An Extension Protocol for Virologically Suppressed Subjects Who Successfully Completed PRO140_CD03 Study
Phase: PHASE2
Conditions: HIV-1-infection
Sponsor: CytoDyn, Inc.

 
 
CytoDyn Inc.    1111 Main Street, Suite 660, Vancouver, Washington 98660   T 360.980.8524  F 360.799.5954 
 
 
Protocol Cover Page 
 
 
Protocol Title: An Extension Protocol for Virologically Suppressed Subjects Who Successfully 
Completed PRO140_CD03 Study 
 
Protocol Number: PRO 140_CD03 Extension 
 
Version: 5.0 
 
Document Date: 30-Mar-2021 
 
NCT Number: NCT05271370 
 

CONFIDENTIAL                                                                                                                              Page 1 of 103 
 
 
 
  
 
An Extension Protocol for Virologically Suppressed Subjects  
Who Successfully Completed PRO140_CD03 Study 
 
 
 
Protocol Number: 
PRO 140_CD03 Extension 
Version: 
5.0 
Date: 
30-Mar-2021 
 
 
 
Sponsor: 
CytoDyn, Inc. 
1111 Main Street, Suite 660 
Vancouver, Washington 98660 
(360) 980-8524-Work 
(360) 980-8549-Fax 
www.cytodyn.com 
 
 
Confidentiality Statement 
This document is a confidential communication of CytoDyn, Inc. It is provided for the conduct of 
a clinical research study. The information contained in this document is confidential and, except 
to the extent necessary to obtain informed consent or IEC/IRB approval, cannot be disclosed unless 
required by governmental regulation. Persons to whom any portion of the contents of this 
document is disclosed must be informed that the information is confidential and may not be further 
disclosed by them. 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                             Page 2 of 103 
PROTOCOL APPROVAL PAGE 
 
 
 
Protocol Number:  
PRO 140_CD03 Extension 
 
Version: 
 
5.0 
 
Date: 
 
30-Mar-2021 
 
PROTOCOL APPROVAL FOR USE 
I have read the protocol and the appendices and agree that it contains all relevant information 
required to meet FDA, GCP and all applicable regulatory guidelines and statutes. 
 
 
Prepared by: 
 
 
 
 
  
 
 
Date 
 
 
 
Reviewed by: 
 
 
 
 
 
 
 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Date 
 
 
 
 
 
 
 
Date 
Approved by: 
 
 
 
 
 
 
 
 
 
Date 
 
 
 
 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                             Page 3 of 103 
INVESTIGATOR’S SIGNATURE PAGE 
 
 
 
Protocol Number:  
PRO 140_CD03 Extension 
 
Version: 
 
5.0 
 
Date: 
 
30-Mar-2021 
 
 
INVESTIGATOR’S SIGNATURE 
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 the applicable US 
Food and Drug Administration (FDA) regulations and Investigational Review Board (IRB) 
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 
  
 
 
  
Address 
 
 
 
  
Site Number 
 
  

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                             Page 4 of 103 
SPONSOR INFORMATION 
CytoDyn, Inc. 
1111 Main Street, Suite 660 
Vancouver, Washington 98660 
(360) 980-8524-Work 
(360) 980-8549-Fax 
www.cytodyn.com 
 
 
 
CONTRACT RESEARCH ORGANIZATION INFORMATION 
 
 
 
 
 
  
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
 
 
  
 
 
 
 
 
  
  
 
 
 
 
 
 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                             Page 10 of 103 
TABLE OF CONTENTS 
 
STUDY TITLE ...............................................................................................................................1 
PROTOCOL SYNOPSIS ..............................................................................................................5 
TABLE OF CONTENTS ............................................................................................................10 
LIST OF TABLES..............................................................................................................................15 
LIST OF FIGURES ............................................................................................................................16 
LIST OF ABBREVIATIONS ................................................................................................................17 
1 INTRODUCTION..................................................................................................................20 
1.1 
STATEMENT OF INTENT ........................................................................................................20 
1.2 
THE PROBLEM STATEMENT ..................................................................................................20 
1.3 
NAME AND DESCRIPTION OF THE INVESTIGATIONAL PRODUCT ............................................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 
1.4.2.1 
PRO 140 1101 Study ...................................................................................................22 
1.4.2.2 
PRO 140 1102 Study ...................................................................................................22 
1.4.2.3 
PRO 140 1103 Study ...................................................................................................23 
1.4.2.4 
PRO 140 1302 Study ...................................................................................................23 
1.4.2.5 
PRO 140 2301 Study ...................................................................................................26 
1.4.2.6 
PRO 140 2101 Study ...................................................................................................26 
1.4.2.7 
PRO 140 _CD01 Study ................................................................................................29 
1.4.2.8 
PRO 140 _CD01-Extension Study...............................................................................30 
1.4.2.9 
PRO 140 _CD02 Study ................................................................................................31 
1.4.2.10 
PRO 140 _CD02 _Open Label ....................................................................................31 
1.4.2.11 
PRO 140 _CD02 Extension Study ...............................................................................31 
1.4.2.12 
PRO 140 _CD03 Study ................................................................................................32 
1.5 
RATIONALE FOR DOSE SELECTION .......................................................................................35 
1.6 
RISKS / BENEFITS ASSESSMENT ............................................................................................36 
1.6.1 
Risks/Discomfort to Subjects and Precautions to Minimize Risk ...............................36 
1.6.1.1 
Risks associated with using monotherapy treatment ...................................................36 
1.6.1.2 
Allergic Reaction .........................................................................................................36 
1.6.1.3 
Immune Response ........................................................................................................37 
1.6.1.4 
Pregnancy .....................................................................................................................37 
1.6.1.5 
Venipuncture for blood sampling and Subcutaneous injection for Study Drug 
Administration .............................................................................................................37 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                             Page 11 of 103 
1.6.1.6 
Risks related to resumption of viral replication in anatomically privileged 
compartments ...............................................................................................................37 
1.6.1.7 
Risks to the Study Personnel and the Environment .....................................................37 
1.6.1.8 
Unknown Risks ............................................................................................................37 
1.6.1.9 
Theoretical risk for increased severity of West Nile virus infection ...........................37 
1.6.2 
Intended Benefit for Subjects .......................................................................................38 
2 STUDY OBJECTIVES ..........................................................................................................39 
3 STUDY DESIGN ....................................................................................................................40 
3.1 
STUDY CENTER(S) ................................................................................................................41 
3.2 
STUDY POPULATION .............................................................................................................41 
3.3 
ELIGIBILITY CRITERIA ..........................................................................................................41 
3.3.1 
Inclusion Criteria .........................................................................................................41 
3.3.2 
Exclusion Criteria ........................................................................................................42 
4 STUDY SCHEDULE .............................................................................................................44 
4.1 
SCREENING PHASE ...............................................................................................................49 
4.1.1 
Screening Phase ...........................................................................................................49 
4.2 
TREATMENT EXTENSION PHASE ...........................................................................................50 
4.2.1 
Treatment Extension Phase: Treatment Extension Visit-1 (TE1) ................................52 
4.2.2 
Treatment Extension Phase: Subsequent Treatment Extension Visits ........................53 
4.2.3 
Treatment Extension Phase: End of Treatment Visit (EOT) .......................................54 
4.3 
VIROLOGIC FAILURE (VF) VISIT ..........................................................................................55 
4.4 
FOLLOW-UP PHASE ...............................................................................................................56 
4.4.1 
Follow-Up Visits ..........................................................................................................57 
4.4.1.1 
Short-Term Follow-Up Visits ......................................................................................57 
4.4.1.1.1 Virologic Failure Subjects ...........................................................................................57 
4.4.1.1.2 Non Virologic Failure Subjects ...................................................................................57 
4.4.1.2 
Long-Term Follow-Up Visits ......................................................................................58 
5 SUBJECT COMPLETION AND WITHDRAWAL...........................................................59 
5.1 
SUBJECT COMPLETION .........................................................................................................59 
5.2 
SUBJECT WITHDRAWAL .......................................................................................................59 
5.2.1 
Discontinuation of Study Treatment ............................................................................60 
5.2.2 
Data Collected for Withdrawn Subjects ......................................................................60 
5.3 
SCREEN FAILURES ................................................................................................................60 
6 STUDY TREATMENT .........................................................................................................62 
6.1 
INVESTIGATIONAL PRODUCT DESCRIPTION ..........................................................................62 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                             Page 12 of 103 
6.2 
INVESTIGATIONAL PRODUCT PACKAGING AND LABELING ...................................................63 
6.3 
INVESTIGATIONAL PRODUCT STORAGE ................................................................................66 
6.4 
INVESTIGATIONAL PRODUCT ADMINISTRATION ...................................................................67 
6.5 
INVESTIGATIONAL PRODUCT RECEIPT AND ACCOUNTABILITY .............................................67 
6.6 
INVESTIGATIONAL PRODUCT DISPOSITION ...........................................................................68 
7 DESCRIPTION OF PROTOCOL ASSESSMENTS AND PROCEDURES ...................69 
7.1 
INFORMED CONSENT ............................................................................................................69 
7.2 
ASSESSMENT OF ELIGIBILITY ...............................................................................................69 
7.2.1 
Re-screening ................................................................................................................69 
7.3 
DEMOGRAPHIC INFORMATION ..............................................................................................69 
7.4 
MEDICAL HISTORY ...............................................................................................................70 
7.5 
CONCOMITANT MEDICATIONS AND NON-STUDY TREATMENTS ...........................................70 
7.5.1 
Excluded Medications and Therapies ..........................................................................70 
7.5.2 
Allowable Medications and Therapies.........................................................................71 
7.6 
PHYSICAL EXAMINATION .....................................................................................................71 
7.7 
ELECTROCARDIOGRAM .........................................................................................................72 
7.8 
NEUROLOGICAL ASSESSMENT ..............................................................................................72 
7.9 
VITAL SIGNS.........................................................................................................................72 
7.10 CLINICAL LABORATORY ASSESSMENTS ...............................................................................72 
7.10.1 
Routine CBC ................................................................................................................73 
7.10.2 
Biochemistry ................................................................................................................73 
7.10.3 
Coagulation Indices .....................................................................................................73 
7.10.4 
Urinalysis .....................................................................................................................73 
7.10.5 
Urine pregnancy test ....................................................................................................73 
7.10.6 
Plasma HIV-1 RNA level and TruCount T Assay .......................................................73 
7.10.7 
HIV-1 Trofile® DNA Assay ........................................................................................74 
7.10.8 
HIV-1 Trofile® RNA Assay .........................................................................................74 
7.10.9 
HIV-1 Drug Resistance Assay .....................................................................................74 
7.10.10 
Plasma HIV-1 RNA Single Copy Assay .....................................................................75 
7.10.11 
PK sample for PRO 140 ...............................................................................................75 
7.10.12 
Anti-idiotypic antibodies to PRO 140..........................................................................75 
7.10.13 
PhenoSense® Entry Assay ..........................................................................................75 
7.10.14 
CCR5 Receptor Occupancy  ........................................................................................75 
7.10.15 
All laboratory reports will be reviewed by the Investigator. .......................................76 
7.11 PRO 140 ADMINISTRATION ..................................................................................................76 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                             Page 13 of 103 
7.12 INJECTION SITE REACTION ASSESSMENT ..............................................................................76 
7.13 COVID-19 GUIDANCE .........................................................................................................76 
8 STATISTICAL CONSIDERATIONS .................................................................................78 
8.1 
TREATMENT GROUPS ...........................................................................................................78 
8.2 
DESCRIPTION OF STUDY OUTCOME MEASURES ....................................................................78 
8.2.1 
Primary Outcome Measures .........................................................................................78 
8.2.2 
Secondary Outcome Measures .....................................................................................78 
8.2.3 
Safety Assessments ......................................................................................................78 
8.3 
SAMPLE SIZE DETERMINATION AND RATIONALE .................................................................79 
8.4 
RANDOMIZATION AND BLINDING .........................................................................................79 
8.5 
INTERIM ANALYSIS ..............................................................................................................79 
8.6 
GENERAL STATISTICAL CONSIDERATIONS ............................................................................79 
8.6.1 
Analysis Populations ....................................................................................................79 
8.6.2 
Statistical Methods .......................................................................................................79 
8.6.3 
Prognostic Factors/Covariates .....................................................................................79 
8.6.4 
Handling of Missing Data ............................................................................................79 
8.6.5 
Multicenter Study.........................................................................................................79 
8.7 
DATA SUMMARY ..................................................................................................................79 
8.7.1 
Subject Disposition ......................................................................................................79 
8.7.2 
Demographic and Baseline Characteristics .................................................................80 
8.7.3 
Prior and Concomitant Medications ............................................................................80 
8.7.4 
Efficacy Analysis .........................................................................................................80 
8.7.5 
Safety Analysis ............................................................................................................80 
8.7.5.1 
Adverse Events ............................................................................................................80 
8.7.5.2 
Tolerability Assessment ...............................................................................................81 
8.7.5.3 
Clinical Laboratory Data ..............................................................................................81 
8.7.5.4 
Physical Examination...................................................................................................81 
8.7.5.5 
Vital Signs ....................................................................................................................81 
8.7.5.6 
ECG Examination ........................................................................................................81 
8.7.5.7 
Neurological Assessment .............................................................................................81 
9 ADVERSE EVENTS (DEFINITIONS AND REPORTING) ............................................82 
9.1 
ADVERSE EVENT ..................................................................................................................82 
9.1.1 
Reporting of Adverse Events .......................................................................................82 
9.1.2 
Impact of Study Treatment ..........................................................................................82 
9.1.3 
DAIDS AE Grade (Severity) Assessment ...................................................................83 
9.1.4 
Causality Assessment...................................................................................................83 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                             Page 14 of 103 
9.1.5 
Treatment Given as a Result of the Event ...................................................................84 
9.1.6 
Outcome Assessment ...................................................................................................84 
9.1.7 
Expected / Anticipated Adverse Events .......................................................................85 
9.1.8 
SC Injection-related Events .........................................................................................85 
9.2 
SERIOUS ADVERSE EVENTS (SAE) .......................................................................................85 
9.2.1 
Reporting of Serious Adverse Events ..........................................................................86 
9.2.2 
SAE Follow-Up ...........................................................................................................87 
10 DIRECT ACCESS TO SOURCE DATA/DOCUMENTATION ......................................88 
11 QUALITY CONTROL AND QUALITY ASSURANCE ...................................................89 
11.1 MONITORING REQUIREMENTS ..............................................................................................89 
11.2 ACCEPTABILITY OF CASE REPORT FORMS (CRFS) ...............................................................89 
11.3 MODIFICATION OF PROTOCOL ..............................................................................................89 
11.4 REPORTING PROTOCOL DEVIATIONS ....................................................................................90 
12 ETHICS AND REGULATORY REQUIREMENTS .........................................................91 
12.1 INSTITUTIONAL REVIEW BOARD/INDEPENDENT ETHICS COMMITTEE (IRB/IEC) .................91 
12.2 INVESTIGATOR’S RESPONSIBILITIES .....................................................................................91 
12.3 SUBJECT INFORMED CONSENT REQUIREMENTS ....................................................................92 
13 DATA HANDLING AND RECORD KEEPING ................................................................93 
13.1 RECORDING AND COLLECTION OF DATA ..............................................................................93 
13.2 CLINICAL DATA MANAGEMENT ...........................................................................................93 
13.3 ARCHIVING ...........................................................................................................................93 
14 PUBLICATION PLAN .........................................................................................................95 
15 REFERENCES .......................................................................................................................96 
16 APPENDIX .............................................................................................................................99 
16.1 APPENDIX I: AIDS-DEFINING CONDITIONS ..........................................................................99 
16.2 APPENDIX II: DIVISION OF AIDS TABLE FOR GRADING THE SEVERITY OF ADULT AND 
PEDIATRIC ADVERSE EVENTS (DAIDS AE GRADING TABLE) ......................................................101 
16.3 APPENDIX III:  ADVERSE EVENTS OF SPECIAL INTEREST: INJECTION SITE REACTIONS ......102 
16.4 APPENDIX V: NEUROLOGICAL ASSESSMENT ......................................................................103 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                             Page 15 of 103 
LIST OF TABLES 
 Table 1-1: 
Clinical Studies with PRO 140 .............................................................................. 33 
Table 4-1: 
Schedule of Assessments – Screening and Treatment Extension Phase ............... 45 
Table 4-2:  
Schedule of Assessments –Follow-Up (FU) Phase ............................................... 47 
Table 4-3: 
Two Groups , Treatment Extension Phase ............................................................ 50 
Table 6-1: 
Investigational Product - PRO 140 ........................................................................ 63 
Table 9-1:  
DAIDS AE Grading General Guidelines .............................................................. 83 
 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                             Page 16 of 103 
LIST OF FIGURES 
Figure 1-1: 
PRO 140 1302 Study: Mean of the maximum (nadir) log10 reductions in HIV RNA
 ............................................................................................................................... 24 
Figure 1-2: 
PRO 140 1302 Study: Mean log10 reductions in HIV RNA over time ................. 24 
Figure 1-3: 
PRO 140 1302 Study: PRO 140 serum concentrations following a single 
intravenous injection in HIV- infected individuals. .............................................. 25 
Figure 1-4: 
PRO 140 2301 Study: Mean change from baseline in HIV-1 RNA (Log10 
copies/mL) over Time (ITT Subjects) ................................................................... 26 
Figure 1-5: 
PRO 140 2101 Study: Mean of the maximum (nadir) log10 reductions in HIV RNA
 ............................................................................................................................... 27 
Figure 1-6: 
PRO 140 2101 Study: Mean change from baseline in HIV-1 RNA (Log10 
copies/mL) over Time (ITT Subjects) ................................................................... 28 
Figure 1-7: 
Change in CD4+ cell counts in subjects treated with subcutaneous PRO 140. .... 28 
Figure 1-8:  Emax analysis of antiviral data generated with IV and SC PRO 140. .................. 35 
Figure 3-1:  Study Flow Diagram ............................................................................................. 43 
Figure 6-1: 
PRO 140 (CHO) 175mg/mL - Vial Label ............................................................. 64 
Figure 6-2: 
PRO 140 (CHO) 175mg/mL - Syringe Label ....................................................... 64 
Figure 6-3: 
PRO 140 (CHO) 175mg/mL - Kit Label ............................................................... 65 
 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                             Page 17 of 103 
LIST OF ABBREVIATIONS 
Abbreviation 
Term 
AE 
Adverse Event 
AIDS 
Acquired Immune Deficiency Syndrome 
ALT 
Alanine Transaminase 
ANC 
Absolute Neutrophil Count 
ART 
Anti Retroviral Therapy 
AST 
Aspartate Transaminase 
ATC 
Anatomic Therapeutic Classification 
AUC 
Area Under Curve 
C 
Celsius 
cART 
Combination Antiretroviral Therapy 
CBC 
Complete Blood Count 
CCR5 
C-C chemokine receptor type 5 
CDC 
Centers for Disease Control and Prevention 
CFR 
Code of Federal Regulations 
CHO 
Chinese Hamster Ovary 
Cm 
Centimeter 
CRF 
Case Report Form 
Cmax 
Maximal Concentration 
CRO 
Contract Research Organization 
CS 
Clinically Significant 
DAIDS 
Division of AIDS 
DMC 
Data Monitoring Committee 
DNA 
Deoxyribonucleic Acid 
DO 
Doctor of Osteopathic Medicine 
ECG 
Electrocardiogram 
eCRF 
Electronic Case Report Form 
Emax 
Maximum drug effect 
et al 
et aliae; Latin for "and others" 
F 
Fahrenheit 
FDA 
U.S. Food and Drug Administration 
FDP 
Fixed Dose Procedure 
FU 
Follow-Up 
GCP 
Good Clinical Practice 
HAART 
Highly Active Antiretroviral Therapy 
Hb 
Hemoglobin 
HCT 
Hematocrit 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                             Page 18 of 103 
Abbreviation 
Term 
HEENT 
Head, Ears, Eyes, Nose, and Throat 
HIPAA 
Health Insurance Portability Accountability Act 
HIV 
Human Immunodeficiency Virus 
IA 
Interim Analysis 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization 
i.e. 
id est; Latin for “that is” 
IEC 
Independent Ethics Committee 
IND 
Investigational New Drug 
INR 
International Normalized Ratio 
IP 
Investigational Product 
IRB 
Institutional Review Board 
ISR 
Injection Site Reactions 
IV 
Intravenous 
LDH 
Lactate dehydrogenase 
LPN 
Licensed Practical Nurse 
LVN 
Licensed Vocational Nurse 
mAb 
Monoclonal Antibody 
MD 
Doctor of Medicine 
MedDRA 
Medical Dictionary for Regulatory Activities 
Mg 
Milligram 
mL 
Milliliter 
Mm 
Millimeter 
MW 
Molecular Weight 
NCS 
Not Clinically Significant 
NP 
Nurse Practitioner 
NTF 
Non-Treatment Failure 
OBT 
Optimized Background Therapy 
PA 
Physician Assistant 
PI 
Principal Investigator 
PK 
Pharmacokinetics 
PP 
Per protocol 
PT 
Prothrombin Time 
QC 
Quality Control 
RBC 
Red Blood Cells 
RN 
Registered Nurse 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                             Page 19 of 103 
Abbreviation 
Term 
RNA 
Ribonucleic acid 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SC 
Subcutaneous 
SD 
Standard Deviation 
SOP 
Standard Operating Procedure 
SV 
Screening Visit 
TEAE 
Treatment Emergent Adverse Events 
TF 
Treatment Failure 
USA 
United States of America 
VF 
Virologic Failure 
WBC 
White Blood Cells 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                             Page 20 of 103 
1 
INTRODUCTION 
1.1 
STATEMENT OF INTENT 
The design, conduct and reporting of this trial 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 
 as the Contract Research Organization (CRO). 
1.2 
THE PROBLEM STATEMENT 
Substantial progress has been made over the past two decades in the development of effective and 
well tolerated combination antiretroviral regimens. Most HIV-1 infected persons who initiate 
antiretroviral therapy at early stages in the disease process and who are fully adherent to their 
antiretroviral regimens can anticipate life expectancies that are measured in decades. Although 
these advances have revolutionized antiretroviral therapy for most HIV-1 infected patients, 
contemporary lifelong daily adherence to treatment regimens remains challenging for a significant 
subset of patients. A number of studies have been conducted to evaluate the possibility of treatment 
simplification following control of viral replication with an induction regimen [Arribas JR, 
2005][Pulido F, 2008][Moltó J, 2007] [Cameron DW, 2008][Nunes EP, 2009][Meynard JL, 
2010][Katlama C, 2010][Gutmann C, 2010][Cahn P, 2011][Guiguet M et al., 2012]. Most of these 
simplification trials have involved the substitution of a boosted HIV-1 protease inhibitor such as 
lopinavir or darunavir for an effective combination regimen. Although the strategy has been 
successful in a substantial fraction of those who undergo regimen simplification, the overall body 
of evidence suggests that boosted protease inhibitor maintenance therapy is generally less effective 
than maintenance on a three drug regimen [Calza L, 2012][Thompson MA, 2012]. Factors 
influencing the likelihood of success include the duration of successful suppression prior to the 
regimen simplification and the extent to which patients are adherent to their simplified regimens 
[Calza L, 2012]. Although it has also been suggested that some patients may fail because of 
variability in trough concentrations of protease inhibitors, this has not been substantiated in 
rigorously conducted studies [Boffito M, 2003]. Other concerns that have been raised include the 
ability of HIV-1 protease inhibitors to achieve suppressive levels in the central nervous system 
[Thompson MA, 2012]. The current consensus appears to be that this approach should be reserved 
for specific patient populations in which considerations related to chronic nucleoside toxicity 
and/or adherence to complex antiretroviral regimens are dominant. In these situations, the 
importance of adherence and of close monitoring of plasma HIV-1 RNA levels has been 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                             Page 21 of 103 
emphasized. In the case of HIV-1 protease inhibitor maintenance therapy, reestablishment of 
control of retroviral replication has generally been achieved by resumption of combination therapy. 
Also, there is an interest in the development of infrequently administered therapy both as a 
treatment and a prevention strategy. The Long-Acting Antiretroviral Treatment Enabling (LATTE) 
study tested a combination of two oral antiretroviral drugs, the non-nucleoside reverse 
transcriptase inhibitor rilpivirine and the new integrase inhibitor GSK1265744[Spreen WR, 2013]. 
Furthermore, a long-acting injectable medication can be an effective approach to circumvent the 
need for daily medication adherence and/or chronic nucleoside toxicity.  
Although PRO 140 would require either subcutaneous (SC) or intravenous (IV) administration, its 
favorable pharmacokinetics might allow dosing as infrequent as once weekly or bi-weekly. The 
ability to administer the drug infrequently under medical supervision could obviate one of the 
continuing challenges of close adherence to daily boosted protease inhibitor regimens that appear 
to be relatively unforgiving in maintenance settings when administered as the sole antiretroviral 
regimen. This is an open-label study of PRO 140 monotherapy as maintenance therapy for subjects 
previously fully suppressed on combination antiretroviral regimen. PRO 140 is a promising new 
antiretroviral agent that does not show any cross-resistance with drugs from other classes. The 
purpose of this study is to assess the clinical safety and treatment strategy of using PRO 140 SC 
as long-acting, single-agent maintenance therapy for the chronic suppression of CCR5-tropic HIV-
1 infection. 
1.3 
NAME AND DESCRIPTION OF THE INVESTIGATIONAL PRODUCT 
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. 
PRO 140 binds 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. PRO 140 binding to CCR5 blocks the 
final phase of viral binding to the cell surface prior to fusion of the viral and cell membranes. PRO 
140 has been administered intravenously or subcutaneously to 174 HIV-1 infected individuals in 
Phase I/II studies of safety, tolerability, pharmacokinetics and pharmacodynamics [Jacobson JM, 
2010][Jacobson JM, 2010]. The drug has been well tolerated following administration of single 
doses of 0.5 to 5 mg/kg or up to three weekly doses of up to 324 mg. Single subcutaneous doses 
of 324 mg have resulted in drops in plasma HIV-1 RNA levels of approximately 1.0 log10. 
Repetitive weekly administration of this dose of PRO 140 has been associated with drops in plasma 
HIV-1 RNA levels of approximately 1.5 log10. Serum concentrations of PRO 140 above the IC50 
for clinical isolates of HIV-1 are maintained for at least 2 weeks following a single dose of 324 
mg. Plasma HIV-1 RNA levels rise to baseline levels as PRO 140 is cleared from the plasma and, 
presumably, other compartments. 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                             Page 22 of 103 
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 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 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 PRO 140 for 24 weeks without evidence of local or systemic 
toxicity. PRO 140 caused no mortality, cageside observations, in-life injection-site observations, 
or gross pathologic findings. Chronic treatment with 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 PRO 140 in 
monkeys, the maximal concentration (Cmax) was achieved within 56 hours and bioavailability for 
PRO 140 after SC dosing was approximately 70%.  
1.4.2 Clinical Studies with PRO 140 
Current human experience with PRO 140 consists of seven completed and two ongoing clinical 
trials. These studies are summarized in Table 1-1. In all the completed clinical trials, the majority 
of adverse events (AEs) were 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 
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 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. 75% of subjects reported TEAEs, most of which were deemed unrelated to study treatment. 
1.4.2.2 PRO 140 1102 Study 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                             Page 23 of 103 
In PRO 140 1102 study, 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 SC 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 study, administration of PRO 140 at 350 mg using Autoject® 2 appeared well 
tolerated. Manual injections, on the other hand, were associated with a greater number of AEs. 
There did not appear, however, to be any substantial difference in subject perception of pain or 
discomfort related to site of drug administration. No anti-PRO 140 antibodies were detected in any 
subjects in this study. There was a tendency of higher exposure associated with SC administration 
of PRO 140 at 350 mg in the abdomen and the thigh. A higher number of AEs was associated with 
injections in the arm. Based on these observations, thigh and abdominal administration of PRO 
140 were preferred over arm injection. 
1.4.2.4 PRO 140 1302 Study 
This 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. 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.  
The study enrolled 31 males and 8 females. The median age, CD4+ cell count and HIV-1 RNA at 
baseline were 40.3 years, 484cells/μL and 26,900 copies/mL, respectively. The baseline 
characteristics were similar for all treatment groups. 
PRO 140 demonstrated potent, rapid, prolonged and dose-dependent antiviral activity (Figure 1-1 
and Figure 1-2). A single 5mg/kg dose reduced viral loads by 1.83 log10 on average (Figure 1-2). 
These reductions represent the largest antiviral effects reported after just one dose of any HIV-1 
drug [Jacobson JM, 2008]. In the 5 mg/kg group, mean viral load reductions of greater than 1 log10 
were sustained for 2-3 weeks post-treatment (Figure 1-2).  

