An Extension Protocol for Subjects Who Successfully Completed PRO140_CD02 or PRO140_CD02_Open Label Study
Phase: PHASE2
Conditions: Human Immunodeficiency Virus (HIV)
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 Subjects who Successfully Completed PRO140_CD02 
or PRO140_CD02_Open Label Study 
 
Protocol Number: PRO 140_CD 02 Extension 
 
Version: 5.0 
 
Document Date: 02-Apr-2021 
 
NCT Number: NCT02990858 
 

CONFIDENTIAL 
 
                  Page 1 of 96 
  
 
 
  
 
An Extension Protocol for Subjects who Successfully Completed PRO140_CD02 
or PRO140_CD02_Open Label Study 
 
 
 
Protocol Number: 
PRO 140_CD 02 Extension 
Version: 
5.0 
Date: 
02 Apr 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. 

 
 
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PROTOCOL APPROVAL PAGE 
 
 
 
Protocol Number:  
PRO 140_CD 02 Extension 
 
Version: 
 
5.0 
 
Date: 
 
02 Apr 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 
 
 
 
 

 
 
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INVESTIGATOR’S SIGNATURE PAGE 
 
 
 
Protocol Number:  
PRO 140_CD 02 Extension 
 
Version: 
 
5.0 
 
Date: 
 
02 Apr 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 
 
  

 
 
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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 
 
 
 
 
 
  
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
 
 
  
 
 
 
 
 
  
  
 
 
 
 
 
 

 
 
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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 .........................................................21 
1.4.1 
Pre-Clinical Studies with PRO 140 ...................................................................21 
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 .........................................................................................22 
1.4.2.4 
PRO 140 1302 Study .........................................................................................23 
1.4.2.5 
PRO 140 2301 Study .........................................................................................25 
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 ............................................................................32 
This clinical study is currently ongoing. .............................................................................32 
1.4.2.11 
PRO 140 _CD03 Study .....................................................................................32 
1.4.2.12 
PRO 140 _CD03 Extension 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 virologic failure ..............................................................36 
1.6.1.2 
Allergic Reaction ...............................................................................................37 
1.6.1.3 
Immune Response .............................................................................................37 

 
 
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1.6.1.4 
Pregnancy ..........................................................................................................37 
1.6.1.5 
Venipuncture .....................................................................................................37 
1.6.1.6 
Risks to the Study Personnel and the Environment ..........................................37 
1.6.1.7 
Unknown Risks .................................................................................................38 
1.6.1.8 
Theoretical risk for increased severity of West Nile virus infection .................38 
1.6.2 Intended Benefit for Subjects ..............................................................................................38 
2 STUDY OBJECTIVES ..........................................................................................................39 
3 STUDY DESIGN ....................................................................................................................40 
3.1 
Study Center(s) ....................................................................................................................40 
3.2 
Study Population .................................................................................................................41 
3.3 
Eligibility Criteria ................................................................................................................42 
3.3.1 
Inclusion Criteria ...............................................................................................42 
3.3.2 
Exclusion Criteria ..............................................................................................42 
4 STUDY SCHEDULE .............................................................................................................44 
4.1 
Screening Phase ...................................................................................................................49 
4.2 
Treatment Extension Phase .................................................................................................49 
4.2.1 
Treatment Extension Visit (TE1) ......................................................................51 
4.2.2 
Subsequent Treatment Extension Visits ............................................................52 
4.2.3 
Virologic Failure (VF) Visit ..............................................................................53 
4.3 
Follow-up Phase ..................................................................................................................53 
4.3.1 
Follow-Up Visits ...............................................................................................54 
4.4 
Unscheduled Visits ..............................................................................................................54 
5 SUBJECT COMPLETION AND WITHDRAWAL...........................................................55 
5.1 
Subject Completion .............................................................................................................55 
5.2 
Subject Withdrawal .............................................................................................................55 
5.2.1 
Discontinuation of Study Treatment .................................................................56 
5.2.2 
Data Collected for Withdrawn Subjects ............................................................56 
5.3 
Screen Failures ....................................................................................................................57 
6 STUDY TREATMENT .........................................................................................................58 
6.1 
Investigational Product Description ....................................................................................58 
6.2 
Investigational Product Packaging and Labeling ................................................................58 
6.3 
Investigational Product Storage ...........................................................................................60 
6.4 
Investigational Product Administration ...............................................................................61 

 
 
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6.5 
Investigational Product Receipt and Accountability ...........................................................61 
6.6 
Investigational Product Disposition ....................................................................................62 
7 DESCRIPTION OF PROTOCOL ASSESSMENTS AND PROCEDURES ...................63 
7.1 
Informed Consent ................................................................................................................63 
7.2 
Assessment of Eligibility .....................................................................................................63 
7.3 
Demographic Information ...................................................................................................63 
7.4 
Medical History ...................................................................................................................64 
7.5 
HIV History .........................................................................................................................64 
7.6 
Prior / Concomitant Medications and Non-Study Treatments ............................................64 
7.7 
Physical Examination ..........................................................................................................65 
7.8 
Electrocardiogram ...............................................................................................................65 
7.9 
Neurological Assessment ....................................................................................................65 
7.10 Vital Signs ...........................................................................................................................66 
7.11 Clinical Laboratory Assessments ........................................................................................66 
7.11.1 
Routine CBC .....................................................................................................66 
7.11.2 
Biochemistry .....................................................................................................66 
7.11.3 
Coagulation indices ...........................................................................................67 
7.11.4 
Urinalysis...........................................................................................................67 
7.11.5 
Urine pregnancy test ..........................................................................................67 
7.11.6 
Plasma HIV-1 RNA level and TruCount T Assay ............................................67 
7.11.7 
HIV-1 Trofile® Assay .......................................................................................67 
7.11.8 
HIV-1 Drug Resistance Assay ..........................................................................68 
7.11.9 
HIV-1 PhenoSense® Entry assay ......................................................................68 
7.11.10 
CCR5 Receptor Occupancy...............................................................................68 
7.12 Investigational Product Administration ...............................................................................68 
7.13 Injection Site Reaction assessment ......................................................................................68 
7.14 COVID-19 Guidance ...........................................................................................................69 
8 STATISTICAL CONSIDERATIONS .................................................................................71 
8.1 
Treatment Groups ................................................................................................................71 
8.2 
Description of Safety Measures ..........................................................................................71 
8.3 
Sample Size Determination and Rationale ..........................................................................72 
8.4 
Randomization and Blinding ...............................................................................................72 
8.5 
Interim Analysis ..................................................................................................................72 

 
 
