Conditions: HIV
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 52
Healthy volunteers: no

Brief summary:
This is a Phase 2b/3, multi-center, two part study, designed to evaluate the efficacy, safety, and tolerability of PRO 140 in conjunction with existing ART (failing regimen) for one week and Optimized Background Therapy (OBT) for 24 weeks respectively. Study population includes treatment-experienced HIV-infected patients with CCR5-tropic virus who demonstrates evidence of HIV-1 replication despite ongoing antiretroviral therapy with documented genotypic or phenotypic resistance to ART drugs within three drug classes (or within two 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.

Detailed description:
PRO 140, in combination with other antiretroviral agents, is indicated for treatment experienced adult HIV-1 patients infected with CCR5-tropic virus. These patients must demonstrate evidence of HIV-1 replication despite ongoing antiretroviral therapy and have documented genotypic or phenotypic resistance to at least one ART drug within three drug classes (or within two or more drug classes with limited treatment option). The options may be limited as a result of drug antiviral class cross-resistance, documented treatment intolerance, documented objective assessments such as renal or hepatic insufficiency (e.g. high creatinine at baseline, limiting treatment options due to potential for toxicity), past adverse reactions such as hypersensitivity reactions or neuropsychiatric issues that could limit use of currently approved drugs.

Study population includes treatment-experienced HIV-infected patients with CCR5-tropic virus who demonstrates evidence of HIV-1 replication despite ongoing antiretroviral therapy with documented genotypic or phenotypic resistance to ART drugs within three drug classes (or within two drug classes with limited treatment option).

Enrollment will be stratified to have HIV-1 virus resistant to ART drugs within three drug classes or within two drug classes with limited treatment option.

The primary objective is to assess the efficacy, clinical safety and tolerability parameters of PRO 140 compared to placebo in reducing HIV-1 viral load during the 1-week double-blind treatment period. The secondary objectives of the trial are to assess the efficacy, clinical safety and tolerability parameters of PRO 140 in combination with Optimized Background Therapy during the 24-week single-arm, open-label treatment period.

Arms:
arm 1: PRO140 350mg weekly SC Inj. + existing ART for one week. After one week, all subjects will enter the 24-week single-arm, open-label treatment period. During this period, all subjects will receive PRO 140 SC injection and Optimized Background Therapy. arm 2: Placebo weekly SC Inj. + existing ART for one week. After one week, all subjects will enter the 24-week single-arm, open-label treatment period. During this period, all subjects will receive PRO 140 SC injection and Optimized Background Therapy.

Interventions: intervention 1: PRO 140 intervention 2: Placebo intervention 3: Optimized Background Regimen
Intervention descriptions: intervention 1: PRO 140 is a humanized IgG4,κ monoclonal antibody (mAb) to the chemokine receptor CCR5. intervention 2: None intervention 3: Optimized background therapy (OBT) is chosen on the basis of a subject's resistance test results and treatment history.

Protocol document:
Prot_000.pdf: 
CONFIDENTIAL 
Page 1 of 115 
 
 
 
 
 
 
A Multi-center, Randomized, Double-blind, Placebo-controlled Trial, Followed 
by Single-arm Treatment of PRO 140 in Combination With Optimized 
Background Therapy in Treatment-Experienced HIV-1 Subjects. 
 
 
 
 
Protocol Number: 
PRO 140_CD 02 
Version: 
9.0 
Date: 
08-Jan-2018 
 
 
 
 
Sponsor: 
CytoDyn, Inc. 
1111 Main Street, Suite 660 
Vancouver, Washington 98660 
(360) 980-8524-Work 
(360) 980-8549-Fax 
www.cytodyn.com 
 
 
 
 
 
Confidentiality Statement 
This document is a confidential communication of CytoDyn, Inc. It is provided for the conduct 
of a clinical research study. The information contained in this document is confidential and, 
except to the extent necessary to obtain informed consent or IEC/IRB approval, cannot be 
disclosed unless required by governmental regulation. Persons to whom any portion of the 
contents of this document is disclosed must be informed that the information is confidential and 
may not be further disclosed by them. 
 
 
 


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PROTOCOL APPROVAL PAGE 
 
Protocol Number: 
PRO 140_CD 02 
Version: 
9.0 
Date: 
08-Jan-2018 
 
 
 
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 02 
Version: 
9.0 
Date: 
08-Jan-2018 
 
 
 
 
 
INVESTIGATOR’S SIGNATURE 
I have read the protocol specified above and agree to participate in and comply with the 
procedures, as outlined herein for the conduct of this clinical trial. I also agree to comply with the 
applicable US Food and Drug Administration (FDA) regulations and Investigational Review Board 
(IRB) requirements for testing on human subjects. I agree to ensure that the requirements for 
obtaining informed consent are met. 
 
 
 
 
 
Principal Investigator’s Signature 
Date 
 
 
 
Print Name 
 
 
 
Address 
 
 
 
Site Number 


Protocol # PRO 140_CD 02 
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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 ............................................................................................................ 14 
List of Tables ................................................................................................................................ 19 
List of Figures ............................................................................................................................... 20 
List of Abbreviations .................................................................................................................... 21 
1 INTRODUCTION ................................................................................................................. 24 
1.1 
Statement of Intent .............................................................................................................. 24 
1.2 
The Problem Statement ....................................................................................................... 24 
1.3 
Name and Description of the Investigational Product ........................................................ 25 
1.4 
Summary of Prior Pre-Clinical And Clinical Studies ......................................................... 25 
1.4.1 
Pre-Clinical Studies with PRO 140 ................................................................... 25 
1.4.2 
Clinical Studies with PRO 140 ......................................................................... 26 
1.4.2.1 
PRO 140 1101 Study ........................................................................................ 26 
1.4.2.2 
PRO 140 1102 Study ........................................................................................ 26 
1.4.2.3 
PRO 140 1103 Study ........................................................................................ 26 
1.4.2.4 
PRO 140 1302 Study ........................................................................................ 27 
1.4.2.5 
PRO 140 2301 Study ........................................................................................ 30 
1.4.2.6 
PRO 140 2101 Study ........................................................................................ 30 
1.4.2.7 
PRO 140 _CD01 Study ..................................................................................... 33 
1.4.2.8 
PRO 140 _CD01-Extension Study ................................................................... 35 
1.4.2.9 
PRO 140 _CD03 Study ..................................................................................... 35 
1.5 
Rationale for Dose Selection .............................................................................................. 38 
1.6 
Risks / Benefits Assessment ............................................................................................... 39 
1.6.1 Risks/Discomfort to Subjects and Precautions to Minimize Risk....................................... 39 
1.6.1.1 
Risks associated with continuation of Failing Antiretroviral Treatment 
Regimen ............................................................................................................ 39 
1.6.1.2 
Allergic Reaction .............................................................................................. 39 
1.6.1.3 
Immune Response ............................................................................................. 40 
1.6.1.4 
Pregnancy ......................................................................................................... 40 
1.6.1.5 
Venipuncture ..................................................................................................... 40 
1.6.1.6 
Risks to the Study Personnel and the Environment .......................................... 40 


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1.6.1.7 
Unknown Risks .................................................................................................. 40 
1.6.1.8 
Theoretical risk for increased severity of West Nile virus infection ................. 40 
1.6.2 Intended Benefit for Subjects ............................................................................................... 41 
2 STUDY OBJECTIVES .......................................................................................................... 42 
3 STUDY DESIGN .................................................................................................................... 43 
3.1 
Study Center(s) .................................................................................................................... 43 
3.2 
Study Population ................................................................................................................... 44 
3.3 
Eligibility Criteria ................................................................................................................ 44 
3.3.1 
Inclusion Criteria ............................................................................................... 44 
3.3.2 
Exclusion Criteria .............................................................................................. 45 
4 STUDY SCHEDULE ............................................................................................................. 49 
4.1 
Screening Phase ................................................................................................................... 56 
4.1.1 
Screening Visits ................................................................................................. 56 
4.2 
Treatment Phase ................................................................................................................... 57 
4.2.1 
Treatment Visit (T1) - Part 1 of Treatment Phase ............................................. 60 
4.2.2 
Treatment Visit-2 (T2) to Treatment Visit-25 (T25) - Part 2 of Treatment Phase62 
4.2.3 
End of Treatment (EOT) Visit ........................................................................... 63 
4.2.4 
Treatment Failure (TF) Visit ............................................................................. 64 
4.3 
Follow-up Phase ................................................................................................................... 65 
4.3.1 
Follow-Up Visits ............................................................................................... 65 
4.4 
Unscheduled Visits .............................................................................................................. 66 
5 SUBJECT COMPLETION AND WITHDRAWAL ........................................................... 67 
5.1 
Subject Completion ............................................................................................................. 67 
5.2 
Subject Withdrawal .............................................................................................................. 67 
5.2.1 
Discontinuation of Study Treatment ................................................................... 68 
5.2.2 
Data Collected for Withdrawn Subjects ............................................................ 69 
5.3 
Screen Failures ..................................................................................................................... 69 
6 STUDY TREATMENT .......................................................................................................... 70 
6.1 
Investigational Product Description ...................................................................................... 70 
6.2 
Investigational Product Packaging and Labeling ................................................................. 71 
6.3 
Investigational Product Storage ........................................................................................... 74 
6.4 
Investigational Product Administration ................................................................................. 74 
6.5 
Investigational Product Receipt and Accountability ............................................................ 75 