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                             Page 26 of 103 
There was no significant effect on QTc interval intervals or other electrocardiographic parameters, 
and there were no remarkably laboratory findings. There was no loss or depletion of CD4+ or 
CCR5+ cells from the circulation. At the 5 mg/kg dose, there was a trend towards increased CD4+ 
cell counts from baseline, with mean changes of +129, +96 and +83 cells/μL observed on days 8, 
15, and 22, respectively.  
1.4.2.5 PRO 140 2301 Study 
PRO 140 2301 was a multi-center, randomized, double-blind, placebo-controlled, parallel group 
study in 30 male and female adult subjects infected with HIV-1. 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 (mean max log10 
reductions were 1.83 for treatment groups and 0.32 for placebo) (Figure 1-4). 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.  
Figure 1-4: 
PRO 140 2301 Study: Mean change from baseline in HIV-1 RNA (Log10 
copies/mL) over Time (ITT Subjects) 
 
 
1.4.2.6 PRO 140 2101 Study 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                             Page 30 of 103 
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.  
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-nine (29) 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, 17 subjects, multi-center) seeks to evaluate the 
efficacy, safety, and tolerability of PRO 140 monotherapy (350 mg subcutaneous injection weekly 
for up to 160 weeks) for the continued maintenance of viral suppression following substitution of 
antiretroviral therapy in HIV patients (with exclusive CCR5-tropic virus). Participants in this study 
were HIV-infected individuals who were virologically suppressed on combination antiretroviral 
therapy and completed the first 12 weeks of CD01 study without experiencing virologic failure. 
As with the CD01 study, virologic failure was defined as two consecutive HIV-1 RNA levels of ≥ 
400 copies/mL separated by at least 3 days. Consenting patients may remain on PRO 140 
monotherapy for up to 160 weeks.  
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 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                             Page 31 of 103 
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. 
PRO 140 was generally well tolerated, and no drug-related SAEs were observed. 
The clinical study is currently ongoing. 
1.4.2.9 PRO 140 _CD02 Study 
PRO 140_CD02 study (double blind, placebo controlled, 50 subjects, multi-center) evaluated the 
efficacy, safety, and tolerability of PRO 140 in combination with existing ART (failing regimen) 
for one week and Optimized Background Therapy (OBT) for 24 weeks in patients infected with 
HIV-1.  The study population included 50 treatment-experienced HIV-infected adult patients with 
CCR5-tropic virus who demonstrated evidence of HIV-1 replication despite ongoing antiretroviral 
therapy with documented history of genotypic or phenotypic resistance to at least one ART drug 
within three drug classes (or within two or more drug classes with limited treatment options). The 
options may be limited as a result of drug antiviral class cross-resistance or documented treatment 
intolerance. 
In double-blind treatment period, virally non-suppressed subjects were randomized and treated 
with either PRO 140 or Placebo in combination with the failing ART regimen for 7 days.  The 
primary efficacy endpoint was 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. 
During the 24-week open-label period, all subjects received PRO 140 along with Optimized 
Background Therapy (OBT).  
This clinical study is completed. 
1.4.2.10 PRO 140 _CD02 _Open Label 
PRO 140_CD02_Open Label (open label, single arm, 25 subjects, multicenter) seeks to evaluate 
the efficacy, clinical safety, and tolerability parameters of PRO140 in combination with existing 
ART (failing regimen) for one week and Optimized Background Therapy (OBT) for 24 weeks. 
The patient population for this trial are treatment-experienced HIV-infected patients with CCR5-
tropic virus and demonstrate evidence of HIV-1 replication despite ongoing antiretroviral therapy 
with documented genotypic or phenotypic resistance to ART drugs within three drug classes (or 
within two drug classes with limited treatment options). 
This clinical study is currently ongoing. 
1.4.2.11 PRO 140 _CD02 Extension Study 
PRO 140_CD02 Extension study (open label, 50 subjects, multi-center) seeks to evaluate the long 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                             Page 32 of 103 
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 50 
treatment-experienced HIV-infected adult patients with CCR5-tropic virus who successfully 
completed PRO 140_CD02 or PRO 140_CD02_Open Label study and continue to demonstrate 
HIV-1 viral suppression.   
This clinical study is currently ongoing. 
1.4.2.12 PRO 140 _CD03 Study 
PRO 140_CD03 study (open-label, two-arm comparator, 500 subjects, multi-center) seeks to 
evaluate the clinical safety and treatment strategy of using PRO 140  SC as a long-acting, single-
agent maintenance therapy for 48 weeks in virologically suppressed subjects with CCR5-tropic 
HIV-1 infection. 
The first ~150 eligible subjects were enrolled to receive PRO140 350mg SC weekly injection in a 
single-arm study. Subsequently, the next ~150 subjects were randomized 1:1 to PRO140 350mg 
(Group A) or PRO 140 525mg (Group B).  
An additional ~200 subjects will be randomized 1:1 to PRO 140 525mg (Group B) or PRO 140 
700mg (Group C).  
This clinical study is currently ongoing. 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL     
                                                                                                                          
Page 34 of 103 
PRO 140 _CD01-
Extension 
2b 
17/17 
350 mg SC weekly dose for 160 
weeks of Monotherapy (total 
treatment duration 161 weeks) 
CHO 
HIV-1 
positive 
This clinical study is currently ongoing. 
PRO 140 
_CD02 
2b/3 
50/52 
Placebo or 350mg SC for 1 dose, 
followed by 350mg SC weekly 
dose for 24 weeks (total treatment 
duration 25 weeks) 
CHO 
HIV-1 
positive 
This clinical study is completed 
PRO 140 
_CD02_Open Label 
2b/3 
25/2 
700mg SC + existing ART for 1 
week followed by 700mg SC 
weekly OBT for 24 weeks 
CHO 
HIV-1 
positive 
This clinical study is currently ongoing 
PRO 140 
_CD02 Extension 
2b/3 
50/TBD 
700 mg SC weekly dose in 
combination with Optimized 
Background Therapy (OBT) 
CHO 
HIV-1 
positive 
This clinical study is currently ongoing.  
PRO 140 
_CD03 
2b/3 
500/TBD 
350 mg,  525 mg, or 700 mg SC 
weekly dose for 48 weeks of 
Monotherapy 
CHO 
HIV-1 
positive 
This clinical study is currently ongoing. 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL 
 
           
 Page 35 of 103 
1.5 
RATIONALE FOR DOSE SELECTION 
The dose of 350 mg administered SC was chosen in light of a previous analysis suggesting that 
such a dose would be likely to provide maximal viral load suppression. 
In studies with antiviral agents that block viral entry through the CCR5 receptor, there is a general 
consensus that in order to achieve robust antiviral effects and minimize the potential for drug 
resistance in combination therapy, the dose of drug should result in exposures that fall on the 
plateau of a Maximum Drug Effect (Emax) plot. 
Figure 1-8:  Emax analysis of antiviral data generated with IV and SC PRO 140. 
 