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8.6 
General Statistical Considerations .......................................................................................72 
8.6.1 
Analysis Populations .........................................................................................72 
8.6.1.1 
Safety Population ..............................................................................................72 
8.6.2 
Statistical Methods ............................................................................................72 
8.6.3 
Prognostic Factors/Covariates ...........................................................................72 
8.6.4 
Handling of Missing Data .................................................................................72 
8.7 
Data Summary .....................................................................................................................72 
8.7.1 
Subject Disposition ...........................................................................................72 
8.7.2 
Demographic and Baseline Characteristics .......................................................73 
8.7.3 
Prior and Concomitant Medications ..................................................................73 
8.7.4 
Safety Measures ................................................................................................73 
8.7.5 
Safety Analysis ..................................................................................................73 
8.7.5.1 
Adverse Events ..................................................................................................74 
8.7.5.2 
Tolerability Assessment ....................................................................................74 
8.7.5.3 
Clinical Laboratory Data ...................................................................................74 
8.7.5.4 
Physical Examination ........................................................................................74 
8.7.5.5 
Vital Signs .........................................................................................................74 
8.7.5.6 
ECG Examination..............................................................................................74 
8.7.5.7 
Neurological Assessment ..................................................................................74 
9 ADVERSE EVENTS (DEFINITIONS AND REPORTING) ............................................75 
9.1 
Adverse Event .....................................................................................................................75 
9.1.1 
Reporting of Adverse Events ............................................................................75 
9.1.2 
Impact of Study Treatment ................................................................................75 
9.1.3 
DAIDS AE Grade (Severity) Assessment .........................................................76 
9.1.4 
Causality Assessment ........................................................................................76 
9.1.5 
Treatment Given as a Result of the Event .........................................................77 
9.1.6 
Outcome Assessment ........................................................................................77 
9.1.7 
Expected / Anticipated Adverse Events ............................................................77 
9.1.8 
SC Injection-related Events ...............................................................................78 
9.2 
Serious Adverse Events (SAE) ............................................................................................78 
9.3 
Reporting of Serious Adverse Events .................................................................................79 
9.3.1 
SAE Follow-Up .................................................................................................80 
10 DIRECT ACCESS TO SOURCE DATA/DOCUMENTATION ......................................81 
11 QUALITY CONTROL AND QUALITY ASSURANCE ...................................................82 
11.1 Monitoring Requirements ....................................................................................................82 

 
 
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11.2 Acceptability of Case Report Forms (CRFs) ......................................................................82 
11.3 Modification of Protocol .....................................................................................................82 
11.4 Reporting Protocol Deviations ............................................................................................83 
12 ETHICS AND REGULATORY REQUIREMENTS .........................................................84 
12.1 Institutional Review Board/Independent Ethics Committee (IRB/IEC) .............................84 
12.2 Investigator’s Responsibilities ............................................................................................84 
12.3 Subject Informed Consent Requirements ............................................................................85 
13 DATA HANDLING AND RECORD KEEPING ................................................................86 
13.1 Recording and Collection of Data .......................................................................................86 
13.2 Clinical Data Management ..................................................................................................86 
13.3 Archiving .............................................................................................................................87 
14 PUBLICATION PLAN .........................................................................................................88 
15 REFERENCES .......................................................................................................................90 
16 APPENDIX .............................................................................................................................92 
16.1 Appendix I: AIDS-Defining Conditions .............................................................................92 
16.2 Appendix II: Division of AIDS Table for Grading the Severity of Adult and Pediatric 
Adverse Events (DAIDS AE Grading Table) ................................................................................94 
16.3 Appendix III:  Adverse Events of Special Interest: Injection Site Reactions .....................95 
16.4 Appendix V: Neurological Assessment ..............................................................................96 
 
 
 
 
 
 
 
 
 
 

 
 
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LIST OF TABLES 
  
Table 1-1: 
Clinical Studies with PRO 140 .............................................................................. 33 
Table 4-1: 
Schedule of Assessments – Screening and Treatment Phasea ............................... 46 
Table 4-2:  
Schedule of Assessments –Follow-Up (FU) Phase ................................................ 48 
Table 4-3: 
52-week Treatment Phase [PRO 140 + OBT] ....................................................... 50 
Table 6-1: 
Investigational Product - PRO 140 at TE1 - TE52 visit ........................................ 58 
Table 9-1:  
DAIDS AE Grading Table v2 General Guidelines ............................................... 76 
 

 
 
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LIST OF FIGURES 
Figure 1-1: 
PRO 140 1302 Study: Mean of the maximum (nadir) log10 reductions in HIV RNA
 ............................................................................................................................... 23 
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. .... 29 
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: 
Investigational Product - Vial Label ..................................................................... 59 
Figure 6-2: 
Investigational Product - Syringe Label ................................................................ 59 
Figure 6-3: 
Investigational Product - Kit Label ....................................................................... 60 
 

 
 
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LIST OF ABBREVIATIONS 
Abbreviation 
Term 
AE 
Adverse Event 
AIDS 
Acquired Immune Deficiency Syndrome 
ALT 
Alanine Transaminase 
ANC 
Absolute Neutrophil Count 
ANCOVA 
Analysis of Covariance 
ART 
Anti Retroviral Therapy 
AST 
Aspartate Transaminase 
ATC 
Anatomic Therapeutic Classification 
AUC 
Area Under Curve 
C 
Celsius 
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 
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" 

 
 
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Abbreviation 
Term 
EOT 
End of Treatment 
EOT2 
End of Treatment Extension 
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 
HBsAg 
Hepatitis B Surface Antigen 
HCT 
Hematocrit 
HEENT 
Head, Ears, Eyes, Nose, and Throat 
HIPAA 
Health Insurance Portability Accountability Act 
HIV 
Human Immunodeficiency Virus 
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 
ITT 
Intent-to-treat 
IV 
Intravenous 
LAR 
Legally Acceptable Representative  
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 

 
 
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Abbreviation 
Term 
MOCA 
Montreal Cognitive Assessment 
MW 
Molecular Weight 
NCS 
Not Clinically Significant 
NP 
Nurse Practitioner 
NVF 
Non-Virologic Failure 
OBT 
Optimized Background Therapy 
PA 
Physician Assistant 
PI 
Principal Investigator 
PK 
Pharmacokinetics 
PP 
Per Protocol 
Pr 
Protease 
PT 
Prothrombin Time 
QC 
Quality Control 
RBC 
Red Blood Cells 
RN 
Registered Nurse 
RNA 
Ribonucleic acid 
RT 
Reverse Transcriptase 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SC 
Subcutaneous 
SD 
Standard Deviation 
SOP 
Standard Operating Procedure 
SV 
Screening Visit 
TE 
Treatment Extension 
TEAE 
Treatment Emergent Adverse Events 
ULN 
Upper limit of normal 
USA 
United States of America 
VF 
Virologic Failure 
WBC 
White Blood Cells 

 
 
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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 
Though substantial progress has been made over the past two decades in the development of 
effective and well tolerated combination antiretroviral regimens, nearly 25% of patients 
receiving Highly Active Antiretroviral Therapy (HAART) are not virologically suppressed due 
to various reasons.  Recent data suggest that most virologic failure on first-line regimens occurs 
because of either pre-existing (transmitted) drug resistance or suboptimal adherence.  Patient- 
and regimen-related factors play a crucial role in determining whether an antiretroviral regimen 
is successful or result in virologic failure [Office of AIDS Research Advisory Council, 2014]. 
In general, drug resistance can be considered a core issue in patients with limited treatment 
options.  However, there are other known factors apart from drug resistance (such as incomplete 
adherence, medication intolerance, pharmacokinetic issues, etc.) which also contribute to 
limiting treatment options in constructing a new regimen for patients who experience treatment 
failure. New agents and drug classes (e.g., integrase inhibitors, fusion inhibitors and CCR5 
antagonists) are necessary to keep up with ongoing viral mutations in an attempt to prevent viral 
replication and transmission [Tang MW, 2012][Gulick RM, 2008][Moyle G, 2008]. The 
availability of an effective maintenance regimen would benefit a subset of HIV-1 infected 
persons who are challenged by transferred resistance, medication adherence and/or chronic 
nucleoside toxicity.  
PRO 140 is a promising new antiretroviral agent that does not have any cross-resistance with 
drugs from other classes. Although PRO 140 would require subcutaneous (SC) administration, 
its favorable pharmacokinetics allows for weekly dosing. The purpose of this study is to exhibit 
antiviral activity of PRO 140 in combination with other antiretroviral agents for treatment of 
antiretroviral-experienced persons infected with CCR5-tropic HIV-1 virus. 
 