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6.6 
Investigational Product Disposition ...................................................................................... 75 
7 DESCRIPTION OF PROTOCOL ASSESSMENTS AND PROCEDURES ..................... 76 
7.1 
Informed Consent ................................................................................................................ 76 
7.2 
Assessment of Eligibility ..................................................................................................... 76 
7.3 
Demographic Information .................................................................................................... 76 
7.4 
Medical History ................................................................................................................... 76 
7.5 
HIV History ......................................................................................................................... 77 
7.6 
Prior / Concomitant Medications and Non-Study Treatments ............................................. 78 
7.6.1 
Excluded Medications and Therapies ................................................................ 79 
7.6.2 
Allowable Medications and Therapies ............................................................... 79 
7.7 
Physical Examination .......................................................................................................... 79 
7.8 
Electrocardiogram ................................................................................................................ 80 
7.9 
Neurological Assessment ..................................................................................................... 80 
7.10 Vital Signs (inc. height and weight) .................................................................................... 80 
7.11 Clinical Laboratory Assessments .......................................................................................... 81 
7.11.1 
Routine CBC ...................................................................................................... 81 
7.11.2 
Biochemistry ...................................................................................................... 81 
7.11.3 
PK sample for PRO 140 ..................................................................................... 81 
7.11.4 
Anti-idiotypic antibodies to PRO 140 ............................................................... 81 
7.11.5 
Serum pregnancy test ......................................................................................... 82 
7.11.6 
Urine pregnancy test .......................................................................................... 82 
7.11.7 
Plasma HIV-1 RNA level and TruCount T Assay ............................................. 82 
7.11.8 
HIV-1 Trofile® Assay ....................................................................................... 82 
7.11.9 
HIV-1 Drug Resistance Assay ............................................................................ 82 
7.11.10 
HIV-1 PhenoSense® Entry assay ...................................................................... 83 
7.11.11 
Serum Concentration of ART drugs .................................................................. 83 
7.11.12 
Blood sample collection for Exploratory/Confirmatory analysis ...................... 83 
7.11.13 
Urinalysis ........................................................................................................... 84 
7.12 Randomization ..................................................................................................................... 84 
7.13 Investigational Product Administration ................................................................................. 84 
7.14 Injection Site Reaction assessment ...................................................................................... 84 
7.15 Pain Assessment using Visual Analog Scale (VAS) ............................................................ 85 
8 STATISTICAL CONSIDERATIONS .................................................................................. 86 
8.1 
Treatment Groups ................................................................................................................ 86 


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8.2 
Description of Study Endpoints ........................................................................................... 86 
8.2.1 
Primary Efficacy Endpoints ............................................................................... 86 
8.2.2 
Secondary Efficacy Endpoints ........................................................................... 86 
8.2.3 
Safety Assessments ............................................................................................ 87 
8.3 
Sample Size Determination and Rationale .......................................................................... 87 
8.4 
Randomization and Blinding ............................................................................................... 87 
8.5 
Interim Analysis ................................................................................................................... 88 
8.6 
General Statistical Considerations ....................................................................................... 88 
8.6.1 
Analysis Populations .......................................................................................... 88 
8.6.1.1 
Intent-to-Treat Population.................................................................................. 88 
8.6.1.2 
Per Protocol Population ..................................................................................... 89 
8.6.1.3 
Safety Population ............................................................................................... 89 
8.6.2 
Statistical Methods ............................................................................................. 89 
8.6.3 
Prognostic Factors/Covariates ............................................................................ 89 
8.6.4 
Handling of Missing Data .................................................................................. 89 
8.7 
Data Summary ..................................................................................................................... 89 
8.7.1 
Subject Disposition ............................................................................................ 89 
8.7.2 
Demographic and Baseline Characteristics........................................................ 90 
8.7.3 
Prior and Concomitant Medications .................................................................... 90 
8.7.4 
Efficacy Analysis ............................................................................................... 90 
8.7.4.1 
Primary Analysis ................................................................................................ 90 
8.7.4.2 
Supportive Analysis ........................................................................................... 91 
8.7.5 
Safety Analysis .................................................................................................. 91 
8.7.5.1 
Adverse Events ................................................................................................... 91 
8.7.5.2 
Tolerability Assessment ..................................................................................... 92 
8.7.5.3 
Clinical Laboratory Data ................................................................................... 92 
8.7.5.4 
Physical Examination ........................................................................................ 92 
8.7.5.5 
Vital Signs .......................................................................................................... 92 
8.7.5.6 
ECG Examination .............................................................................................. 92 
8.7.5.7 
Neurological Assessment ................................................................................... 92 
9 ADVERSE EVENTS (DEFINITIONS AND REPORTING) .............................................. 93 
9.1 
Adverse Event ...................................................................................................................... 93 
9.1.1 
Reporting of Adverse Events ............................................................................. 93 
9.1.2 
Impact of Study Treatment ................................................................................ 93 
9.1.3 
DAIDS AE Grade (Severity) Assessment .......................................................... 93 


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9.1.4 
Causality Assessment ....................................................................................... 94 
9.1.5 
Treatment Given as a Result of the Event ........................................................ 95 
9.1.6 
Outcome Assessment ........................................................................................ 95 
9.1.7 
Expected / Anticipated Adverse Events............................................................ 95 
9.1.8 
SC Injection-related Events .............................................................................. 96 
9.2 
Serious Adverse Events (SAE) ........................................................................................... 96 
9.3 
Reporting of Serious Adverse Events ................................................................................. 97 
9.3.1 
SAE Follow-Up ................................................................................................ 98 
10 DIRECT ACCESS TO SOURCE DATA/DOCUMENTATION ....................................... 99 
11 QUALITY CONTROL AND QUALITY ASSURANCE ................................................. 100 
11.1 Monitoring Requirements ................................................................................................. 100 
11.2 Acceptability of Case Report Forms (CRFs) .................................................................... 100 
11.3 Modification of Protocol ................................................................................................... 101 
11.4 Reporting Protocol Deviations .......................................................................................... 101 
12 DATA MONITORING COMMITTEE (DMC) ............................................................... 102 
13 ETHICS AND REGULATORY REQUIREMENTS ....................................................... 103 
13.1 Institutional Review Board/Independent Ethics Committee (IRB/IEC) ........................... 103 
13.2 Investigator’s Responsibilities .......................................................................................... 103 
13.3 Subject Informed Consent Requirements ......................................................................... 104 
14 DATA HANDLING AND RECORD KEEPING .............................................................. 105 
14.1 Recording and Collection of Data .................................................................................... 105 
14.2 Clinical Data Management ............................................................................................... 105 
14.3 Archiving .......................................................................................................................... 106 
15 PUBLICATION PLAN ....................................................................................................... 107 
16 REFERENCES .................................................................................................................... 109 
17 APPENDIX .......................................................................................................................... 111 
17.1 Appendix I: AIDS-Defining Conditions ........................................................................... 111 
17.2 Appendix II: Division of AIDS Table for Grading the Severity of Adult and Pediatric 
Adverse Events (DAIDS AE Grading Table) .............................................................................. 113 
17.3 Appendix III: Adverse Events of Special Interest: Injection Site Reactions ................... 114 
17.4 Appendix V: Neurological Assessment ............................................................................ 115 