The maximal viral load reduction was analyzed with regard to drug exposure for PRO 140. Figure 
1-8 above shows this relationship. Analysis shows that PR0 140 350mg weekly dose is expected 
to fall on the plateau of the Emax plot. 
The maximal change in HIV-1 viral load from baseline was determined at any point 59 days after 
initiation of therapy. To allow approximate comparisons between the IV and SC doses, the overall 
AUC observed for repeat SC doses was conservatively estimated by multiplying the measured 
AUC0-7d by the number of doses administered. Viral load and AUC data were fit to an Emax 
equation: E = Emax x AUC/(AUC + AUC50). The orange diamond indicates projected data for three 
weekly 350 mg doses based on the mean exposure observed in the PRO 140 1103 study. 
It is important to note that when larger proteins (MW > 10,000) are administered SC, they initially 
traffic through the lymphatic system. Uptake into the bloodstream occurs after the proteins reach 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL     
                                                                                                                         
 
Page 36 of 103 
the thoracic duct [Nishikawa M, 2005]. In addition, based on pharmacodynamic data from our 
prior SC and IV studies, maximum virologic suppression is expected to be achieved with trough 
concentrations that equal or exceed approximately 5 µg/mL.  
Finally, the mean nadir reduction in viral load achieved with 3 weekly 324 mg SC doses (1.65 
log10) was similar to the mean nadir reductions observed with single 5 or 10 mg/kg IV doses (1.8 
log10 in each case), and higher viral load reductions are expected in the present study based on the 
use of the 350 mg CHO formulation. Overall, several lines of evidence indicate that maximum 
virologic suppression will be achieved with 350 mg weekly dosing in the present study. 
Majority of subjects receiving 350 mg weekly SC dosing in monotherapy setting experienced 
virologic failure in CD01-Extension study. Review of PRO 140 clinical data to date with 350mg 
SC weekly dosing, suggests no evidence of emergence of viral isolates with reduced susceptibility 
to PRO 140, no altered viral tropism or anti-PRO 140 antibodies formation suggesting the most 
likely cause of viral rebound is inadequate dosing to fully cover CCR5 receptor populations. Based 
on pharmacologic modeling studies, we anticipate that the 525mg and 700 mg dose will result in 
a lower fraction of study participants with trough levels below that which will ‘uncoat’ a significant 
number of CD4 cells (i.e., less than a certain multiple of the IC50 or IC90 for PRO 140). 
1.6 
RISKS / BENEFITS ASSESSMENT 
1.6.1 Risks/Discomfort to Subjects and Precautions to Minimize Risk 
1.6.1.1 Risks associated with using monotherapy treatment  
Study treatment (PRO 140 350mg, 525mg, or 700 mg SC injection) may not be effective in 
achieving a reduction in viral load for all subjects. Such cases could lead to an increased risk of 
developing drug resistance, opportunistic infections and clinical progression of the disease. As 
patients will not be receiving concomitant antiretroviral drugs of other antiviral classes, should 
PRO 140 therapy fail, selection of viral variants with reduced susceptibility to these agents would 
be unlikely (and was not observed in the PRO 140_CD 01 or PRO 140_CD 01-Extension studies). 
1.6.1.2 Allergic Reaction 
PRO 140 belongs to the monoclonal antibody class of drugs. Monoclonal antibodies are sometimes 
associated with allergic reactions (fatigue, diarrhea, fever, vomiting, headache, nausea, pain at the 
site of injection, low blood pressure, rash, itching, and chills) or flu-like reactions such as fever, 
chills, and aches. These events 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 PRO 140, infusion of proteins always carries with it the theoretical risk for anaphylactic 
shock. Accordingly, whenever PRO 140 is initially administered to subjects, there should be 
available and in place the procedures required to manage anaphylactic shock. 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL     
                                                                                                                         
 
Page 37 of 103 
1.6.1.3 Immune Response 
Subjects who take PRO 140 or other monoclonal antibodies can also develop an immune response 
to 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. 
1.6.1.4 Pregnancy 
Risks to unborn babies are unknown at this time; pregnant females will be excluded from this 
study. Females of childbearing potential must have a negative pregnancy test prior to enrollment. 
Both male and female patients and their partners of childbearing potential must agree to use 
appropriate birth control methods throughout the study duration (excluding women who are not of 
childbearing potential and men who have been sterilized).  
1.6.1.5 Venipuncture for blood sampling and Subcutaneous injection for Study Drug 
Administration 
Venipuncture for blood sample collection and subcutaneous injection for study drug administration 
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. 
1.6.1.6 Risks related to resumption of viral replication in anatomically privileged 
compartments 
It is possible that penetration of PRO 140 into certain key anatomic compartments such as the 
central nervous system (CNS) or the male genital tract will be insufficient to control viral 
replication in those locations. Loss of control of viral replication in the CNS could result in the 
development or exacerbation of HIV-1 Associated Neurocognitive Disorders (HAND) and that a 
lack of control of HIV-1 replication in the male genital tract could be associated with an increased 
risk of HIV-1 transmission following unprotected sexual encounters. 
1.6.1.7 Risks to the Study Personnel and the Environment 
The principal risk in the clinical setting is in the handling of needles that may be contaminated 
with HIV, or other human pathogens. Adherence to universal precautions for working with 
infectious agents will reduce the risk of exposure to these individuals. All bio-hazardous waste 
will be disposed of as stipulated by local, state, and federal regulations and in accordance with 
study site Standard Operating Procedures (SOPs). 
1.6.1.8 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.  
1.6.1.9 Theoretical risk for increased severity of West Nile virus infection 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL     
                                                                                                                         
 
Page 38 of 103 
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, PRO 
140 weakly antagonizes the natural activity of CCR5 and thus is less likely to adversely affect 
immune function. Furthermore, this has not been established to be a risk with maraviroc, the anti-
CCR5 drug already FDA-approved for the treatment of HIV. 
Collectively, the experience with both IV and SC, simulation modeling and the recent confirmation 
that a higher concentration of 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.  
1.6.2 Intended Benefit for Subjects 
This study provides an opportunity for subjects to receive once weekly SC treatment with PRO 
140. Subjects participating in this Extension monotherapy study will contribute to the development 
of a drug which has the potential to become a treatment option for them and others in the future. 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL 
 
                 Page 39 of 103 
2 
STUDY OBJECTIVES 
The objective of this study is to assess the long term safety of using PRO 140 SC as single-agent 
maintenance therapy for the chronic suppression of CCR5-tropic HIV-1 infection.  
The primary outcome measures will be to assess the clinical safety of PRO 140 monotherapy 
regimen and proportion of participants experiencing virologic failure for all subjects and within 
each treatment group. 
In addition, time to virologic failure for all subjects and within each treatment group, proportion 
of participants achieving viral re-suppression (HIV-1 RNA < 50 copies/mL) after experiencing 
virologic failure for all subjects and within each treatment group, time to achieving viral re-
suppression (HIV-1 RNA < 50 copies/mL) after experiencing virologic failure for all subjects and 
within each treatment group, proportion of virologic failure subjects achieving viral re-suppression 
with re-initiation of previous baseline antiretroviral regimen for all subjects and within each 
treatment group, mean change in CD4 cell count, at each visit within the Treatment Phase for all 
subjects and within each treatment group.  
Note: Virologic failure is defined as two (2) consecutive plasma HIV-1 RNA levels of ≥ 200 
copies/mL. 
Safety assessments include evaluation of tolerability of repeated subcutaneous administration of 
PRO 140 as assessed by investigator –evaluation of injection site reactions for all subjects and 
within each treatment group, frequency of Grade 3 or 4 adverse events as defined by the DAIDS 
Adverse Event scale and frequency of treatment-emergent serious adverse events. 
 
 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL     
                                                                                                                         
 
Page 40 of 103 
3 
STUDY DESIGN  
This study is an extension study designed to assess the long-term safety of using PRO 140 350mg, 
525mg, or 700mg SC as single-agent maintenance therapy for the chronic suppression of CCR5-
tropic HIV-1 infection after initial 48 weeks in virologically suppressed subjects. 
Consenting subjects will continue weekly PRO 140 350mg, 525mg, or 700mg monotherapy during 
the Treatment Extension Phase with the one week overlap of existing retroviral regimen and PRO 
140 at the end of PRO 140 treatment in subjects who do not experience virologic failure. 
Note: Subjects who intend and consent to participate in Treatment Extension phase study will not 
initiate ART Regimen therapy at T47.  
Three groups of subjects included in the study: 
• Subjects who continue receiving PRO 140 350mg SC weekly injection  
• Subjects who continue receiving PRO 140 525mg SC weekly injection 
• Subjects who continue receiving PRO 140 700mg SC weekly injection  
Subjects receiving  PRO 140 350mg that experience virologic failure during the Treatment 
Extension phase will  have the option of receiving the higher dose of PRO 140 525mg for the 
remainder of the Treatment Extension phase or may re-initiate prior ART regimen (or an 
alternative regimen selected by their treating physician). 
Subjects receiving PRO 140 525mg that experience virologic failure during the Treatment 
Extension phase will have the option of receiving the higher dose of PRO 140 700mg for the 
remainder of the Treatment Extension phase or may re-initiate prior ART regimen (or an 
alternative regimen selected by their treating physician). 
Subjects who move to the higher dose after experiencing virologic failure will continue on 
treatment at the higher dose from the remaining of the treatment phase. The decision to stop 
treatment at the higher dose will be at the investigator’s discretion based on the subject’s viral load 
at the time of virologic failure, and viral load at subsequent higher dose treatment visits. The study 
will have three phases: Screening Phase, Treatment Extension Phase and Follow-up Phase. 
Screening Phase begins with signing of Informed Consent and lasts up to 21 days. All subjects 
will continue receiving PRO 140 350mg, 525mg, or 700mg monotherapy during the Screening 
Phase. 
Treatment Extension Phase begins once viral load from Treatment Visit 48 under PRO 140_CD 
03 study is available for Investigator review. The first Treatment Extension Visit (TE1) will take 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL     
                                                                                                                         
 
Page 41 of 103 
place within 10 days of last treatment visit under CD03 study (i.e. T48 visit), with weekly visits 
(± 3 days) thereafter. 
Study participants will be regularly monitored for viral load and will cease weekly study treatment 
injections should they experience virologic failure. Virologic failure is defined as two consecutive 
HIV-1 RNA levels ≥ 200 copies/mL. 
All subjects who experience virologic failure at any time during the Treatment Extension Phase 
will undergo the Virologic Failure (VF) Visit assessments and then exit the Treatment Extension 
Phase to enter the Follow-up Phase of the study unless subjects receiving PRO 140 350mg or PRO 
140 525mg opt to receive the higher dose of PRO 140 525mg or 700mg, respectively, for the 
remainder of Treatment Extension Phase. Subjects who do not experience virologic failure will 
complete EOT assessments and then enter the Follow-up Phase of the study at the end of Treatment 
Extension Phase. 
Duration of Follow-up Phase is determined based on whether or not subject has experienced 
virologic failure during the Treatment Extension Phase. 
Subjects receiving PRO 140 350mg who do not switch to PRO 140 525mg or subjects receiving 
PRO 140 525mg who do not switch to PRO 140 700mg, and all subjects receiving PRO 140 700mg 
who experience virologic failure during the Treatment Extension Phase will be assessed every 4 
weeks until the viral suppression is achieved (i.e., plasma HIV-1 RNA levels decline to < 50 
copies/mL).  Additionally, virologic failure subjects will return to clinic for long-term follow-up 
at 6 months and at one year from the time of the Virologic Failure (VF) Visit. 
Subjects who do not experience virologic failure at the end of Treatment Extension Phase, will be 
assessed every 2 weeks for a total of 4 weeks. 
3.1 
STUDY CENTER(S) 
Site(s) participating in the PRO140_CD03 protocol 
3.2 
STUDY POPULATION 
Study population consists of virally suppressed HIV-1 patients with CCR5-tropic virus who 
complete the PRO140_CD03 study. 
3.3 
ELIGIBILITY CRITERIA 
3.3.1 Inclusion Criteria 
Subjects must meet all of the following criteria to be included in the study: 
1. Subjects who have completed 48 weeks of treatment in PRO140_CD03 study. 
2. Last known Plasma HIV-1 RNA < 50 copies/mL within the PRO140_CD03 study.  

