Extension of Protocol PRO140_CD01 to Further Evaluate Long-term Suppression of HIV-1 Replication Following Substitution of Stable Combination ART With PRO 140 (Monoclonal CCR5 Antibody) Monotherapy in Adult Subjects With HIV-1 Infection
Phase: PHASE2
Conditions: HIV, Human Immunodeficiency Virus
Sponsor: CytoDyn, Inc.

CONFIDENTIAL 
 
                   Page 1 of 133 
 
 
 
  
An extension of Protocol PRO 140_CD 01 to further evaluate the long-term 
Suppression of HIV-1 Replication following Substitution of Stable Combination 
Antiretroviral Therapy with a PRO 140 (Monoclonal CCR5 antibody) 
Monotherapy in Adult Subjects with HIV-1 infection 
 
 
Protocol Number: 
PRO 140_CD 01-Extension 
Version: 
12.0 
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 01-Extension 
 
Version: 
 
12.0 
 
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. 
 
 
 
 

 
 
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INVESTIGATOR’S SIGNATURE PAGE 
 
 
 
Protocol Number:  
PRO 140_CD 01-Extension 
 
Version: 
 
12.0 
 
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 ............................................................................................................11 
List of Tables .................................................................................................................................17 
List of Figures ...............................................................................................................................18 
List of Abbreviations .....................................................................................................................19 
1 INTRODUCTION..................................................................................................................22 
1.1 
Statement of Intent ..............................................................................................................22 
1.2 
The Problem Statement .......................................................................................................22 
1.3 
Background and Historical Data .........................................................................................23 
1.4 
Name and Description of the Investigational Product .........................................................26 
1.5 
Summary of Prior Pre-Clinical And Clinical Studies .........................................................27 
1.5.1 
Pre-Clinical Studies with PRO 140 ...................................................................27 
1.5.2 
Clinical Studies with PRO 140 ..........................................................................27 
1.5.2.1 
PRO 140 1101 Study .........................................................................................28 
1.5.2.2 
PRO 140 1102 Study .........................................................................................28 
1.5.2.3 
PRO 140 1103 Study .........................................................................................28 
1.5.2.4 
PRO 140 1302 Study .........................................................................................28 
1.5.2.5 
PRO 140 2301 Study .........................................................................................32 
1.5.2.6 
PRO 140 2101 Study .........................................................................................32 
1.5.2.7 
PRO 140 _CD 01 Study ....................................................................................35 
1.5.2.8 
PRO 140 _CD02 Study .....................................................................................36 
1.5.2.9 
PRO 140 _CD02 _Open Label ..........................................................................37 
1.5.2.10 
PRO 140_CD02 Extension Study .....................................................................37 
1.5.2.11 
PRO 140 _CD03 Study .....................................................................................38 
1.5.2.12 
PRO 140_CD03 Extension Study .....................................................................38 
1.6 
Rationale for Dose Selection ...............................................................................................42 
1.7 
Risks / Benefits Assessment ................................................................................................43 
1.7.1 Risks/Discomfort to Subjects and Precautions to Minimize Risk .......................................43 
1.7.1.1 
Risks associated with Temporary Discontinuation of current Antiretroviral 
Treatment Regimen ...........................................................................................43 
1.7.1.2 
Allergic Reaction ...............................................................................................44 
1.7.1.3 
Immune Response .............................................................................................44 

 
 
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1.7.1.4 
Pregnancy ..........................................................................................................44 
1.7.1.5 
Venipuncture for blood sampling and Subcutaneous injection for Study Drug 
Administration ...................................................................................................44 
1.7.1.6 
Risks to the Study Personnel and the Environment ..........................................44 
1.7.1.7 
Unknown Risks .................................................................................................45 
1.7.1.8 
Theoretical risk for increased severity of West Nile virus infection .................45 
1.7.2 Intended Benefit for Subjects ..............................................................................................45 
2 STUDY OBJECTIVES ..........................................................................................................46 
3 STUDY DESIGN ....................................................................................................................47 
3.1 
Study Center(s) ....................................................................................................................47 
3.2 
Study Population .................................................................................................................47 
3.3 
Eligibility Criteria ................................................................................................................47 
3.3.1 
Inclusion Criteria ...............................................................................................47 
3.3.2 
Exclusion Criteria ..............................................................................................47 
4 STUDY SCHEDULE .............................................................................................................50 
4.1 
Screening Phase ...................................................................................................................71 
4.1.1 
Screening Visits 1 & 2.......................................................................................71 
4.2 
Treatment Extension Phase .................................................................................................71 
4.2.1 
Treatment Visit-1 (TE1) ....................................................................................73 
4.2.2 
Treatment Visit-2 (TE2) to Visit-59 (TE59) – Bi-weekly Visits ......................74 
4.2.3 
Treatment Visit-60 (TE60) onwards – Monthly Visits .....................................75 
4.2.4 
Virologic Failure (VF) Visit ..............................................................................76 
4.3 
Follow-up Phase ..................................................................................................................77 
4.3.1 
Follow-Up Visits ...............................................................................................77 
5 SUBJECT COMPLETION AND WITHDRAWAL...........................................................79 
5.1 
Subject Completion .............................................................................................................79 
5.2 
Subject Withdrawal .............................................................................................................79 
5.2.1 
Discontinuation of Study Treatment .................................................................79 
5.2.2 
Data Collected for Withdrawn Subjects ............................................................80 
5.3 
Screen Failures ....................................................................................................................80 
6 STUDY TREATMENT .........................................................................................................81 
6.1 
Investigational Product Description ....................................................................................81 
6.2 
Investigational Product Packaging and Labeling ................................................................82 
6.3 
Investigational Product Storage ...........................................................................................84 

 
 
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6.4 
Investigational Product Administration ...............................................................................84 
6.5 
Investigational Product Receipt and Accountability ...........................................................85 
6.6 
Investigational Product Disposition ....................................................................................86 
7 DESCRIPTION OF PROTOCOL ASSESSMENTS AND PROCEDURES ...................87 
7.1 
Informed Consent ................................................................................................................87 
7.2 
Assessment of Eligibility .....................................................................................................87 
7.3 
Demographic Information ...................................................................................................88 
7.4 
Medical History ...................................................................................................................88 
7.5 
Prior / Concomitant Medications and Non-Study Treatments ............................................88 
7.5.1 
Excluded Medications and Therapies................................................................89 
7.5.2 
Allowable Medications and Therapies ..............................................................89 
7.6 
Physical Examination ..........................................................................................................89 
7.7 
Neurological Assessment ....................................................................................................90 
7.8 
Quality of Life (QoL) ..........................................................................................................90 
7.9 
Vital Signs ...........................................................................................................................90 
7.10 Clinical Laboratory Assessments ........................................................................................91 
7.10.1 
Routine CBC .....................................................................................................91 
7.10.2 
Biochemistry .....................................................................................................91 
7.10.3 
PK sample for PRO 140 ....................................................................................91 
7.10.4 
Serum pregnancy test ........................................................................................92 
7.10.5 
Urine pregnancy test ..........................................................................................92 
7.10.6 
Plasma HIV-1 RNA level and TruCount T Assay ............................................92 
7.10.7 
Anti-idiotypic antibodies to PRO 140 ...............................................................92 
7.10.8 
Trofile® RNA or Trofile® DNA and PhenoSense® Entry Assay (Trofile® with 
enhanced sensitivity) .........................................................................................93 
7.10.9 
HIV Genotyping Assay .....................................................................................93 
7.10.10 
Serum Concentration of ART drugs ..................................................................93 
7.10.11 
Blood sample collection for Exploratory/Confirmatory analysis ......................93 
7.10.12 
CCR5 Receptor Occupancy...............................................................................93 
7.11 PRO 140 Administration .....................................................................................................94 
7.12 Injection Site Reaction assessment ......................................................................................94 
7.13 Pain Assessment using Visual Analog Scale (VAS) ...........................................................94 
7.14 COVID-19 Guidance ...........................................................................................................95 

 
 
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8 STATISTICAL CONSIDERATIONS .................................................................................97 
8.1 
Treatment Groups ................................................................................................................97 
8.2 
Description of Study Endpoints ..........................................................................................97 
8.2.1 
Primary Efficacy Endpoints ..............................................................................97 
8.2.2 
Secondary Efficacy Endpoints ..........................................................................97 
8.2.3 
Safety Endpoints................................................................................................97 
8.3 
Sample Size Determination and Rationale ..........................................................................98 
8.4 
Randomization and Blinding ...............................................................................................98 
8.5 
Interim Analysis ..................................................................................................................98 
8.5.1 
Analysis Population ...........................................................................................98 
8.5.2 
Procedures .........................................................................................................98 
8.5.3 
Data and Information Provided to DMC ...........................................................98 
8.5.4 
Type I Error Rate Adjustment ...........................................................................98 
8.6 
General Statistical Considerations .......................................................................................98 
8.6.1 
Analysis Populations .........................................................................................98 
8.6.1.1 
Intent-to-Treat Population .................................................................................99 
8.6.1.2 
Per Protocol Population .....................................................................................99 
8.6.1.3 
Safety Population ..............................................................................................99 
8.6.2 
Statistical Methods ............................................................................................99 
8.6.3 
Prognostic Factors/Covariates ...........................................................................99 
8.6.4 
Handling of Missing Data .................................................................................99 
8.6.5 
Multiplicity ........................................................................................................99 
8.7 
Data Summary .....................................................................................................................99 
8.7.1 
Subject Disposition ...........................................................................................99 
8.7.2 
Demographic and Baseline Characteristics .....................................................100 
8.7.3 
Prior and Concomitant Medications ................................................................100 
8.7.4 
Efficacy Analysis ............................................................................................100 
8.7.4.1 
Primary Analysis .............................................................................................100 
8.7.4.2 
Secondary Analysis .........................................................................................100 
8.7.4.3 
Supportive Analysis ........................................................................................101 
8.7.5 
Safety Analysis ................................................................................................101 
8.7.5.1 
Adverse Events ................................................................................................101 
8.7.5.2 
Tolerability Assessment ..................................................................................101 
8.7.5.3 
Clinical Laboratory Data .................................................................................101 
8.7.5.4 
Physical Examination ......................................................................................101 
8.7.5.5 
Vital Signs .......................................................................................................101 

 
 
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8.7.5.6 
ECG Examination............................................................................................101 
8.7.5.7 
Neurological Assessment ................................................................................102 
8.7.5.8 
Quality of Life Assessment .............................................................................102 
9 ADVERSE EVENTS (DEFINITIONS AND REPORTING) ..........................................103 
9.1 
Adverse Event ...................................................................................................................103 
9.1.1 
Reporting of Adverse Events ..........................................................................103 
9.1.2 
Impact of Study Treatment ..............................................................................103 
9.1.3 
CTCAE Grade (Severity) Assessment ............................................................104 
9.1.4 
Causality Assessment ......................................................................................104 
9.1.5 
Treatment Given as a Result of the Event .......................................................105 
9.1.6 
Outcome Assessment ......................................................................................105 
9.1.7 
Expected / Anticipated Adverse Events ..........................................................106 
9.1.8 
SC Injection-related Events .............................................................................106 
9.2 
Serious Adverse Events (SAE) ..........................................................................................106 
9.3 
Reporting of Serious Adverse Events ...............................................................................107 
9.3.1 
SAE Follow-Up ...............................................................................................108 
10 DIRECT ACCESS TO SOURCE DATA/DOCUMENTATION ....................................109 
11 QUALITY CONTROL AND QUALITY ASSURANCE .................................................110 
11.1 Monitoring Requirements ..................................................................................................110 
11.2 Acceptability of Case Report Forms (CRFs) ....................................................................110 
11.3 Modification of Protocol ...................................................................................................111 
11.4 Reporting Protocol Deviations ..........................................................................................111 
12 DATA MONITORING COMMITTEE (DMC) ................................................................112 
13 ETHICS AND REGULATORY REQUIREMENTS .......................................................113 
13.1 Institutional Review Board/Independent Ethics Committee (IRB/IEC) ...........................113 
13.2 Investigator’s Responsibilities ..........................................................................................113 
13.3 Subject Informed Consent Requirements ..........................................................................114 
14 DATA HANDLING AND RECORD KEEPING ..............................................................115 
14.1 Recording and Collection of Data .....................................................................................115 
14.2 Clinical Data Management ................................................................................................116 
14.3 Archiving ...........................................................................................................................116 

 
 