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LIST OF TABLES 
 
Table 1-1: 
Clinical Studies with PRO 140 .............................................................................. 36 
Table 4-1: 
Schedule of Assessments – Screening and Treatment Phase ................................. 52 
Table 4-2: 
Schedule of Assessments –Follow-Up (FU) Phase ................................................ 55 
Table 4-3 
Part 1: One week double-blind, placebo-controlled period [IP (PRO 140 or 
Placebo) + existing ART] ...................................................................................... 58 
Table 4-4 
Part 2: 24-week treatment maintenance period [PRO 140 + OBT] ....................... 58 
Table 6-1: 
Investigational Product - PRO 140/Placebo at T1 visit ......................................... 70 
Table 6-2: 
Investigational Product - PRO 140 at T2 - T25 visit ............................................. 71 
Table 9-1: 
DAIDS AE Grading Table v2 General Guidelines ................................................ 94 


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LIST OF FIGURES 
Figure 1-1: 
PRO 140 1302 Study: Mean of the maximum (nadir) log10 reductions in HIV RNA 
. .............................................................................................................................. 27 
Figure 1-2: 
PRO 140 1302 Study: Mean log10 reductions in HIV RNA over time .................. 28 
Figure 1-3: 
PRO 140 1302 Study: PRO 140 serum concentrations following a single 
intravenous injection in HIV- infected individuals ............................................... 29 
Figure 1-4: 
PRO 140 2301 Study: Mean change from baseline in HIV-1 RNA (Log10 
copies/mL) over Time (ITT Subjects) ................................................................... 30 
Figure 1-5: 
PRO 140 2101 Study: Mean of the maximum (nadir) log10 reductions in HIV RNA 
. .............................................................................................................................. 31 
Figure 1-6: 
PRO 140 2101 Study: Mean change from baseline in HIV-1 RNA (Log10 
copies/mL) over Time (ITT Subjects) ................................................................... 32 
Figure 1-7: 
Change in CD4+ cell counts in subjects treated with subcutaneous PRO 140. ..... 33 
Figure 1-8: 
Emax analysis of antiviral data generated with IV and SC PRO 140. ................... 38 
Figure 3-1: 
Study Flow Diagram .............................................................................................. 48 
Figure 4-1: 
Study Schematic .................................................................................................... 49 
Figure 6-1: 
Investigational Product - Vial Label ...................................................................... 71 
Figure 6-2: 
Investigational Product - Syringe Label ................................................................ 72 
Figure 6-3: 
Investigational Product - Kit Label ........................................................................ 73 
Figure 7-1: 
Visual Analog Scale ............................................................................................... 85 


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LIST OF ABBREVIATIONS 
Abbreviation 
Term 
AE 
Adverse Event 
AIDS 
Acquired Immune Deficiency Syndrome 
ALT 
Alanine Transaminase 
ANC 
Absolute Neutrophil Count 
ANCOVA 
Analysis of Covariance 
ART 
Anti Retroviral Therapy 
AST 
Aspartate Transaminase 
ATC 
Anatomic Therapeutic Classification 
AUC 
Area Under Curve 
°C 
Celsius 
CBC 
Complete Blood Count 
CCR5 
C-C chemokine receptor type 5 
CDC 
Centers for Disease Control and Prevention 
CFR 
Code of Federal Regulations 
CHO 
Chinese Hamster Ovary 
cm 
Centimeter 
CRF 
Case Report Form 
Cmax 
Maximal Concentration 
CRO 
Contract Research Organization 
CS 
Clinically Significant 
DAIDS 
Division of AIDS 
DMC 
Data Monitoring Committee 
DNA 
Deoxyribonucleic Acid 
DO 
Doctor of Osteopathic Medicine 
ECG 
Electrocardiogram 
eCRF 
Electronic Case Report Form 
Emax 
Maximum drug effect 
et al 
et aliae; Latin for "and others" 
EOT 
End of Treatment 
°F 
Fahrenheit 
FDA 
U.S. Food and Drug Administration 
FDP 
Fixed Dose Procedure 
FU 
Follow-Up 
GCP 
Good Clinical Practice 


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Abbreviation 
Term 
HAART 
Highly Active Antiretroviral Therapy 
Hb 
Hemoglobin 
HBsAg 
Hepatitis B Surface Antigen 
HCT 
Hematocrit 
HEENT 
Head, Ears, Eyes, Nose, and Throat 
HIPAA 
Health Insurance Portability Accountability Act 
HIV 
Human Immunodeficiency Virus 
IA 
Interim Analysis 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization 
i.e. 
id est; Latin for “that is” 
IEC 
Independent Ethics Committee 
IND 
Investigational New Drug 
INR 
International Normalized Ratio 
IP 
Investigational Product 
IRB 
Institutional Review Board 
ISR 
Injection Site Reactions 
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 
NP 
Nurse Practitioner 
NTF 
Non-Treatment Failure 
OBT 
Optimized Background Therapy 


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Abbreviation 
Term 
PA 
Physician Assistant 
PI 
Principal Investigator 
PK 
Pharmacokinetics 
PP 
Per Protocol 
Pr 
Protease 
PT 
Prothrombin Time 
QC 
Quality Control 
RBC 
Red Blood Cells 
RN 
Registered Nurse 
RNA 
Ribonucleic acid 
RT 
Reverse Transcriptase 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SC 
Subcutaneous 
SD 
Standard Deviation 
SOP 
Standard Operating Procedure 
SV 
Screening Visit 
TEAE 
Treatment Emergent Adverse Events 
TF 
Treatment Failure 
ULN 
Upper limit of normal 
USA 
United States of America 
VAS 
Visual Analogue Scale 
WBC 
White Blood Cells 


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1 
INTRODUCTION 
 
1.1 
STATEMENT OF INTENT 
The design, conduct and reporting of this trial shall be conducted in compliance with the 
protocol, International Conference on Harmonization/Good Clinical Practice (ICH/GCP), and all 
appropriate regulatory requirements. Investigator(s) participating in this study will have 
documented training in GCP. Independent monitoring of the trial will be accomplished utilizing 
 as the Contract Research Organization (CRO). 
 
1.2 
THE PROBLEM STATEMENT 
Though substantial progress has been made over the past two decades in the development of 
effective and well tolerated combination antiretroviral regimens, nearly 25% of patients 
receiving Highly Active Antiretroviral Therapy (HAART) are not virologically suppressed due 
to various reasons. Recent data suggest that most virologic failure on first-line regimens occurs 
because of either pre-existing (transmitted) drug resistance or suboptimal adherence. Patient- 
and regimen-related factors play a crucial role in determining whether an antiretroviral regimen 
is successful or result in virologic failure [Office of AIDS Research Advisory Council, 2014]. 
In general, drug resistance can be considered a core issue in patients with limited treatment 
options. However, there are other known factors apart from drug resistance (such as incomplete 
adherence, medication intolerance, pharmacokinetic issues, etc.) which also contribute to 
limiting treatment options in constructing a new regimen for patients who experience treatment 
failure. New agents and drug classes (e.g., integrase inhibitors, fusion inhibitors and CCR5 
antagonists) are necessary to keep up with ongoing viral mutations in an attempt to prevent viral 
replication and transmission [Tang MW, 2012][Gulick RM, 2008][Moyle G, 2008]. The 
availability of an effective maintenance regimen would benefit a subset of HIV-1 infected 
persons who are challenged by transferred resistance, medication adherence and/or chronic 
nucleoside toxicity. 
PRO 140 is a promising new antiretroviral agent that does not have any cross-resistance with 
drugs from other classes. Although PRO 140 would require subcutaneous (SC) administration, 
its favorable pharmacokinetics allows for weekly dosing. The purpose of this study is to exhibit 
antiviral activity of PRO 140 in combination with other antiretroviral agents for treatment of 
antiretroviral-experienced persons infected with CCR5-tropic HIV-1 virus. 