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL     
                                                                                                                         
 
Page 42 of 103 
3. Both male and female subjects and their partners of childbearing potential must agree to use 2 
medically accepted methods of contraception (e.g., barrier contraceptives [male condom, 
female condom, or diaphragm with a spermicidal gel], hormonal contraceptives [implants, 
injectables, combination oral contraceptives, transdermal patches, or contraceptive rings], and 
intrauterine devices) during the course of the study (excluding women who are not of 
childbearing potential and men who have been sterilized). Females of childbearing potential 
must have a negative serum pregnancy test at Screening visit and negative urine pregnancy test 
prior to receiving the first dose of study drug. 
4. Willing and able to participate in all aspects of the study, including use of SC medication, 
completion of subjective evaluations, attendance at scheduled clinic visits, and compliance 
with all protocol requirements as evidenced by providing written informed consent. 
3.3.2 Exclusion Criteria 
Potential subjects meeting any of the following criteria will be excluded from enrollment: 
1. Not currently enrolled in PRO140_CD03 study.  
2. Any active infection or malignancy requiring acute therapy (with the exception of local 
cutaneous Kaposi’s sarcoma). 
3. Females who are pregnant, lactating, or breastfeeding, or who plan to become pregnant during 
the study. 
4. Subjects weighing < 35kg.  
5. History of anaphylaxis to any oral or parenteral drugs.  
6. History of Bleeding Disorder or subjects on anti-coagulant therapy (except aspirin).  
Note: Subjects with well-controlled bleeding disorder while on stable anti-coagulant therapy 
dose with documented stable INRs can be enrolled as per discretion of the Investigator.  
7. Any other clinical condition that, in the Investigator's judgment, would potentially compromise 
study compliance or the ability to evaluate safety/efficacy. 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL     
                                                                                                                         
 
Page 44 of 103 
4 
STUDY SCHEDULE 
The study is divided into three phases: Screening, Treatment and Follow-up.  
1. Screening Phase begins with signing of Informed Consent and lasts up to 21 days. Subject 
will enter the Treatment Extension Phase as soon as HIV-1 viral load and CD4 count results 
from T48 visit are available for review by Investigator. 
2. Treatment Extension Phase begins with evaluation of results of laboratory samples collected 
during Screening Phase within the PRO140_CD03 study. The first treatment extension visit 
(TE1) will be administered within 10 days of treatment visit 48, with weekly visits (± 3 days) 
thereafter. 
All subjects will continue taking PRO 140 350mg, 525mg, or 700mg SC monotherapy during 
the Screening Phase.  
Study participants will be regularly monitored for viral load during Treatment Extension phase, 
and will cease weekly study treatment injections should they experience virologic failure. 
Subjects who experience virologic failure at any point during the Treatment Extension Phase 
will undergo the Virologic Failure (VF) Visit assessments and then exit the Treatment Phase 
to enter the Follow-up Phase of the study unless: subjects receiving PRO 140 350mg opt to 
receive PRO 140 525mg SC weekly injections and subjects receiving PRO 140 525mg opt to 
receive PRO 140 700mg SC for the remainder of Treatment Extension Phase. 
Subjects who do not experience virologic failure will enter the Follow-up Phase of the study at 
the end of the Treatment Extension Phase. 
3. Follow-Up Phase: The duration of follow-up depends on the status of viral load suppression. 
• Subjects receiving PRO 140 350mg or 525mg who do not elect to receive the higher dose 
of PRO 140 525mg or 700mg, respectively, in the Treatment Extension Phase and all 
subjects receiving PRO 140 700mg who experience virologic failure will be followed up 
every 4 weeks until viral suppression is achieved (i.e., plasma HIV-1 RNA levels to return 
to < 50 copies/mL). Additionally, virologic failure subjects will return to clinic at 6 months 
and at one year from the time of the Virologic Failure (VF) Visit. 
• Subjects who do not experience virologic failure at the end of Treatment Extension Phase, 
will be followed up every 2 weeks for a total of 4 weeks. 
Procedures to be performed during each of these study phases are described below and provided 
as a Schedule of Assessments in Table 4-1and Table 4-2.  
 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL     
                                                                                                                           
 
    Page 46 of 103 
X – Indicate assessments performed at T46/47/48 under PRO140_CD03 study 
Foot Notes: 
(1) Informed consent must be obtained prior to patient participation in any protocol-related activities that are not part of routine care. 
(2) Complete physical performed by Investigator at SV, EOT or VF. 
(3) Symptom-directed physical examination performed at clinic visits. 
(4) The neurological assessment tool is based on the three question survey used by Simioni et al. (Simioni S, 2010). Additional neurological assessment modalities may be 
used as per Investigator’s discretion. 
(5) Post-treatment vital signs (blood pressure, heart rate, respiration rate, and temperature) will be measured within 15 minutes of study treatment administration when 
visit performed at clinic.  
(6) Hemoglobin, Hematocrit (HCT), Red Blood Cells (RBC), White Blood Cells (WBC) with total and differential count, Absolute Neutrophil Count (ANC) and platelets. 
(7) Serum Biochemistry 
 
o Hepatic function indicators: total and direct bilirubin, alkaline phosphatase, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total protein, Lactate 
dehydrogenase (LDH) 
o Renal function indicators: BUN, creatinine 
o Electrolytes: sodium, potassium, chloride, calcium and bicarbonate 
o Other: glucose (random), cholesterol (total) 
(8) ONLY performed on women of childbearing potential. 
(9) Plasma HIV-1 RNA and TruCount T Assay will be performed once every four (4) weeks when subject comes to clinic.  TruCount T Assay includes: Absolute 
Lymphocytes, CD3 cell count, CD4 cell count, CD8 cell count, CD3%, CD4% and CD8% 
(10) Monogram Biosciences Trofile® DNA or RNA assay (or both) will be performed at the Virologic Failure Visit depending on the last known HIV-1 RNA levels, along 
with PhenoSense® Entry assay using AMD3100 (X4 inhibitor drug), Maraviroc and PRO 140 (R5 inhibitor drugs). 
(11) Sample will be collected at least once every eight (8) weeks when subject comes to clinic. 
(12) Single copy HIV-1 RNA Assay will be performed only if preceding viral load result is <20 copies/ml. 
 
(13) Monogram Biosciences GenoSure Archive Assay will be collected at SV, EOT, and in case of VF if last known HIV-1 RNA level is < 1000 copies/mL.  
(14) PhenoSense® GT (and PhenoSense Integrase and GeneSeq Integrase testing, if applicable, will also be collected if part of baseline ART regimen in PRO140_CD03 
study) will be collected at VF visit if last known HIV-1 RNA level is >1000 copies/mL.. 
(15) PRO 140 injections should be administered by qualified healthcare professional or self-administered by trained subjects 
(16) Baseline ART regimen will be restarted one week prior to final PRO 140 treatment visit and overlap with study treatment given at EOT or reinitiated at the time of 
virologic failure.  
(17) Injection Site Reaction Assessment as assessed by Investigator (or designee) at clinic visits and by visiting nurse or qualified medical professional during home visits. 
Injection Site Reaction Assessment will not be applicable if PRO 140 is self-administered by subjects at home.  
(18) Only AEs occurring after treatment injection at TE1 onwards will be captured, in addition to any ongoing AEs from PRO140_CD03 study.   
(19) To be collected every 12 weeks during the treatment extension phase. 
(20) Refer to Section 7.10.14. 
 
 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                              Page 49 of 103 
4.1 
SCREENING PHASE 
4.1.1 Screening Phase 
The subject 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.  The unique identification number (screening number) assigned under 
PRO140_CD03 study will be retained.  
All study centers will be instructed to maintain the study-specific screening and enrollment logs at 
their sites.   
Once the ICF has been signed, screening procedures and information will be obtained to confirm 
subject eligibility including: 
• Demographic information (see Section 7.3),  
• Current medications review (see Section 7.5),  
• Physical examination (see Section 7.6),  
• Electrocardiogram (ECG) (see Section 7.7),  
• Post-treatment vital signs (see Section 7.9), 
• Collection of Blood Specimens (see Section 7.10) for 
o Complete Blood Count 
o Biochemistry 
o Plasma HIV-1 RNA level 
o TruCount T Assay 
o PK sample for PRO 140 
o Anti-idiotypic Antibody for PRO 140 
o HIV-1 Drug Resistance Assay (GenoSure Archive® Assay) 
o HIV-1 Co-Receptor Tropism (Trofile® DNA Assay) 
▪ CCR5 Genotyping will be tested using residual whole blood sample from 
tropism sample collected at Screening 
o HIV-1 PhenoSense® Entry (Monogram BioSciences) 
All screening information will be fully documented in the subject’s medical records (i.e., source 
documents).  

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                              Page 51 of 103 
As shown in Figure 3-1, subjects receiving PRO 140 350mg or 525mg experiencing virologic 
failure in Treatment Extension Phase will have option of reinitiating ART regimen or beginning 
PRO 140 525mg or 700mg SC weekly injections, respectively, for the remainder of Treatment 
Extension Phase.  
All subjects who experience virologic failure at any point during the Treatment Extension Phase 
will undergo the Virologic Failure (VF) Visit assessments and will be followed up every 4 weeks 
until viral suppression is achieved (i.e., plasma HIV-1 RNA levels decline to < 50 copies/mL). 
Virologic failure subjects will also return to clinic for long-term follow-up at 6 months and at one 
year from the time of the Virologic Failure (VF) Visit. Subjects who do not experience virologic 
failure will be followed up every 2 weeks for total of 4 weeks. 
Study subjects will resume prior or alternate HAART regimen: 
•  One week prior to the end of Treatment Extension Phase, or  
• 
Anytime during the Treatment Extension Phase, if virologic failure occurs or have met any other 
criteria for discontinuation of study treatment as specified in Section 5.2.1 of the protocol. Subjects 
will be allowed to continue PRO 140 monotherapy while waiting for new ART regimen to be 
constructed by the Investigator. 
Note: 
➢ Subjects may return to clinic for an additional blood draw in-between the clinic visits for 
plasma HIV-1 RNA levels, per the discretion of the Investigator. 
➢ Virologic failure is defined as two consecutive levels of ≥ 200 copies/mL. Subjects 
experiencing virologic failure while on 350 mg or 525mg dose have option of re-initiating 
ART regimen or continuing the treatment with higher dose of PRO 140 (525mg SC or 
700mg) weekly injection for remainder of Treatment Phase or until subsequent virologic 
failure event after viral re-suppression on higher dose. Subjects who meet any criteria (other 
than virologic failure) for discontinuation of study treatment as specified in Section 5.2.1 of 
the protocol, will undergo EOT Visit assessments and enter the Follow-up Phase of the 
study. 
➢ Subjects who do not experience virologic failure will enter the Follow-up Phase of the study 
at the end of Treatment Extension Phase. 
 
Visits during the Treatment Extension Phase will commence on TE1, i.e. the date of first treatment, 
with weekly visits (± 3 days) thereafter.  The first Treatment Extension Visit (TE1) will take place 
within 10 days of last treatment visit under CD03 study (i.e. T48 visit). 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                              Page 52 of 103 
Note: Although the screening visit for CD03-Extn can be done at T46, 47, or 48 visit for CD03 
study, all subjects must complete T48 treatment dosing under the CD03 study, before receiving first 
Treatment (at TE1 visit) under the CD03 Extension study. 
4.2.1 Treatment Extension Phase: Treatment Extension Visit-1 (TE1)  
The following assessments will be performed at TE1 visit, unless otherwise specified: 
Pre-Treatment 
• Confirmation of eligibility criteria by reviewing test results and other criteria assessments 
performed at Screening Visit (see Section 7.2 ) 
• Symptom-directed physical examination (see Section 7.6) 
• Change in concomitant medications (see Section 7.5) 
• Assessment of Adverse Events (AE) (see Section 9)  
• Vital signs, pre- and post-treatment (see Section 7.9) 
• Collection of blood specimens (see Section 7.10) for 
o Plasma HIV-1 RNA level  
o TruCount T Assay 
o CCR5 Receptor Occupancy (IncellDx Lab) 
o HIV Drug Resistance Assay 
o Plasma HIV-1 RNA Single Copy Assay 
o PK sample for PRO 140 
o Anti-idiotypic Antibody for PRO 140 
• Urine pregnancy test (see Section 7.10.3) 
Administration of PRO 140 
Study treatment will be administered as a subcutaneous injection in the abdomen.  
Subjects will receive PRO 140 350mg, delivered as two 1 mL injections on opposite sides of the 
abdomen. PRO 140 525mg is delivered as two 1.5mL injections on opposite sides of the abdomen 
and PRO 140 700mg is delivered as two 2 mL injections on opposite sides of the abdomen. 
Alternatively, the 525mg dose can be delivered as three 1mL injections (one injection on one side 
of the abdomen and two injections on the opposite side of the abdomen) or a single 3.0mL injection 
on either side of the abdomen, and the 700mg dose can be delivered as four 1mL injections (two 
injections on opposite sides of the abdomen) 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                              Page 53 of 103 
Note: All treatment injections must be administered by a qualified medical professional (MD, DO, 
PA, LPN, LVN, NP, RN, or CMA if permitted by state law) at clinic site or home visit or self-
administered by subjects, for the duration of the Treatment Extension Phase. 
Post-Treatment 
• Injection Site Reaction Assessment (see Section 7.12) 
➢ Note: To assess injection site reactions, the Investigator will use the DAIDS AE grading 
table (refer to Section 16.3). 
• Vital signs (see Section 7.9) will be assessed again within 15 minutes of study treatment 
administration. 
4.2.2 Treatment Extension Phase: Subsequent Treatment Extension Visits 
The following assessments will be performed at each treatment visit, unless otherwise specified: 
• Assess for any Adverse Events and changes in Concomitant Medications (see Section 9 and 
7.5), 
• Symptom-directed physical examination (see Section 7.6),  
• Vital Signs (see Section 7.9) 
➢ Note: Post-treatment vital signs will be assessed within 15 minutes following study 
treatment administration 
• Collection of blood specimens (see Section 7.10) for 
o Plasma HIV-1 RNA level  
o TruCount T Assay 
➢ Note: Blood sample for plasma HIV-1 RNA level and , TruCount T Assay 
should be collected at least once every four weeks starting from TE1 when 
subject comes to clinic. 
o Plasma HIV-1 RNA Single Copy Assay  
o PK for PRO 140 
o Anti-idiotypic antibody for PRO 140 
➢ Note: Blood sample for plasma HIV-1 RNA Single Copy Assay, PK sample for 
PRO 140 and Anti-idiotypic antibody to PRO 140 should be collected at least 
once every eight weeks starting from TE1 when subject comes to clinic. 
o Complete Blood Count 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                              Page 54 of 103 
o Biochemistry 
o Coagulation Indices 
➢ Note: Complete Blood Count, Biochemistry, and Coagulation Indices should 
be collected once every 12 weeks when subject comes to clinic. 
o CCR5 Receptor Occupancy 
➢ Note: Blood will be taken prior to PRO 140 injection (trough sample) and 24-
48 hours (peak sample) after the PRO 140 injection to check for CCR5 
occupancy, and correlative analysis will be performed with PRO 140 PK 
concentration and HIV-1 RNA levels. This assessment will be performed up to 5 
times at different treatment visits.  
• Urinalysis 
➢ Note: Urinalysis should be collected once every 12 weeks when subject comes 
to clinic. 
• Study treatment administration (PRO 140) 
Note: All treatment injections must be administered by a qualified medical professional 
(MD, DO, PA, LPN, LVN, NP, RN, or CMA if permitted by state law) at clinic site or home 
visit or self-administered by subjects during the Treatment Extension Phase. 
• Injection site reaction assessment (see Section 7.12) 
➢ Note: To assess injection site reactions, the Investigator will use the DAIDS AE grading 
table (refer to Section 16.3). 
• Re-initiate previous antiretroviral regimen or an alternative regimen selected by the treating 
physician one week prior to EOT, if viral load remain suppressed. 
4.2.3 Treatment Extension Phase: End of Treatment Visit (EOT) 
The following assessments will be performed at End of Treatment (EOT) visit: 
• Assess for any Adverse Events and changes in Concomitant Medications (see Section 9 and 
7.5), 
• Complete physical examination (see Section 7.6),  
• Neurological assessment (see Section 7.8)  
• Vital signs (see Section 7.9) 
• Electrocardiogram (ECG) (see Section 7.7)  

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                              Page 55 of 103 
• Collection of blood specimens (see Section 7.10) for 
o Complete Blood Count 
o Biochemistry 
o Coagulation Indices 
o Plasma HIV-1 RNA level  
o TruCount T Assay 
o HIV-1 Single Copy RNA Assay 
o HIV-1 Drug Resistance Assay (GenoSure Archive) 
o Trofile DNA/RNA Assay 
o PhenoSense® Entry Assay 
o PK for PRO 140 
o Anti-idiotypic antibody for PRO 140 
o CCR5 Receptor Occupancy 
• Urinalysis 
• Study treatment administration (PRO 140) 
Note: All treatment injections must be administered by a qualified medical professional 
(MD, DO, PA, LPN, LVN, NP, or RN) at clinic site or home visit or self-administered by 
subjects during the Treatment Extension Phase. 
• Injection site reaction assessment (see Section 7.12) 
➢ Note: To assess injection site reactions, the Investigator will use the DAIDS AE grading 
table (refer to Section 16.3). 
• Continue previous antiretroviral regimen or alternative regimen that was initiated one week 
prior to EOT, if viral load remain suppressed. 
4.3 
VIROLOGIC FAILURE (VF) VISIT  
Virologic failure is defined as two consecutive levels of ≥ 200 copies/mL. 
Subjects receiving PRO 140 350mg or 525mg that experience virologic failure have the option of 
re-initiating ART regimen or receiving a higher dose of PRO 140. 
 Subjects receiving 350 mg can increase their dose to 525mg for the remainder of the Treatment 
Extension Phase and those receiving 525 mg can increase their dose to 700 mg for the remainder 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                              Page 56 of 103 
of the Treatment Extension Phase. 
 