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15 PUBLICATION PLAN .......................................................................................................118 
16 REFERENCES .....................................................................................................................119 
17 APPENDIX ...........................................................................................................................122 
17.1 Appendix I: AIDS-Defining Conditions ...........................................................................122 
17.2 Appendix II: Division of AIDS Table for Grading the Severity of Adult and Pediatric 
Adverse Events (DAIDS AE Grading Table) ..............................................................................124 
17.3 Appendix III:  Adverse Events of Special Interest: Injection Site Reactions ...................125 
17.4 Appendix IV: Common Terminology Criteria for Adverse Events v4.03 ........................126 
17.5 Appendix V: Neurological Assessment ............................................................................127 
17.6 Appendix V1: Quality of Life Assessment – ACTG SF-21 ..............................................128 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
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LIST OF TABLES 
Table 1-1: 
Clinical Studies with PRO 140 .............................................................................. 39 
Table 4-1: 
Schedule of Assessments – Screening and Treatment Extension Phase (1 of 8) .. 51 
Table 4-2: 
Schedule of Assessments – Screening and Treatment Extension Phase (2 of 8) .. 53 
Table 4-3:  
Schedule of Assessments – Screening and Treatment Extension Phase (3 of 8) .. 55 
Table 4-4: 
Schedule of Assessments – Screening and Treatment Extension Phase (4 of 8) .. 57 
Table 4-5: 
Schedule of Assessments – Screening and Treatment Extension Phase (5 of 8) .. 59 
Table 4-6: 
Schedule of Assessments – Screening and Treatment Extension Phase (6 of 8) .. 62 
Table 4-7: 
Schedule of Assessments – Screening and Treatment Extension Phase (7 of 8) .. 65 
Table 4-8: 
Schedule of Assessments – Screening and Treatment Extension Phase (8 of 8) .. 67 
Table 4-9: 
Schedule of Assessments –Follow-Up (FU) Phase ................................................ 69 
Table 6-1:      PRO140 Dose Administration: Kit Information ................................................... 81 
Table 6-2: 
Investigational Product - PRO 140 ........................................................................ 82 
Table 9-1:  
CTCAE v4.03 General Guidelines ...................................................................... 104 
 

 
 
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LIST OF FIGURES 
Figure 1-1: 
Historical Data: Kalpan-Meier Estimates for the time to HIV-1 RNA >500 
copies/mL .............................................................................................................. 24 
Figure 1-2: 
Historical Data: Median (95% C.I.) ATI log10 HIV-1 RNA copies by treatment 
arm ......................................................................................................................... 25 
Figure 1-3: 
Historical Data: Median (95% C.I.) ATI CD4+ cell count by treatment arm ....... 26 
Figure 1-4: 
PRO 140 1302 Study: Mean of the maximum (nadir) log10 reductions in HIV RNA
 ............................................................................................................................... 29 
Figure 1-5: 
PRO 140 1302 Study: Mean log10 reductions in HIV RNA over time ................. 30 
Figure 1-6: 
PRO 140 1302 Study: PRO 140 serum concentrations following a single 
intravenous injection in HIV- infected individuals. .............................................. 31 
Figure 1-7: 
PRO 140 2301 Study: Mean change from baseline in HIV-1 RNA (Log10 
copies/mL) over Time (ITT Subjects) ................................................................... 32 
Figure 1-8: 
PRO 140 2101 Study: Mean of the maximum (nadir) log10 reductions in HIV RNA
 ............................................................................................................................... 33 
Figure 1-9: 
PRO 140 2101 Study: Mean change from baseline in HIV-1 RNA (Log10 
copies/mL) over Time (ITT Subjects) ................................................................... 34 
Figure 1-10: Change in CD4+ cell counts in subjects treated with subcutaneous PRO 140. .... 35 
Figure 1-11:  Emax analysis of antiviral data generated with IV and SC PRO 140. .................. 42 
Figure 3-1:  Study Flow Diagram ............................................................................................. 49 
Figure 6-1: 
PRO 140 (CHO), 175 mg/mL Vial Label ............................................................. 83 
Figure 6-2: 
PRO 140 (CHO), 175 mg/mL Syringe Label ........................................................ 83 
Figure 6-3: 
PRO 140 (CHO), 175 mg/mL Kit Label ............................................................... 83 
Figure 7-1: 
Visual Analog Scale .............................................................................................. 95 
 

 
 
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LIST OF ABBREVIATIONS 
Abbreviation 
Term 
ADL 
Activities of Daily Living 
AE 
Adverse Event 
AIDS 
Acquired Immune Deficiency Syndrome 
ALT 
Alanine Transaminase 
ANC 
Absolute Neutrophil Count 
ART 
Antiretroviral Therapy 
AST 
Aspartate Transaminase 
ATC 
Anatomic Therapeutic Classification 
AUC 
Area Under Curve 
BMI 
Body Mass Index 
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 
CMA 
Certified Medical Assistant 
CRA 
Clinical Research Associate 
CRF 
Case Report Form 
Cmax 
Maximal Concentration 
CRO 
Contract Research Organization 
CS 
Clinically Significant 
CTCAE 
Common Terminology Criteria for Adverse Events 
CV 
Curriculum Vitae 
DAIDS 
Division of AIDS 
DMC 
Data Monitoring Committee 
DNA 
Deoxyribonucleic acid 
DO 
Doctor of Osteopathic Medicine 
ECG 
Electrocardiogram 
EOT 
End of Treatment 
eCRF 
Electronic Case Report Form 
Emax 
Maximum drug effect 
et al 
et aliae; Latin for "and others" 
F 
Fahrenheit 

 
 
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Abbreviation 
Term 
FDA 
U.S. Food and Drug Administration 
FDP 
Fixed Dose Procedure 
FU 
Follow-Up 
GCP 
Good Clinical Practice 
GMP 
Good Manufacturing Practices 
HAART 
Highly Active Antiretroviral Therapy 
Hb 
Hemoglobin 
HCT 
Hematocrit 
HEENT 
Head, Ears, Eyes, Nose, and Throat 
HIPAA 
Health Insurance Portability Accountability Act 
HIV 
Human Immunodeficiency Virus 
IA 
Interim Analysis 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization 
i.e. 
id est; Latin for “that is” 
IEC 
Independent Ethics Committee 
IND 
Investigational New Drug 
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 
MoCA 
Montreal Cognitive Assessment  
MW 
Molecular Weight 
NCS 
Not Clinically Significant 

 
 
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Abbreviation 
Term 
NP 
Nurse Practitioner 
NVF 
Non-Virologic Failure 
PA 
Physician Assistant 
PI 
Principal Investigator 
PK 
Pharmacokinetics 
PP 
Per Protocol 
Pr 
Protease 
QC 
Quality Control 
QoL 
Quality of Life 
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 
TE 
Treatment Extension 
TEAE 
Treatment Emergent Adverse Events 
USA 
United States of America 
VAS 
Visual Analogue Scale 
VF 
Virologic Failure 
WBC 
White Blood Cells 
WHO 
World Health Organization 

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

 
 
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emphasized. In the case of HIV-1 protease inhibitor maintenance therapy, reestablishment of 
control of retroviral replication has generally been achieved by resumption of combination therapy. 
The availability of an effective, simplified maintenance regimen would be of benefit to a subset of 
HIV-1 infected persons who are challenged by adherence and/or chronic nucleoside toxicity. 
Although PRO 140 would require either subcutaneous (SC) or intravenous (IV) administration, its 
favorable pharmacokinetics might allow dosing as infrequent as once or twice monthly. The ability 
to administer the drug infrequently under medical supervision could obviate one of the continuing 
challenges of close adherence to daily boosted protease inhibitor regimens that appear to be 
relatively unforgiving in maintenance settings when administered as the sole antiretroviral 
regimen. This is an open-label pilot study of PRO 140 monotherapy as maintenance therapy for 
those previously fully suppressed on combination antiretroviral regimens. 
1.3 
BACKGROUND AND HISTORICAL DATA 
Based on published data from ACTG5197 trial entitled “A Phase II double-blind, randomized, 
placebo-controlled study to evaluate the antiretroviral effect of immunization with the MRY Ad5 
HIV-1 GAG vaccine in HIV-1 infected individuals who interrupt antiretroviral drug therapy” the 
viral load will increase within 4 weeks after treatment interruption. The impact of treatment 
interruption on the CD4 cell count reduction is also observed after 4 weeks, actually the downward 
trend in CD4 cell counts can be observed by week 1, as it is depicted in Figure 1-3.  
This study was conducted in HIV infected men and women of 18 to 55 year old (inclusive), who 
have maintained viral load suppression for at least 24 months and had a CD4 cell counts of greater 
than 500 cells/mm3 and HIV-1 RNA < 50 copies/mL. 
These changes in both viral load and CD4 counts are depicted in the following figures: 
a. Viral Load: As it is depicted in Figure 1-1 if the subjects who have their viral load below 50 
copies/mL and their CD4 cell counts > 500 cells/mm3 have a treatment interruption, then after 
4 weeks approximately 50% of them will have a viral load of >500 copies/mL; and almost 
100% of the subjects will have a viral load of >500 copies/mL by 10 weeks.  

 
 
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Figure 1-1: 
Historical Data: Kalpan-Meier Estimates for the time to HIV-1 RNA >500 
copies/mL 
 
 
 
 
 
 
 
 
 
 

 
 
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Figure 1-2 depicts the actual change in the median viral load and their 95% Confidence Intervals 
over a period of 16 weeks. After week 3 there is a clear increase in the viral load and by week 6 
the viral load reaches the highest level and was maintained through week 16. 
 
 
Figure 1-2: 
Historical Data: Median (95% C.I.) ATI log10 HIV-1 RNA copies by 
treatment arm 
 
 
 
 
b. CD4 Cell count: As it is depicted in Figure 1-3, subjects who have CD4 cell count of greater 
than 500 cells/mm3 and have a treatment interruption, a trend toward a decline in CD4 observed 
by week 1. This downward trend in CD4 cell count continued and after 4 weeks of treatment 

 
 
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interruption approximately 10% and by week 16 more than 30% reduction in their viral load 
was observed. 
 
Figure 1-3: 
Historical Data: Median (95% C.I.) ATI CD4+ cell count by treatment arm 
 
 
 
1.4 
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 therapy for human immunodeficiency virus (HIV) infection. 
PRO 140 is directed at an ECL2 domain of the CCR5 cell surface receptor for HIV-1. Binding of 
this domain of the CCL5 molecule interferes with 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 114 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 

 
 
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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. 
1.5 
SUMMARY OF PRIOR PRE-CLINICAL AND CLINICAL STUDIES 
1.5.1 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 weights, food 
consumption, hematology, clinical chemistry or coagulation parameters. 
Both IV and SC administration resulted in elimination half-lives of approximately 200 hours, and 
overall exposure increased with increasing doses. Following SC administration of PRO 140 in 
monkeys, the maximal concentration (Cmax) was achieved within 56 hours and bioavailability for 
PRO 140 after SC dosing was approximately 70%.  
1.5.2 Clinical Studies with PRO 140 
Current human experience with PRO 140 consists of six 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. 