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1.3 
NAME AND DESCRIPTION OF THE INVESTIGATIONAL PRODUCT 
PRO 140 is a humanized IgG4,κ monoclonal antibody (mAb) to the C-C chemokine receptor 
type 5 (CCR5), under development as a therapy for human immunodeficiency virus (HIV) 
infection. 
PRO 140 binds to the N terminus (Nt) and the extracellular loop 2 (ECL2) domain of the CCR5 
cell surface receptor that HIV-1 uses to gain entry to a cell. PRO 140 binding to CCR5 blocks 
viral entry by interfering with the final phase of viral binding to the cell surface prior to fusion of 
the viral and cell membranes. PRO 140 has been administered intravenously or subcutaneously 
to 174 HIV-1 infected individuals in Phase I/II studies of safety, tolerability, pharmacokinetics 
and pharmacodynamics [Jacobson JM, 2010][Jacobson JM, 2010]. The drug has been well 
tolerated following administration of single doses of 0.5 to 5 mg/kg or up to three weekly doses 
of up to 324 mg. Single subcutaneous doses of 324 mg have resulted in drops in plasma HIV-1 
RNA levels of approximately 1.0 log10. Repetitive weekly administration of this dose of PRO 
140 has been associated with drops in plasma HIV-1 RNA levels of approximately 1.5 log10. 
Serum concentrations of PRO 140 above the IC50 for clinical isolates of HIV-1 are maintained 
for at least 2 weeks following a single dose of 324 mg. Plasma HIV-1 RNA levels rise to 
baseline levels as PRO 140 is cleared from the plasma and, presumably, other compartments. 
 
1.4 
SUMMARY OF PRIOR PRE-CLINICAL AND CLINICAL STUDIES 
1.4.1 Pre-Clinical Studies with PRO 140 
In vitro and in vivo preclinical studies have been conducted to determine the pharmacokinetic, 
immunogenicity, and toxicity profiles of PRO 140 following IV and SC administration. Several 
acute and chronic toxicity studies have been conducted to support the clinical development plan. 
Acute toxicity of PRO 140 was evaluated in New Zealand rabbits, following IV administration 
of 5 or 15 mg/kg. Chronic toxicity was evaluated in cynomolgus monkeys following biweekly 
administration of IV doses up to 10 mg/kg for six months and biweekly administration of 
various SC doses up to 50 mg/kg for 24 weeks. The drug was generally well tolerated. Biweekly 
administration of IV doses up to 10 mg/kg for six months resulted in minimum to mild 
lymphoid hyperplasia in assorted lymph nodes and spleen, which was considered an expected 
immune response to a foreign protein. Biweekly administration of SC doses up to 50 mg/kg for 
24 weeks resulted in minimum injection-site reactions (minimal, multifocal, mononuclear cell 
infiltrates in the subcutis), which were considered due to an inflammatory response to the 
injected antigen. Monkeys tolerated treatment with PRO 140 for 24 weeks without evidence of 
local or systemic toxicity. PRO 140 caused no mortality, cageside observations, in-life 
injection-site observations, or gross pathologic findings. Chronic treatment with PRO 140 did 
not affect body weight, food consumption, hematology, clinical chemistry or coagulation 


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parameters. 
Both IV and SC administration resulted in elimination half-lives of approximately 200 hours, 
and overall exposure increased with increasing doses. Following SC administration of PRO 140 
in monkeys, the maximal concentration (Cmax) was achieved within 56 hours and bioavailability 
for PRO 140 after SC dosing was approximately 70%. 
1.4.2 Clinical Studies with PRO 140 
Current human experience with PRO 140 consists of seven completed clinical trials. These 
studies are summarized in Table 1-1. In all clinical trials, the majority of adverse events (AEs) 
were mild or moderate. No dose-limiting toxicities or patterns of drug-related toxicities were 
observed. Antiviral activity was potent, rapid, prolonged, dose-dependent, and highly 
significant. 
1.4.2.1 PRO 140 1101 Study 
For the first-in-human trial, PRO 140 1101, the drug was administered IV at 0.1, 0.5, 2.0, or 5.0 
mg/kg and was generally well tolerated, non-immunogenic, and without clinically relevant 
toxicity. Treatment Emergent Adverse Events (TEAEs) did not increase with rising PRO 140 
dose levels. 75% of subjects reported TEAEs, most of which were deemed unrelated to study 
treatment. 
1.4.2.2 PRO 140 1102 Study 
In PRO 140 1102 study, the majority of AEs, other than injection-site reactions, were considered 
mild and possibly related to drug administration. The majority of injection-site reactions were 
considered mild, self-resolving, and definitely related to drug administration. PRO 140 derived 
from Chinese Hamster Ovary (CHO) cells and administered SC at 100 mg/mL was generally 
well tolerated in healthy, normal volunteers. Overall, PRO 140 administered SC using Autoject® 
2 appeared better tolerated than manual injection. 
1.4.2.3 PRO 140 1103 Study 
In PRO 140 1103 study, administration of PRO 140 at 350 mg using Autoject® 2 appeared well 
tolerated. Manual injections, on the other hand, were associated with a greater number of AEs. 
There did not appear, however, to be any substantial difference in subject perception of pain or 
discomfort related to site of drug administration. No anti-PRO 140 antibodies were detected in 
any subjects in this study. There was a tendency of higher exposure associated with SC 
administration of PRO 140 at 350 mg in the abdomen and the thigh. A higher number of AEs 
were associated with injections in the arm. Based on these observations, thigh and abdominal 
administration of PRO 140 were preferred over arm injection. 




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Figure 1-2:  PRO 140 1302 Study: Mean log10 reductions in HIV RNA over time 
 
There was no change in CCR5 virus susceptibility to PRO 140 following treatment. All subjects 
had CCR5-only virus at screening in the first-generation Trofile assay. CCR5-only tropism 
results were observed in all subjects at all other timepoints, with two exceptions: One of nine 
(11%) of placebo subjects had dual/mixed virus at baseline and all subsequent timepoints, 
reflecting a spontaneous and stable switch in co-receptor tropism results. One of 30 (3%, 0.5 
mg/kg group) had a dual/mixed tropism result on day 8 and CCR5-only results at all other 
timepoints, including the end of the day [Jacobson JM, 2008]. Clonal analysis of the dual/mixed 
virus revealed that it reflected outgrowth of pre-existing undetected virus rather than mutation of 
an CCR5 virus to a dual/mixed virus following treatment [Marozsan, 2008]. Therefore, no 
significant development of viral resistance to PRO 140 was observed despite potent and 
prolonged (2-3 weeks on average) viral suppression, followed by slow washout of the drug. 
Given that resistance to other classes of HIV-1 drugs can develop within one week of 
monotherapy [Demeter LM, 2000] [Saag, 1993][Richman, 1994], the findings indicate that PRO 
140 presents a high barrier to viral resistance in vivo. 
Figure 1-3 illustrates the mean serum concentrations of PRO 140 after IV injection. Serum levels 
increased with increasing dose. The mean Area Under Curve (AUC) from time zero to infinity 




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1.4.2.5 PRO 140 2301 Study 
PRO 140 2301 was a multi-center, randomized, double-blind, placebo-controlled, parallel group 
study in 30 male and female adult subjects infected with HIV-1. Subjects were randomized to 
one of three groups (N=10/group), each receiving one of three treatments: (i) a single IV dose of 
5 mg/kg by 30-minute IV infusion; (ii) a single IV dose of 10 mg/kg by 30-minute IV infusion; 
(iii) a single placebo dose by 30-minute IV infusion. The objective of the study was to assess and 
characterize the PK and PD of PRO 140 administered by IV infusion, assess efficacy at a new 
dosage level, and safety and tolerability of single doses of PRO 140. 
All PRO 140-treated subjects had more than 10-fold reduction in viral loads (mean max log10 
reductions were 1.83 for treatment groups and 0.32 for placebo) (Figure 1-4). Both the 5 mg/kg 
and 10 mg/kg doses have shown favorable tolerability and no dose-limiting toxicity has been 
observed. High levels of receptor occupancy (>85% reduction in the number of cells detected) 
were observed for 29 days after treatment with both 5 and 10 mg/kg doses. 
 