 

 
 
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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 
viral entry by interfering with 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. 
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 

 
 
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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 clinical trials. These 
studies are summarized in Table 1-1. In all 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 
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 
were associated with injections in the arm. Based on these observations, thigh and abdominal 
administration of PRO 140 were preferred over arm injection. 

 
 
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PRO 140 2301 was a multi-center, randomized, double-blind, placebo-controlled, parallel group 
study in 30 male and female adult subjects infected with HIV-1. 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 
A subcutaneous (SC) form of PRO 140 was tested in HIV-infected subjects. The trial was a 
randomized, double-blind, placebo-controlled study in subjects (n=44) with early-stage, 
asymptomatic HIV infection, only CCR5 HIV-1 detectable, and no antiretroviral therapy for 12 

 
 
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weeks [Thompson, 2009]. Placebo (n=10) and three PRO 140 doses were examined: 162mg 
weekly for three weeks (n=11), 324mg weekly for three weeks (n=11), and 324mg biweekly 
(every other week) for two doses (n=12). Subjects were followed for 44 days after the final dose. 
The study enrolled 40 males and 4 females. The median age, weight, CD4+ cell count and HIV-1 
RNA at baseline were 42.3 years, 79.1 kg, 410 cells/μL and 20,000 copies/mL, respectively. 
Baseline characteristics were similar for the different treatment groups. 
Potent, dose-dependent and highly statistically significant antiviral activity was observed (Figure 
1-5 and Figure 1-6). The 324mg weekly dose resulted in a mean 1.65 log10 reduction in viral 
load, and highly significant reductions were observed for the other dose groups as well (Figure 
1-5). There was no viral rebound between 324mg doses, and the antiviral effects persisted for 
one week after the final dose (Figure 1-6). The trial established the first antiviral proof of 
concept for a long-acting, self-administrable drug for HIV-1 infection [Thompson, 2009].  
Figure 1-5: 
PRO 140 2101 Study: Mean of the maximum (nadir) log10 reductions in HIV 
RNA 
 
 
 
0
0.5
1
1.5
2
0.23
0.58
1.37
1.65
Mean Maximum Log10 Reduction in HIV RNA
placebo
162mg Days 1,8,15
324mg Days 1, 15
324mg Days 1,8,15

 
 
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of antiretroviral therapy in HIV-1 infected patients (with exclusive CCR5-tropic virus). Participants 
in this study were experienced HIV-infected individuals who were virologically suppressed on 
combination antiretroviral therapy. Consenting patients were shifted from combination antiretroviral 
regimen to PRO 140 monotherapy for 12 weeks.  
Forty (43) subjects (M/F: 40/3) with median age of 55.5 years (26-72) and median CD4 T-cell count 
of 604.5 cells/mm3 (365-1240) were enrolled in the CD01 study. Overall, twenty-three out of 43 
(54%) enrolled subjects completed 12 weeks of PRO140 monotherapy without experiencing 
virologic failure. Virologic failure was defined as two consecutive HIV-1 RNA levels ≥ 400 
copies/mL separated by at least 3 days.  
Of the first 40 enrolled subjects enrolled under cohort 1 and cohort 2, three subjects were found to 
have Dual/Mixed (D/M) tropism [1 at baseline and 2 at the time of virologic failure] and 40 subjects 
were found to have exclusive CCR5-tropic virus. A letter of amendment was filed to increase the 
planned number of subjects from 40 to 43 subjects to compensate for the 3 Dual/Mixed subjects 
enrolled in the study.  
All virologic failure subjects who had available lab data in both studies achieved viral suppression to 
< 400 HIV-1 RNA copies/mL, as well as viral suppression to ‘Non Detectable’ or < 50 HIV-1 RNA 
copies/mL after re-initiation of ART.  
The by-subject analysis of PhenoSense® Entry Assay data for PRO140, maraviroc, and AMD3100 
shows no significant changes in the post-treatment IC50 and IC90 values were noted when compared 
with baseline values in virologic failure and non-virologic failure groups of subjects.  
Anti-PRO140 antibodies were not identified in any available 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 (70/87; 80.4%) were 
deemed either unlikely or not related to study treatment by the Investigator. Similarly, the majority of 
the reported AEs (72/89; 80.8%) 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 

 
 
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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 ≥ 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 are participating 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 loads 
≥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 (175-198 weeks). Overall, 12 subjects completed at 
least one year of treatment and 9 subjects completed at least two years of treatment in this study 
PRO140 was generally well tolerated, and no drug-related SAEs were observed.  
This clinical study is currently ongoing. 
1.4.2.9 PRO 140 _CD02 Study 
PRO 140_CD02 study (double blind, placebo controlled, 52 subjects, multi-center) 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 52 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 
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This clinical study is completed. 
1.4.2.10 PRO 140 _CD02 Open Label 
PRO140_CD02 Open Label  (open label, single-arm, 25 subjects,  multi-center) 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 is treatment-experienced HIV-infected patients with CCR5-
tropic virus and demonstrates 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 _CD03 Study 
PRO 140_CD03 study (open-label, two-arm comparator, 500 subjects, multi-center) seeks to 
evaluate the treatment strategy of using PRO 140 SC as a long-acting single-agent maintenance 
therapy versus continuing combination ART for 48 weeks in virologically suppressed subjects 
with CCR5-tropic HIV-1 infection. The first ~150 eligible subjects were enrolled to receive PRO 
140 350mg SC weekly injection in a single-arm study. Subsequently, 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. 
1.4.2.12 PRO 140 _CD03 Extension Study 
PRO 140_CD03 Extension study (open label, 300 subjects, multi-center) seeks to evaluate the 
long term efficacy, safety and tolerability of PRO 140 weekly injection as long-acting single-
agent maintenance therapy versus continuing combination ART in patients infected with HIV-1. 
The study population includes treatment-experienced HIV-infected adult patients with CCR5-
tropic virus who successfully completed PRO 140_CD03 study and continue to demonstrate 
HIV-1 viral suppression. 
This clinical study is currently ongoing. 
 