 
 
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1.5.2.1 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. 
1.5.2.2 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 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. 
1.5.2.3 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. 
1.5.2.4 PRO 140 1302 Study 
This initial proof-of-concept study was a randomized, double-blind, placebo-controlled study in 
subjects with early-stage, asymptomatic HIV infection, only R5 HIV-1 detectable, and no 
antiretroviral therapy for 12 weeks. Subjects (n=39) were randomized to receive a single IV 
injection of placebo or PRO 140 at doses of 0.5, 2, or 5 mg/kg. Subjects were monitored for 
antiviral effects, safety and PRO 140 pharmacokinetics (PK) for 58 days.  
The study enrolled 31 males and 8 females. The median age, CD4+ cell count and HIV-1 RNA at 
baseline were 40.3 years, 484cells/μL and 26,900 copies/mL, respectively. The baseline 
characteristics were similar for the different treatment groups. 
PRO 140 demonstrated potent, rapid, prolonged and dose-dependent antiviral activity (Figure 1-4 
and Figure 1-5). A single 5mg/kg dose reduced viral loads by 1.83 log10 on average (Figure 1-5). 
These reductions represent the largest antiviral effects reported after just one dose of any HIV-1 

 
 
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1.5.2.5 PRO 140 2301 Study 
PRO 140 2301 was a multi-center, randomized, double-blind, placebo-controlled, parallel group 
study in 30 male and female adult subjects infected with HIV-1. Subjects were randomized to one 
of three groups (N=10/group), each receiving one of three treatments: (i) a single IV dose of 5 
mg/kg by 30-minute IV infusion; (ii) a single IV dose of 10 mg/kg by 30-minute IV infusion; (iii) 
a single placebo dose by 30-minute IV infusion. The objective of the study was to assess and 
characterize the PK and PD of PRO 140 administered by IV infusion, assess efficacy at a new 
dosage level, and safety and tolerability of single doses of PRO 140. 
All PRO 140-treated subjects had more than 10-fold reduction in viral loads (mean max log10 
reductions were 1.83 for treatment groups and 0.32 for placebo) (Figure 1-7). 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 1-7: 
PRO 140 2301 Study: Mean change from baseline in HIV-1 RNA (Log10 
copies/mL) over Time (ITT Subjects) 
 
 
1.5.2.6 PRO 140 2101 Study 
A subcutaneous (SC) form of PRO 140 was tested in HIV-infected subjects. The trial was a 
randomized, double-blind, placebo-controlled study in subjects (n=44) with early-stage, 
asymptomatic HIV infection, only R5 HIV-1 detectable, and no antiretroviral therapy for 12 weeks 

 
 
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[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 
1-8 and Figure 1-9). 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 1-8). 
There was no viral rebound between 324mg doses, and the antiviral effects persisted for one week 
after the final dose (Figure 1-9). The trial established the first antiviral proof of concept for a long-
acting, self-administrable drug for HIV-1 infection [Thompson, 2009].  
Figure 1-8: 
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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substitution of antiretroviral therapy in HIV-1 infected patients (with exclusive CCR5-tropic 
virus). Participants in this study were experienced HIV-infected individuals who were 
virologically suppressed on combination antiretroviral therapy. Consenting patients were shifted 
from combination antiretroviral regimen to PRO 140 monotherapy for 12 weeks.  
Forty (43) subjects (M/F: 40/3) with median age of 55 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 of ≥ 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 37 
subjects were found to have exclusive CCR5-tropic virus. A letter of amendment was filed to 
increase the planned number of subjects from 40 to 43 subjects to compensate for the 3 
Dual/Mixed subjects enrolled in the study. 
All virologic failure subjects who had available lab data in both studies achieved viral suppression 
to < 400 HIV-1 RNA copies/mL, as well as viral suppression to ‘Non Detectable’ or < 50 HIV-1 
RNA copies/mL after re-initiation of ART.  
The by-subject analysis of PhenoSense® Entry Assay data for PRO140, maraviroc, and 
AMD3100 shows no significant changes in the post-treatment IC50 and IC90 values were noted 
when compared with baseline values in virologic failure and non-virologic failure groups of 
subjects.  
Anti-PRO140 antibodies were not identified in any post-treatment sample and data derived from 
the CD01 study further supports the favorable PRO140 PK profile data generated from both pre-
clinical as well as prior Phase 1/2 clinical trials. 
Safety data were analyzed for all 43 enrolled subjects. One (1) of 43 subjects experienced an SAE 
that was deemed not related to the study drug by the Principal Investigator. Twenty-nine (29) of 
43 subjects (67%) experienced one or more adverse events (AEs) after receiving at least one dose 
of PRO140. The most commonly occurring AEs were infections and infestation conditions which 
were reported by 14 of 43 (32.5%) subjects. The majority of the reported AEs (62/87; 71.2%) 
were deemed either unlikely or not related to study treatment by the Investigator. Similarly, the 
majority of the reported AEs (70/87; 80.4%) were deemed mild in nature. 
 
1.5.2.8 PRO 140 _CD02 Study 
PRO 140_CD02 study (double blind, placebo controlled, 52 subjects, multi-center) evaluated the 

 
 
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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 is proportion of participants with ≥ 0.5 log10 reduction in HIV-1 RNA 
viral load from baseline at the end of the 7 day functional monotherapy period. 
During the 24-week open-label period, all subjects received PRO 140 along with Optimized 
Background Therapy (OBT).  
This clinical study is completed. 
1.5.2.9 PRO 140 _CD02 _Open Label 
PRO 140_CD02_Open Label (open label, single arm, 25 subjects, multicenter) seeks to evaluate 
the efficacy, clinical safety, and tolerability parameters of PRO140 in combination with existing 
ART (failing regimen) for one week and Optimized Background Therapy (OBT) for 24 weeks. 
The patient population for this trial are treatment-experienced HIV-infected patients with CCR5-
tropic virus and demonstrate evidence of HIV-1 replication despite ongoing antiretroviral therapy 
with documented genotypic or phenotypic resistance to ART drugs within three drug classes (or 
within two drug classes with limited treatment options). 
This clinical study is currently ongoing. 
 
1.5.2.10 PRO 140_CD02 Extension Study 
The primary objective of this study is to provide PRO 140 on a continued basis to subjects who 
complete participation in PRO140_CD02 or PRO140_CD02_OpenLabel and would require 
continued access to PRO 140 to form a viable regimen, in the opinion of the treating physician. 
The patient population for this trial are 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 PRO140_CD02_OpenLabel study. 
 

 
 
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1.5.2.11 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 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 
PRO140 350mg SC weekly injection in a single-arm study. Subsequently, the next ~150 subjects 
were randomized 1:1 to PRO140 350mg (Group A) or PRO 140 525mg (Group B).  
An additional ~200 subjects will be randomized 1:1 to PRO 140 525mg (Group B) or PRO 140 
700mg (Group C).  
This clinical study is currently ongoing. 
 
1.5.2.12 PRO 140_CD03 Extension Study 
The objective of this study is to assess the long-term safety of using PRO 140 SC as single-agent 
maintenance therapy for the chronic suppression of CCR5-tropic HIV-1 infection. Study 
population includes treatment-experienced HIV-infected patients with CCR5-tropic virus who 
successfully complete 48 weeks of treatment with PRO140 SC monotherapy under CD03 study.

 
 
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Table 1-1: 
Clinical Studies with PRO 140 
 
Protocol 
Number 
Phase 
No. of Subjects 
(Planned/Analyzed) 
Doses 
Cell line used to 
make PRO-140 
Subject 
Population 
Comments 
PRO 140 
1101 
1 
20/20 
Single 0.1, 
0.5, 2.0, or 
5.0 mg/kg 
Sp2/0 myeloma 
Healthy 
Generally well tolerated; non-immunogenic; dose-
dependent coating of CCR5; significant coating of 
CCR5 over placebo at 0.5, 2, and 5 mg/kg 
PRO 140 
1102 
1 
20/20 
Either two or 
three doses 
totaling 200 
or 350 mg 
respectively 
CHO 
Healthy 
Generally well tolerated; drug derived from CHO cells 
well tolerated also; SC administration by Autoject® 2 
better tolerated than manual injection 
PRO 140 
1103 
1 
15/14 
Two doses, 
each of 350 
mg 
CHO 
Healthy 
More AEs associated with arm injection; trend of lower 
exposure in arm injections; thigh and abdominal 
administration preferred 
PRO 140 
1302 
1b 
40/39 
Single 0.5, 
2.0, or 5.0 
mg/kg 
Sp2/0 myeloma 
HIV-1 
positive 
Generally well tolerated; antiviral suppression 
maintained for approx. 10 days with higher doses; 
favorable tolerability and potent, dose-dependent 
antiviral activity provide proof-of-concept 
PRO 140 
2301 
2a 
30/31 
Single 5.0 or 
10.0 mg/kg 
CHO 
HIV-1 
positive 
Generally well tolerated with no dose-limiting 
toxicities; potent antiviral suppression maintained for 
approx. 20 days when administered IV at 5 or 10 
mg/kg. No dose-limiting toxicities at 10 mg/kg. 
PRO 140 
2101 
2a 
40/44 
Three doses 
of 162 or 324 
mg each 
CHO 
HIV-1 
positive 
Generally well tolerated, no drug-related SAEs or dose-
limiting toxicity; antiviral activity was statistically 
significant; two-fold exposure at higher dose; single 
dose demonstrated favorable tolerability, and potent, 
long-acting, dose-dependent antiviral activity. 

 
 
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Protocol 
Number 
Phase 
No. of Subjects 
(Planned/Analyzed) 
Doses 
Cell line used to 
make PRO-140 
Subject 
Population 
Comments 
PRO 140 
_CD 01 
2b 
43/40 
350 mg SC 
weekly dose 
for 12 Weeks 
of 
Monotherapy 
(total 
treatment 
duration 14 
Weeks) 
CHO 
HIV-1 
positive 
Generally well tolerated, no drug-related SAEs, weekly 
dose demonstrated favorable tolerability, and potent, 
long-acting, dose-dependent antiviral activity. Results 
are pending publication. 
PRO 140 
_CD02 
2b/3 
50/52 
Placebo or 
350mg SC for 
1 dose, 
followed by 
350mg SC 
weekly dose 
for 24 weeks 
(total 
treatment 
duration 25 
Weeks) 
CHO 
HIV-1 
positive 
This clinical study is completed  
PRO140_C
D02OpenL
abel 
2b/3 
25/3 
700mg SC + 
existing ART 
for 1 week 
followed by 
700mg SC 
weekly OBT 
for 24 weeks 
CHO 
HIV-1 
positive 
This clinical study is currently ongoing 
PRO 140 
_CD02 
Extension 
2b/3 
50/TBD 
350mg SC 
weekly dose 
CHO 
HIV-1 
positive 
This clinical study is currently ongoing. 

 
 
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Protocol 
Number 
Phase 
No. of Subjects 
(Planned/Analyzed) 
Doses 
Cell line used to 
make PRO-140 
Subject 
Population 
Comments 
PRO 140 
_CD 03 
2b/3 
500/TBD 
350 mg, 
525mg, or 
700mg SC 
weekly dose 
for 48 Weeks 
of 
Monotherapy 
CHO 
HIV-1 
positive 
This clinical study is currently ongoing. 
PRO 140 
_CD 03 
Extension 
2b/3 
300/TBD 
350 mg SC 
weekly 
monotherapy 
dose 
CHO 
HIV-1 
positive 
This clinical study is currently ongoing. 

 
 
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1.6 
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 1-11:  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 
1-11 above shows this relationship. Analysis shows that PR0 140 350mg weekly dose is expected 
to fall on the plateau of the Emax plot. 
The maximal change in HIV-1 viral load from baseline was determined at any point 59 days after 
initiation of therapy. To allow approximate comparisons between the IV and SC doses, the overall 
AUC observed for repeat SC doses was conservatively estimated by multiplying the measured 
AUC0-7d by the number of doses administered. Viral load and AUC data were fit to an Emax 
equation: E = Emax x AUC/(AUC + AUC50). The orange diamond indicates projected data for 
three weekly 350 mg doses based on the mean exposure observed in the PRO 140 1103 study. 
It is important to note that when larger proteins (MW>10,000) are administered SC, they initially 
traffic through the lymphatic system. Uptake into the bloodstream occurs after the proteins reach 

 
 
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the thoracic duct [Nishikawa M, 2005]. As a consequence, a significant percentage of SC PRO 
140 can be expected to encounter and bind CCR5-expressing cells and exert antiviral effects 
without ever reaching the bloodstream. For this reason, the serum AUC observed for SC 
administration may provide a conservative measure of drug exposure relative to that observed with 
IV administration. 
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 We expect that this target will be achieved by most or all of the dosing 
regimens to be studied in PRO 140 2103. 
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. 
Due to the majority of subjects receiving 350 mg weekly SC dosing in monotherapy setting 
experiencing virologic failure in the CD03 study, a dose increase was proposed. 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). 
Subjects enrolled under a previous Protocol version have the option to continue receiving the 350 mg 
dose or increase to the 700 mg dose. 
1.7 
RISKS / BENEFITS ASSESSMENT 
1.7.1 RISKS/DISCOMFORT TO SUBJECTS AND PRECAUTIONS TO MINIMIZE RISK 
1.7.1.1 Risks associated with Temporary Discontinuation of current Antiretroviral 
Treatment Regimen 
The study treatment (PRO 140 monotherapy) may not be effective in maintaining the viral 
suppression for all subjects. In such cases, temporary discontinuation of antiretroviral therapy 
could lead to a rebound in viral load and might be associated with an increase risk of developing 
drug resistance, opportunistic infections and clinical progression of the disease. 