 
Figure 1-4: 
PRO 140 2301 Study: Mean change from baseline in HIV-1 RNA (Log10 
copies/mL) over Time (ITT Subjects) 
 
 
 
 
1.4.2.6 PRO 140 2101 Study 
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, 


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asymptomatic HIV infection, only CCR5 HIV-1 detectable, and no antiretroviral therapy for 12 
weeks [Thompson, 2009]. Placebo (n=10) and three PRO 140 doses were examined: 162mg 
weekly for three weeks (n=11), 324mg weekly for three weeks (n=11), and 324mg biweekly 
(every other week) for two doses (n=12). Subjects were followed for 44 days after the final dose. 
The study enrolled 40 males and 4 females. The median age, weight, CD4+ cell count and HIV-1 
RNA at baseline were 42.3 years, 79.1 kg, 410 cells/μL and 20,000 copies/mL, respectively. 
Baseline characteristics were similar for the different treatment groups. 
Potent, dose-dependent and highly statistically significant antiviral activity was observed (Figure 
1-5 and Figure 1-6). The 324mg weekly dose resulted in a mean 1.65 log10 reduction in viral 
load, and highly significant reductions were observed for the other dose groups as well (Figure 
1-5). There was no viral rebound between 324mg doses, and the antiviral effects persisted for 
one week after the final dose (Figure 1-6). The trial established the first antiviral proof of 
concept for a long-acting, self-administrable drug for HIV-1 infection [Thompson, 2009]. 
 
Figure 1-5:  PRO 140 2101 Study: Mean of the maximum (nadir) log10 reductions in HIV 
RNA 
 
 
placebo 
 
162mg Days 1,8,15 
 
324mg Days 1, 15 
 
2 
 
 
1.5 
 
 
1 
 
 
0.5 
 
 
0 
324mg Days 1,8,15 
1.65 
1.37 
0.58 
0.23 
Mean Maximum Log10 Reduction in HIV RNA 




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Figure 1-7:  Change in CD4+ cell counts in subjects treated with subcutaneous PRO 140. 
Subjects (n=10 to 12 per group) were randomized to received placebo weekly (Days 1, 8, 15), 
162mg PRO 140 weekly (Days 1, 8, 15), 324mg PRO 140 biweekly (Days 1, 15, with placebo on 
Day 8), or 324mg PRO 140 weekly (Days 1, 8, 15). CD4+ cell counts were measured over time, 
and the median change from baseline was determined for each treatment group. 
 
125 
100 
75 
50 
25 
0 
-25 
-50 
 
 
1 8 15 22 29 36 43 50 57 64 
125 
100 
75 
50 
25 
0 
-25 
-50 
 
 
1 8 15 22 29 36 43 50 57 64 
 
 
 
125 
100 
75 
50 
25 
0 
-25 
-50 
 
 
1 8 15 22 29 36 43 50 57 64 
Study Day 
 
125 
100 
75 
50 
25 
0 
-25 
-50 
 
 
1 8 15 22 29 36 43 50 57 64 
Study Day 
 
 
 
 
1.4.2.7 PRO 140 _CD01 Study 
PRO 140_CD01 study (open-label, 43 subjects, multi-center) evaluated the efficacy, safety, and 
tolerability of PRO 140 monotherapy (350 mg subcutaneous injection weekly for up to 12 weeks) for 
the maintenance of viral suppression following substitution of antiretroviral therapy in HIV-1 
324mg Days 1,8,15 
324mg Days 1,15 
162mg Days 1,8,15 
Placebo 
Median Change in CD4+ Cells 
Median Change in CD4+ Cells 


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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 (40) subjects (M/F: 37/3) with median age of 54.5 years (26-72) and median CD4 T-cell count 
of 604.5 cells/mm3 (365-1240) were enrolled in the CD01 study. Overall, twenty-two out of 40 
(55%) enrolled subjects completed 12 weeks of PRO140 monotherapy without experiencing 
virologic failure. Virologic failure was defined as two consecutive HIV-1 RNA levels of ≥ 400 
copies/mL separated by at least 3 days. Of the 40 enrolled subjects, 3 subjects were found to have 
Dual/Mixed (D/M) tropism [1 at baseline and 2 at the time of virologic failure] and 37 subjects were 
found to have exclusive CCR5-tropic virus. Fifty-nine percent (59%) of CCR5-exclusive subjects 
compared to zero percent (0%) of D/M subjects experienced virologic success within 12 weeks of 
PRO140 monotherapy (p=0.0465). All virologic failure subjects who had available lab data in both 
studies achieved viral suppression to < 400 HIV-1 RNA copies/mL, as well as viral suppression to 
‘Non Detectable’ or < 50 HIV-1 RNA copies/mL after re-initiation of ART. 
The by-subject analysis of PhenoSense® Entry Assay data for PRO140, maraviroc, and AMD3100 
shows no significant changes in the post-treatment IC50 and IC90 values were noted when compared 
with baseline values in virologic failure and non-virologic failure groups of subjects. As the 
aggregate analysis shows, the subjects who experienced virologic failure had higher IC90 value for 
PR0140 at baseline compared to subjects without virologic failure. The mean IC90 for subjects who 
experienced virologic failure was higher (10.84 µg/mL) than the IC90 for subjects without virologic 
failure (6.70 µg/mL) in the CD01 study (p=0.0115). 
Anti-PRO140 antibodies were not identified in any post-treatment sample and data derived from the 
CD01 study further supports the favorable PRO140 PK profile data generated from both pre-clinical 
as well as prior Phase 1/2 clinical trials. 
Safety data were analyzed for all 40 enrolled subjects. One (1) of 40 subjects experienced an SAE 
that was deemed not related to the study drug by the Principal Investigator. Twenty-eight (28) of 40 
subjects (70%) 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 40 (35%) subjects. The majority of the reported AEs (63/89; 70.7%) were deemed 
either unlikely or not related to study treatment by the Investigator. Similarly, the majority of the 
reported AEs (72/89; 80.8%) were deemed mild in nature. 
Additionally, a letter of amendment has been filed to increase the planned number of subjects from 
40 to 43 subjects to compensate for the 3 Dual/Mixed subjects (1 at baseline and 2 at the time of 
virologic failure) enrolled in the study. This clinical study is currently ongoing. 


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1.4.2.8 PRO 140 _CD01-Extension Study 
PRO 140_CD01-Extension study (open-label, 28 subjects, multi-center) seeks to evaluate the 
efficacy, safety, and tolerability of PRO 140 monotherapy (350 mg subcutaneous injection weekly 
for up to 108 weeks) for the continued maintenance of viral suppression following substitution of 
antiretroviral therapy in HIV patients (with exclusive CCR5-tropic virus). Participants in this study 
were HIV-infected individuals who were virologically suppressed on combination antiretroviral 
therapy and completed the first 12 weeks of CD01 study without experiencing virologic failure. As 
with the CD01 study, virologic failure was defined as two consecutive HIV-1 RNA levels of ≥ 400 
copies/mL separated by at least 3 days. Consenting patients may remain on PRO 140 monotherapy 
for up to 108 weeks. 
A total of 16 subjects participated in the CD01-Extension study of which one subject was considered 
not eligible as subject experienced virologic failure prior to first extension treatment. 
Fifteen (15) eligible subjects (M/F: 13/2) with median age of 55.3 years (26-68) and median CD4 T- 
cell count of 586 cells/mm3 (365-1059) were enrolled in an extension study. Eleven (11) subjects are 
currently receiving weekly 350 mg PRO140 SC monotherapy and have completed more than one 
year of treatment (56 - 67 wks). One subject with undetectable viral load did not continue beyond 47 
weeks due to relocation, and 3 subjects experienced virologic failure after a median time of 169 days 
(106-193). 
PRO140 was generally well tolerated, and no drug-related SAEs were observed. The final clinical 
study report is expected to be available in 2017. 
This clinical study is currently ongoing. 
 
1.4.2.9 PRO 140 _CD03 Study 
PRO 140_CD03 study (open-label, two-arm comparator, 400 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 study has been submitted to clinical sites and the start-up 
process is ongoing. 






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


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It is important to note that when larger proteins (MW> 10,000) are administered SC, they 
initially traffic through the lymphatic system. Uptake into the bloodstream occurs after the 
proteins reach the thoracic duct [Nishikawa M, 2005]. 
In addition, based on pharmacodynamic data from our prior SC and IV studies, maximum 
virologic suppression is expected to be achieved with trough concentrations that equal or exceed 
approximately 5 µg/mL. 
Finally, the mean nadir reduction in viral load achieved with 3 weekly 324 mg SC doses (1.65 
log10) was similar to the mean nadir reductions observed with single 5 or 10 mg/kg IV doses (1.8 
log10 in each case), and higher viral load reductions are expected in the present study based on 
the use of the 350 mg CHO formulation. Overall, several lines of evidence indicate that 
maximum virologic suppression will be achieved with 350 mg weekly dosing in the present 
study. 
 