The following assessments will be performed for subjects who experience virologic failure at any 
time during the Treatment Extension Phase prior to entering Follow-up Phase: 
• Assess for any Adverse Events and changes in Concomitant Medications (see Section 9 and 
7.5), 
• Complete physical examination (see Section 7.6), 
• Vital signs (see Section 7.9), 
• Neurological assessment (see Section7.8), 
• Electrocardiogram (ECG) (see Section 7.7) 
• Collection of blood specimens (see Section 7.10) for 
o Complete Blood Count 
o Biochemistry 
o Plasma HIV-1 RNA level 
o TruCount T Assay  
o HIV Drug Resistance Assay (PhenoSense GT) 
o HIV Trofile® RNA/DNA Assay  
o CCR5 Receptor Occupancy (IncellDx Lab) 
o PhenoSense® Entry Assay 
o Quest Diagnostics Tropism Assay 
o PK for PRO 140 
o Anti-idiotypic antibody for PRO 140 
• Re-initiate previous antiretroviral regimen or an alternative regimen selected by the treating 
physician 
4.4 
FOLLOW-UP PHASE 
The duration of follow-up depends on whether subject experiences virologic failure. 
• Subjects who experience virologic failure within the Treatment Extension Phase will be 
assessed every 4 weeks until viral suppression is achieved (i.e., plasma HIV-1 RNA levels 
decline to < 50 copies/mL). Additionally, virologic failure subjects will return to clinic for 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                              Page 57 of 103 
long-term follow-up at 6 months and at one year from the time of the Virologic Failure (VF) 
Visit. 
• Subjects who do not experience virologic failure at the end of the Treatment Extension 
Phase, will be assessed every 2 weeks for total of 4 weeks. 
4.4.1 Follow-Up Visits 
4.4.1.1 Short-Term Follow-Up Visits 
4.4.1.1.1 Virologic Failure Subjects 
Subjects who experience virologic failure during the Treatment Extension Phase will be assessed 
every 4 weeks until the viral suppression is achieved (i.e., plasma HIV-1 RNA levels decline to < 
50 copies/mL). 
The following assessments will be performed at each follow-up visit (VF-FU1, VF-FU2, VF-FU3 
etc.), unless otherwise specified: 
• Assess for any Adverse Events and changes in Concomitant Medications (see Section 9 and 
7.5), 
• Symptom-directed physical examination (see Section 7.6), 
• Vital signs (see Section 7.9), 
• Collection of blood specimens (see Section 7.10) for 
o Plasma HIV-1 RNA level 
o TruCount T Assay 
o Anti-idiotypic antibody for PRO 140 (VF-FU2 only) 
• Continue previous antiretroviral regimen or an alternative regimen selected by treating 
physician 
4.4.1.1.2 Non Virologic Failure Subjects 
Subjects who do not experience virologic failure at the end of the Treatment Extension Phase, will 
be assessed every 2 weeks for total of 4 weeks. 
The following assessments will be performed at each follow-up visit (NVF-FU1 and NVF-FU2 
visits), unless otherwise specified: 
• Assess for any Adverse Events and changes in Concomitant Medications (see Section 9 and 
7.5), 
• Symptom-directed physical examination (see Section 7.6), 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                              Page 58 of 103 
• Vital signs (see Section 7.9), 
• Collection of blood specimens (see Section 7.10) for 
o Plasma HIV-1 RNA level 
o TruCount T Assay 
o Anti-idiotypic antibody for PRO 140 (NVF-FU2 only) 
• Continue previous antiretroviral regimen or an alternative regimen selected by treating 
physician 
4.4.1.2 Long-Term Follow-Up Visits 
Additionally, subjects who experience virologic failure will also return to clinic for the long-term 
follow-up at 6 months and at one year from the time of the Virologic Failure Visit. 
The following assessments will be performed at VF-6mFU and VF-12mFU visit, unless otherwise 
specified: 
• Assess for any Adverse Events and changes in combination antiretroviral therapy (see 
Section 9 and 7.5) 
➢ 
Note: Only SAEs and any AE that is considered possibly or probably or definitely 
related to the study treatment by the Investigator will be captured during the long-
term follow-up phase. 
• Collection of blood specimens (see Section 7.10) for 
o Plasma HIV-1 RNA level 
o TruCount T Assay  
o HIV Drug Resistance Assay (PhenoSense GT) 
o HIV Trofile® DNA or RNA Assay  
o HIV PhenoSense Entry® Assay 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                              Page 59 of 103 
5 
SUBJECT COMPLETION AND WITHDRAWAL 
5.1 
SUBJECT COMPLETION 
• A subject who completes the Treatment Extension Phase and 4-week Non-Virologic 
Failure Follow-Up Phase will be considered as having completed the study. 
• A subject who experiences virologic failure during the Treatment Extension Phase, 
undergoes the Virologic Failure (VF) Visit assessments and is followed up until viral 
suppression is achieved in addition to completing the Virologic Failure – 12 month 
Follow-Up (VF-12mFU) Visit, will be considered as having completed the study. 
5.2 
SUBJECT WITHDRAWAL 
A subject who enters the Treatment Extension Phase but does not complete the study, as defined in 
Section 5.1, is considered to have prematurely withdrawn from the Study. 
All subjects have the right to withdraw at any point during treatment without prejudice to future 
care. It will be documented whether or not each subject completed the clinical study. If for any 
subject, study treatment or observations were discontinued, the reason(s) will be recorded. 
The Investigator can discontinue a subject at any time if it is considered medically necessary.  
In addition, subjects WILL be withdrawn from the study, in consultation with the Medical Monitor 
and the Investigator, if any of the following are met: 
• A subject is significantly non-compliant with the requirements of the protocol 
• The Investigator determines that it is in the best interest of the subject 
• Subject chooses to withdraw or is withdrawn due to an adverse event 
• Recurring Grade 2 study drug injection related AE at two consecutive visits  
• Occurrence of Grade 3 study drug injection related AE  
• A subject becomes pregnant  
Note: The pregnancy will be followed to term for safety follow-up. Relevant safety information 
collected after the study has completed will be reported as supplemental information.  
• Discontinuation of study by Sponsor 
Premature withdrawal from the study MAY occur if, in consultation with the Medical Monitor and 
the Investigator, any of the following are met: 
• A subject is treated with a prohibited medication.  
• Major protocol violation 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                              Page 60 of 103 
5.2.1 Discontinuation of Study Treatment 
Discontinuation of study treatment (PRO 140) and resumption of previous or alternative 
antiretroviral regimen is recommended if: 
• Subject experiences virologic failure (defined as two consecutive HIV-1 RNA levels of ≥ 200 
copies/mL)  
Note: Subjects receiving PRO 140 350mg or 525mg that experience virologic failure have the 
option of re-initiating ART regimen or receiving a higher dose of PRO 140 525mg or 700mg, 
respectively, for the remainder of the Treatment Extension Phase or until subsequent virologic 
failure event after viral re-suppression on higher dose. 
• Develops AIDS-defining conditions as specified in Appendix I (Section 16.1) under which 
subject is unable to continue treatment with study drug (PRO 140), or subject require treatment 
with prohibited concomitant medications 
• Shows signs or symptoms of clinically significant immunosuppression 
• Subject or the subject’s clinician wishes to restart ART 
• Subject becomes pregnant 
5.2.2 Data Collected for Withdrawn Subjects 
Subjects may withdraw from the study or discontinue study treatment at any time; however, 
CytoDyn is dedicated to minimizing missing data in this study. It is therefore suggested that all 
subjects, regardless of whether they continue to receive study treatment, continue within the 
study. 
Investigators considering discontinuing study treatment should contact the medical monitor prior 
to such discontinuation. Subjects who have study treatment discontinued will continue to be 
followed, per protocol, whenever possible. Subjects who have study treatment discontinued due 
to a serious adverse event will be followed until resolution or stabilization of the event. 
In the event that a subject is withdrawn from the study at any time due to an adverse event or serious 
adverse event (SAE), the procedures stated in Section 9.1.1 or 9.2.1, respectively must be followed. 
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 eCRF. 
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.  
5.3 
SCREEN FAILURES 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                              Page 61 of 103 
A subject who has signed a consent form, but is not treated is classified as a screen failure. Subject 
number, demographics and reason for screen failure will be recorded. 
If a subject initially fails to meet inclusion/exclusion criteria and is later reconsidered for 
participation, the subject will be re-consented and retain the unique screening number assigned 
under the PRO 140_CD 03 study. 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                              Page 62 of 103 
6 
STUDY TREATMENT 
6.1 
INVESTIGATIONAL PRODUCT DESCRIPTION 
PRO 140 is a humanized IgG4, monoclonal antibody (mAb) to the chemokine receptor CCR5. 
PRO 140 is provided at a concentration of 175 mg/mL and is intended for SC route of 
administration. 
Kits will be labeled with a unique identification number. Each kit used during the Treatment Phase 
will contain vials of PRO 140 for SC injection. For the 350 mg dose, one milliliter (1 mL) of PRO 
140 solution will be drawn from each vial and loaded into the syringe. A total of 350mg, 525mg, 
or 700mg (175 mg/mL) of PRO 140 is delivered as two 1 mL, 1.5 mL, or 2mL injections, 
respectively, administered subcutaneously on opposite sides of the abdomen or as one of the 
alternative methods listed in the table below. One study injection kit will be assigned per subject 
per treatment, except for 350mg dose in which one kit can be used for 2 visits. Each vial of the PRO 
140 product contains ~1.4 or 2.4 mL antibody at 175mg/mL in a buffer containing 5 mM L-
histidine, 15.0 mM glycine, 95 mM sodium chloride, 0.3% (w/v) sorbitol, 0.005% (w/v) polysorbate 
20 (Tween 20®), and sterile water for injection, at pH of 5.5. 
PRO 140 Kits Containing 1.4 mL per Vial 
PRO 140 
Dose 
# of Vials 
Used per 
Dose 
Total 
Injection 
Volume (mL) 
Volume (mL) 
Administered 
per Injection* 
Volume (mL) 
Discarded per 
Vial 
350 mg 
2 
2 
1 
0.4 
525 mg 
3 
3 
1.5 
0.4 
700 mg 
4 
4 
2 
0.4 
PRO 140 Kits Containing 2.4 mL per Vial 
PRO 140 
Dose 
# of Vials 
Used per 
Dose 
Total 
Injection 
Volume (mL) 
Volume (mL) 
Administered 
per Injection* 
Volume (mL) 
Discarded per 
Vial 
350 mg 
1** 
2 
1 
0.4 
525 mg 
2 
3 
1.5 
0.9 
700 mg 
2 
4 
2 
0.4 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                              Page 64 of 103 
Figure 6-3) designated for use in this clinical protocol. Each 350mg kit contains two labeled vials 
and syringe labels, and each 525mg kit contains three labeled vials and syringe labels. The 700mg 
dose will consist of two 350mg kits (4 labeled vials and syringes total). 
 
Figure 6-1: 
PRO 140 (CHO) 175mg/mL - Vial Label 
Protocol: PRO 140_CD03/Ext                  Kit No. xxxxx 
Subject No. _________               
Single use 3 mL vial contains 1.4 mL of PRO 140 (175 
mg/mL) solution for subcutaneous injection 
Store at 2oC to 8oC (36oF to 46oF) 
USE AS PER STUDY PROTOCOL 
Caution: New Drug – Limited by Federal (or United States) 
Law to Investigational Use 
CytoDyn Inc., Vancouver, WA, USA 
Protocol: PRO 140_CD03/Ext                   Kit No.  xxxxx 
Subject No. _________               
Single use 3 mL vial contains 1.4 mL of PRO 140 (175 
mg/mL) solution for subcutaneous injection 
Store at 2oC to 8oC (36oF to 46oF) 
USE AS PER STUDY PROTOCOL 
Caution: New Drug – Limited by Federal (or United States) 
Law to Investigational Use 
CytoDyn Inc., Vancouver, WA, USA 
 
Protocol: PRO 140_CD03/Ext                  Kit No. xxx 
Subject No. _________               
Single use 3 mL vial contains 2.4 mL of PRO 140 (175 
mg/mL) solution for subcutaneous injection 
Store at 2oC to 8oC (36oF to 46oF) 
USE AS PER STUDY PROTOCOL 
Caution: New Drug – Limited by Federal (or United States) 
Law to Investigational Use 
CytoDyn Inc., Vancouver, WA, USA 
Protocol: PRO 140_CD03/Ext                   Kit No.  xxx 
Subject No. _________               
Single use 3 mL vial contains 2.4 mL of PRO 140 (175 
mg/mL) solution for subcutaneous injection 
Store at 2oC to 8oC (36oF to 46oF) 
USE AS PER STUDY PROTOCOL 
Caution: New Drug – Limited by Federal (or United States) 
Law to Investigational Use 
CytoDyn Inc., Vancouver, WA, USA 
 
Figure 6-2: 
PRO 140 (CHO) 175mg/mL - Syringe Label 
Protocol: PRO 140_CD03/Ext                                     Contents of Kit No. xxxxx 
This syringe contains 1mL, 1.5mL, or 2mL PRO 140 (175 mg/mL) solution for 
subcutaneous injection 
USE AS PER STUDY PROTOCOL 
Caution:  New Drug – Limited by Federal (or United States) Law to 
Investigational Use 
CytoDyn Inc., Vancouver, WA, USA 
 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                              Page 65 of 103 
Protocol: PRO 140_CD03/Ext                                     Contents of Kit No. xxxxx 
This syringe contains 1.5 mL PRO 140 (175 mg/mL) solution for subcutaneous 
injection 
USE AS PER STUDY PROTOCOL 
Caution:  New Drug – Limited by Federal (or United States) Law to 
Investigational Use 
CytoDyn Inc., Vancouver, WA, USA 
 
 
 
Figure 6-3: 
PRO 140 (CHO) 175mg/mL - Kit Label 
Protocol: PRO 140_CD03/Ext                                                      Kit No. xxxxx 
Site No. ____________                           Subject No.  ________________    
This kit contains 2 single-use vials 
Each 3 mL vial contains 1.4 mL of PRO 140 (175 mg/mL) solution for 
subcutaneous injection 
Store at 2oC to 8oC (36oF to 46oF) 
USE AS PER STUDY PROTOCOL 
Caution: New Drug – Limited by Federal (or United States) Law to Investigational 
Use 
CytoDyn Inc., Vancouver, WA, USA 
 
Protocol: PRO 140_CD03/Ext                                                      Kit No. xxxxx 
Site No. ____________                           Subject No.  ________________    
This kit contains 3 single-use vials 
Each 3 mL vial contains 1.4 mL of PRO 140 (175 mg/mL) solution for 
subcutaneous injection 
Store at 2oC to 8oC (36oF to 46oF) 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                              Page 66 of 103 
USE AS PER STUDY PROTOCOL 
Caution: New Drug – Limited by Federal (or United States) Law to Investigational 
Use 
CytoDyn Inc., Vancouver, WA, USA 
 
Protocol: PRO 140_CD03                                                          Kit No. xxx 
Site No. ____________                           Subject No.  ________________    
This kit contains 2 single-use vials 
Each 3 mL vial contains 2.4 mL of PRO 140 (175 mg/mL) solution for 
subcutaneous injection 
Store at 2oC to 8oC (36oF to 46oF) 
USE AS PER STUDY PROTOCOL 
Caution: New Drug – Limited by Federal (or United States) Law to Investigational 
Use 
CytoDyn Inc., Vancouver, WA, USA 
 
NOTE: Subjects with low body fat percentages may find subcutaneous injections uncomfortable esp. in case 
of 1.5 mL or 2 mL injection for the 525mg or 700mg dosing. In such cases, PRO 140 525 mg can be injected 
as three 175mg/ml injections and PRO 140 700mg 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. 
The pharmacy manual provides the criteria regarding vial acceptance or rejection, as well as 
instructions for the preparation of the IP syringes to be used to administer drug.  
6.3 
INVESTIGATIONAL PRODUCT STORAGE  
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 for each subject must be available for inspection at any time. A study CRA assigned 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                              Page 67 of 103 
to monitor the investigational site will review these documents once study drug has been received 
by the investigational site. Study drug will be accounted for on an ongoing basis during the study. 
6.4 
INVESTIGATIONAL PRODUCT ADMINISTRATION 
Guidelines for dose preparation can be found in the pharmacy manual. 
PRO 140 will be provided to the administering personnel in single-use syringes prepared from vials 
of study drug stored at 2-8°C at the site pharmacy prior to use. Each of two syringes is filled to 
deliver 1 mL, 1.5 mL, or 2 mL of study drug.  
Equivalent volumes of study drug will be administered subcutaneously on opposite sides of the 
abdomen.  However, based on subject preference or investigator discretion subjects receiving each 
of the doses can be administered using an alternate approach as follows: 
350mg Dose: 
• One 2 mL injection on one side of the abdomen. 
525mg Dose: 
• One 3 mL injection on one side of the abdomen. 
• Three 1 mL injections, two on one side of the abdomen and one on the other side. 
700 mg Dose: 
• Four 1 mL injections, on opposite sides of the abdomen, or other location. 
 