 
 
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Study participants will be regularly monitored for viral rebound following initiation of PRO 140 
monotherapy and will re-initiate their previous antiretroviral regimen if plasma HIV-1 RNA levels 
rise up to or above 400 copies/ml on two consecutive blood draws at least 3 days apart.  
1.7.1.2 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 administered to subjects, there should be available and 
in place the procedures required to manage anaphylactic shock. 
1.7.1.3 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. 
1.7.1.4 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).  
1.7.1.5 Venipuncture for blood sampling and Subcutaneous injection for Study Drug 
Administration 
Venipuncture for blood sample collection and subcutaneous injection for study drug administration 
carries a minimal risk of minor discomfort and the possibility of minor bruising at the site of the 
needle puncture and, rarely, the possibility of infection at the needle puncture site. 
1.7.1.6 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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1.7.1.7 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.  
1.7.1.8 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.  
1.7.2 INTENDED BENEFIT FOR SUBJECTS 
This is a proof of concept study for the purpose of selecting a dose and regimen for further clinical 
testing. The most significant limitation with highly active antiretroviral therapy (HAART) has 
been the necessity and challenge of continued daily adherence to the medications. This study 
provides opportunity to the subjects to have once weekly SC treatment with PRO 140. Subjects 
participating in the present monotherapy study will contribute to the development of a drug which 
has the potential to become a treatment option for them and others in the future. 

 
 
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2 
STUDY OBJECTIVES 
The primary objective is to assess the long-term efficacy of PRO 140 monotherapy for the 
maintenance of viral suppression in patients who have completed 12 weeks of treatment under 
Protocol PRO 140_CD 01 without experiencing virologic failure. 
The secondary objective of the trial is to assess the long-term clinical safety and tolerability 
parameters of continued PRO 140 use in patients who have completed 12 weeks of treatment under 
Protocol PRO 140_CD 01 without experiencing virologic failure.  
The primary efficacy endpoint for this study is time to virologic failure after initiating PRO 140 
monotherapy. Virologic failure is defined as two consecutive HIV-1 RNA levels of ≥ 400 
copies/ml separated by at least 3 days. 
The secondary efficacy endpoints will be proportion of participants with virologic failure after 
initiating PRO 140 monotherapy, mean change in viral load (HIV-1 RNA levels), mean change in 
CD4 cell count, and change in Quality of Life (QoL) up to TE107 within the treatment extension 
phase. 
Safety assessments include evaluation of tolerability of repeated subcutaneous administration of 
PRO 140 as assessed by study participants (using Visual Analogue Scale) and by investigator –
evaluation of injection site reactions, frequency of Grade 3 or 4 adverse events and frequency of 
Treatment-emergent serious adverse events. 
 
 

 
 
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3 
STUDY DESIGN  
3.1 
STUDY CENTER(S) 
Site(s) participating in PRO 140 _CD 01 Protocol 
3.2 
STUDY POPULATION 
This study will recruit subjects with HIV-1 infection who did not experience virologic failure 
while in the treatment phase of the PRO 140_CD 01 study. 
3.3 
ELIGIBILITY CRITERIA 
3.3.1 Inclusion Criteria 
Subjects must meet all of the following criteria to be included in the study: 
1. Subjects who have completed 12 weeks of treatment in PRO 140_CD 01 study without 
experiencing virologic failure. 
2. Both male and female patients and their partners of childbearing potential must agree to use 
appropriate birth control methods (birth control pills, barriers, or abstinence) throughout the 
study duration (excluding women who are not of childbearing potential and men who have 
been sterilized). Females of childbearing potential must have a negative urine pregnancy test 
prior to receiving the first dose of study drug. 
3. 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 01 Treatment Substitution Study 
2. Any acquired immune deficiency syndrome (AIDS)-defining illness according to the 1993 
Centers for Disease Control and Prevention (CDC) AIDS surveillance definition 
3. Laboratory test values  grade 4 DAIDS laboratory abnormality. 
4. Females who are pregnant, lactating, or breastfeeding, or who plan to become pregnant 
during the study 
5. Unexplained temperature 38.5OC (101.3OF) for seven consecutive days within 14 days 
prior to the first study dose 

 
 
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6. Diagnosed with either substance dependence or substance abuse or any history of a 
concomitant condition (e.g., medical, psychological, or psychiatric) that in the opinion of 
the primary care provider and/or site investigator would interfere with the subject’s 
successful completion of the study requirements 
7. Any other clinical condition that, in the Investigator's judgment, would potentially 
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4 
STUDY SCHEDULE 
This research study is divided into three study phases:  
(1) Screening Phase: This phase lasts up to 14 days and consists of two Screening Visits (SV1 
and SV2) which are 7 (±3) days apart.   
SV1 begins with signing of Informed Consent and corresponds to T12 of the PRO 140_CD 
01 protocol.  SV2 corresponds with T13 of the PRO 140_CD 01 protocol.   
Assessments from both T12 and T13 will be used to determine final eligibility for PRO 
140_CD 01-Extension protocol.  First treatment will be administered within 14 days of 
SV1. 
(2) Treatment Extension Phase (weekly ± allowed windows): Subjects will receive weekly 
treatments (window period of ±3 days).  
Any time during the Treatment Extension Phase, if virologic failure occurs, subject will 
stop the study treatment and re-start their previous antiretroviral regimen. 
(3) Follow-Up Phase: The duration of follow-up depends on the status of viral load 
suppression. 
• Subjects who experience virologic failure will be followed up every 4 weeks until the 
viral load suppression is achieved (i.e., plasma HIV-1 RNA levels to return back to <50 
copies/mL)  
• Subjects who do not experience virologic failure at the end of Treatment Extension 
Period, will be followed up every 2 week for total of 4 weeks. 
 
➢ Note: Virologic failure subjects will have a long term safety follow up visit once a year 
within 2 years of completing the last VF-FU visit. 
Procedures to be performed during each of these study phases are described below and provided 
as a Schedule of Assessments in Table 4-1, Table 4-2, Table 4-3, Table 4-4, Table 4-5, Table 4-6, 
Table 4-7, Table 4-8, and Table 4-9.  
 

 
 
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X (red bold): Activities performed under Extension study protocol  
-X- : Activities performed under PRO 140_CD 01 protocol 
[1] 
Informed consent must be obtained at the Screening Visit 1 (SV1) coincides with the T12 clinic visit under the PRO 140_CD 01 protocol. 
[2] 
Initial evaluation of patient eligibility will be performed by Investigator. 
[3] 
Based on results of lab samples collected at the Screening Visit 1 under Extension protocol / T12 clinic visit under the PRO 140_CD 01 protocol 
[4] 
Medical history collected at the time of screening for PRO 140_CD 01 protocol will be carried forward. Medical history will not be collected for the PRO 
140_CD 01-Extension protocol. 
[5] 
Symptom-directed physical examination 
[6] 
Performed by Principal Investigator or designated study personnel.  The neurological assessment tool is based on the three question survey used by Simioni et al. 
(Simioni S, 2010). Additional neurological assessment modalities may be used as per Investigator’s discretion. 
[7] 
Performed by Principal Investigator or Study Coordinator 
[8] 
Blood pressure, heart rate, respiration rate, temperature assessed before and 15 minutes after study treatment administered at clinic  
[9] 
Hemoglobin, Hematocrit (HCT), Red Blood Cells (RBC), White Blood Cells (WBC) with total and differential count, Absolute Neutrophil Count (ANC) and platelets. 
[10] 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) 
[11] ONLY performed on women of childbearing potential. 
[12] Includes: Absolute Lymphocytes, CD3 cell count, CD4 cell count, CD8 cell count, CD3 %, CD4 %, and CD8 % 
[13] PK samples for PRO 140 may be collected at during Treatment Extension Phase and at virologic  failure 
[14] To assess subject compliance in abstaining from previous ART regimen after SV1 visit;  
[15] Blood sample collection prior to first treatment administration at SV2 and at the time of early breakthrough/virologic failure will be used for exploratory or confirmatory 
purposes. 
[16] ONLY for subjects trained to perform self-administration of study treatment on weeks when clinic visit optional, i.e., no lab samples are required  
[17] Study treatment for self-administration will be provided to subjects during treatment visits at clinic; used vials from prior self-administration must be collected and 
accounted for (see Section 4.2.2) 
[18] All study subjects will re-initiate their previous antiretroviral regimen: (1) One week prior to the end of 161-week Treatment Extension Phase, or (2) Anytime during the 
Treatment Extension Phase, if virologic failure occurs or have met any other criteria for discontinuation of study treatment as specified in the protocol. 
[19] As assessed by Investigator when study treatment administered at the clinic.   
[20] Subject-perceived injection site pain (average pain since last treatment) will be assessed using the Pain Visual Analog Scale (VAS) prior to each study treatment 
administration for subject’s randomized to PRO 140 
 
 
 
 

 
 
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[32] Refer to Section 7.10.12. 
 
 
 
 

 
 
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[33] In-clinic assessment(s) should be performed at least once every 4 weeks from TE108 onwards. 
[34] Subjects should be instructed to report any new AEs that occur between clinic visits to site promptly 
[35] Performed by Principal Investigator (or designee) when subject comes to clinic. NOTE: The neurological assessment tool is based on the three question survey used by 
Simioni et al. (Simioni S, 2010). Additional neurological assessment modalities may be used as per Investigator’s discretion. 
[36] Blood pressure, heart rate, respiration rate, temperature assessed before and 15 minutes after study treatment administered at clinic  
[37] Hemoglobin, Hematocrit (HCT), Red Blood Cells (RBC), White Blood Cells (WBC) with total and differential count, Absolute Neutrophil Count (ANC) and platelets. 
[38] 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) 
[39] Sample may be collected on ad hoc basis, as per discretion of Sponsor/Investigator during the Treatment Extension Phase 
[40] ONLY for subjects trained to perform self-administration of study treatment on weeks when clinic visit optional, i.e., no lab samples are required 
[41] Study treatment for self-administration will be provided to subjects during treatment visits at clinic; used vials from prior self-administration must be collected and 
accounted for (see Section 4.2.2). 
[42] Study treatment should be administered at clinic. 
[43] All study subjects will re-initiate their previous antiretroviral regimen: (1) One week prior to the end of Treatment Extension Phase, or (2) Anytime during the 
Treatment Extension Phase, if virologic failure occurs or have met any other criteria for discontinuation of study treatment as specified in the protocol. 
[44] As assessed by Investigator when study treatment administered at the clinic.  
[45] Subject-perceived injection site pain (average pain since last treatment) will be assessed using the Pain Visual Analog Scale (VAS) prior to each study treatment 
administration for subjects randomized to PRO 140.   
 
 
 

 
 
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[32] In-clinic assessment(s) should be performed at least once every 4 weeks from TE108 onwards. 
[33] Subjects should be instructed to report any new AEs that occur between clinic visits to site promptly 
[34] Performed by Principal Investigator (or designee) when subject comes to clinic. NOTE: The neurological assessment tool is based on the three question survey used by 
Simioni et al. (Simioni S, 2010). Additional neurological assessment modalities may be used as per Investigator’s discretion. 
[35] Blood pressure, heart rate, respiration rate, temperature assessed before and 15 minutes after study treatment administered at clinic  
[36] Hemoglobin, Hematocrit (HCT), Red Blood Cells (RBC), White Blood Cells (WBC) with total and differential count, Absolute Neutrophil Count (ANC) and platelets. 
[37] 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) 
[38] Sample may be collected on ad hoc basis, as per discretion of Sponsor/Investigator during the Treatment Phase 
[39] Subjects will attend clinic visits, and receive PRO 140 treatment in clinic, on weeks when lab samples are required (at least once every 4 weeks). Subjects trained to 
perform self-administration of study treatment may do so outside of the clinic (at home) on weeks when no lab samples are required.   
[40]   Study treatment should be administered at clinic. 
[41] PRO 140 for subsequent self-administration visits will be provided to subjects during treatment visits at clinic; used vials from prior self-administration must be 
collected and accounted for (see Section 4.2.2). 
[42] All study subjects will re-initiate their previous antiretroviral regimen: (1) One week prior to the end of Treatment Extension Phase, or (2) Anytime during the 
Treatment Extension Phase, if virologic failure occurs or have met any other criteria for discontinuation of study treatment as specified in the protocol. 
[43] As assessed by Investigator when study treatment administered at the clinic.  
[44] Subject-perceived injection site pain (average pain since last treatment) will be assessed using the Pain Visual Analog Scale (VAS) prior to each study treatment 
administration for subjects randomized to PRO 140.   
[45] Should be performed at least once every 12 weeks from TE160 onwards. 
 