 
 

 
 
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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 
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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 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 700mg 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). 
As of Protocol v4.0, newly enrolled subjects will receive 700 mg.  The dose of 700 mg 
administered SC was chosen to provide maximum viral load suppression in a heavily treatment 
experienced population to avoid developing resistance to current OBT therapies.   
1.6 
RISKS / BENEFITS ASSESSMENT 
1.6.1 RISKS/DISCOMFORT TO SUBJECTS AND PRECAUTIONS TO MINIMIZE RISK 
1.6.1.1 Risks associated with virologic failure 
Subjects participating in the PRO140_CD02 or CD02 Open Label study will continue to receive 
study treatment (PRO 140 700mg SC injection) in addition to Optimized Background Therapy 
(OBT). Addition of study treatment (PRO 140 700mg SC injection) to OBT may not be effective 
for continued suppression of viral load for all subjects.   
Note:  Investigator will construct a new HAART regimen should viral rebound occur, where 
HIV-1 viral load meets virologic failure criteria.     
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have the option of increasing their dose to 700mg. 
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. 
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 
Blood sampling is required as part of the study protocol. Blood sampling carries a minimal risk 
of minor discomfort and the possibility of minor bruising at the site of the needle puncture and, 
rarely, the possibility of infection at the needle puncture site. 
1.6.1.6 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). 
 

 
 
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1.6.1.7 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.  
1.6.1.8 Theoretical risk for increased severity of West Nile virus infection 
Individuals who lack a functional CCR5 gene are at increased risk for severe infection by West 
Nile virus [Thompson, 2009] Because of this, treatment with CCR5 co-receptor antagonists 
poses a theoretical risk for increased severity of West Nile virus infection. However, this concern 
is mitigated by several factors. First, no increased risk was observed for individuals who possess 
one functional and one non-functional CCR5 gene, indicating that an intermediate amount of 
CCR5 is sufficient for defense against West Nile virus [Thompson, 2009]. Second, use of CCR5 
co-receptor antagonists is unlikely to completely abrogate CCR5 function, and there has been no 
association reported to date between CCR5 co-receptor use and severe West Nile virus. 
Additionally, 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 have once weekly SC treatment with PRO 140 
in addition to an optimized and simplified ART regimen. Subjects participating in this 
combination therapy study will contribute to the development of a drug which has the potential 
to become a treatment option for them and others in the future. 

 
 
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2 
STUDY OBJECTIVES 
The primary objective is to provide continued access to PRO 140 to subjects who complete 
participation in PRO140_CD02 or CD02_OpenLabel and continue to receive clinical benefit and 
would require PRO 140 to form a viable regimen, in the opinion of the treating physician. 
Study endpoints include mean change in viral load (HIV-1 RNA levels) at the conclusion of the 
treatment period, mean change in CD4 cell count at the conclusion of the treatment period, 
emergence of Dual/Mixed (D/M)- and CXCR4-tropic virus in patients who had exclusive CCR5-
tropic virus at study entry, tolerability of repeated subcutaneous administration of PRO 140 as 
assessed by investigator-evaluation of injection site reactions, frequency of treatment-related 
adverse events resulting in study drug discontinuation, frequency of Grade 3 or 4 adverse events 
as defined by the DAIDS Adverse Event scale and frequency of treatment–emergent serious 
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3 
STUDY DESIGN  
This is an extension study, to provide continued access to PRO 140 to subjects who complete 
participation in PRO140_CD02 or CD02_OpenLabel and continue to receive clinical benefit and 
would require PRO 140 to form a viable regimen, in the opinion of the treating physician. The 
patient population for this trial is treatment-experienced HIV-infected patients with CCR5-tropic 
virus who demonstrate evidence of HIV-1 suppression after successfully completed 24 weeks of 
treatment in the PRO140_CD02 or CD02_Open Label study. 
Subjects participating under Protocol versions 1.0-3.0 received 350 mg of PRO 140.  Dose was 
increased from 350 mg to 700 mg weekly to provide maximum viral load suppression in a 
heavily treatment experienced population to avoid developing resistance to current OBT 
therapies.   
Those that were enrolled under version 1.0-3.0 have the option of remaining on their current 
dose of 350mg or increasing their dose to 700 mg for the remainder of the trial. 
The study is divided into three phases: Screening, Treatment Extension and Follow-up.  
Screening Phase begins with signing of Informed Consent and lasts up to 21 days. All subjects 
will continue taking PRO 140 SC injection in addition to OBT during the Screening Phase. 
Subject will enter the Treatment Extension Phase as soon as HIV-1 viral load results are 
available for review by Investigator.  Treatment Extension Phase consists of weekly study 
treatment injections along with OBT.  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 two consecutive HIV-1 RNA levels  ≥ 400 copies/mL. 
Note:  Subjects will be allowed to continue PRO 140 with existing OBT regimen while waiting 
for new regimen to be constructed by the Investigator. 
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 below level of detection) or 
up to a maximum of 6 months after cessation of therapy if the treating physician does not feel 
that there is an antiretroviral regimen that will regain full viral suppression. Subjects who do not 
experience virologic failure, will be followed up every 2 weeks for total of 4 weeks. 
3.1 
STUDY CENTER(S) 
Up to 30 centers in the United States 
 

 
 
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3.2 
STUDY POPULATION 
Study population includes treatment-experienced HIV-infected patients with CCR5-tropic virus 
that successfully complete 24 weeks of treatment with PRO140 in addition to Optimized 
Background Therapy within the PRO140_CD02 or CD02_OpenLabel protocol.  Investigator 
believes subject requires continued access to PRO 140 in order to continue deriving clinical 
benefit and maintain HIV-1 viral suppression. 
 
 

 
 
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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 24 weeks of treatment in PRO 140_CD 02 or 
CD02_OpenLabel study, and Investigator believes subject requires continued access to 
PRO 140 in order to continue deriving clinical benefit and maintain HIV-1 viral 
suppression. 
2. HIV-1 RNA <50 at T23 Visit in PRO140_CD02 or CD02_Open Label study  
3. Both male and female patients 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 
Subjects meeting any of the following criteria will be excluded from the study: 
1. Not currently enrolled in PRO 140_CD 02 or CD02_OpenLabel 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. Any other clinical condition that, in the Investigator's judgment, would potentially 
compromise study compliance or the ability to evaluate safety measures 

 
 
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4 
STUDY SCHEDULE 
This study is divided into three phases: Screening, Treatment and Follow-up. 
(1) Screening Phase: This phase lasts up to 21 days and begins with signing of Informed 
Consent. Assessments performed during this phase determine the subject’s final 
eligibility for study participation. Subjects who meet all eligibility criteria will receive 
first treatment injection at Treatment Extension Visit 1 (which corresponds to EOT from 
PRO140_CD02 or CD02_OpenLabel study). 
All subjects will continue taking PRO 140 along with OBT during the Screening Phase. 
Note:  Subject consent and screening assessments should be completed prior to EOT visit 
in the PRO140_CD02 or CD02_OpenLabel study. 
(2) Treatment Extension Phase: Subjects will receive weekly treatments (window period of 
±3 days)  until virologic failure is experienced, consent is withdrawn, the study drug is 
approved, or the trial is completed/ended by CytoDyn, whichever comes first.  
Virologic failure is defined as two consecutive HIV-1 RNA levels ≥ 400 copies/mL. 
Subjects who meet all eligibility criteria will receive first treatment injection at Treatment 
Extension Visit 1 (which corresponds to EOT from PRO140_CD02 or CD02_OpenLabel 
study).  
PRO 140 will be administered by a qualified medical professional (MD, DO, PA, LPN, 
LVN, NP, RN, or CMA if permitted by state law) or self-administered by subjects. 
Any time during the Treatment Extension Phase, if virologic failure occurs, Investigator 
will readjust antiretroviral regimen based on HIV-1 genotypic and/or phenotypic drug 
resistance results obtained during the VF visit. 
Subjects will be allowed to continue PRO 140 with existing OBT regimen while waiting 
for new regimen to be constructed by the Investigator. 
(3) Follow-Up Phase: The duration of follow-up depends on whether or not subject has 
experienced virologic failure during the Treatment Extension Phase. 
• Subjects who experience virologic failure within Treatment Extension Phase will be 
followed up every 4 weeks until viral suppression is achieved (i.e., plasma HIV-1 
RNA levels below level of detection) or up to a maximum of 6 months after cessation 
of therapy if the treating physician does not feel that there is an antiretroviral regimen 
that will regain full viral suppression. 
• Subjects who do not experience virologic failure at the end of Treatment Extension 
Phase, will be followed up every 2 weeks for total of 4 weeks. 