1.6 
RISKS / BENEFITS ASSESSMENT 
 
1.6.1 RISKS/DISCOMFORT TO SUBJECTS AND PRECAUTIONS TO MINIMIZE RISK 
1.6.1.1 Risks associated with continuation of Failing Antiretroviral Treatment Regimen 
As per standard of care, patients who failing on their ART remain on failing regimen while 
waiting for the results of HIV-1 drug resistance tests. A new drug regimen is constructed by the 
Investigator based on the subject’s resistance test results and treatment history. This duration 
corresponds with the screening phase of the study. 
Once the results of resistance and tropism tests are available, the study treatment (PRO 140 
350mg SC injection / placebo) will be added to the failing regimen for one week. After one week 
all subjects will receive PRO 140 SC injection and Optimized Background Therapy (OBT). 
Addition of study treatment (PRO 140 350mg SC injection / placebo) to the failing regimen may 
not be effective in achieving a reduction in viral load for all subjects. Such cases could lead to 
an increased risk of developing drug resistance, opportunistic infections and clinical progression 
of the disease. 
1.6.1.2 Allergic Reaction 
PRO 140 belongs to the monoclonal antibody class of drugs. Monoclonal antibodies are 
sometimes associated with allergic reactions (fatigue, diarrhea, fever, vomiting, headache, 
nausea, pain at the site of injection, low blood pressure, rash, itching, and chills) or flu-like 
reactions such as fever, chills, and aches. These events are usually of short duration if they occur 
at all. Severe allergic reactions, however, can be life-threatening. Although anaphylaxis has not 


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been observed in prior trials of PRO 140, infusion of proteins always carries with it the 
theoretical risk for anaphylactic shock. Accordingly, whenever PRO 140 is initially administered 
to subjects, there should be available and in place the procedures required to manage 
anaphylactic shock. 
1.6.1.3 Immune Response 
Subjects who take PRO 140 or other monoclonal antibodies can also develop an immune 
response to PRO 140 that may affect their ability to receive monoclonal antibodies, or to benefit 
from diagnosis or therapy with a monoclonal antibody in the future. 
1.6.1.4 Pregnancy 
Risks to unborn babies are unknown at this time; pregnant females will be excluded from this 
study. Females of childbearing potential must have a negative pregnancy test prior to enrollment. 
Both male and female patients and their partners of childbearing potential must agree to use 
appropriate birth control methods throughout the study duration (excluding women who are not 
of childbearing potential and men who have been sterilized). 
1.6.1.5 Venipuncture 
Blood sampling is required as part of the study protocol. Blood sampling carries a minimal risk 
of minor discomfort and the possibility of minor bruising at the site of the needle puncture and, 
rarely, the possibility of infection at the needle puncture site. 
1.6.1.6 Risks to the Study Personnel and the Environment 
The principal risk in the clinical setting is in the handling of needles that may be contaminated 
with HIV, or other human pathogens. Adherence to universal precautions for working with 
infectious agents will reduce the risk of exposure to these individuals. All bio-hazardous waste 
will be disposed of as stipulated by local, state, and federal regulations and in accordance with 
study site Standard Operating Procedures (SOPs). 
1.6.1.7 Unknown Risks 
As with all research there is the remote possibility of risks that are unknown or that cannot be 
foreseen based on current information. 
1.6.1.8 Theoretical risk for increased severity of West Nile virus infection 
Individuals who lack a functional CCR5 gene are at increased risk for severe infection by West 
Nile virus [Thompson, 2009] Because of this, treatment with CCR5 co-receptor antagonists 
poses a theoretical risk for increased severity of West Nile virus infection. However, this concern 
is mitigated by several factors. First, no increased risk was observed for individuals who possess 


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one functional and one non-functional CCR5 gene, indicating that an intermediate amount of 
CCR5 is sufficient for defense against West Nile virus [Thompson, 2009]. Second, use of CCR5 
co-receptor antagonists is unlikely to completely abrogate CCR5 function, and there has been no 
association reported to date between CCR5 co-receptor use and severe West Nile virus. 
Additionally, PRO 140 weakly antagonizes the natural activity of CCR5 and thus is less likely to 
adversely affect immune function. Furthermore, this has not been established to be a risk with 
maraviroc, the anti-CCR5 drug already FDA-approved for the treatment of HIV. 
Collectively, the experience with both IV and SC, simulation modeling and the recent 
confirmation that a higher concentration of PRO 140 synthesized using a highly efficient CHO 
cell line can be conveniently and safely administered has resulted in the design of the current 
study. 
 
1.6.2 INTENDED BENEFIT FOR SUBJECTS 
This study provides an opportunity for subjects to have supervised once weekly SC treatment 
with PRO 140 in addition to an optimized and simplified ART regimen. Subjects participating in 
the present short term combination therapy study for 25 weeks 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 safety, efficacy and tolerability parameters of PRO 140 
compared to placebo in reducing HIV-1 viral load in patients on their current ART (failing 
regimen) during the one week double-blind treatment period. 
The secondary objectives are to assess the efficacy, clinical safety and tolerability parameters of 
PRO 140 in combination with optimized background therapy in patients during the 24-week 
single-arm, open-label treatment period. 
The primary efficacy endpoint will be proportion of participants with a 0.5 log10 or greater 
reduction in HIV-1 RNA viral load from baseline at the end of the one week double-blind 
treatment period (Part 1). 
The secondary efficacy endpoints will be proportion of participants with ≥ 0.5 log10 reduction in 
HIV-1 RNA viral load from baseline at the end of the 1-week double-blind treatment period, 
stratified to each group: (a) resistance to ART drugs within three drug classes, (b) resistance to 
ART drugs within two drug classes with limited treatment option, proportion of participants with 
≥ 1 log10 reduction in HIV-1 RNA viral load from baseline at the end of the 1-week double-blind 
treatment period (Part 1) for all patients and within each stratum, mean change from Baseline in 
HIV-1 RNA levels (log10 copies/mL) at the end of the 1-week double-blind treatment period 
(Part 1) for all patients and within each stratum, percentage of participants achieving HIV-1 
RNA < 400 copies/mL at week 25, percentage of participants achieving HIV-1 RNA < 50 
copies/mL at week 25 for all patients and within each stratum, mean change from Baseline in 
HIV-1 RNA levels (log10 copies/mL) at week 25 for all patients and within each stratum, mean 
change from Baseline in CD4 cell count at the end of the 1-week double-blind treatment period 
(Part 1) for all patients and within each stratum and mean change from Baseline in CD4 cell 
count at week 25 for all patients and within each stratum. 
Safety assessments include evaluation of emergence of Dual/Mixed (D/M)- and CXCR4-tropic 
virus in patients who had exclusive CCR5-tropic virus at study entry, tolerability of repeated 
subcutaneous administration of PRO 140 as assessed by study participants (using Visual 
Analogue Scale) and by investigator –evaluation of injection site reactions, frequency of 
treatment-related adverse events resulting in study drug discontinuation, frequency of Grade 3 or 
4 adverse events and frequency of treatment-emergent serious adverse events. 


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3 
STUDY DESIGN 
This is a Phase 2b/3, multi-center, two part study, designed to evaluate the efficacy, safety and 
tolerability of PRO 140 in conjunction with existing ART (failing regimen) for one week and 
Optimized Background Therapy (OBT) for 24 weeks respectively. The patient population for 
this trial are treatment-experienced patients with CCR5-tropic virus and demonstrates evidence 
of HIV-1 replication despite ongoing antiretroviral therapy with documented genotypic or 
phenotypic resistance to ART drugs within three drug classes (or within two drug classes with 
limited treatment option). 
The study is divided into three phases: Screening, Treatment and Follow-up. 
Screening Phase begins with signing of Informed Consent and lasts up to 6 weeks. Subject will 
enter the Treatment Phase as soon as HIV-1 viral tropism, genotypic and/or phenotypic 
resistance results are available for review by Investigator. 
The Treatment phase is divided into two parts: 
• Part 1: One-week randomized, double-blind, placebo-controlled period consisting of two 
treatment arms (PRO 140 or Placebo) along with existing ART (failed regimen). 
• Part 2: 24-week single-arm, open-label treatment period with all subjects receiving PRO 
140 along with Optimized Background Therapy (OBT) 
All subjects will continue taking their existing ART (failed regimen) during the Screening Phase 
and first week of the Treatment Phase (Part 1). After Part 1 of the Treatment Phase (1 week), all 
subjects will enter the 24-week single-arm, open-label treatment period. During this period, all 
subjects will receive PRO 140 SC injection and OBT. 
Study participants will be regularly monitored for viral load following initiation of PRO 140, and 
will cease weekly study treatment injections should they experience treatment failure. 
Subjects who experience treatment failure at any point during the Open-Label Period of the 
Treatment Phase will undergo the Treatment Failure (TF) Visit assessments and will be followed 
up every 4 weeks until viral suppression is achieved (i.e., plasma HIV-1 RNA levels below level 
of detection) or up to a maximum of 6 months after cessation of therapy if the treating physician 
does not feel that there is an antiretroviral regimen that will regain full viral suppression. 
Subjects who do not experience treatment failure, will be followed up every 2 weeks for total of 
4 weeks. 
 
