groups using Cox proportional 
hazards model with the stratification factors in the model. 
Kaplan-Meier analysis will also be used to depict the median time (days) to clinical resolution for 
the treatment groups. The likelihood score test in the Cox proportional hazards model (which is the 
equivalent of the Log Rank test) will be used to compare the time to clinical resolution between the 
treatment groups. 
 
9.2.2.2 Change from baseline in National Early Warning Score 2 (NEWS2) at Days 3, 7, and 14 
 
The change in National Early Warning Score 2 of subject at Days 3, 7 and 14 will be summarized 
descriptively and compared using ANCOVA. 
If the normality assumption is not met, a non-parametric method or a rank-ANCOVA analysis i.e., 
an ANCOVA analysis on rank-transformed data will be used. 
 
9.2.2.3 Change from baseline in pulse oxygen saturation (SpO2) at Days 3, 7, and 14 
 
The change from baseline in oxygen saturation (SpO2) at Days 3, 7, and 14 will be summarized 
descriptively and compared using ANCOVA . 
If the normality assumption is not met, a non-parametric method or a rank-ANCOVA analysis i.e., 
an ANCOVA analysis on rank-transformed data will be used. 
 
9.2.2.4 Change from baseline in the patient’s health status on a 7-category ordinal scale at Days 
3, 7, and 14. 
The change from baseline in patient’s health status on a 7-category ordinal scale at Days 3, 7, and 
14 will be summarized descriptively and compared using ANCOVA. 
If the normality assumption is not met, a non-parametric method or a rank-ANCOVA analysis i.e., 
an ANCOVA analysis on rank-transformed data will be used. 
 
9.2.2.5 Incidence and duration (days) of hospitalization 
 
Incidence and duration (days) of hospitalization will be summarized descriptively by treatment 


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group. The duration of hospitalization will be compared between the treatment groups using the a 
non-parametric method or a rank-ANCOVA analysis i.e., an ANCOVA analysis on rank- 
transformed data. 
 
9.2.2.6 Incidence and duration (days) of mechanical ventilation supply 
 
Incidence and duration (days) of mechanical ventilation supply will be summarized descriptively by 
treatment group. The duration (days) of mechanical ventilation supply will be compared between 
the treatment groups using the a non-parametric method or a rank-ANCOVA analysis i.e., an 
ANCOVA analysis on rank-transformed data. 
 
9.2.2.7 Incidence and duration (days) of oxygen use 
 
Incidence and duration (days) of oxygen use will be summarized descriptively by treatment group. 
The duration (days) of oxygen use will be compared between the treatment groups using the a non- 
parametric method or a rank-ANCOVA analysis i.e., an ANCOVA analysis on rank-transformed 
data. 
 
9.2.2.8 Mortality rate at Day 14 
 
Mortality rate at Day 14 will be summarized. The estimated difference in mortality rates will be 
calculated using Logistic Regression adjusting for stratification factors. 
 
9.2.2.9 Time to return to normal activity 
 
Time to return to normal activity will be compared between the treatment groups using Cox 
proportional hazards model with the stratification factors in the model. Kaplan-Meier analysis will 
also be used to depict the median time (days) to return to normal activity for the treatment groups. 
The likelihood score test in the Cox proportional hazards model (which is the equivalent of the Log 
Rank test) will be used to compare the time to return to normal activity between the treatment 
groups. 


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9.2.3 Exploratory Outcome Measures (Endpoints) 
Analysis of the exploratory endpoints will be summarized according to the variable type: 
• Continuous data summaries will include: 
o If the Normality assumption is met, Analysis of Covariance (ANCOVA) would be 
used. 
o If the Normality assumption is not met, a non-parametric method or a rank – 
ANCOVA analysis i.e., an ANCOVA analysis on rank-transformed data will be 
used. 
• Categorical data summaries will be based on Logit model. 
• Time-dependent data: Cox proportional hazards model will be used to analyze time 
dependent data and to depict the time to event data. 
9.3 Analysis of Safety Data 
 
The Safety population will be used for the analysis of safety assessments. 
 
9.3.1 Adverse Events 
 
Adverse events will be coded using the most recent version of Medical Dictionary for Regulatory 
Activities (MedDRA). Treatment Emergent AE’s (TEAE) are defined as events with an onset on or 
after the first treatment. TEAEs will be summarized by System Organ Class and preferred term by 
treatment group. The following TEAE summaries will be provided: 
• Overall (i.e., regardless of severity or relationship to treatment); 
• By intensity (mild, moderate, severe, life threatening or death); 
• By causality (definitely, probably, possibly, remotely or unrelated); 
• By impact on study treatment (dose increased, dose not changed, dose rate reduced, dose 
reduced, drug interrupted, drug withdrawn, not applicable, or unknown). 
In addition, separate summaries of serious adverse events, and adverse events resulting in 
discontinuation of study treatment will be presented. 
 