 
 
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Procedures to be performed during each of these study phases are described below and provided 
as a Schedule of Assessments in Table 4-1 and Table 4-2.  

 
 
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a Schedule of assessment (Screening/Treatment Phase) can be modified by the Investigator based on clinical judgment and in the best 
interest of the subject. 
b Subject eligibility should be confirmed prior to study treatment administration at TE1. 
Foot Notes: 
[1] 
Informed consent must be obtained prior to subject participation in any protocol-related activities that are not part of routine care. 
[2] 
Medical history, past surgeries, disease history, history of substance abuse, social history, blood transfusion history, and current 
therapies (medications and non-medications) will be brought forward from PRO140_CD02 or CD02_OpenLabel. 
[3] 
Symptom-directed physical examination. Complete physical examination at TE1, EOT2 and VF. 
[4] 
The screening tool for this assessment is based on the three question survey used by Simioni et al. (Simioni S, 2010).  Additional 
modalities may be used for this assessment at the discretion of the Investigator. 
[5] 
Vital signs (i.e., blood pressure, heart rate, respiration rate and temperature) will be recorded post-treatment whenever IP 
administered at the 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 
 
Hepatic function indicators: total and direct bilirubin, alkaline phosphatase, aspartate aminotransferase (AST), alanine 
aminotransferase (ALT), total protein, Lactate dehydrogenase (LDH) 
Renal function indicators: BUN, creatinine 
Electrolytes: sodium, potassium, chloride, calcium and bicarbonate 
Other: glucose (random), cholesterol (total) 
[8] 
Prothrombin time (PT) and International Normalized Ratio (INR) 
[9] 
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. 
[10] ONLY performed on women of childbearing potential. Subject will not be allowed to participate if the result is positive.  
[11] Plasma HIV-1 RNA and TruCount T Assay will be performed once every 4 weeks when subject comes to clinic.  TruCount T Assay 
includes: CD3 %, CD4 %, CD8 %, Absolute Lymphocytes, CD3 cell count, CD4 cell count, and CD8 cell count 
[12] Injection Site Reaction will be assessed by the Investigator whenever IP administered at the clinic.  
[13] Monogram Biosciences Trofile® RNA and PhenoSense® Entry Assays [AMD3100 (CXCR4 inhibitor drug), Maraviroc and PRO 
140 (CCR5 inhibitor drugs)] 
[14] Monogram Biosciences PhenoSense® GT Assay 
[15] Every 12 weeks during Treatment Extension. 
[16] Refer to Section 7.11.10. 
 
 

 
 
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4.1 
 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 to each 
subject under PRO140_CD02 or CD02_OpenLabel 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),  
• Prior and current medications review (see section 7.6),  
• Symptom-directed physical examination (see section 7.7),  
• Electrocardiogram (ECG) (see section 7.8),  
• Vital Signs (see section 7.10), 
• Collection of Blood Specimens (see section 7.11) for 
o Plasma HIV-1 RNA level 
o TruCount T Assay 
All screening information will be fully documented in the subject’s medical records (i.e., source 
documents).  
• For consented subjects who do not meet eligibility criteria, a Screen Failure electronic 
Case Report Form (eCRF) will be completed. The Screen Failure eCRF will contain the 
following details: the subject identification number, the date of ICF signature, 
demographic information (see section 7.3), and the reason for screen failure. No additional 
information will be required for subjects who fail screening.  
• For consented subjects who meet eligibility criteria, all required screening information 
will be transcribed onto the appropriate page of the eCRF. 
4.2 
TREATMENT EXTENSION PHASE 
Treatment Extension Phase begins with an evaluation of viral load results collected during the 
Screening Phase. Subjects who meet all eligibility criteria, as per data gathered from Screening 

 
 
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Extension Phase (EOT2) 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.  Subjects who meet all eligibility criteria will 
receive first treatment injection at Treatment Extension Visit 1 (which corresponds to EOT from 
PRO140_CD02 or CD02_OpenLabel study).  
4.2.1 Treatment Extension Visit (TE1)  
The following assessments will be performed at the first treatment visit, unless otherwise 
specified: 
Pre-Treatment 
• Confirmation of eligibility criteria by reviewing test results and other criteria assessments 
performed during Screening Phase (see section 7.2 ) 
• Neurological assessment (see section 7.9) 
• Complete physical examination (see section 7.7), 
• Assess for any changes in Concomitant medications (see section 7.6) 
• Collection of Blood Specimens (see section 7.11) for 
o Complete Blood Count 
o Biochemistry 
o Plasma HIV-1 RNA level  
o TruCount T Assay 
o Urine Pregnancy Test (see section 7.11.5), for female subjects of childbearing 
potential.  Childbearing potential is defined as someone who is not surgically 
sterile or is not more than one year past complete cessation of menstrual cycles. 
Administration of study treatment [PRO 140] 
Study treatment will be administered weekly as a subcutaneous injection in the abdomen.  
Subjects will receive the study treatment delivered as two 2 mL injections on opposite sides of the 
abdomen.  

 
 
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Note:  IP must be administered by a qualified medical professional (MD, DO, PA, LPN, LVN, 
NP,  RN, or CMA if permitted by state law) or self-administered by subjects. 
Post-Treatment 
• Injection Site Reaction Assessment (see section 7.13) 
➢ Note: To assess injection site reactions, the investigator will use the DAIDS AE 
grading table (refer to section 16.3). 
• Assess for any Adverse Events (see section 9) 
• Vital Signs (see section 7.10) will be assessed within 15 minutes of study treatment 
administration. 
4.2.2 Subsequent Treatment Extension Visits 
The following assessments will be performed at each treatment extension visit beyond TE1, 
unless otherwise specified: 
• Assess for any Adverse Events and changes in Concomitant medications (see section 9 
and 7.6), 
• Neurological assessment (see section 7.9) [at EOT2], 
• Symptom-directed physical examination (see section 7.7), 
• Electrocardiogram (ECG) (see section 7.8) [at EOT2], 
• Vital Signs (see section 7.10) 
➢ Note: Post-treatment vital signs will be assessed within 15 minutes following IP 
administration performed at clinic. 
• Collection of Blood Specimens (see section 7.11) for 
o Plasma HIV-1 RNA level  
o TruCount T Assay 
➢ Note: Occurs once every 4 weeks when subject is at clinic. 
o Complete Blood Count (CBC) 
o Biochemistry 
o Coagulation indices 
o Urinalysis 