A 25-guage needle should be used to remove IP from vial and for administration to subjects, and 
drug should not be held in syringe for longer than 1 hour. 
IP should be administered slowly over 15 seconds per mL. 
Following each SC delivery of drug, careful examination will be made to assess the appearance of 
any study drug Injection Site Reactions (ISRs) as described in Section 16.3.  
All doses of study drug will be administered as SC injection by a qualified medical professional 
(MD, DO, PA, LPN, LVN, NP, RN, or CMA if state law permits) at clinic site or home visit or 
self-administered by subjects. 
Note: It is preferred that the same area of the abdomen 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. 
6.5 
INVESTIGATIONAL PRODUCT RECEIPT AND ACCOUNTABILITY 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                              Page 68 of 103 
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 drug in compliance with applicable regulations. 
6.6 
INVESTIGATIONAL PRODUCT 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. 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                              Page 69 of 103 
7 
DESCRIPTION OF PROTOCOL ASSESSMENTS AND PROCEDURES 
7.1 
INFORMED CONSENT 
Written informed consent will be obtained for this study by the Investigator or designee from all 
subjects before the performance of any protocol-specific procedure. This study will be conducted 
in accordance with the provisions of the Declaration of Helsinki.  
In obtaining and documenting informed consent, the Investigator must comply with applicable 
regulatory requirements and must adhere to Good Clinical Practice (GCP). The Investigator, or 
designee, must fully inform subjects of all pertinent aspects of the study. Before informed consent 
may be obtained, the Investigator, or a person designated by the Investigator, must provide the 
subject ample time and opportunity to inquire about details of the study and to decide whether or 
not to participate in the trial. All questions about the trial 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 
During the Screening Visit and at TE1 Visit (prior to treatment administration), the Investigator 
must assess a subject’s continued suitability and eligibility for the trial. The Inclusion and Exclusion 
criteria of this Protocol are described in Sections 3.3.1 and 3.3.2. If the subject is not suitable or 
eligible for the trial then the subject will be a screen failure.  
7.2.1 Re-screening 
If a subject initially fails to meet inclusion/exclusion criteria, and is later reconsidered for 
participation, the subject will be re-consented and retain the unique screening number assigned 
under PRO 140_CD 03 study. 
7.3 
DEMOGRAPHIC INFORMATION 
For the purposes of this study, demographic information will include: 
• Dates of ICF signature  
• Date of birth 
• Gender 
• Race (American Indian/Alaskan Native, Asian, Black/African American, Native 
Hawaiian/Pacific Islander, Caucasian, or other) 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                              Page 70 of 103 
• 
Ethnicity (Hispanic/Latino or Not Hispanic/Latino) 
7.4 
MEDICAL HISTORY 
Medical history will be brought forward from PRO140_CD03 study. 
7.5 
CONCOMITANT MEDICATIONS AND NON-STUDY TREATMENTS  
Prior medications/therapies will be brought forward from PRO140_CD03 study. 
Subjects must be questioned at each study visit concerning any new medications or changes in 
current medications including over-the-counter 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) 
Please refer to Exclusion Criteria (Section 3.3.2) for a list of prohibited treatments and/or 
procedures. All other medications that are appropriate for the care of the subject may be prescribed. 
If concomitant medications are started during the study, the indication for the concomitant 
medication should be considered an AE. 
7.5.1 Excluded Medications and Therapies 
1. Use of concomitant antiretroviral therapy is NOT allowed during the Treatment Extension 
Phase of the study EXCEPT for one week overlap of existing retroviral regimen and PRO 140 
at the end of the treatment in subjects who do not experience virologic failure. Subject is allowed 
to re-initiate antiretroviral therapy during the Treatment Extension Phase, if virologic failure 
occurs or if subject meets any other criteria for discontinuation of study treatment as specified 
in Section 5.2.1 of the protocol. 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                              Page 71 of 103 
2. Use of oral or parenteral corticosteroids (> 5 mg/day) is NOT allowed during the study, with 
the following exceptions:  
o Use of chronic systemic corticosteroids at replacement doses (e.g., < 5mg/day prednisone) 
AND use of inhaled, nasal, or topical steroids are allowed. 
o Use of short course of systemic corticosteroids (Medrol pack) after TE2 will only be allowed 
with prior approval from the sponsor. 
3. Use of radiation or cytotoxic chemotherapy, immunosuppressants and immunomodulating 
agents (e.g., interleukins, interferons) or agents with known anti-HIV activity (i.e., 
hydroxyurea, foscarnet) are NOT allowed during the study. 
4. Use of any non-FDA approved/investigational therapy  
7.5.2 Allowable Medications and Therapies 
All other medications/therapies that are not otherwise prohibited and, in the judgment of the 
Investigator, are required for proper medical care of the subject may be prescribed. 
7.6 
PHYSICAL EXAMINATION 
The complete physical examination will include routine examinations for the following: 
• General Appearance 
• Head, Ears, Eyes, Nose, Throat (HEENT) 
• Lymph Nodes 
• Heart/Cardiovascular abnormalities 
• Respiratory 
• Abdomen 
• Genitourinary 
• Musculoskeletal and Extremities  
• Neurologic abnormalities  
• Dermatologic abnormalities 
• Any other body system for which an abnormality is noted and which, in the opinion of the 
Investigator, is relevant to the safety of the subject or could impact safety or efficacy results 
for the subject; i.e., the abnormality is clinically significant (CS).  
Each abnormality will be recorded and the Investigator will record an assessment of its clinical 
significance.  

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                              Page 72 of 103 
The complete physical examination will be conducted at the Screening Visit (SV), End of 
Treatment Visit (EOT) and at Virologic Failure (VF) Visit. Only symptom-directed physical 
examination will be performed at scheduled and unscheduled treatment and follow-up visits 
conducted within the clinic. 
7.7 
ELECTROCARDIOGRAM 
A resting 12-lead ECG will be conducted at the Screening Visit (SV) and at EOT/VF visit and the 
results will be evaluated by the Investigator. Only those subjects who have normal or not-clinically 
significant results at the Screening Visit (SV) will be enrolled in this study. 
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.  
7.8 
NEUROLOGICAL ASSESSMENT 
Neurological assessment will be performed by the Principal Investigator or Study Coordinator at 
SV and EOT/VF Visit.  
The neurological assessment tool is based on the three question survey used by Simioni et al. 
[Simioni S, 2010]. Refer to Section 16.4 for further details. Additional neurological assessment 
modalities may be used as per Investigator’s discretion. 
7.9 
VITAL SIGNS  
Vital signs will be collected at all study visits performed at the clinic. Vital signs collected during 
the Treatment Extension Phase will be performed post-treatment, and assessed within 15 minutes 
following study treatment administration.  
The following vital signs will be collected at all visits, unless otherwise stated:  
• Seated blood pressure (taken after the subject has been seated for at least 5 minutes) 
• Heart Rate 
• Respiration Rate 
• Temperature 
7.10 CLINICAL LABORATORY ASSESSMENTS 
Blood and urine samples will be collected according to the time points in the schedule of 
assessments for analysis of the following parameters: 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                              Page 73 of 103 
7.10.1 Routine CBC  
• Frequency of testing: At SV, at least once every twelve (12) weeks during Treatment 
Extension Phase, EOT or VF  
• Includes hemoglobin, hematocrit (HCT), red blood cell (RBC) count, white blood cell 
(WBC) count, WBC differential count (%), absolute neutrophils count and platelets count. 
7.10.2 Biochemistry 
• Frequency of testing: At SV, at least once every twelve (12) weeks during Treatment 
Extension Phase, EOT or VF  
• Biochemistry profile includes assessment of: 
Hepatic function indicators: total and direct bilirubin, alkaline phosphatase, aspartate 
aminotransferase (AST), alanine aminotransferase (ALT), total protein, LDH 
Renal function indicators: BUN, creatinine 
Electrolytes: sodium, potassium, chloride, calcium and bicarbonate 
Other: glucose (random), cholesterol (total) 
7.10.3 Coagulation Indices 
• Frequency of testing: At least once every twelve (12) weeks during Treatment Extension 
Phase, EOT, or VF 
• Prothrombin time (PT) and International Normalized Ratio (INR) 
7.10.4 Urinalysis 
• Frequency of testing: At least once every twelve (12) weeks during Treatment Extension 
Phase, EOT, or VF 
• 
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 
7.10.5 Urine pregnancy test  
• Frequency of testing: At TE1 prior to first treatment administration 
• A urine sample will be collected from female subjects of childbearing potential. This test 
will be performed at the study site using a commercially available kit. 
7.10.6 Plasma HIV-1 RNA level and TruCount T Assay 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                              Page 74 of 103 
• Frequency of testing: At SV, prior to administration of PRO 140 at Treatment Extension 
Visit 1 (TE1), at least once every four (4) weeks during Treatment Extension Phase, EOT, 
and at VF visit when subject comes to clinic. In addition, blood sample will also be collected 
at all Virologic Failure Follow-up (VF-FU) and Non-Virologic Failure Follow-up (NVF-
FU) visits. 
• To assess antiretroviral therapeutic response to PRO 140 or cART regimen 
Note: Plasma HIV-1 RNA level will be measured using Human Immunodeficiency Virus 1 
(HIV-1), Quantitative, RNA (Taqman® Real-Time PCR) test. 
TruCount T Assay includes measurement of Absolute Lymphocytes, CD3 cell count, CD4 
cell count, CD8 cell count, CD3%, CD4% and CD8% 
7.10.7 HIV-1 Trofile® DNA Assay 
• Frequency of testing: At SV, EOT/VF visits, in addition to VF-6mFU and VF-12mFU visits 
if last known HIV-1 RNA level is <1000 copies/mL.  
• To assess HIV-1 co-receptor tropism. This test determines eligibility for CCR5 antagonist 
therapy for patients infected with HIV-1. Only those subjects who have exclusive CCR5-
tropic virus will be eligible to participate in this study. 
• Unlike the standard Trofile® assay (which uses viral RNA), Trofile® DNA Assay can 
determine the coreceptor tropism of a patient’s HIV-1 strain when the patient's viral load is 
undetectable. 
7.10.8 HIV-1 Trofile® RNA Assay 
• Frequency of testing: At VF, VF-6mFU and VF12mFU Visits, if last known HIV-1 RNA 
level is >1000 copies/mL.  
7.10.9 HIV-1 Drug Resistance Assay 
a. GenoSure Archive Assay 
o GenoSure Archive assay provides HIV-1 antiretroviral drug resistance data when 
standard resistance testing cannot be performed due to inadequate plasma viral load. 
o Frequency of sample collection: At SV, and, EOT at VF, VF-6mFU and VF-
12mFU visits, if last known HIV-1 RNA level is <1000 copies/mL. 
b. PhenoSense® GT  
PhenoSense® GT is a combination resistance test for three classes of antiretroviral drugs 
(i.e., nucleoside/nucleotide, non-nucleoside, and protease inhibitors), that provides both 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                              Page 75 of 103 
phenotypic and genotypic results from the same blood sample (viral load ≥500 
copies/mL).  
o Frequency of sample collection: At VF, VF-6mFU and VF-12mFU visits, if last 
known HIV-1 RNA level is >1000 copies/mL. 
c. PhenoSense Integrase and GeneSeq Integrase testing  
PhenoSense Integrase and GeneSeq Integrase testing will be additionally performed in 
conjunction with PhenoSense® GT, if subject has past exposure to an integrase or in 
cases where complex drug resistance patterns is known or suspected. 
Samples for PhenoSense® GT (and PhenoSense Integrase and GeneSeq Integrase 
testing, if collected) will be stored at Lab and will be analyzed only if subject experiences 
virologic failure. 
7.10.10 Plasma HIV-1 RNA Single Copy Assay 
• Frequency of sample collection: At TE1 prior to first treatment administration and at least 
once every eight (8) weeks during Treatment Extension Phase, if last known viral load is < 
20 copies/mL, and EOT. 
• To assess antiretroviral therapeutic response to PRO 140 cART regimen 
7.10.11 PK sample for PRO 140 
• Frequency of testing: At SV, at least once every eight (8) weeks during Treatment Extension 
Phase, EOT/VF visits. 
7.10.12 Anti-idiotypic antibodies to PRO 140 
Frequency of sample collection: At SV, at least once every eight (8) weeks during Treatment 
Extension Phase, EOT/VF visits Additionally, sample will be collected at Virologic Failure 
Follow-up Visit 1 (VF-FU1) and Non-Virologic Failure Follow-up Visit 2 (NVF-FU2) 
7.10.13 PhenoSense® Entry Assay 
• Frequency of testing: At SV, EOT, VF, VF-6mFU and VF-12mFU visits in conjunction 
with tropism assessment  
• 
With AMD3100 (X4 inhibitor drug), Maraviroc and PRO 140 (R5 inhibitor drugs). 
7.10.14 CCR5 Receptor Occupancy  
• 
To assess the number CCR5 receptors on patients’ CD4 cell surface. Of those CCR5 
receptors, the test will also assess the number and percentage of CCR5 receptors that are 
covered by PRO 140. 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                              Page 76 of 103 
• Frequency of testing: This assessment will be performed up to 5 times at different treatment 
visits. Blood will be taken prior to PRO 140 injection (trough sample) and 24-48 hours (peak 
sample) after the PRO 140 injection to check for CCR5 occupancy, and correlative analysis 
will be performed with PRO 140 PK concentration and HIV-1 RNA levels 
7.10.15 All laboratory reports will be reviewed by the Investigator. 
Post-treatment abnormal results that are considered by the Investigator to be clinically significant 
will be recorded as adverse events. If the Investigator judges it necessary, testing may be repeated 
in order to make the determination of clinical significance. Validated, quality-controlled laboratory 
data will be transferred to the main database for analyses. 
7.11 PRO 140 ADMINISTRATION 
Refer to Section 6.4 for details. 
7.12 INJECTION SITE REACTION ASSESSMENT 
At each treatment visit that occurs at the clinical site, an injection site reaction assessment will be 
made for the current and previous injection sites. Injection site reaction assessments are recorded 
by the Investigator starting after the first injection is given. Refer to Sections 9.1.8 and 16.3 for 
more details. 
7.13 COVID-19 GUIDANCE 
The purpose of this guidance is to inform sites how to proceed in light of the challenges faced by 
patients and clinical trial sites as a result of COVID-19 shelter-in-place mandates from state 
governments. The content of this letter is based on FDA Guidance on Conduct of Clinical Trials of 
Medical Products during COVID-19 Pandemic (18 Mar 2020). 
• 
The current schedule of assessments requires subjects to visit the clinic at least once every 
four weeks for lab assessments. Subjects may still continue to receive treatment with PRO 
140 if they are unable to visit the clinic. 
• 
Site staff may visit subjects’ homes to conduct study assessments and/or deliver PRO 140. 
• 
Sites may ship PRO 140 to subjects’ homes if subjects are unable to visit the clinic. 
• If subjects are unable to visit the clinic at least once every four weeks lab assessments will 
be missed. If this occurs site staff should contact subjects weekly by phone to assess: 
o Compliance to study treatment 
o Potential adverse events 
o Changes in concomitant medications 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                              Page 77 of 103 
• 
Sites should document phone calls and include confirmation of compliance to study 
treatment, and report any adverse events and/or changes in medications. 
• 
Subjects who report positive tests results for COVID-19 should have the diagnosis recorded 
as an adverse event. 
• 
Sites should clearly document reasons for failing to obtain required assessments (e.g., 
limitation imposed by COVID-19 leading to the inability to perform the protocol-specified 
assessment). 
• 
Any changes in the study visit schedule or missed visit should be entered as protocol 
deviation in the EDC and reason should be documented as missed study visit or visit 
performed out of window period due to COVID-19. 
• 
If subject is early withdrawn from the study due to COVID-19, the reason should be clearly 
documented in the End of Study (EOS) section in EDC as “study discontinuation due to 
COVID-19”. 
• 
Monitoring activities will be performed remotely until Centers for Disease Control (CDC) 
recommendations allow travel to resume. 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                              Page 78 of 103 
8 
STATISTICAL CONSIDERATIONS 
This section presents general information about statistical considerations and concepts such as 
statistical power, sample size, 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  
All eligible subjects in the study will receive PRO 140 as a 350mg, 525mg, or 700mg subcutaneous 
injection weekly. 
8.2 
DESCRIPTION OF STUDY OUTCOME MEASURES 
8.2.1 Primary Outcome Measures 
The primary outcome measures for this study are: 
• To assess the long term clinical safety of PRO 140 monotherapy regimen 
• Proportion of participants experiencing virologic failure for all subjects and within each 
treatment group 
8.2.2 Secondary Outcome Measures 
There are multiple secondary outcome measures to be assessed in this study: 
• 
Time to virologic failure for all subjects and within each treatment group 
• 
Proportion of participants achieving viral re-suppression (HIV-1 RNA < 50 copies/mL) 
after experiencing virologic failure for all subjects and within each treatment group 
• 
Time to achieving viral re-suppression (HIV-1 RNA < 50 copies/mL) after experiencing 
virologic failure for all subjects and within each treatment group 
• 
Proportion of virologic failure subjects achieving viral re-suppression with re-initiation of 
previous baseline antiretroviral regimen for all subjects and within each treatment group 
• 
Mean change in CD4 cell count, at each visit within the Treatment Phase for all subjects 
and within each treatment group 
Note: Virologic failure is defined as two (2) consecutive plasma HIV-1 RNA levels of ≥ 200 
copies/mL. 
8.2.3 Safety Assessments 
Safety measurements will include:  
• Tolerability of repeated subcutaneous administration of PRO 140 as assessed by Investigator-
evaluation of injection site reactions for all subjects and within each treatment group. 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                              Page 79 of 103 
• Frequency of Grade 2, 3 or 4 adverse events as defined by the DAIDS Adverse Event scale 
• Frequency of treatment–emergent serious adverse events 
8.3 
SAMPLE SIZE DETERMINATION AND RATIONALE 
Sample size determination is not applicable as only those subjects who are currently enrolled in 
PRO 140_CD 03 study are allowed to participate in this study. 
8.4 
RANDOMIZATION AND BLINDING 
This study is an open label study with two treatment arms with no randomization and blinding 
requirements.  
8.5 
INTERIM ANALYSIS  
No planned interim analysis. 
8.6 
GENERAL STATISTICAL CONSIDERATIONS  
8.6.1 Analysis Populations  
 The Safety population is defined as all subjects who received at least one dose of PRO 140. This 
population will be used for the analysis of primary and secondary outcome measures for this study. 
8.6.2 Statistical Methods  
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.  
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 efficacy and safety data from this trial. 
8.6.3 Prognostic Factors/Covariates 
Not applicable.  
8.6.4 Handling of Missing Data 
There will be no imputation of missing data for this study.   
8.6.5 Multicenter Study 
This is a multicenter clinical trial. 
8.7 
DATA SUMMARY 
8.7.1 Subject Disposition 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                              Page 80 of 103 
The disposition of all subjects who sign an ICF will be provided. The number of subjects screened, 
received 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.  
8.7.2 Demographic and Baseline Characteristics 
Demographics and baseline characteristics (i.e., Age, Gender, Time since HIV diagnosis, Viral load 
at Screening Visit, etc.) will be summarized using appropriate descriptive statistics. 
Medical history of the subjects will also be provided as a by-subject listing.  
8.7.3 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. 
8.7.4 Efficacy Analysis 
All data from the primary and secondary outcome measures will be summarized and tabulated 
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.  
8.7.5 Safety Analysis 
The Safety population will be used for the analysis of safety assessments.  
For continuous variables data will be summarized using n, mean, Standard Deviation (SD), 
minimum and maximum values. For categorical variables data will be summarized using frequency 
and percentage.  
8.7.5.1 Adverse Events  
Adverse events will be coded using Medical Dictionary for Regulatory Activities (MedDRA). 
TEAEs are defined as events with an onset on or after the first treatment. TEAEs will be 
summarized by treatment group, System Organ Class, and preferred term. The following TEAE 
summaries will be provided: 
• TEAEs by severity grade 
• TEAEs by relationship to study treatment. 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                              Page 81 of 103 
In addition, separate summaries of SAEs, and AEs resulting in discontinuation of study treatment 
will be presented. 
8.7.5.2 Tolerability Assessment 
All data from tolerability assessments of repeated subcutaneous administration of PRO 140 as 
assessed by Investigator-evaluation of injection site reactions will be summarized.  
8.7.5.3 Clinical Laboratory Data 
All laboratory values will be listed. Laboratory measurements will also be summarized.  
8.7.5.4 Physical Examination  
All physical examination findings will be listed and any abnormality will be summarized.  
8.7.5.5 Vital Signs  
All vital sign assessment findings will be listed and summarized.  
8.7.5.6 ECG Examination  
All ECG examination findings will be listed and any abnormality will be summarized.  
8.7.5.7 Neurological Assessment  
All neurological assessment findings will be listed and any abnormality will be summarized. 
 