9.3.2 Clinical Laboratory Evaluations 
 
All available results of the clinical laboratory evaluations will be listed and summarized. 
Laboratory evaluations include serum biochemical, hematologic, coagulation, urinalysis, and 
serum/urine pregnancy (if applicable). 


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9.3.2.1 Laboratory Values over Time 
 
Summary statistics of raw data and change from baseline values for each laboratory parameter will 
be presented. Data will be summarized as appropriate to the variable type. 
For change from baseline summaries, subjects with an undefined change from baseline, because of 
missing data, will be excluded. 
 
9.3.2.2 Individual Subject Changes (Shift Tables) 
 
Individual subject changes will be identified through shift tables. Shift tables will be presented for 
each laboratory parameter with counts and percentages of subjects, for shift (change) from baseline. 
 
9.3.2.3 Clinically Significant Abnormalities 
 
A by-subject listing of treatment-emergent clinically significant laboratory values, by treatment 
group, will be prepared. 
 
9.3.3 Vital Signs 
 
Tabulations of raw data and change from baseline values will be presented by time point for each 
vital sign parameter including temperature, pulse, respiratory rate, systolic and diastolic blood 
pressure. 
Tabulations will include the number of observations, mean, standard deviation, median, and 
minimum and maximum values. For change from baseline summaries, subjects with an undefined 
change from baseline, because of missing data, will be excluded. 
 
9.3.4 Electrocardiogram (ECGs) 
 
The ECG parameters include ventricular rate (beats per minute), PR interval (msec), QRS interval 
(msec), QT interval (msec), and QTc interval (msec). 


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9.3.4.1 ECG Values over Time 
 
Descriptive statistics of raw data and change from baseline values for each ECG measurement will 
be presented by treatment group. For change from baseline summaries, subjects with an undefined 
change from baseline, because of missing baseline data, will be excluded. 
 
9.3.4.2 Individual Subject Changes (Shift Tables) 
 
Individual subject changes will be identified through shift tables. Shift tables will be presented for 
the investigator ECG interpretation (i.e., Normal, Abnormal (not clinically significant) and 
Abnormal (clinically significant)) with counts and percentages of subjects, by treatment group, for 
shift (change) from baseline, using the normal ranges. 
 
9.3.5 Physical Examination 
 
All physical examination findings will be listed and/or summarized by treatment group. 


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10. APPENDIX – PLANNED TLG 
10.1 Planned by-subject listings 
DISPOSITION/WITHDRAWALS (LISTINGS 16.2.1.X) 
ELIGIBILTY AND PROTOCOL DEVIATIONS (LISTINGS 16.2.2.X) 
EXCLUDED SUBJECTS (LISTINGS 16.2.3.X) 
DEMOGRAPHICS, 
POPULATION, 
AND 
BASELINE 
CHARACTERISTICS 
(LISTINGS 16.2.4.X) 
TREATMENT ADMINISTRATION LISTINGS (LISTINGS 16.2.5.X) 
EFFICACY RESPONSE DATA (LISTINGS 16.2.6.X) 
ADVERSE EVENT DATA (LISTINGS 16.2.7.X) 
SAFETY DATA (LISTINGS 16.2.8.X) 


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10.2 Planned Summary Tables 
 
POPULATION DISPOSITION AND PROTOCOL DEVIATIONS 
POPULATION DEMOGRAPHICS AND BASELINE CHARACTERISTICS 
CONCOMITANT MEDICATION USAGE 
EFFICACY SUMMARIES 
SAFETY SUMMARIES 
ADVERSE EVENT SUMMARIES 
SERIOUS ADVERSE EVENTS 
LABORATORY 
VITAL SIGNS 
PE 
ECG 
OTHER SAFETY 


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11. 
VERSION HISTORY 
This is the first version of the SAP. 


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12. 
REFERENCES 
1. 
ASA. (2016) Ethical Guidelines for Statistical Practice. Prepared by the 
Committee on Professional Ethics, April, 2016. 
2. 
The Royal Statistical Society: Code of Conduct (2014). 
3. 
E8 General Considerations for Clinical Trials, ICH Guidance, Federal Register, 
1997. 
4. 
E9 Statistical Principles for Clinical Trials, ICH Guideline, Federal Register, 
1998 
5. 
Guideline for the Format and Content of the Clinical and Statistical Section of 
an Application, 1988. 
6. 
Guideline for Industry: Structure and Content of Clinical Study Reports (ICH 
E3), July 1996.