3.1 
STUDY CENTER(S) 
Up to 60 centers in the United States 


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3.2 
STUDY POPULATION 
Study population includes treatment-experienced HIV-infected patients with CCR5-tropic virus 
who demonstrates evidence of HIV-1 replication despite ongoing antiretroviral therapy with 
documented genotypic or phenotypic resistance to ART drugs within three drug classes (or 
within two drug classes with limited treatment option). The options may be limited as a result of 
drug antiviral class cross-resistance, documented treatment intolerance, documented objective 
assessments such as renal or hepatic insufficiency (e.g. high creatinine at baseline, limiting 
treatment options due to potential for toxicity), past adverse reactions such as hypersensitivity 
reactions or neuropsychiatric issues that could limit use of currently approved drugs. 
Note: Enrollment will be stratified to have HIV-1 virus resistant to ART drugs within three drug 
classes or within two drug classes with limited treatment option. 
 
3.3 
ELIGIBILITY CRITERIA 
3.3.1 Inclusion Criteria 
Subjects must meet all of the following criteria to be included in the study: 
1. Males and females, age ≥18 years 
2. Exclusive CCR5-tropic virus at Screening Visit as determined by Monogram Biosciences 
Trofile® Assay 
3. Have a history of at least 3 months on current antiretroviral regimen 
4. Treatment-experienced HIV-infected patients with documented genotypic or phenotypic 
resistance to at least one ART drug within three drug classes 
OR 
Treatment-experienced HIV-infected patients with documented genotypic or phenotypic 
resistance to at least one ART drug within two drug classes and have limited treatment 
option. The options may be limited as a result of drug antiviral class cross-resistance, 
documented treatment intolerance, documented objective assessments such as renal or 
hepatic insufficiency (e.g. high creatinine at baseline, limiting treatment options due to 
potential for toxicity), past adverse reactions such as hypersensitivity reactions or 
neuropsychiatric issues that could limit use of currently approved drugs. 
5. Be willing to remain on treatment without any changes or additions to the OBT regimen, 
except for toxicity management or upon meeting criteria for treatment failure. 
6. Plasma HIV-1 RNA ≥ 400 copies/mL at Screening Visit as determined by Human 
Immunodeficiency Virus 1 (HIV-1) Quantitative, RNA (Roche Taqman® Real-Time PCR) 


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and documented detectable viral load (HIV-1 RNA >50 copies/ml) within the last 3 months 
prior to Screening Visit. 
7. Laboratory values at Screening of: 
a. Absolute neutrophil count (ANC) ≥750/mm3 
b. Hemoglobin (Hb) ≥10.5 gm/dL (male) or ≥ 9.5 gm/dL (female) 
c. Platelets ≥75,000 /mm3 
d. Serum alanine transaminase (SGPT/ALT) <5 x upper limit of normal (ULN) 
e. Serum aspartate transaminase (SGOT/AST) <5 x ULN 
f. Bilirubin (total) <2.5 x ULN unless Gilbert's disease is present or subject is receiving 
atazanavir in the absence of other evidence of significant liver disease 
g. Creatinine ≤1.5 x ULN 
8. Clinically normal resting 12-lead ECG at Screening Visit or, if abnormal, considered not 
clinically significant by the Principal Investigator 
9. Both male and female patients and their partners of childbearing potential must agree to use 2 
medically accepted methods of contraception (e.g., barrier contraceptives [male condom, 
female condom, or diaphragm with a spermicidal gel], hormonal contraceptives [implants, 
injectables, combination oral contraceptives, transdermal patches, or contraceptive rings], 
and intrauterine devices) during the course of the study (excluding women who are not of 
childbearing potential and men who have been sterilized). Females of childbearing potential 
must have a negative serum pregnancy test at Screening visit and negative urine pregnancy 
test prior to receiving the first dose of study drug 
10. 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. 
Note: Subjects diagnosed with either substance dependence or substance abuse or any history 
of a concomitant condition (e.g., medical, psychologic, or psychiatric) may be enrolled if in 
the opinion of site investigator these circumstances would not interfere with the subject’s 
successful completion of the study requirements. 
3.3.2 Exclusion Criteria 
Subjects meeting any of the following criteria will be excluded from the study: 
1. Documented CXCR4-tropic virus or Dual/Mixed tropic (R5X4) virus as determined by 
HIV-1 tropism assay. 


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2. Patients with no viable treatment options ( i.e., no fully active antiretroviral drug 
available which can be effectively combined to form a viable new OBT) 
3. Any active infection or malignancy requiring acute therapy (with the exception of local 
cutaneous Kaposi’s sarcoma) 
Note: Subjects infected by the hepatitis B virus or hepatitis C virus will be eligible for the 
study if they have no signs of hepatic decompensation and meet the liver function tests 
eligibility criteria 
4.  Laboratory test values of ≥ grade 3 DAIDS laboratory abnormality with the exception of 
the absolute CD4+ count criterion of <200/mm3 
5. Females who are pregnant, lactating, or breastfeeding, or who plan to become pregnant 
during the study 
6. Unexplained fever or clinically significant illness within 1 week prior to the first study 
dose 
7. Any vaccination within 2 weeks prior to the first study dose. 
8. Subjects weighing < 35kg 
9. History of anaphylaxis to oral or parenteral drugs 
10. History of Bleeding Disorder or patients on anti-coagulant therapy 
11. 
12. Participation in an experimental drug trial(s) within 30 days of the Screening Visit 
13. Any known allergy or antibodies to the study drug or excipients 
14. Treatment with any of the following: 
a. Radiation or cytotoxic chemotherapy with 30 days prior to the screening visit 
b. Immunosuppressants within 60 days prior to the screening visit 
c. Immunomodulating agents (e.g., interleukins, interferons), hydroxyurea, or 
foscarnet within 60 days prior to the screening visit 
d. Oral or parenteral corticosteroids within 30 days prior to the Screening Visit. 
Subjects on chronic steroid therapy >5 mg/day will be excluded with the 
following exception: 
o Subjects on inhaled, nasal, or topical steroids will not be excluded 
15. Any other clinical condition that, in the Investigator's judgment, would potentially 
compromise study compliance or the ability to evaluate safety/efficacy 


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[Note: Exclusion Criteria #11 was removed from protocol version 8.0. The exclusion 
criteria numbering/order is retained to maintain consistency.] 