 
 
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➢ Note: Occurs once every 12 weeks when subject is at clinic. 
• Study Treatment Administration (PRO 140) 
• Injection Site Reaction Assessment (see section 7.13) 
➢ Note: To assess injection site reactions, the investigator will use the DAIDS AE 
grading table (refer to section 16.3). 
4.2.3 Virologic Failure (VF) Visit  
Virologic failure is defined as two consecutive HIV-1 RNA levels ≥ 400 copies/mL. 
The following assessments will be performed for subjects who experience virologic failure at any 
time during the Treatment Phase: 
• Assess for any Adverse Events and changes in Concomitant medications (see section 9 
and 7.5), 
• Complete Physical Examination (see section 7.7), 
• Vital Signs (see section 7.10), 
• Neurological Assessment (see section 7.9), 
• Subject-perceived Injection Site Pain Assessment (see section 7.13), 
• Collection of Blood Specimens (see section 7.11) for 
o Plasma HIV-1 RNA level 
o TruCount T Assay  
o Complete Blood Count 
o Biochemistry 
o HIV Drug Resistance Assay  
o HIV PhenoSense Entry® Assay 
o HIV Trofile® Assay  
• Change in Optimized Background Therapy based on genotypic and phenotypic results 
obtained at VF visit. 
4.3 
FOLLOW-UP PHASE 
The duration of follow-up depends on whether subject experiences virologic failure. 

 
 
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• Subjects who experience virologic failure within the Treatment Extension Phase will be 
followed up every 4 weeks until viral suppression is achieved (i.e., plasma HIV-1 RNA 
levels below level of detection) or up to a maximum of 6 months after cessation of therapy 
if the treating physician does not feel that there is an antiretroviral regimen that will regain 
full viral suppression. 
• Subjects who do not experience virologic failure at the end of the Treatment Extension 
Phase, will be followed up every 2 weeks for total of 4 weeks. 
4.3.1 Follow-Up Visits 
The following assessments will be performed at each follow-up visit, unless otherwise specified: 
• Assess for any Adverse Events and changes in Concomitant medications (see section 9 
and 7.6), 
• Symptom-directed physical examination (see section 7.7), 
• Vital Signs (see section 7.10), 
• Collection of Blood Specimens (see section 7.11) for 
o Plasma HIV-1 RNA level 
o TruCount T Assay 
4.4 
UNSCHEDULED VISITS 
In the event that the patient returns to clinic at a time other than a regularly scheduled study visit, 
the visit will be regarded as an unscheduled visit. Assessments at unscheduled visits are at the 
discretion of the Investigator.  
 

 
 
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5 
SUBJECT COMPLETION AND WITHDRAWAL 
5.1 
SUBJECT COMPLETION 
• A subject who completes the Treatment Extension Phase (without virologic failure) 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 or up to a maximum of 6 months after experiencing virologic 
failure if the treating physician does not feel that there is an antiretroviral regimen that 
will regain full viral suppression 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 
• 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.  

 
 
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• Major protocol violation 
5.2.1 Discontinuation of Study Treatment 
Discontinuation of study treatment (PRO 140) and continuation of HAART as per standard of 
care is recommended if: 
• Subject experiences virologic failure, defined as two consecutive HIV-1 RNA levels ≥ 400 
copies/mL 
Note: Subjects will be allowed to continue PRO 140 with existing OBT regimen while 
waiting for new regimen to be constructed by the Investigator. 
• 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 adjust OBT (except in the event of toxicity 
management). 
• Subject becomes pregnant. 
 
5.2.2 Data Collected for Withdrawn Subjects 
Patients 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 patients, 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. Patients who have study treatment discontinued will continue 
to be 
followed, per protocol, whenever possible. Patients 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 9.3, 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. 

 
 
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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 
A subject who has signed a consent form, has been assigned a screening number, but is not treated 
is classified as a screen failure. Subject number, demographics and reason for screen failure will 
be recorded. 

 
 
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Below are representative samples of the Investigational Product, FDP individual vial (Figure 6-1), 
syringe label (Figure 6-2), and kit label (Figure 6-3) designated for use in this clinical protocol. 
Each kit contains two labeled vials and two syringe labels.  
Figure 6-1: 
Investigational Product - Vial Label 
 
Protocol: PRO 140_CD02                   Kit No.  2-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_CD02                   Kit No.  2-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 
 
Figure 6-2: 
Investigational Product - Syringe Label 
 
 
Protocol: PRO 140_CD02                                 Contents of Kit No. 2-xxxxx 
This syringe contains 2 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 
 
 
 

 
 
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Figure 6-3: 
Investigational Product - Kit Label 
 
Protocol: PRO 140_CD02                                                          Kit No. 2-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 
Pharmacy manual for PRO140_CD02 study 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 to each subject must be available for inspection at any time. A study CRA 
assigned to monitor the investigational site will review these documents once study drug has been 
received by the investigational site. Study drug will be accounted for on an ongoing basis during 
the study. 
 
 

 
 
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6.4 
INVESTIGATIONAL PRODUCT ADMINISTRATION 
Guidelines for dose preparation can be found in the PRO140_CD02 or CD02_OpenLabel 
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 2.0 mL of study drug.  
Equivalent volumes of study drug will be administered subcutaneously on opposite sides of the 
abdomen.  
A 25-guage needle should be used to remove IP from vial and for administration to subjects. 
IP should be administered slowly over 15 seconds per mL. IP should not be kept in syringe for 
longer than 60 minutes. 
Following each SC delivery of drug, careful examination will be made to assess the appearance of 
any study drug Injection Site Reactions (ISRs) as described in Section 16.3.  
All doses of study drug will be prepared by either the credentialed pharmacist or qualified 
medical professional and will be administered as SC injection by a qualified medical professional 
(MD, DO, PA, LPN, LVN, NP, RN, or CMA if permitted by state law) or self-administered by 
subjects depending on the study visit week. 
Note: It is preferred that the same injection site be used throughout the study. At the same time, it 
is not recommended to inject the study drug into areas where skin shows signs of a previous 
injection site reaction. It is advised to change the injection site if any previous injection site 
reaction remains unresolved. Alternatively, the 700 mg dose may be delivered as four 1mL doses 
(two SC injections on opposite sides of abdomen) for those that experience discomfort with the 
2mL injections (i.e. subjects with low body fat percentages). 
6.5 
INVESTIGATIONAL PRODUCT RECEIPT AND ACCOUNTABILITY 
Study drug must be used in accordance with this protocol and only under the direction of the 
responsible investigator. The investigational site must maintain complete and accurate records 
showing receipt and disposition of all study drug, including master records listing the date of 
receipt, the number and nature of medication units received, and a dispensing record which 
includes each quantity dispensed, identification of the staff member/subject to whom dispensed, 
the date of dispensing, the intended study participant, and the identification of the preparer. All 
used and unused study kits will be retained by the investigational site until drug accountability 
can be confirmed by study CRA during the monitoring visits. Instructions will be provided by 
Sponsor regarding final disposition of all study drug in compliance with applicable regulations. 