 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                              Page 82 of 103 
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 
An adverse event (AE) is defined as any unfavorable or unintended sign, symptom, or disease that 
occurs or is reported by the subject to have occurred, or a worsening of a pre-existing condition. 
An AE may or may not be related to the study treatment.  
AEs will be elicited through direct questioning and subject reports. Any abnormalities in visit 
evaluations, physical examination findings or laboratory results that the Investigator believes are 
clinically significant to the research subject and that occurred after initiation of the first study 
treatment will be reported as AEs. Abnormal findings that are NOT clinically significant (NCS) 
should not be recorded as an AE. 
9.1.1 Reporting of Adverse Events 
Report initiation for all AEs and SAEs will begin at the time of the first treatment extension visit 
and continue up until the final study visit (i.e. up to NVF-FU2 for subject who do not experience 
virologic failure or until viral suppression is achieved for subjects who experience virologic failure). 
Additionally, virologic failure subjects will have a long-term follow-up visits at 6 months and at 
one year from the time of the Virologic Failure Visit. Only SAEs and any AE that is considered 
possibly or probably or definitely related to the study treatment by the Investigator will be captured 
during the Long-term Follow-up Phase of the study. All events will be followed to resolution or 
until 30 days after the subject completes the study. A final assessment of outcome will be made at 
that time. 
All AEs must be recorded in the subject’s medical records and on the eCRFs. 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 9.2), the impact the event had on 
study treatment (see Section 9.1.2 ), the DAIDS AE grade (intensity) of the event (see Section 
9.1.3), the causality of the event (see Section 9.1.4), whether treatment was given as a result of the 
event (see Section 9.1.5), and the outcome of the event (see Section 9.1.6). 
9.1.2 Impact of Study Treatment 
The impact the event had on the study treatment will be assessed as either: none, study treatment 
interrupted, study treatment discontinued, or not applicable. The “not applicable” assessment will 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                              Page 84 of 103 
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 
pattern to treatment with the study treatment.  
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.  
9.1.5 Treatment Given as a Result of the Event 
The event impact in terms of treatment provided will be as either: none, medication administered, 
non-medication therapy administered, surgery, or other (with a specification). 
9.1.6 Outcome Assessment 
The outcome of the event will be assessed as either: resolved, resolved with sequelae, ongoing, or 
death. 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.  
 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                              Page 85 of 103 
9.1.7 Expected / Anticipated Adverse Events 
The most common potential study drug-related adverse reaction reported is mild headache. Other 
adverse events likely to be related to the drug include mild to moderate diarrhea, nausea, and 
fatigue.  
9.1.8 SC Injection-related Events 
SC and IV injections of concentrated protein materials can be associated with injection-related AEs 
that impact the ability to safely and successfully deliver the drug. Local injection-site reactions may 
include pain/discomfort, induration, erythema, nodules/cysts, pruritus, ecchymosis, etc. For SC 
injections, bleeding, absorption of the drug, leakage of drug, and induration at the local injection 
site can be additional complications. Other AEs that are common to monoclonal antibody-based 
therapies are chills, headache, backache, malaise, fever, pruritus, rash, nausea, tingling, and 
hypertension.  
SC injection-related events will be monitored according to the guidelines provided in Section 16.2 
(Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events [DAIDS 
AE Grading Table]). Injection-site reactions thought to be directly related to the injection are 
considered to be AEs of special interest, and a separate guideline for the acquisition of data related 
to this AE of special interest is provided in Section 16.3. 
For subjects who develop grade 1 event or first occurrence of grade 2 events, continue therapy as 
per protocol. If a subject chooses to discontinue study treatment, the site should notify the protocol 
team leadership, and encourage the subject to complete any remaining study visits until the toxicity 
resolves. 
For subjects who develop grade 2 event following study drug injection, the subject should be 
reevaluated closely until the AE returns to Grade ≤1, at which time study treatment may be 
reintroduced at the discretion of the site Investigator. If the same Grade 2 AE recurs following the 
next administration of study drug, study treatment must be permanently discontinued. Subjects 
experiencing Grade 3 AEs requiring permanent discontinuation of study treatment should be 
followed closely for resolution of the AE to Grade ≤ 2 and the team leadership must be notified. 
Subjects with Grade 3 asymptomatic laboratory abnormalities in cholesterol, creatine kinase (CK) 
or triglycerides may continue study treatment. 
For grade 4 events permanently discontinue therapy. 
9.2 
SERIOUS ADVERSE EVENTS (SAE) 
A SAE is defined as any AE that: 
• Results in death 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                              Page 86 of 103 
• Is life threatening (the subject is at immediate risk of dying from the AE) 
• Requires subject hospitalization or prolongs existing hospitalization 
• Results in persistent or significant disability/incapacity  
• Is a congenital anomaly/birth defect 
Important medical events that may not result in death, be life-threatening, or require hospitalization 
may be considered a serious adverse event when, based upon appropriate medical judgment, they 
may jeopardize the subject and may require medical or surgical intervention to prevent one of the 
outcomes listed in this definition. 
If a pregnancy occurs in a subject or partner of a male subject during the study, it must also be 
reported to CytoDyn, Inc. Any pregnant subject must be followed up by the Investigator or designee 
until the child is born. 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. Participants who become 
pregnant will be entered into the Antiretroviral Pregnancy Registry (http://www.apregistry.com). 
9.2.1 Reporting of Serious Adverse Events 
The Investigator is required to report all SAEs that occur during the time period specified in Section 
9.1.1. Once the Investigator becomes aware of an SAE, the SAE should be submitted to 
 
 within 24 hours: 
CRO Medical Monitor 
 
 
 
 
 
 
 
 
 
The 
 may request additional supporting documentation as it becomes 
available, such as lab reports, ECG reports, discharge summary, hospital notes, etc.  
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. Under 
21 CFR 312.32(c), the sponsor is required to notify FDA and all participating investigators in an 
IND safety report (i.e., 7- or 15-day expedited report) of potentially serious risks from clinical trials 
or any other source as soon as possible, but no later than 15 calendar days after the sponsor receives 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                              Page 87 of 103 
the safety information and determines that the information qualifies for reporting. Participating 
investigators include all Investigators to whom the sponsor is providing drug under any of its INDs 
or under any investigator’s IND (21 CFR 312.32(c)(1)). 
9.2.2 SAE Follow-Up 
All subjects experiencing an SAE, including the discontinued subjects, must be closely followed 
until sufficient information is obtained to indicate a return to normal status or until the event 
stabilizes at a level acceptable to the Investigator (i.e., recovery, return to baseline status, no further 
improvement expected, or death). 
For each SAE indicated as an unresolved event on the initial report, regardless of whether the 
subject completed the study or withdrew, the site should submit a follow-up report with updated 
information. 
 
 
 
 
 
 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                              Page 88 of 103 
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/initials 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 monitors, auditors, personnel authorized by the Sponsor, the local IRB, and the FDA are 
eligible to review medical and research records related to this study as a part of their responsibility 
to protect human subjects in clinical research and 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. 
 
 
 
 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                              Page 89 of 103 
11 QUALITY CONTROL AND QUALITY ASSURANCE 
11.1 MONITORING REQUIREMENTS 
In an effort to fulfill the obligations outlined in 21 Code of Federal Regulations (CFR) Part 312 and 
ICH guidelines which requires the Sponsor to maintain current personal knowledge of the progress 
of a study, the Sponsor's designated monitor will visit the center(s) 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.  
The Investigator will permit representatives of the Sponsor and/or designated CRO to inspect all 
eCRFs 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 and diagnostic reports, neurological 
assessment results, etc.  
Site inspections serve to verify strict adherence to the protocol and the accuracy of the data being 
entered on the case report forms, in accordance with federal regulations. A Monitoring Log will be 
maintained at each study site which the monitor will sign, date and state 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. 
For the IA, a cut-off date for data collection and monitoring will be determined and sites will be 
requested to provide current information up to the cut-off date. 
11.2 ACCEPTABILITY OF CASE REPORT FORMS (CRFS) 
Electronic CRFs must be completed for each subject who has signed an informed consent form. 
For subjects who are screen failures, this would be limited to the screen failure eCRF page. All 
source documents and eCRFs will be completed as soon as possible after the subject's visit. 
Corrections to data on the eCRFs will be documented. The Investigator will review eCRFs to 
indicate that, to his/her knowledge, they are complete and accurate. Electronic 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.  

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                              Page 90 of 103 
Approval by the Investigator’s IRB must also be obtained prior to implementation of the change, 
with two exceptions: 
1. When necessary to eliminate apparent immediate hazard to the subject; or 
2. When the modification does not involve the subject’s participation in the trial. 
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 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 eCRFs. 
 
 
 
 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                              Page 91 of 103 
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 Part 312, 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, all study products used in this study are manufactured, handled and stored in 
accordance with applicable GMP and the products 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 at the site will provide the Institutional Review Board/Independent 
Ethics Committee (IRB/IEC) with all appropriate materials as required by their IRB/IEC, including 
but not limited to the clinical study protocol, informed consent form, and any advertising materials. 
The study will not be initiated until the IRB/IEC provides written approval of the aforementioned 
documents and until approval documents have been obtained by the Principal Investigator and 
Sponsor or Sponsor designee. The Investigator will not participate in the decision. If the 
Investigator is an IRB or IEC member, documentation must be provided indicating recusal from 
the approval process. Appropriate reports on the progress of this study by the Principal Investigator 
will be made to the IRB/IEC as required by local and applicable government regulations and in 
agreement with policy established by the Sponsor. The Investigator is required to maintain an 
accurate and complete record of all written correspondence to and received from the IRB/IEC, and 
must agree to share all such documents and reports with the Sponsor. 
No changes from the final approved protocol will be initiated without the IRB/IEC’s prior written 
approval or favorable opinion of a written amendment, except when necessary to eliminate 
immediate hazards to the subjects or when the modification does not involve the subject’s 
participation in the trial.  
12.2 INVESTIGATOR’S RESPONSIBILITIES 
The Investigators are responsible for performing the study in full accordance with the protocol and 
the current revision of the Declaration of Helsinki, the Good Clinical Practice: Consolidated 
Guideline, approved by the ICH, and any applicable national and local laws and regulations. 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                              Page 92 of 103 
Information regarding any study centers participating in this study that cannot comply with these 
standards will be documented. 
12.3 SUBJECT INFORMED CONSENT REQUIREMENTS 
Written and oral information about the study in a language understandable by the subject will be 
given to all subjects by the Investigator and/or designee. Written informed consent will be obtained 
from each subject before 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 is to 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. Each 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.  
 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                              Page 93 of 103 
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 the approved eCRFs. The Investigator is 
ultimately responsible for the accuracy of the data transcribed on the forms. All source documents 
and eCRFs will be completed as soon as possible after the subject's visit. 
The Investigator will review eCRFs 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 eCRFs 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 (QC) 
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 QC, 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. 
13.3 ARCHIVING 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                              Page 94 of 103 
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 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 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 
• Product (e.g., IP supplies) 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 and enrollment log 
• SAE reports 
• IRB approval and re-approval letters 
• Other documents pertaining to the conduct of the study 
These documents must be maintained and kept on file by the Investigator so that the conduct of the 
study can be fully documented and monitored. 
At the completion of the study, details of the archival process must be provided to the Sponsor. 
Study records should not be transferred from site or destroyed without prior written agreement 
between the Sponsor and the study Investigator.  