 
 
 

 
 
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4.1 
SCREENING PHASE 
4.1.1 Screening Visits 1 & 2 
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) that was assigned for PRO 140_CD 01 study 
will continue to be used for this extension study.  
Once the ICF has been signed, screening procedures and information will be obtained to confirm 
subject eligibility.  Assessments that are in addition to those performed at T12 or T13 of the PRO 
140_CD 01 protocol are noted below:  
• Detailed medical history – SV1 (see section 7.4), 
• Demographic information (see section 7.3),  
• Collection of Blood Specimens (see section 7.10) for 
o Serum pregnancy test, 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 (SV1) 
o Blood sample collection for Exploratory/Confirmatory analysis (SV2) 
• Urine pregnancy test at second Screening Visit, for female subjects of childbearing 
potential (see section 7.10.5) 
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. 
Eligible subjects that are not enrolled within 14 days of Screening Visit 1 must enter the Follow-
up Phase of PRO 140_CD 01 Treatment Substitution protocol. 
4.2 
TREATMENT EXTENSION PHASE 

 
 
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Treatment Extension Phase begins with an evaluation of results of laboratory samples collected 
during the Screening Phase. Subjects who meet all eligibility criteria, as per data gathered from 
Screening Phase are to be treated. All subjects who fail to meet eligibility criteria will be 
considered screen failures, exit the study without further evaluation and enter the Follow-up Phase 
of the PRO 140_CD 01 Treatment Substitution protocol. 
Eligible subjects will receive PRO 140 weekly SC treatments, given every week (± 3 days) or until 
virologic failure, whichever occurs first.   
PRO 140 will be administered as a 350 mg subcutaneous injection weekly. The study treatment 
(PRO 140 SC injections) will be administered by a qualified medical professional (MD, DO, PA, 
LPN, LVN, NP, RN, or CMA if permitted by state law) or subjects trained to perform self-
administration of study treatment (see section 6.4). 
Note: Patients enrolled under a previous Protocol (V.1.0-9.0)  have the option of increasing their 
dose to receive 700mg weekly for the remainder of the Treatment Extension Phase. 
 
All study subjects will re-initiate their previous antiretroviral regimen: 
•  One week prior to the end of Treatment Extension Phase, or  
• Anytime during the Treatment Extension Phase, if virologic failure occurs or have met any 
other criteria for discontinuation of study treatment as specified in section 5.2.1 of the protocol. 
Note: 
➢ In case of increase in plasma HIV-1 RNA levels above 200 copies/mL, subjects will return 
to clinic for another blood draw in-between the Treatment Visits for repeat plasma HIV-1 
RNA levels, as per the discretion of the Investigator. 
➢ Subjects who experience virologic failure (defined as two consecutive HIV-1 RNA levels 
of ≥ 400 copies/ml separated by at least 3 days) at any time during the Treatment Extension 
Phase will undergo the Virologic Failure (VF) Visit assessments and enter the Follow-up 
Phase of the study.  
➢ Subjects who meet any criteria (other than virologic failure) for discontinuation of study 
treatment as specified in section 5.2.1 of the protocol, will undergo TE161 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 161-week Treatment Extension Phase. 
 

 
 
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Visits during the Treatment Extension Phase will commence on TE1, i.e. the date of first 
treatment, with weekly visits (± 3 days) thereafter. 
4.2.1 Treatment Visit-1 (TE1) 
The following assessments will be performed at the first treatment visit. 
Pre-Treatment 
• Confirmation of eligibility criteria by reviewing test results and other criteria 
assessments performed at the Screening Visits (see section 7.2 ) 
• Change in concomitant medications (see section 7.5) 
• Vital signs (see section 7.9), 
• Any changes in medical history since Screening Visit (see section 7.4), 
• Symptom-directed physical examination (see section 7.6), 
• Neurological assessment (see section 7.7) 
• Quality of life assessment (see section 7.8) 
• Subject-perceived Injection Site Pain Assessment (see section 7.13) 
➢ Note: Subject-perceived injection site pain will be assessed using the Pain Visual 
Analog Scale (VAS) prior to study treatment administration assessing average pain 
since last treatment. 
Administration of PRO 140 
PRO 140 350 mg is administered as subcutaneous injection in the abdomen weekly. A total of 350 
mg (175 mg/mL) is delivered as two 1 mL injections on opposite sides of the abdomen. Subjects 
who were enrolled under a previous Protocol version and are still receiving the 350 mg dose, have 
the option of increasing their dose to 700mg for the remainder of the Treatment Extension Phase.  
PRO 140 700 mg is delivered as two 2 mL injections on opposite sides of the abdomen.  
Note: 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). 
 The study treatment (PRO 140 SC injections) will be administered by a qualified medical 
professional (MD, DO, PA, LPN, LVN, NP, RN, or CMA if permitted by state law) or subjects 
trained to perform self-administration of study treatment. 
 

 
 
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Post-Treatment 
• Injection Site Reaction Assessment (see section 7.12) 
➢ Note: To assess injection site reactions, the investigator will use the DAIDS AE 
grading table (refer to section 17.3). 
➢ Note:  Performed when treatment visit occurs at clinic    
• Assessment of Adverse Events (AE) (see section 9)  
• Vital Signs (see section 7.9) will be assessed within 15 minutes of study treatment 
administration. 
4.2.2 Treatment Visit-2 (TE2) to Visit-59 (TE59) – Bi-weekly Visits 
The following assessments will be performed at each visit, unless otherwise specified: 
• Assess for any Adverse Events and changes in Concomitant medications (see section 9 
and 7.5), 
• Symptom-directed physical examination (see section 7.6), 
• Neurological Assessment (see section 7.7) 
➢ Note: Performed by Principal Investigator (or designee) when subject comes to clinic; 
additional neurological assessment modalities may be used as per Investigator’s 
discretion. 
• Quality of Life Assessment (see section 7.8) 
➢ Note:  Performed by Principal Investigator (or designee) when subject comes to clinic 
• Vital Signs (see section 7.9) 
➢ Note: Vitals not obtained when subject self-administers study treatment outside clinic  
• Collection of Blood Specimens (see section 7.10) for 
o Plasma HIV-1 RNA level  
o TruCount T Assay 
o PK sample for PRO 140  
o Serum concentration of ART drugs  
o Anti-idiotypic antibodies to PRO 140 
o Blood sample for exploratory analysis 

 
 
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➢ Note:  Lab samples to be collected at the time of clinic visit 
• Study Treatment Administration (PRO 140) 
➢ Note: Subjects trained to perform self-administration of study treatment may self-
administer when clinic visit not required (no lab sample collection needed), at odd 
numbered treatment visits beyond TE2  
• Injection Site Reaction Assessment (see section 7.12) 
➢ Note: To assess injection site reactions, the investigator will use the DAIDS AE 
grading table (see section 17.3). 
➢ Note: Assessment will be performed when subject administered study treatment at 
clinic visit 
• Subject-perceived Injection Site Pain Assessment (see section 7.13) 
➢ Note: Subject-perceived injection site pain will be assessed using the Pain Visual 
Analog Scale (VAS) prior to study treatment administration assessing average pain at 
injection site since last treatment. 
➢ Note: Performed at the time of clinic visit. 
4.2.3 Treatment Visit-60 (TE60) onwards – Monthly Visits 
Patients are required to have a clinic visit at least once every four weeks from TE60 onwards.  
Subjects will re-initiate previous antiretroviral regimen at end of treatment extension phase (one 
week prior to last PRO 140 treatment), if viral load remain suppressed. 
The following assessments will be performed at every clinic visit: 
• Assess for any Adverse Events and changes in Concomitant medications (see section 9 
and 7.5), 
• Symptom-directed physical examination (see section 7.6), 
• Neurological Assessment (see section 7.7) 
• Vital Signs (see section 7.9) 
➢ Note: Vitals not obtained when subject self-administers study treatment outside clinic 
• Study Treatment Administration (PRO 140) 
➢ Note: Subjects trained to perform self-administration of study treatment may self-
administer when clinic visit not required (no lab sample collection needed) 

 
 
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• Injection Site Reaction Assessment (see section 7.12) 
➢ Note: To assess injection site reactions, the investigator will use the DAIDS AE 
grading table (see section 17.3). 
➢ Note: Assessment will be performed when subject administered study treatment at 
clinic visit 
• Subject-perceived Injection Site Pain Assessment (see section 7.13) 
➢ Note: Subject-perceived injection site pain will be assessed using the Pain Visual 
Analog Scale (VAS) prior to study treatment administration assessing average pain at 
injection site since last treatment. 
➢ Note: Performed at the time of clinic visit. 
• Collection of Blood Specimens (see section 7.10) for 
o Plasma HIV-1 RNA level  
o TruCount T Assay 
o Routine CBC  
o Biochemistry  
o PK sample for PRO 140  
o Serum concentration of ART drugs  
o Anti-idiotypic antibodies to PRO 140 
o Blood sample for exploratory analysis 
➢ Note:  Trofile® RNA or Trofile® DNA and PhenoSense Entry Assay will be performed 
at the last treatment visit (EOT) 
o CCR5 Receptor Occupancy 
➢ Note: Blood will be taken prior to PRO 140 injection (trough sample) and 24-48 hours 
(peak sample) after the PRO 140 injection to check for CCR5 occupancy, and 
correlative analysis will be performed with PRO 140 PK concentration and HIV-1 RNA 
levels. This assessment will be performed up to 5 times at different treatment visits.  
 
4.2.4 Virologic Failure (VF) Visit  

 
 
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The following assessments will be performed for subjects who experience virologic failure at any 
time during the Treatment Extension Phase: 
• Assess for any Adverse Events and changes in Concomitant medications (see section 9 
and 7.5), 
• Complete Physical Examination (see section 7.6), 
• Vital Signs (see section 7.9), 
• Neurological Assessment (see section 7.7), 
• Collection of Blood Specimens (see section 7.10) for 
o Plasma HIV-1 RNA level 
o TruCount T Assay  
o HIV Genotyping Assay  
o Trofile® RNA or Trofile® DNA and PhenoSense Entry Assay 
o Anti-idiotypic antibodies to PRO 140 
o Routine CBC 
o Biochemistry 
o PK sample for PRO 140 
o Blood sample collection for Exploratory/Confirmatory analysis 
• Re-initiate previous Antiretroviral Regimen 
4.3 
FOLLOW-UP PHASE 
The duration of follow-up depends on the status of viral load suppression. 
➢ Subjects who experience virologic failure will be followed up every 4 weeks until the 
viral load suppression is achieved (i.e., plasma HIV-1 RNA levels to return to <50 
copies/mL)  
➢ Subjects who do not experience virologic failure at the end of Treatment Extension 
Period, will be followed up every 2 weeks for total of 4 weeks. 
➢ Note: Virologic failure subjects will have a long term safety follow up visit once a year 
within 2 years of completing the last VF-FU visit. 
4.3.1 Follow-Up Visits 
The following assessments will be performed at each follow-up visit, unless otherwise specified: 

 
 
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• Assess for any Adverse Events and changes in Concomitant medications (see section 9 
and 7.5), 
• Symptom-directed physical examination (see section 7.6) at NVF-EFU and short term 
VF-EFU visits, 
• Vital Signs (see section 7.9), 
• Collection of Blood Specimens (see section 7.10) for 
o Plasma HIV-1 RNA level 
o TruCount T Assay 
o Anti-idiotypic antibodies to PRO 140 (NVF-EFU2 and VF-EFU1 visits) 
o Trofile® DNA or RNA Assay (VF-12mFU and VF-24mFU visits) 
o PhenoSense® Entry Assay (VF-12mFU and VF-24mFU visits) 
o HIV-1 Drug Resistance Assay (VF-12mFU and VF-24mFU visits) 

 
 
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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 VF Visit assessments and is followed up until viral suppression is 
achieved, 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.  
• Major protocol violation 
5.2.1 Discontinuation of Study Treatment 

 
 