 
 
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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. 

 
 
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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 Phase 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.  
7.3 
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) 
• 
Ethnicity (Hispanic/Latino or Not Hispanic/Latino) 
 
 

 
 
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7.4 
MEDICAL HISTORY 
Medical history obtained within PRO140_CD02 or CD02_OpenLabel study will be brought 
forward.  
Events that emerge after first treatment (TE1) will be recorded as AE under this protocol.  
7.5 
HIV HISTORY 
HIV history obtained within PRO140_CD02 or CD02_OpenLabel study will be brought 
forward. 
7.6 
PRIOR / CONCOMITANT MEDICATIONS AND NON-STUDY TREATMENTS  
A complete record of current antiretroviral therapies will be recorded in the source documents and 
on the appropriate page of the eCRF.  
In addition to this, all other medications and therapies administered or taken by the subject 
throughout the study will be recorded. Subjects must be questioned at each study visit concerning 
any new medications or changes in current medications including over-the-counter medication. 
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. 
 

 
 
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7.7 
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 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.  
The complete physical examination will be conducted at the TE1, EOT2 and at Virologic Failure 
(VF) visit. Only symptom-directed physical examination will be performed during Screening 
Phase, at treatment and follow-up visits conducted within the clinic, and at unscheduled visits 
within the Treatment and Follow-up Phases. 
7.8 
ELECTROCARDIOGRAM 
A 12-lead ECG will be conducted at EOT2 and results will be evaluated by the Investigator. The 
following parameters will be recorded: ventricular rate (beats per minute), PR interval (msec), 
QRS interval (msec), QT interval (msec), and QTc interval (msec). Additionally, the investigator 
will record the overall results of the ECG reading as either normal or abnormal, and as either not 
clinically significant or clinically significant. If abnormalities are observed, each will be recorded.  
7.9 
NEUROLOGICAL ASSESSMENT 
Neurological assessment will be performed by the Principal Investigator (or delegated personnel) 
or a Neurologist during Screening Phase, at TE1, EOT2 and Virologic Failure (VF) visit.   

 
 
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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 assessment modalities can 
be used for further assessment as per Investigator’s discretion. 
7.10 VITAL SIGNS  
Vital signs will be collected at all study visits performed at the clinic.  Vital signs collected during 
the Treatment Extension Phase (except for TE1) will be performed post-treatment, 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 
7.11 CLINICAL LABORATORY ASSESSMENTS 
Unless stated otherwise, blood and urine samples will be collected once every eight weeks 
according to the time points in the schedule of assessments for analysis of the following 
parameters: 
7.11.1 Routine CBC  
• Frequency of testing: At TE1, once every 12 weeks during Treatment Extension, EOT2 or 
Virologic Failure visit  
• Includes hemoglobin, hematocrit (HCT), red blood cell (RBC) count, white blood cell 
(WBC) count, WBC differential count (%), absolute neutrophils count and platelets count. 
7.11.2 Biochemistry 
• Frequency of testing: At TE1, once every 12 weeks during Treatment Extension, EOT2 or 
Virologic Failure visit  
• 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 

 
 
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Other: glucose (random), cholesterol (total) 
7.11.3 Coagulation indices 
• 
Frequency of testing: At TE1, once every 12 weeks during Treatment Extension, EOT2 or 
Virologic Failure visit. 
• 
Prothrombin time (PT) and International Normalized Ratio (INR) 
7.11.4 Urinalysis 
• Frequency of testing: At TE1, once every 12 weeks during Treatment Extension, EOT2 or 
Virologic Failure visit. 
• 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 
7.11.5 Urine pregnancy test  
• Frequency of testing: At first treatment visit (TE1) prior to 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. 
7.11.6 Plasma HIV-1 RNA level and TruCount T Assay 
• Frequency of testing:  During Screening, at first treatment visit (TE1) prior to treatment 
administration, at least once every four weeks during Treatment Extension Phase, EOT2,  
at VF, and at all Virologic Failure Follow-up (VF-EFU) or Non- Virologic Failure 
Follow-up (NVF-EFU) visits. 
• To assess antiretroviral therapeutic response to PRO 140 
Note: Plasma HIV-1 RNA level will be measured using Human Immunodeficiency Virus 1 
(HIV-1), Quantitative, RNA (Taqman®) test. 
TruCount T Assay includes measurement of Absolute Lymphocytes, CD3 cell count, CD4 
cell count, CD8 cell count, CD3%, CD4% and CD8% 
7.11.7 HIV-1 Trofile® Assay 
• Includes: 
a. Trofile® RNA Assay 
Trofile® RNA is the primary assay used to assess HIV-1 co-receptor tropism status.  
• 
Frequency of testing: At Virologic Failure visit 

 
 
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7.11.8 HIV-1 Drug Resistance Assay 
• Includes: 
a. 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 
phenotypic and genotypic results from the same blood sample (viral load ≥500 copies/ml).  
• Frequency of sample collection: At Virologic Failure visit   
7.11.9   HIV-1 PhenoSense® Entry assay 
• Frequency of testing: At Virologic Failure visit, in conjunction with HIV-1 tropism testing  
• With AMD3100 (CXCR4 inhibitor drug), Maraviroc and PRO 140 (CCR5 inhibitor 
drugs). 
7.11.10CCR5 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. 
• 
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. 
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. 
7.12 INVESTIGATIONAL PRODUCT ADMINISTRATION 
Refer to Section 6.4 for details. 
7.13 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 

 
 
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by the Investigator starting after the first injection is given. Refer to sections 9.1.8 and 16.3 for 
more details. 
7.14 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 
• 
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”. 

 
 
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• 
Monitoring activities will be performed remotely until Centers for Disease Control (CDC) 
recommendations allow travel to resume. 
 

 
 
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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  
This is a single arm study.  All eligible subjects will receive PRO 140 as a 700mg subcutaneous 
injection weekly until one of the following occurs: 
▪ virologic failure  
▪ consent withdrawn 
▪ PRO 140 is approved 
▪ CytoDyn decides to discontinue its development  
Note: Subjects enrolled prior to Protocol v4.0 may still be receiving the original 350mg dose and 
have the option of increasing their dose to 700mg. 
8.2 
DESCRIPTION OF SAFETY MEASURES 
The following safety measures will be assessed in this study.  
1. Mean change in viral load (HIV-1 RNA levels) at the conclusion of the treatment period 
2. Mean change in CD4 cell count at the conclusion of the treatment period 
3. Emergence of Dual/Mixed (D/M)- and CXCR4-tropic virus in patients who had exclusive 
CCR5-tropic virus at study entry. 
4. Tolerability of repeated subcutaneous administration of PRO 140 as assessed by 
investigator-evaluation of injection site reactions 
5. Frequency of treatment-related adverse events resulting in study drug discontinuation 
6. Frequency of Grade 3 or 4 adverse events as defined by the DAIDS Adverse Event scale 
7. Frequency of treatment–emergent serious adverse events 
 
 
 

 
 
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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 02 or CD02_OpenLabel study are allowed to participate in this study.  
8.4 
RANDOMIZATION AND BLINDING 
No blinding or randomization requirement. 
8.5 
INTERIM ANALYSIS  
No interim analysis planned. 
8.6 
GENERAL STATISTICAL CONSIDERATIONS  
8.6.1 Analysis Populations  
8.6.1.1 Safety Population 
The Safety population is defined as the set of subjects who received at least one dose of PRO 140. 
This population will be used for the analysis of safety parameters. 
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 9.3 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 safety data from this trial including 
details of appropriate statistical tests to examine underlying assumptions. 
8.6.3 Prognostic Factors/Covariates 
There are no pre-planned covariates analyses of the data from this study. 
8.6.4 Handling of Missing Data 
The methodology of imputing missing data, if applicable, will be detailed in the SAP. 
8.7 
DATA SUMMARY 
8.7.1 Subject Disposition 
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.  