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                              Page 95 of 103 
14 PUBLICATION PLAN 
All information supplied by CytoDyn in connection with this study and not previously published, 
is considered confidential information. This information includes, but is not limited to, the 
Investigator’s Brochure (IB), clinical protocol, case report forms and other scientific data. Any 
data collected during the study are also considered confidential. This confidential information 
shall remain the sole property of CytoDyn, shall not be disclosed to others without the written 
consent of CytoDyn, and shall not be used except in the performance of this study. 
It is understood by the Investigator that the Sponsor will use the information collected in this clinical 
trial in connection with the development of PRO 140. 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: Because this is a multi-center trial, the site and Investigator shall not 
independently publish, publicly disclose, present or discuss any results of or information pertaining 
to the site’s and Investigator’s activities conducted under this protocol until such multi-center 
publication is released with the written approval and under the direction of Sponsor. 
Notwithstanding the foregoing, if a multi-center publication is not released within eighteen (18) 
months after completion of analysis of all study data from all studies conducted within the multi-
center trial, both the site and Investigator shall have the right to publish the results of and 
information pertaining to the site’s and Investigator’s activities conducted under this protocol and 
the clinical trial agreement, subject to the prior review and written approval of Sponsor. The site 
and Investigator agree to submit any proposed manuscript, presentation or other public disclosure 
regarding the study to Sponsor for review at least thirty (30) days prior to submitting such proposed 
manuscript to a publisher or delivering or making such presentation or other public disclosure to 
any third party. Within thirty (30) days of its receipt, Sponsor shall advise the site and/or 
Investigator, as the case may be, in writing of any information contained therein that is confidential 
information (other than research results included in a proposed manuscript) or that may impair 
Sponsor’s ability to obtain patent protection. Sponsor shall have the right to require the site and/or 
Investigator, as applicable, to remove specifically identified confidential information (but may not 
require removal of research results from a proposed manuscript) and/or to delay the proposed 
submission or delivery of the proposed manuscript or presentation, or other public disclosure, for 
an additional sixty (60) days to enable Sponsor to seek patent protection. The site and Investigator 
shall not publish, publicly disclose, present or discuss any results of or information pertaining to 
the site’s and Investigator’s activities prior to completion of the trial, even if the multi-center trial 
or the study is terminated before its completion and the final clinical study report is signed off, or 
with respect to any outcome measures or analyses other than those specified in this protocol. 
 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                              Page 96 of 103 
15 REFERENCES 
Arribas JR Pulido F, Delgado R, Lorenzo A, Miralles P, Arranz A, González-García JJ, 
Cepeda C, Hervás R, Paño JR, Gaya F, Carcas A, Montes ML, Costa JR, Peña JM. 
Lopinavir/ritonavir as single-drug therapy for maintenance of HIV-1 viral suppression: 48-week 
results of a randomized, controlled, open-label, proof-of-concept pilot clinical trial (OK Study).  J 
Acquir Immune Defic Syndr.. - 2005. - Vol. 40. - pp. 280-287. 
Boffito M Back DJ, Hoggard PG, Caci A, Bonora S, Raiteri R, Sinicco A, Reynolds HE, 
Khoo S, Di Perri G. Intra-individual variability in lopinavir plasma trough concentrations 
supports therapeutic drug monitoring.  AIDS. - 2003. - Vol. 17. - pp. 1107-1108. 
Cahn P Montaner J, Junod P, Patterson P, Krolewiecki A, Andrade-Villanueva J, Cassetti 
I, Sierra-Madero J, Casiró AD, Bortolozzi R, Lupo SH, Longo N, Rampakakis E, Ackad N, 
Sampalis JS. Pilot, randomized study assessing safety, tolerability and efficacy of simplified 
LPV/r maintenance therapy in HIV patients on the 1st PI-based regimen.  PLoS One.. - 2011. - 
Vol. 6. - p. e23726. 
Calza L Manfredi R. Protease inhibitor monotherapy as maintenance regimen in patients with 
HIV infection.  Curr HIV Res.. - 2012. - Vol. 10. - pp. 661-72.. 
Cameron DW da Silva BA, Arribas JR, Myers RA, Bellos NC, Gilmore N, King MS, 
Bernstein BM, Brun SC, Hanna GJ. A 96-week comparison of lopinavir-ritonavir combination 
therapy followed by lopinavir-ritonavir monotherapy versus efavirenz combination 
therapy.  Infect Dis.. - 2008. - Vol. 198. - pp. 234-240. 
Demeter LM Shafer RW, Meehan PM, Holden-Wiltse J, Fischl MA, Freimuth WW, Para 
MF, Reichman RC. Delavirdine susceptibilities and associated reverse transcriptase mutations in 
human immunodeficiency virus type 1 isolates from patients in a phase I/II trial of delavirdine 
monotherapy (ACTG 260).  Antimicrob.Agents Chemother.. - 2000. - Vol. 44. - pp. 794-797. 
Guiguet M Ghosn J, Duvivier C, Meynard JL, Gras G, Partisani M, Teicher E, Mahamat A, 
Rodenbourg F, Launay O, Costagliola D and CO4. FHDH-ANRS Boosted protease inhibitor 
monotherapy as a maintenance strategy: an observational study.  AIDS. - 2012. - Vol. 26. - pp. 
2345-50. 
Gutmann C Cusini A, Günthard HF, Fux C, Hirschel B, Decosterd LA, Cavassini M, Yerly 
S, Vernazza PL. Randomized controlled study demonstrating failure of LPV/r monotherapy in 
HIV: the role of compartment and CD4-nadir.  AIDS. - 2010. - Vol. 24. - pp. 2347-2354.. 
Jacobson JM Lalezari JP, Thompson MA, Fichtenbaum CJ, Saag MS, Zingman BS, 
D'Ambrosio P, Stambler N, Rotshteyn Y, Marozsan AJ, Maddon PJ, Morris SA, Olson WC. 
study of the CCR5 monoclonal antibody PRO 140 administered intravenously to HIV-infected 
adults.  Antimicrob Agents Chemother.. - 2010. - Vol. 54. - pp. 4137-42.. 
Jacobson JM Saag MS, Thompson MA, Fischl MA, Liporace R, Reichman RC, Redfield 
RR, Fichtenbaum CJ, Zingman BS, Patel MC, Murga JD, Pemrick SM, D'Ambrosio P, 
Michael M, Kroger H, Ly H, Rotshteyn Y, Buice R, Morris SA, Stavola JJ, Maddon PJ, 
Kremer AB, Ols Antiviral activity of single-dose PRO 140, a CCR5 monoclonal antibody, in 
HIV-infected adults.  J Infect Dis.. - 2008. - Vol. 198. - pp. 1345-52.. 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                              Page 97 of 103 
Jacobson JM Thompson MA, Lalezari JP, Saag MS, Zingman BS, D'Ambrosio P, Stambler 
N, Rotshteyn Y, Marozsan AJ, Maddon PJ, Morris SA, Olson WC. Anti-HIV-1 activity of 
weekly or biweekly treatment with subcutaneous PRO 140, a CCR5 monoclonal antibody.  J 
Infect Dis.. - 2010. - Vol. 201. - pp. 1481-7. 
Katlama C Valantin MA, Algarte-Genin M, et al. Efficacy of darunavir/ritonavir maintenance 
monotherapy in patients with HIV-1 viral suppression: a randomized open-label, noninferiority 
trial MONOI-ANRS 136  AIDS. - 2010. - Vol. 24. - pp. 2365-2374. 
Marozsan A. J., T. Parsons, W. Huang, E. Stawiski, J. M. Whitcomb, P. J. Maddon, and W. 
C. Olson. Clonal analysis of HIV-1 co-receptor tropism change following treatment with PRO 
140, a CCR5 monoclonal antibody.  48th Annual ICAAC / IDSA 46th Annual Meeting. - 
Washington, DC. : [s.n.], 2008. - Vols. Abstract H-1218. 
Meynard JL Bouteloup V, Landman R, Bonnard P, Baillat V, Cabie A, Kolta S, Izopet J, 
Taburet AM, Mercie P, Chene G, Girard PM. Lopinavir/ritonavirmonotherapy versus current 
treatment continuation for maintenance therapy of HIV-1infection: the KALESOLO trial.  J 
Antimicrob Chemother.. - 2010. - Vol. 65. - pp. 2436-2444. 
Moltó J Santos JR, Negredo E, Miranda C, Videla S, Clotet B. Lopinavir/ritonavir 
monotherapy as a simplification strategy in routine clinical practice.  J Antimicrob Chemother.. - 
2007. - 60. - pp. 436-439. 
Nishikawa M Takashima K, Nishi T, Furuta RA, Kanzaki N, Yamamoto Y et al. Analysis of 
binding sites for the new small-molecule CCR5 antagonist TAK-220 on human 
CCR5.  Antimicrob Agents Chemother. - 2005. - Vol. 49(11). - pp. 4708-4715.. 
Nunes EP Santini de Oliveira M, Merçon M, Zajdenverg R, Faulhaber JC, Pilotto JH, 
Ribeiro JE, Norton M, Schechter M. Monotherapy with Lopinavir/Ritonavir as maintenance 
after HIV-1 viral suppression: results of a 96-week randomized, controlled, open-label, pilot trial 
(KalMo study).  HIV Clin Trials.. - 2009. - Vol. 10. - pp. 368-374.. 
Pulido F Arribas JR, Delgado R, Cabrero E, González-García J, Pérez-Elias MJ, Arranz A, 
Portilla J, Pasquau J, Iribarren JA, Rubio R, Norton M. Lopinavir-ritonavir monotherapy 
versus lopinavir-ritonavir and two nucleosides for maintenance therapy of HIV.  AIDS. - 2008. - 
Vol. 22. - pp. F1-9. 
Richman D. D., D. Havlir, J. Corbeil, D. Looney, C. Ignacio, S. A. Spector, J. Sullivan, S. 
Cheeseman, K. Barringer, D. Pauletti. Nevirapine resistance mutations of human 
immunodeficiency virus type 1 selected during therapy.  J Virol.. - 1994. - Vol. 68. - pp. 1660-
1666.. 
Saag M. S., E. A. Emini, O. L. Laskin, J. Douglas, W. I. Lapidus, W. A. Schleif, R. J. 
Whitley, C. Hildebrand, V. W. Byrnes, J. C. Kappes. A short-term clinical evaluation of L-
697,661, a non-nucleoside inhibitor of HIV-1 reverse transcriptase.  N.Engl.J Med.. - 1993. - Vol. 
329. - pp. 1065-1072.. 
Simioni S Cavassini M, Annoni J, Abraham AR, Bourquin I, Schiffer V, Calmy A, Chave J, 
Giacobini E, Hirschel B, Du Pasquier RA Cognitive dysfunction in HIV patients despite long-
standing suppression of viremia.. - 2010. - Vol. 24. - pp. 1243-1250. 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                              Page 98 of 103 
Spreen WR Margolis DA, Pottage JC Jr Long-acting injectable antiretrovirals for HIV 
treatment and prevention.. - [s.l.] : Curr Opin HIV AIDS., 2013. - Vol. 8(6):565571. 
Thompson M., Lalezari, J., Saag, M., Jacobson, J., Zingman, B., Stambler, N., D'Ambrosio, 
P., Maddon, P., Olson, W., and Morris, S. Weekly and bi-weekly subcutaneous PRO 140 
demonstrates potent, sustained antiviral activity.  16th Conference on Retroviruses and 
Opportunistic Infections. - Montreal QE, Canada, : [s.n.], 2009. - Vol. Abstract #571a. 
Thompson MA Aberg JA, Hoy JF, Telenti A, Benson C, Cahn P, Eron JJ, Gunthard HF, 
Hammer SH, Reiss P, Richman DD, Rizzardini G, Thomas DL, Jacobsen DM, Volberding 
PA. Antiretroviral Treatment of Adult HIV Infection: 2012 Recommendations of the International 
Antiviral Society–USA Panel  JAMA. - 2012. - Vol. 308. - pp. 387-402. 
 
 
 
 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                              Page 99 of 103 
16 APPENDIX 
16.1 APPENDIX I: AIDS-DEFINING CONDITIONS 
• Bacterial infections, multiple or recurrent* 
• Candidiasis of bronchi, trachea, or lungs 
• Candidiasis of esophagus† 
• Cervical cancer, invasive§ 
• Coccidioidomycosis, disseminated or extrapulmonary 
• Cryptococcosis, extrapulmonary 
• Cryptosporidiosis, chronic intestinal (> 1 month's duration) 
• Cytomegalovirus disease (other than liver, spleen, or nodes), onset at age > 1 
month 
• Cytomegalovirus retinitis (with loss of vision)† 
• Encephalopathy, HIV related 
• Herpes simplex: chronic ulcers (> 1 month's duration) or bronchitis, 
pneumonitis, or esophagitis (onset at age > 1 month) 
• Histoplasmosis, disseminated or extrapulmonary 
• Isosporiasis, chronic intestinal (> 1 month's duration) 
• Kaposi sarcoma† 
• Lymphoid interstitial pneumonia or pulmonary lymphoid hyperplasia complex*† 
• Lymphoma, Burkitt (or equivalent term) 
• Lymphoma, immunoblastic (or equivalent term) 
• Lymphoma, primary, of brain 
• Mycobacterium avium complex or Mycobacterium kansasii, disseminated or 
extrapulmonary† 
• Mycobacterium tuberculosis of any site, pulmonary,†§ disseminated,† or 
extrapulmonary† 
• Mycobacterium, other species or unidentified species, disseminated† or 
extrapulmonary† 
• Pneumocystis jirovecii pneumonia† 
• Pneumonia, recurrent†§ 
• Progressive multifocal leukoencephalopathy 
• Salmonella septicemia, recurrent 
• Toxoplasmosis of brain, onset at age > 1 month† 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                              Page 100 of 103 
• Wasting syndrome attributed to HIV 
 
* Only among children aged < 13 years. (CDC. 1994 Revised classification system for human immunodeficiency 
virus infection in children less than 13 years of age. MMWR 1994;43[No. RR-12].) 
† Condition that might be diagnosed presumptively. 
§ Only among adults and adolescents aged ≥ 13 years. (CDC. 1993 Revised classification system for HIV infection 
and expanded surveillance case definition for AIDS among adolescents and adults. MMWR 1992;41[No. RR-17].) 
 
Source: http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5710a2.htm 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                              Page 101 of 103 
16.2 APPENDIX II: DIVISION OF AIDS TABLE FOR GRADING THE SEVERITY OF ADULT AND 
PEDIATRIC ADVERSE EVENTS (DAIDS AE GRADING TABLE) 
http://rsc.tech-
res.com/Document/safetyandpharmacovigilance/DAIDS_AE_Grading_Table_v2_NOV2014.pdf 
 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                              Page 102 of 103 
16.3 APPENDIX III:  ADVERSE EVENTS OF SPECIAL INTEREST: INJECTION SITE REACTIONS 
The following table should be used to characterize injection-site reactions and provide appropriate 
grading of severity (DAIDS and modified additions).  
 
Injection-site Reactions 
Parameter 
Grade 1 (Mild) 
Grade 2 
(Moderate) 
Grade 3 (Severe) 
Grade 4 
(Potentially life-
threatening) 
Injection-site pain 
Pain without 
touching or pain 
when area is 
touched: no or 
minimal limitation 
of use of limb 
Pain without 
touching or pain 
when area is 
touched limiting 
use of limb OR 
causing greater 
than minimal 
interference with 
usual social and 
functional 
activities 
Pain without 
touching or pain 
when area is 
touched causing 
inability to perform 
usual social and 
functional 
activities 
Pain without 
touching or pain 
when area is 
touched causing 
inability to perform 
basic self-care 
function OR 
hospitalization 
(other than 
emergency room 
visit) indicated for 
management of 
pain/tenderness 
Characterization of 
the injection site, if 
not normal 
Erythema OR 
induration of 5x5 
cm - 9x9 cm (or 25 
cm2-81 cm2) 
Erythema OR 
induration OR 
Edema > 9 cm any 
diameter (or > 81 
cm2) 
Ulceration OR 
secondary infection 
OR Phlebitis or 
Sterile abscess OR 
drainage 
Necrosis 
(involving dermis 
and deeper tissue) 
Pruritus associated 
with injection 
Itching localized to 
injection site AND 
relieved 
spontaneously or  
< 48 hours of 
treatment 
Itching beyond the 
injection site but 
not generalized OR 
itching localized to 
injection site 
requiring ≥ 48 
hours treatment 
Generalized itching 
causing inability to 
perform usual 
social and 
functional 
activities 
N/A 
Bleeding 
Initial bleed that 
does not exceed 
bandage and 
spontaneously 
stops 
Bleeding that 
exceeds bandage 
and spontaneously 
stops  
Continued bleeding 
that requires 
change of dressing 
and alternative 
injection site 
N/A 
Absorption of drug 
Minor elevation of 
skin at injection 
site but no leakage 
of injection 
material 
Leakage at 
injection site 
ceases with 
decrease in 
injection rate  
Leakage at 
injection site that 
does not cease with 
decrease in 
injection rate 
 
 
 

 
 
Protocol # PRO 140_CD 03 Extension 
 
 
Version 5.0 
Date: 30-Mar-2021 
CONFIDENTIAL                                                                                                                              Page 103 of 103 
16.4 APPENDIX V: NEUROLOGICAL ASSESSMENT 
 
Three Question Screening Survey (Simioni, et al, 2010)  
1. ‘Do you experience frequent memory loss (e.g. do you forget the occurrence of special 
events even the more recent ones, appointments, etc.)’?  
2. ‘Do you feel that you are slower when reasoning, planning activities, or solving problems’? 
3. ‘Do you have difficulties paying attention (e.g. to a conversation, a book, or a movie)’?  
For each question, subjects should provide one of the following answers: ‘never’, ‘hardly ever’, 
or ‘yes, definitely’. 
If subject answers “yes, definitely” to any question, additional neurological assessment modalities 
may be used as per Investigator’s discretion.