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Discontinuation of study treatment and resumption of previous antiretroviral therapy is 
recommended if: 
• Subject experiences virologic failure (defined as two consecutive HIV-1 RNA levels of ≥ 400 
copies/ml separated by at least 3 days) 
• Develops retroviral rebound syndrome or AIDS-defining conditions as specified in Appendix 
I (Section 17.1). 
• Shows signs or symptoms of clinically significant immunosuppression 
• Subject or the subject’s clinician wishes to restart ART. 
• Subject becomes pregnant. 
5.2.2 Data Collected for Withdrawn Subjects 
Patients may withdraw from the study or discontinue study treatment at any time; however, 
CytoDyn, Inc. 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. 
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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6 
STUDY TREATMENT 
6.1 
INVESTIGATIONAL PRODUCT DESCRIPTION 
PRO 140 is a humanized IgG4, monoclonal antibody (mAb) to the chemokine receptor CCR5. 
PRO 140 is provided at a concentration of 175 mg/mL and is intended for SC route of 
administration. 
Kits will be labeled with a unique identification number. Each kit used during Study Treatment 
will contain vials of PRO 140 for SC injection. Based on the dose administered to the subjects, 1 
mL (350 mg dose) or 2 mL (700 mg dose) PRO 140 solution will be drawn from a vial and loaded 
into the syringe. A total of 350 mg or 700 mg  of PRO 140 (from stock concentration 175mg/mL) 
is delivered as two injections administered subcutaneously on opposite sides of the abdomen or as 
one of the alternative methods listed in Section 6.4 below. One study injection kit will be assigned 
per subject per treatment visit (with exception for 350 mg dose with 2.4 mL fill volume in which 
one kit can be used for two doses). 
Table 6-1: PRO140 Dose Administration: Kit Information 
PRO 140 Kits Containing 1.4 mL per Vial 
PRO 140 Dose 
# of Vials 
Used per Dose 
Total Injection 
Volume (mL) 
Volume (mL) 
Administered 
per Injection* 
Volume (mL) 
Discarded per Vial 
350 mg 
2 
2 
1 
0.4 
700 mg 
4 
4 
2 
0.4 
PRO 140 Kits Containing 2.4 mL per Vial 
PRO 140 Dose 
# of Vials 
Used per Dose 
Total Injection 
Volume (mL) 
Volume (mL) 
Administered 
per Injection 
Volume (mL) 
Discarded per Vial 
350 mg* 
1 
2 
1 
0.4 
700 mg** 
2 
4 
2 
0.4 
 

 
 
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PRO 140 175 mg/mL will be provided in 3 mL vials containing ~ 2.4 mL of PRO 140 in a sterile 
buffered solution of 5mM Histidine, 15 mM Glycine, 95 mM Sodium Chloride, 0.3% (w/v) 
Sorbitol, 0.005% (w/v) Polysorbate 20, at pH of 5.5.  
Note: *Since each vial contains 2.4 mL of PRO140, only 1 vial is needed for the 350 mg dose. 
2 mL injection will be drawn from 12.4 mL solution in a vial. The second vial can be utilized to 
administer 350 mg dose at the subsequent visit. Remaining 0.4 mL medication will be discarded 
appropriately from each vial. 
**Alternatively, when 2.4 mL vials are provided, 2 mL injection will be drawn from each vial 
and the remaining 0.4 mL medication will be discarded. Unused content of PRO 140 in a vial 
should remain in the vial and not be administered to any other subject. 
Table 6-2 provides the unit strength, dosing frequency and mode of administration for the study 
drug. 
Table 6-2: 
Investigational Product - PRO 140 
Study Drug 
Dosage 
Form 
Dose 
PRO 140 
concentration 
Dosing Frequency and Amount 
Route of 
Administration 
PRO 140 
Parenteral 
solution 
350
mg 
175 mg/mL 
Two 1 mL inj. on opposite sides of 
abdomen 
Weekly SC doses of PRO 140 (2x1 mL) 
SC injection 
PRO 140 
Parenteral 
solution 
700 
mg 
175 mg/mL 
Two 2 mL inj. on opposite sides of 
abdomen 
Weekly SC doses of PRO 140 (2x2 mL) 
SC injection 
6.2 
INVESTIGATIONAL PRODUCT PACKAGING AND LABELING 
Study drug will be prepared by Ajinomoto Althea, Inc. and will be packaged, labeled, and shipped 
by PCI Clinical Services. 
The contents of each vial are described in Section 6.1. PRO 140 kits will be labeled with 
information such as: study protocol #; fill volume; concentration; storage condition; a “use as per 
study protocol” statement; a cautionary statement; sponsor’s name and address; and the kit 
number. 
Note: PRO 140 kits prepared for Protocol: PRO 140_CD 01 will be used for the extension 
protocol. 
Below are representative samples of the PRO 140 (CHO), 175 mg/mL, FDP individual vial (Figure 
6-1), syringe label (Figure 6-2), and kit labels (Figure 6-3) designated for use in this clinical 
protocol. Each kit contains two labeled vials and two syringe labels.  
 
 

 
 
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Figure 6-1: 
PRO 140 (CHO), 175 mg/mL Vial Label 
Vial Label: 
Protocol: PRO 140_CD 01                   Kit No.  xxx 
Subject No. _________               
Single use 3 mL vial contains 2.4 mL of PRO 140 
(175 mg/mL) solution for subcutaneous injection 
Store at 2oC to 8oC (36oF to 46oF) 
USE AS PER STUDY PROTOCOL 
Caution: New Drug – Limited by Federal (or United 
States) Law to Investigational Use 
CytoDyn Inc., Vancouver, WA, USA 
Protocol: PRO 140_CD 01                   Kit No.  xxx 
Subject No. _________               
Single use 3 mL vial contains 2.4 mL of PRO 140 (175 
mg/mL) solution for subcutaneous injection 
Store at 2oC to 8oC (36oF to 46oF) 
USE AS PER STUDY PROTOCOL 
Caution: New Drug – Limited by Federal (or United 
States) Law to Investigational Use 
CytoDyn Inc., Vancouver, WA, USA 
 
Figure 6-2: 
PRO 140 (CHO), 175 mg/mL Syringe Label 
Syringe Label: 
Protocol: PRO 140_CD 01                                        Contents of Kit No. xxx 
This syringe contains 1 mL or 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 
Note:  Subjects on 700 mg dose require a total of 4ml of study drug for single dose, given as two 
2ml injections, or four 1 mL injections 
 
 
Figure 6-3: 
PRO 140 (CHO), 175 mg/mL Kit Label 
Kit Label: 
Protocol: PRO 140_CD 01                                                          Kit No. xxx 

 
 
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Site No. ____________                           Subject No.  ________________    
This kit contains 2 single-use vials 
Each 3 mL vial contains 2.4 mL of PRO 140 (175 mg/mL) solution for 
subcutaneous injection 
Store at 2oC to 8oC (36oF to 46oF) 
USE AS PER STUDY PROTOCOL 
Caution: New Drug – Limited by Federal (or United States) Law to Investigational 
Use 
CytoDyn Inc., Vancouver, WA, USA 
The pharmacy manual provides the criteria regarding vial acceptance or rejection, as well as 
instructions for the preparation of the filled 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. 
6.4 
INVESTIGATIONAL PRODUCT ADMINISTRATION 
Guidelines for dose preparation can be found in the pharmacy manual. 
PRO 140 will be provided to the administering personnel in single-use syringes prepared from 
vials of study drug stored at 2-8°C at the site pharmacy prior to use. Each of two syringes is filled 
to deliver 1.0 mL or 2.0 mL of study drug for the 350 mg or 700mg dose, respectively 
Equivalent volumes of study drug will be administered subcutaneously on opposite sides of the 
abdomen. However, based on subject preference or investigator discretion subjects receiving each 
of the doses can be administered using an alternate approach as follows: 

 
 
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350 mg Dose: 
• One 2.0 mL injection on one side of the abdomen 
700 mg Dose: 
• Four 1.0 mL injections, on opposite sides of the abdomen, or other location 
Note:  Patients with low body fat percentages may find subcutaneous injections uncomfortable especially 
in case of 2mL injection for the 700mg dosing. In such cases, PRO 140 700 mg can be injected as four 
175mg/ml injections and/or subcutaneous injections can be placed at different areas other than abdomen 
as per discretion of the Investigator. 
 
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 
more 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 17.3.  
All doses of study drug will be prepared by the credentialed pharmacist 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 subject trained to self-administer study treatment. 
Prior to self-administration, PI and/or study coordinator will train subjects on IP administration 
technique. Subject must demonstrate ability to perform injection in presence of PI/study 
coordinator before being allowed to administer subsequent weekly dose of study treatment outside 
clinic.   
Site will dispense study treatment and injection administration supplies (i.e., syringes, needles, 
alcohol pads, gauze, band-aids, sharps container, frozen cooler pack, etc), and instruct subjects to 
return used IP vials/injection kit at next clinic visit. 
Note: It is preferred that the same injection site be used throughout the study. At the same time, it 
is not recommended to inject the study drug into areas where skin shows signs of a previous 
injection site reaction. It is advised to change the injection site if any previous injection site 
reaction remains unresolved. 
6.5 
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 

 
 
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includes each quantity dispensed, identification of the staff member to whom dispensed, the date 
of dispensing, the intended study participant, and the identification of the preparer.  
Note: Site has option to maintain IP accountability via WebView IP Management system. 
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. Similarly, accurate record of vials 
dispensed and returned to the investigational site should be kept for subjects performing self-
administration.   
Instructions will be provided by Sponsor regarding final disposition of all study drug in compliance 
with applicable regulations. 
6.6 
INVESTIGATIONAL PRODUCT DISPOSITION 
All drug supplies are to be used only for this protocol and not for any other purpose. The 
investigator must not destroy any drug labels or any partially used or unused drug supply. 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 

 
 
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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) 
• Time Since HIV Diagnosis (yrs.) 
 
7.4 
MEDICAL HISTORY 
Note: Medical history collected at the time of screening for PRO 140_CD 01 protocol will be 
carried forward. Medical history will not be collected for the PRO 140_CD 01-Extension protocol. 
7.5 
PRIOR / CONCOMITANT MEDICATIONS AND NON-STUDY TREATMENTS  
A complete history of 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 
beginning 30 days prior to first Screening Visit and 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 

 
 
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acceptable to enter the range of the dosage, including the start and stop dates for 
which the specified dosage range was used. 
• Route of dosing 
• Indication for use 
• The start date  
• The stop date (if medication/therapy is not ongoing) 
Please refer to Exclusion Criteria (Section 3.3.2) for a list of prohibited treatments and/or 
procedures. All other medications that are appropriate for the care of the subject may be prescribed. 
If concomitant medications are started during the study, the indication for the concomitant 
medication should be considered an AE. 
7.5.1 Excluded Medications and Therapies 
1. Use of concomitant antiretroviral therapy is NOT allowed during the Treatment Extension 
Phase of the study EXCEPT for one week overlap of oral retroviral regimen and PRO 140 at 
the end of the treatment in subjects who do not experience virologic failure. Subject is allowed 
to re-initiate their previous antiretroviral regimen during the Treatment Extension Phase, if 
virologic failure occurs or if subject meets any other criteria for discontinuation of study 
treatment as specified in section 5.2.1 of the protocol. 
2. Use of oral or parenteral corticosteroids (>5 mg/day) is NOT allowed during the study, with 
the following exceptions:  
o Use of chronic systemic corticosteroids at replacement doses (e.g., < 5mg/day prednisone) 
AND use of inhaled, nasal, or topical steroids are allowed. 
3. Use of radiation or cytotoxic chemotherapy, immunosuppressants and immunomodulating 
agents (e.g., interleukins, interferons) or agents with known anti-HIV activity (i.e., 
hydroxyurea, foscarnet) are NOT allowed during the study. 
7.5.2 Allowable Medications and Therapies 
All other medications/therapies that are not otherwise prohibited and, in the judgment of the 
Investigator, are required for proper medical care of the subject may be prescribed. 
7.6 
PHYSICAL EXAMINATION 
The complete physical examination will include routine examinations for the following: 
• Head, Ears, Eyes, Nose, Throat (HEENT) 

 
 
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• Abnormalities of the extremities 
• Neurologic abnormalities 
• Heart/cardiovascular abnormalities 
• Musculoskeletal abnormalities 
• Dermatologic abnormalities 
• Any other body system for which an abnormality is noted and which, in the opinion of the 
Investigator, is relevant to the safety of the subject or could impact safety or efficacy results 
for the subject; i.e., the abnormality is clinically significant (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 first Screening Visit (SV1), End of 
Treatment (EOT) Visit, and at VF visit in case of virologic failure. Only symptom-directed 
physical examination will be performed at other Treatment Visits. 
 