 
 
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8.7.2 Demographic and Baseline Characteristics 
Demographics and baseline characteristics (i.e., Age, Gender, Time since HIV diagnosis, Viral 
load at T1, 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 Safety Measures 
The following safety measures will be evaluated: 
• Mean change in viral load (HIV-1 RNA levels) at the conclusion of the treatment period 
• Mean change in CD4 cell count at the conclusion of the treatment period 
• Emergence of Dual/Mixed (D/M)- and CXCR4-tropic virus in patients who had exclusive 
CCR5-tropic virus at study entry. 
• Tolerability of repeated subcutaneous administration of PRO 140 as assessed by 
investigator-evaluation of injection site reactions 
• Frequency of treatment-related adverse events resulting in study drug discontinuation 
• Frequency of Grade 3 or 4 adverse events as defined by the DAIDS Adverse Event scale 
• Frequency of treatment–emergent serious adverse events 
All safety data measures will be summarized and tabulated according to the variable type:  
• Continuous data summaries will include:  
o Number of observations, mean, standard deviation, median, and minimum and 
maximum values.   
• Categorical data summaries will include: 
o Frequency counts and percentages.  
o Logit model will be used for inferential statistics. 
8.7.5 Safety Analysis 
The Safety population will be used for the analysis of safety assessments.  

 
 
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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. No inferential statistics are planned.  
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. 
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. 
 

 
 
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9 
ADVERSE EVENTS (DEFINITIONS AND REPORTING) 
The Investigator is responsible for the detection and documentation of events meeting the criteria 
and definition of an AE or SAE, as provided in this protocol. During the study when there is a 
safety evaluation, the Investigator or site staff will be responsible for detecting, documenting, and 
reporting AEs and SAEs as detailed in this section of the protocol.  
9.1 
ADVERSE EVENT 
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). 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 
be used only when the subject is no longer in the treatment phase of the protocol, or if the 
outcome of the event was “death”. 
 

 
 
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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.  
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.  

 
 
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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 or 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 3 events following study drug injection, the subject should be 
reevaluated closely until the AE returns to Grade ≤2, at which time study treatment may be 
reintroduced at the discretion of the site investigator. If the same Grade 3 AE recurs following the 
next administration of study drug, study treatment must be permanently discontinued. Subjects 
experiencing Grade 3 AEs requiring permanent discontinuation of study treatment should be 
followed closely for resolution of the AE to Grade ≤ 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 
• 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 

 
 
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Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered a serious adverse 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 a clinical study this must 
also be reported to CytoDyn, Inc. The Investigator should discuss the case with the Medical 
Monitor. Any pregnant subject must be followed up by the Investigator or designee until the child 
is born. Any AEs of the subject during pregnancy, that meets serious criteria, must be 
documented and reported CytoDyn, Inc. Participants who become pregnant will be entered into 
the Antiretroviral Pregnancy Registry (http://www.apregistry.com). 
9.3 
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, he/she must report the SAE to 
within 24 hours: 
CRO Medical Monitor 
 
 
 
 
  
 
 
 
 
The Amarex Medical Monitor 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 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)). 
 

 
 
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9.3.1 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. 
 
 
 
 
 
 

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

 
 
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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 examination 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. 
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. Approval by the Investigator’s IRB must also be obtained prior to implementation of 
the change, with two exceptions: 

 
 
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1. When necessary to eliminate apparent immediate hazard to the subject; or 
2. When the modification does not involve the subject’s participation in the trial. 
An amendment may also require modification of the informed consent form. The Investigator will 
provide an approval letter for the amendment and revised informed consent form, if applicable, to 
the Sponsor. An amendment must be 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. 
 
 
 
 

 
 
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12 ETHICS AND REGULATORY REQUIREMENTS 
This study is to be conducted in accordance with the specifications of this protocol and in 
accordance with principles consistent with Declaration of Helsinki, GCP, 21 CFR 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. 

 
 
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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.  
 

 
 
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13 DATA HANDLING AND RECORD KEEPING 
13.1 RECORDING AND COLLECTION OF DATA 
The primary source document for this study will be the subject's medical record. If separate 
research records are maintained by the Investigator(s), the medical record and the research 
records will be considered the source documents for the purposes of auditing the study.  
Applicable source data will be manually transcribed to 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. 
 

 
 
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13.3 ARCHIVING 
All study documentation at the Investigator site and Sponsor site will be archived in accordance 
with ICH GCP E6 and the Sponsor’s quality standards and SOPs. 
The Investigator will maintain all research records, reports, and case history reports for a period 
of two 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.  

 
 
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14 PUBLICATION PLAN 
All information supplied by CytoDyn in connection with this study and not previously 
published, is considered confidential information. This information includes, but is not 
limited to, the Investigator’s Brochure (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 

 
 
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study report is signed off, or with respect to any endpoints or analyses other than those specified 
in this protocol. 
 
  
 
 

 
 
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15 REFERENCES 
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. 
Gulick RM Lalezari J, Goodrich J, Clumeck N, DeJesus E, Horban A, Nadler J, Clotet B, 
Karlsson A, Wohlfeiler M, Montana JB, McHale M, Sullivan J, Ridgway C, Felstead S, 
Dunne MW, van der Ryst E, Mayer H. Maraviroc for Previously Treated Patients with R5 
HIV-1 Infection  NEJM. - October 2, 2008. - Vol. 359 : 14. - pp. 1429-1441. 
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.. 
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. 
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. 
Moyle G Gatell J, Perno CF, Ratanasuwan w, Schechter M, Tsoukas C Potential for new 
antiretrovirals to address unmet needs in the management of HIV-1 infection.  AIDS Patient Care 
STDS. - 2008. - pp. 459-471. 
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.. 
Office of AIDS Research Advisory Council AIDSinfo Guidelines for the Use of Antiretroviral 
Agents in HIV-1-Infected Adults and Adolescents [Online]  AIDS Info. - Nov 13, 2014. - Dec 29, 
2014. - http://aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf. 
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.. 

 
 
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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. 
Tang MW Shafer RW HIV-1 Antiretroviral Resistance: Scientific Principles and Clinical 
Applications  Drugs. - 2012. - pp. e1-e25. 
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. 
 
 
 
 
 
 
 
 

 
 
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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 

 
 
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• Toxoplasmosis of brain, onset at age >1 month† 
• 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 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
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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 
 

 
 
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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 
 
 
 

 
 
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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, Investigator may use additional neurological 
assessment modalities at its discretion.