7.7 
NEUROLOGICAL ASSESSMENT 
Neurological assessment will be performed by the Principal Investigator (or designee) at Screening 
Visit 1 (SV1), TE4, TE40, at least once within TE80-83 and TE116-123, and at Virologic Failure 
(VF) Visit.   
The screening tool is based on the three question survey used by Simioni et al. [Simioni S, 2010]. 
Additional assessment modalities can be used for further assessment as per Investigator’s 
discretion.  Refer to section 17.5 for further details.   
7.8 
QUALITY OF LIFE (QOL)  
A quality of life assessment will be performed by the Principal Investigator or Study Coordinator 
at Screening Visit 1 (SV1), once every four weeks from TE4 through TE107, and at EOT.  The 
instrument used for this assessment is the ACTG SF-21 (ACTG 601-602).  Refer to section 17.6 
for further details. 
7.9 
VITAL SIGNS 
The following vital signs will be collected:  
• Height (at Screening Visit 1 only) 

 
 
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• Weight  
• BMI (derived from the height and weight measurements; at Screening Visit 1 only) 
• Seated blood pressure (taken after the subject has been seated for at least 5 minutes) 
• Heart Rate 
• Respiration Rate 
• Temperature 
Note: Within Treatment Phase, post-treatment vital signs will be assessed within 15 minutes 
following study treatment administration.. 
Note: Vitals will not be collected when subjects perform self-administration. 
7.10 CLINICAL LABORATORY ASSESSMENTS 
Blood samples will be collected according to the time points in the schedule of assessments for 
analysis of the following parameters: 
 
7.10.1 Routine CBC  
• Frequency of testing: Every 12 weeks from TE160 onwards, and at the end of Treatment 
Extension Phase OR at the time of virologic failure 
• Includes hemoglobin, hematocrit (HCT), red blood cell (RBC) count, white blood cell 
(WBC) count, WBC differential count (%), absolute neutrophils count and platelets count. 
7.10.2 Biochemistry 
• Frequency of testing: Every 12 weeks from TE160 onwards, and at the end of Treatment 
Extension Phase OR at the time of virologic failure 
• Biochemistry profile includes assessment of 
Hepatic function indicators: total and direct bilirubin, alkaline phosphatase, aspartate 
aminotransferase (AST), alanine aminotransferase (ALT), total protein, LDH 
Renal function indicators: BUN, creatinine 
Electrolytes: sodium, potassium, chloride, calcium and bicarbonate 
Other: glucose (random), cholesterol (total) 
7.10.3 PK sample for PRO 140 

 
 
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 Frequency of testing:  At first Screening Visit, at Treatment Visits 4, 8, 12, 16, 20, 24, 28, 
32, 36, 40, 44, 48, 52 and 56.  Beyond TE60, PK sample for PRO 140 assessment will be 
performed once every four weeks, and at Virologic Failure (VF) Visit. 
7.10.4 Serum pregnancy test  
• Frequency of testing: At first Screening Visit 
• Only 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. 
7.10.5 Urine pregnancy test  
• Frequency of testing: At second Screening Visit prior to first treatment administration 
• A urine sample will be collected from female subjects of childbearing potential. This test 
will be performed at the study site using a commercially available kit. 
 
 
7.10.6 Plasma HIV-1 RNA level and TruCount T Assay 
• Frequency of testing: At Treatment Visits 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 
30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56 and 58. Beyond TE60, blood sample 
will be collected at least once every four weeks, at EOT, at VF, and at VF-EFU and 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 (Abbott RealTime) test. 
TruCount T Assay includes measurement of Absolute Lymphocytes, CD3 cell count, CD4 
cell count, CD8 cell count, CD3%, CD4% and CD8% 
7.10.7 Anti-idiotypic antibodies to PRO 140 
• Frequency of sample collection*: At first Screening Visit, at Treatment Visits 4, 8, 12, 16, 
20, 24, 28, 32, 36, 40, 44, 48, 52 and 56.  Beyond TE60, ADA sample for PRO 140 
assessment will be performed once every four weeks. Sample also collected at VF, NVF-
EFU2 and VF-EFU1 visits. 
*Note: Sera will be collected from study subjects and stored at -80oC for future analysis. 

 
 
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7.10.8 Trofile® RNA or Trofile® DNA and PhenoSense® Entry Assay (Trofile® with 
enhanced sensitivity) 
• Frequency of testing: At EOT and at the time of virologic failure 
• Trofile® RNA is a phenotypic viral RNA assay to assess any change in HIV-1 co-receptor 
tropism. 
• Unlike the standard Trofile® RNA assay, which uses viral RNA found in the plasma of 
patients with viral loads ≥1000 copies/mL, Trofile® DNA uses viral DNA extracted from 
cells in a whole blood draw is a phenotypic viral RNA assay to assess any change in HIV-
1 co-receptor tropism.  PhenoSense® Entry is a phenotypic viral RNA assay to assess 
resistance of HIV-1 RNA virus to entry inhibitors 
7.10.9 HIV Genotyping Assay 
• Frequency of testing: At the time of virologic failure 
• To identify reverse transcriptase (RT), protease (Pr) and gp120 gene mutations associated 
with current or evolving drug resistance. 
 
7.10.10  Serum Concentration of ART drugs 
• Frequency of testing: At Treatment Extension Visits 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 
48, 52, 56, and at least once every four weeks for the rest of the treatment phase starting at 
Treatment Visit 60. 
• To confirm that enrolled subjects are abstaining from taking their previous ART regimen 
during the monotherapy treatment phase. 
7.10.11  Blood sample collection for Exploratory/Confirmatory analysis 
• Frequency of testing:  At second Screening Visit, at interim treatment visits, EOT and at 
the time of virologic failure 
• CytoDyn is currently investigating the possibility of developing a more accurate test for 
detection of co-receptor tropism in patients with undetectable viral loads and in case of 
early breakthrough/virologic failure during the treatment phase of the study, in addition to 
assessing viral load reduction efficacy with alternate plasma HIV-1 RNA assays.  
7.10.12CCR5 Receptor Occupancy 
  CCR5 Receptor Occupancy  

 
 
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• 
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. 
7.11 PRO 140 ADMINISTRATION 
Refer to Section 6.4 for details. 
7.12 INJECTION SITE REACTION ASSESSMENT 
At each visit during the Treatment Extension Phase, an injection site reaction assessment will be 
made for the current and previous injection sites.  Injection site reaction assessments are recorded 
by the Investigator starting after the first injection is given.  Injection site reaction assessments will 
not be completed when subjects perform self-administration.  Refer to sections 9.1.8 and 17.3 for 
more details. 
7.13 PAIN ASSESSMENT USING VISUAL ANALOG SCALE (VAS) 
Tolerability of repeated subcutaneous administration of PRO 140 is evaluated based on assessment 
of subject-perceived injection site pain using the Pain Visual Analog Scale (VAS).  
Beginning at Screening Visit 1, subjects will be asked to mark the point that best represents the 
average pain intensity over the past week at the injection site on a horizontal line (100 mm in 
length) anchored by the following word descriptors at each end, “no pain" on the left side and 
"pain as bad as it could possibly be" on the right side of the line. The subject marks on the line or 
by pointing to a position on the line the point that they feel represents their perception of their pain 
state. The VAS score is determined by measuring in millimeters from the left-hand end of the line 
to the point that the patient marks. 
 

 
 
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Figure 7-1: 
Visual Analog Scale 
 
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). 

 
 
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• 
Any changes in the study visit schedule or missed visit should be entered as protocol 
deviation in the EDC and reason should be documented as missed study visit or visit 
performed out of window period due to COVID-19. 
• 
If subject is early withdrawn from the study due to COVID-19, the reason should be clearly 
documented in the End of Study (EOS) section in EDC as “study discontinuation due to 
COVID-19”. 
• 
Monitoring activities will be performed remotely until Centers for Disease Control (CDC) 
recommendations allow travel to resume. 
 

 
 
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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 active arm study. All eligible subjects in the study will receive PRO 140 as a 350 
mg subcutaneous injection weekly and have the option of increasing their dose to receive 700mg 
subcutaneous injections weekly. 
8.2 
DESCRIPTION OF STUDY ENDPOINTS  
8.2.1 Primary Efficacy Endpoints 
The primary efficacy endpoint for this study is time to virologic failure after initiating PRO 140 
monotherapy. 
Virologic failure is defined as two consecutive HIV-1 RNA levels of ≥ 400 copies/ml separated 
by at least 3 days. 
8.2.2 Secondary Efficacy Endpoints 
• Proportion of participants with virologic failure after initiating PRO 140 monotherapy. 
• Mean change in viral load (HIV-1 RNA levels)  
• Mean change in CD4 cell count  
• Change in quality of life metrics (up to TE107) 
8.2.3 Safety Endpoints 
Safety measurements will include:  
• Tolerability of repeated subcutaneous administration of PRO 140 as assessed by study 
participants (using Visual Analogue Scale) and by investigator-evaluation of injection site 
reactions. 
• Frequency of Grade 3 or 4 adverse events as defined by the DAIDS Adverse Event scale 
• 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 01 Treatment Substitution Study are allowed to participate in this extension study.  
8.4 
RANDOMIZATION AND BLINDING 
This study is an open label study with one treatment arm with no randomization and blinding 
requirements.  
8.5 
INTERIM ANALYSIS  
There is no planned interim analysis (IA) for efficacy. IA for safety will be conducted after all 
enrolled subjects complete extended treatment with PRO 140 or until study treatment is 
discontinued, whichever comes first. 
8.5.1 Analysis Population 
Subjects who have been treated and completed the treatment extension phase (or until treatment is 
discontinued) will be included in the analysis.  All available data from these subjects will be 
included in the analysis.  
 
8.5.2 Procedures 
a. Cut-off dates for review of eCRFs, data cleaning, database lock and analysis will be established 
based on an estimated target date of all enrolled subjects completing pre-defined treatment 
period.  
b. All data received by the cutoff date will be entered, validated, queries generated and resolved 
or pending queries documented.  
c. The database will be locked for IA.  
d. The statistician will generate planned data and information for the DMC, as described below.  
8.5.3 Data and Information Provided to DMC 
The DMC will receive: AEs, SAEs, labs, ECGs, vital signs, and all other safety related variables 
identified per the DMC Charter. No inferential statistics will be conducted for this interim analysis. 
8.5.4 Type I Error Rate Adjustment 
 
No type I error adjustment will be made due to this safety analysis for this proof of concept study.  
8.6 
GENERAL STATISTICAL CONSIDERATIONS  
8.6.1 Analysis Populations  

 
 
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8.6.1.1 Intent-to-Treat Population 
The Intent-to-Treat (ITT) population is defined as the set of subjects who have at least one dose of 
PRO 140 and have at least one post-treatment efficacy assessment for viral load.  
8.6.1.2 Per Protocol Population 
The Per Protocol (PP) population is defined as the set of subjects who meet the ITT population 
requirements, and were not associated with a major protocol violation. This population will be 
identified before the database lock. The PP population will be the primary analysis population for 
the analysis of primary and secondary endpoints. 
8.6.1.3 Safety Population 
The Safety population is defined as all subjects who received at least one dose of PRO 140. This 
population will be used for the analysis of 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 efficacy and safety data from this trial. 
8.6.3 Prognostic Factors/Covariates 
There are no pre-planned covariates analyses of the data from this proof of concept study. 
8.6.4 Handling of Missing Data 
For the per protocol analysis of efficacy endpoints there will be no imputation of missing data. 
However, missing data will be imputed using different methods that will be detailed in the SAP 
for the ITT analysis of the primary and secondary endpoints.  
8.6.5 Multiplicity  
This is a proof of concept study and there is no need for adjustment of Type I error rate.  
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 Screening Visit, etc.) will be summarized using appropriate descriptive statistics. 
Medical history of the subjects will also be provided as a by-subject listing.  
8.7.3 Prior and Concomitant Medications  
Prior and concomitant medications will be summarized for the Safety population. All prior and 
concomitant medications recorded in the eCRFs will be coded to generic term and all matching 
Anatomic Therapeutic Classification (ATC) codes using WHO Drug Summaries will be prepared 
using the coded terms. All prior and concomitant medications recorded in the eCRFs will also be 
listed. 
8.7.4 Efficacy Analysis 
8.7.4.1 Primary Analysis 
The primary analysis will be conducted on the PP population.  
The primary efficacy endpoint for this study is time to virologic failure after initiating PRO 140 
monotherapy.  
Virologic failure is defined as two consecutive HIV-1 RNA levels of ≥ 400 copies/ml separated 
by at least 3 days. 
The time to virologic failure for the subjects treated with PRO 140 monotherapy will be compared 
to a historical data (i.e., time to HIV-1 RNA viral load > 500 copies/mL of 29 days). The statistical 
comparison will be conducted using Wilcoxon rank sum test and the median time to virologic 
failure for this study will be compared to 30 days. 
8.7.4.2 Secondary Analysis 
• Proportion of participants with virologic failure after initiating PRO 140 monotherapy. 
• Mean change in viral load (HIV-1 RNA levels)  
• Mean change in CD4 cell count  
• Change in quality of life metrics (up to TE107) 
All data from the secondary endpoints will be summarized according to the variable type for the 
PP population: 
• Continuous data summaries will include number of observations, mean, standard deviation, 
median, and minimum and maximum values 
• Categorical data summaries will include frequency counts and percentages 

 
 
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8.7.4.3 Supportive Analysis 
To assess the consistency of the Primary Analysis results, supportive analysis will be conducted 
using the ITT population. Statistical methodology for the supportive analyses will be the same as 
that of the primary analysis, with the exception of the analysis population used.  
8.7.5 Safety Analysis 
The Safety population will be used for the analysis of safety endpoints.  
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 study participants (using Visual Analogue Scale) and 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.  

 
 
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8.7.5.7 Neurological Assessment  
All neurological assessment findings will be listed and any abnormality will be summarized. 
8.7.5.8 Quality of Life Assessment 
All quality of life assessment findings will be listed and summarized. 
 

 
 
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9 
ADVERSE EVENTS (DEFINITIONS AND REPORTING) 
The Investigator is responsible for the detection and documentation of events meeting the criteria 
and definition of an AE or SAE, as provided in this protocol. During the study when there is a 
safety evaluation, the Investigator or site staff will be responsible for detecting, documenting, and 
reporting AEs and SAEs as detailed in this section of the protocol.  
9.1 
ADVERSE EVENT 
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 visit and continue 
up until the final study visit (i.e. up to NVF-EFU2 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 CTCAE 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 extension phase of the protocol, or if 
the outcome of the event was “death”. 

 
 
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consideration at the time they are evaluated, are felt with a high degree of certainty to be 
related to the study treatment. An AE may be considered probable if or when (must have 
three): (1) it follows a reasonable temporal sequence from administration of the study 
treatment. (2) It could not readily have been produced by subject’s clinical state, 
environmental or toxic factors, or other therapies administered to the subject. (3) 
Disappears or is decreased upon discontinuation of the study treatment. (4) It follows a 
known response 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.  

 
 
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9.1.7 Expected / Anticipated Adverse Events 
The most common potential study drug-related adverse reaction reported is mild headache. Other 
adverse events likely to be related to the drug include mild to moderate diarrhea, nausea, and 
fatigue.  
9.1.8 SC Injection-related Events 
SC and IV injections of concentrated protein materials can be associated with injection-related 
AEs that impact the ability to safely and successfully deliver the drug. Local injection-site 
reactions may include pain/discomfort, induration, erythema, nodules/cysts, pruritus, ecchymosis, 
etc. For SC injections, bleeding, absorption of the drug, leakage of drug, and induration at the local 
injection site can be additional complications. Other AEs that are common to monoclonal 
antibody-based therapies are chills, headache, backache, malaise, fever, pruritus, rash, nausea, 
tingling, and hypertension.  
SC injection-related events will be monitored according to the guidelines provided in Section 17.2 
(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 17.3. 
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) 

 
 
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• Requires subject hospitalization or prolongs existing hospitalization 
• Results in persistent or significant disability/incapacity  
• Is a congenital anomaly/birth defect 
Important medical events that may not result in death, be life-threatening, or require hospitalization 
may be considered a serious adverse 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. 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 Amarex 
Safety Department within 24 hours: 
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 
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the safety information and determines that the information qualifies for reporting. Participating 
investigators include all investigators to whom the sponsor is providing drug under any of its INDs 
or under any investigator’s IND (21 CFR 312.32(c)(1)). 
9.3.1 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 
assessment results, quality of life questionnaire, etc.  
Site inspections serve to verify strict adherence to the protocol and the accuracy of the data being 
entered on the case report forms, in accordance with federal regulations. A Monitoring Log will be 
maintained at each study site which the monitor will sign, date and state the type of visit.  
The Investigator should be aware that the study site and subject records may be inspected by the 
Sponsor and or representatives of the designated CRO, FDA or other regional regulatory authority. 
For the IA, a cut-off date for data collection and monitoring will be determined and sites will be 
requested to provide current information up to the cut-off date. 
11.2 ACCEPTABILITY OF CASE REPORT FORMS (CRFS) 
Electronic CRFs must be completed for each subject who has signed an informed consent form. 
For subjects who are screen failures, this would be limited to the screen failure eCRF page. All 
source documents and eCRFs will be completed as soon as possible after the subject's visit. 
Corrections to data on the eCRFs will be documented. The Investigator will review eCRFs to 
indicate that, to his/her knowledge, they are complete and accurate. Electronic CRFs will be 

 
 
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reviewed by the Sponsor’s or designated CRO’s monitor, who will make a decision as to their 
acceptability.  
 
 
11.3 MODIFICATION OF PROTOCOL 
The Investigator will not modify or alter this protocol without first obtaining the concurrence of the 
Sponsor. Approval by the Investigator’s IRB must also be obtained prior to implementation of the 
change, with two exceptions: 
1. When necessary to eliminate apparent immediate hazard to the subject; or 
2. When the modification does not involve the subject’s participation in the trial. 
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 DATA MONITORING COMMITTEE (DMC) 
The study will be monitored by an independent DMC (DMC) to ensure patient safety and to 
assess efficacy. The CRO is responsible for the overall management of DMC, including 
development of its charter and membership selection. The DMC will be managed in 
conformance with the FDA guidelines for DMC independence, management, and oversight. 
DMC will conduct scheduled independent reviews of the data in order to ensure that an ongoing 
acceptable safety profile is being achieved. 
DMC will conduct an independent review after all enrolled subjects complete extended treatment 
with PRO 140 or until study treatment is discontinued, whichever comes first. 
The DMC will consist of at least three independent members (including clinicians with expertise 
in HIV disease, a psychiatrist and at least one biostatistician) and will review all safety signals 
including number of virologic rebounds, unexpected AEs, all related AEs, all SAEs, and all deaths 
during the Treatment and Follow-Up Phases.  
The DMC will make the following recommendations at the end of safety evaluation: 
 
Continue the study as planned; 
 
Modify the study and continue; 
 
Terminate the study;  
 
Gather more data to address a specific safety issue and reconvene; 
 
Other (e.g., request changes to the protocol and propose sanctions). 
The Sponsor retains the responsibility to contact FDA and the final decision regarding the 
recommendation to continue or to terminate the study. 
A further description of the DMC reporting requirements, meeting frequency, and the study 
stopping/continuation criteria can be found in the DMC charter. 
 

 
 
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13 ETHICS AND REGULATORY REQUIREMENTS 
This study is to be conducted in accordance with the specifications of this protocol and in 
accordance with principles consistent with Declaration of Helsinki, GCP, 21 CFR 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. 
13.1 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.  
13.2 INVESTIGATOR’S RESPONSIBILITIES 
The Investigators are responsible for performing the study in full accordance with the protocol and 
the current revision of the Declaration of Helsinki, the Good Clinical Practice: Consolidated 
Guideline, approved by the ICH, and any applicable national and local laws and regulations. 

 
 
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Information regarding any study centers participating in this study that cannot comply with these 
standards will be documented. 
13.3 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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14 DATA HANDLING AND RECORD KEEPING 
14.1 RECORDING AND COLLECTION OF DATA 
The primary source document for this study will be the subject's medical record. If separate research 
records are maintained by the Investigator(s), the medical record and the research records will be 
considered the source documents for the purposes of auditing the study.  
Applicable source data will be manually transcribed to 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 

 
 
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screened for participation in the study; it should include gender, age, eligibility status, reason for 
ineligibility, if applicable; and study allocated subject number, if applicable.  
14.2 CLINICAL DATA MANAGEMENT 
The Sponsor and/or designated CRO will be responsible for the processing and quality control (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. 
 
14.3 ARCHIVING 
All study documentation at the Investigator site and Sponsor site will be archived in accordance 
with ICH GCP E6 and the Sponsor’s quality standards and SOPs. 
The Investigator will maintain all research records, reports, and case history reports for a period of 
two years after regulatory approval of the investigational product. If no application is filed or if the 

 
 
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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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15 PUBLICATION PLAN 
All information supplied by CytoDyn, Inc. in connection with this study and not previously 
published, is considered confidential information. This information includes, but is not limited 
to, the Investigator’s Brochure (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, Inc. shall not be disclosed to others 
without the written consent of CytoDyn, Inc. and shall not be used except in the performance of 
this study. 
It is understood by the Investigator that the Sponsor will use the information collected in this clinical 
trial in connection with the development of PRO 140. Therefore, this information may be disclosed 
as required to other Investigators or appropriate regulatory authorities. By agreeing to participate 
in this clinical trial, the Investigator understands that he/she has an obligation to provide the Sponsor 
with complete test results and all data developed during this trial. 
Publication and Disclosure: Because this is a multi-center trial, the site and Investigator shall not 
independently publish, publicly disclose, present or discuss any results of or information pertaining 
to the site’s and Investigator’s activities conducted under this protocol until such multi-center 
publication is released with the written approval and under the direction of Sponsor. 
Notwithstanding the foregoing, if a multi-center publication is not released within eighteen (18) 
months after completion of analysis of all study data from all studies conducted within the multi-
center trial, both the site and Investigator shall have the right to publish the results of and 
information pertaining to the site’s and Investigator’s activities conducted under this protocol and 
the clinical trial agreement, subject to the prior review and written approval of Sponsor. The site 
and Investigator agree to submit any proposed manuscript, presentation or other public disclosure 
regarding the study to Sponsor for review at least thirty (30) days prior to submitting such proposed 
manuscript to a publisher or delivering or making such presentation or other public disclosure to 
any third party. Within thirty (30) days of its receipt, Sponsor shall advise the site and/or 
Investigator, as the case may be, in writing of any information contained therein that is confidential 
information (other than research results included in a proposed manuscript) or that may impair 
Sponsor’s ability to obtain patent protection. Sponsor shall have the right to require the site and/or 
Investigator, as applicable, to remove specifically identified confidential information (but may not 
require removal of research results from a proposed manuscript) and/or to delay the proposed 
submission or delivery of the proposed manuscript or presentation, or other public disclosure, for 
an additional sixty (60) days to enable Sponsor to seek patent protection. The site and Investigator 
shall not publish, publicly disclose, present or discuss any results of or information pertaining to 
the site’s and Investigator’s activities prior to completion of the trial, even if the multi-center trial 
or the study is terminated before its completion and the final clinical study report is signed off, or 
with respect to any endpoints or analyses other than those specified in this protocol. 

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

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

 
 
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Thompson M., Lalezari, J., Saag, M., Jacobson, J., Zingman, B., Stambler, N., D'Ambrosio, 
P., Maddon, P., Olson, W., and Morris, S. Weekly and bi-weekly subcutaneous PRO 140 
demonstrates potent, sustained antiviral activity.  16th Conference on Retroviruses and 
Opportunistic Infections. - Montreal QE, Canada, : [s.n.], 2009. - Vol. Abstract #571a. 
Thompson MA Aberg JA, Hoy JF, Telenti A, Benson C, Cahn P, Eron JJ, Gunthard HF, 
Hammer SH, Reiss P, Richman DD, Rizzardini G, Thomas DL, Jacobsen DM, Volberding 
PA. Antiretroviral Treatment of Adult HIV Infection: 2012 Recommendations of the International 
Antiviral Society–USA Panel  JAMA. - 2012. - Vol. 308. - pp. 387-402. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
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17 APPENDIX 
17.1 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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17.2 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/Table_for_Grading_Severity_of_Adult_Pediatric
_Adverse_Events.pdf 
 

 
 
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17.3 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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17.4 APPENDIX IV: COMMON TERMINOLOGY CRITERIA FOR ADVERSE EVENTS V4.03 
 
For complete detailed information please refer to the link below 
http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_8.5x11.pdf 
 
 

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

 
 
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17.6 APPENDIX V1: QUALITY OF LIFE ASSESSMENT – ACTG SF-21 
 
 

 
 
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