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Note: Study treatment injections at T1, T2, T3, T7, T11, T15, T19 and T23 must be 
administered at clinic. The remaining study treatment injections may be self- 
administered by subjects outside the clinic. 
Any time during the Open-Label Treatment Phase, if treatment failure occurs, 
Investigator will readjust antiretroviral regimen based on HIV-1 genotypic and/or 
phenotypic drug resistance results obtained during the TF visit. 
Subjects will be allowed to continue PRO 140 with existing OBT regimen while waiting 
for new regimen to be constructed by the Investigator. 
Treatment failure is defined in terms of virologic non-response and virologic rebound in 
the Open-Label Treatment Phase (Part 2) of the study: 
a) Virologic non-response is defined as two consecutive viral load results of: 
• <0.5 log10 copies/mL decrease in HIV-1 RNA at Day 7 of the Open-Label 
Treatment Period. [Assessment Timepoint:T3 visit] 
• <1 log10 copies/mL decrease in HIV-1 RNA at or after Week 4 of the Open-Label 
Treatment Period unless HIV-1 RNA <400 copies/mL. [Assessment Timepoint: 
from T6 up to T25 visit] 
• Confirmed plasma HIV-1 RNA levels ≥400 copies/mL at Week 24 of the Open- 
Label Treatment Period [Assessment Timepoint: T25 visit] 
b) Virologic rebound is defined as two consecutive viral load results of: 
≥1.0 log10 copies/mL increase in plasma HIV-1 RNA above nadir level* in the 
Open-Label Treatment Period [Assessment Timepoint: from T3 up to T25 visit] or 
*Note: This refers to “Nadir” level in the Open-Label Treatment Phase which 
starts from T2 visit 
• ≥400 copies/mL after suppression to <50 copies/mL in the Open-Label Treatment 
Period. [Assessment Timepoint: from T3 up to T25 visit] 
(3) Follow-Up Phase: The duration of follow-up depends on whether or not subject has 
experienced treatment failure during the Open-Label Treatment Phase. 
• Subjects who experience treatment failure within Open-Label Treatment Phase will 
be followed up every 4 weeks until viral suppression is achieved (i.e., plasma HIV-1 
RNA levels below level of detection) or up to a maximum of 6 months after cessation 
of therapy if the treating physician does not feel that there is an antiretroviral regimen 
that will regain full viral suppression. 
• Subjects who do not experience treatment failure at the end of Open-Label Treatment 
Phase, will be followed up every 2 weeks for total of 4 weeks. 


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






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Foot Notes: 
[1] 
Informed consent must be obtained prior to patient participation in any protocol-related activities that are not part of routine care. 
[2] 
Initial evaluation of patient eligibility will be performed by Investigator. 
[3] 
Medical history, past surgeries, disease history, history of substance abuse, social history, blood transfusion history, and current therapies (medications and non- 
medications). 
[4] 
Symptom-directed physical examination 
[5] 
 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. 
[6] 
Post treatment vital signs will be recorded at T1-3, T7, T11, T15, T19, T23, EOT and TF visits blood pressure, heart rate, respiration rate, and temperature.) 
[7] 
Hemoglobin, Hematocrit (HCT), Red Blood Cells (RBC), White Blood Cells (WBC) with total and differential count, Absolute Neutrophil Count (ANC) and platelets. 
[8] 
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) 
[9] 
Prothrombin time (PT) and International Normalized Ratio (INR) 
[10] ONLY performed on women of childbearing potential. 
[11] Urine samples will be tested for color, appearance, specific gravity, pH, protein, glucose, occult blood, ketones, leukocyte esterase, nitrite, bilirubin, urobilinogen, and 
microscopic examination of urine sediment. 
[12] Includes: CD3 %, CD4 %, CD8 %, Absolute Lymphocytes, CD3 cell count, CD4 cell count, and CD8 cell count 
[13] 
PK samples for PRO 140 will be collected prior to IP administration at the T1, T7, T15, EOT and TF visits. 
[14] Serum conc. of ART Drugs prior to IP administration at the T1, T7, T15, EOT and TF visits. 
[15] Randomization via WebView CTMS system 
[16] Injection Site Reaction Assessment as assessed by Investigator (or designee) at each treatment visit that occurs at the clinic . 
[17] 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 
[18] Monogram Biosciences Trofile® (DNA or RNA Assay based on viral load) 
[19] 
Monogram Biosciences PhenoSense® GT (and PhenoSense Integrase and GeneSeq Integrase testing, if applicable) 
[20] Monogram Biosciences HIV-1 PhenoSense® Entry assay with AMD3100 (CXCR4 inhibitor drug), Maraviroc and PRO 140 (CCR5 inhibitor drugs). 
[21] Quest Diagnostics HIV-1 Coreceptor Tropism with Reflex to Ultradeep Sequencing or HIV-1 Proviral Tropism 




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4.1 
SCREENING PHASE 
4.1.1 Screening Visits 
The subject (or Legally Acceptable Representative (LAR)) will sign and date the informed 
consent form (ICF) and Health Insurance Portability Accountability Act (HIPAA) authorization 
(according to site policy and practices) prior to any study-related procedures. A unique 
identification number (screening number) will be assigned to each subject who has provided 
written informed consent. The subject screening number will incorporate a three-digit Study 
Center number (001, 002 or 003….) and a three-digit numeric ID assigned in successive order of 
entering the study after signing the ICF at each center, beginning with 001 at each site (e.g. 001- 
001 or 002-001). 
Subject Screening # : 
XXX 
- 
YYY 
XXX=Study Center 
YYY=Subject Numeric ID 
 
All study centers will be instructed to maintain the study-specific pre-screening, screening and 
enrollment logs at their sites. If a subject initially fails to meet inclusion/exclusion criteria and is 
later reconsidered for participation, the subject will be re-consented and assigned a new screening 
number at the time of re-screening. Subjects who fail their first screening attempt may be re- 
screened a maximum of once and may be enrolled if they are found to meet all inclusion and no 
exclusion criteria when re-screened. 
Once the ICF has been signed, screening procedures and information will be obtained to confirm 
subject eligibility including: 
• Detailed medical history (see section 7.4), 
• Detailed history of HIV infection and treatment (see section 7.5), 
• Demographic information (see section 7.3), 
• Prior and current medications review (see section 7.6), 
• Physical examination (see section 7.7), 
• Electrocardiogram (ECG) (see section 7.8), 
• Body Weight & Height measurements (see section 7.10) 
• Vital Signs (see section 7.10), 
• Collection of Blood Specimens (see section 7.11) for 
o Complete Blood Count 


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o Biochemistry 
o Coagulation Indices [Prothrombin time (PT) and INR] 
o Hepatitis B surface antigen (HBsAg) 
o Plasma HIV-1 RNA level 
o TruCount T Assay 
o HIV-1 viral tropism (Trofile® DNA or RNA Assay) 
o HIV-1 Drug Resistance Assay 
o HIV-1 PhenoSense® Entry (Monogram BioSciences) 
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. 
o Blood sample collection for Exploratory/Confirmatory analysis 
• Collection of Urine Specimen for Urinalysis (see section 7.11.13) 
 
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 42 days of Screening Visit will have screening lab 
assessments repeated, with the exception of HIV-1 viral tropism, genotypic and/or phenotypic 
resistance, to reconfirm eligibility. 
 
4.2 
TREATMENT PHASE 
Treatment 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 
failure and exit the study without further evaluation. 




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Note: 
 Subjects may return to clinic for an additional blood draw in-between the clinic visits for 
plasma HIV-1 RNA levels, per the discretion of the Investigator. 
 Subjects who experience treatment failure at any time during the Treatment Phase will 
undergo the Treatment Failure (TF) Visit assessments and enter the Follow-up Phase of the 
study. 
 Subjects who meet any criteria (other than treatment failure) for discontinuation of study 
treatment as specified in section 5.2.1 of the protocol, will undergo End of Treatment Phase 
(EOT) Visit assessments and enter the Follow-up Phase of the study. 
 Subjects who do not experience treatment failure will enter the Follow-up Phase of the 
study at the end of 25-week Treatment Phase. 
All study subjects will continue or adjust their current Optimized Background Therapy: 
• 
At the end of 25-week Treatment Phase, or 
• Anytime during the Treatment Phase, if treatment failure occurs or have met any other criteria 
for discontinuation of study treatment as specified in section 5.2.1 of the protocol. Subjects 
will be allowed to continue PRO 140 with existing OBT regimen while waiting for new 
regimen to be constructed by the Investigator. 
 
 
Visits during the Treatment Phase will commence on T1, i.e. the date of first treatment, with 
weekly visits (± 3 days) thereafter. The first Treatment Visit (T1) will take place as soon as HIV- 
1 viral tropism, genotypic and/or phenotypic resistance results are available for review by 
Investigator, within 6 weeks of the Screening Visit. 
The following visits will occur during the 25-week Treatment Phase: 
• 
T1 (First Treatment Administration): within 6 weeks of Screening Visit 
• 
T2 (Second Treatment Administration): 7(± 3) days from last visit 
• 
T3 (Third Treatment Administration): 7(± 3) days from last visit 
• 
T4 (Fourth Treatment Administration): 7(± 3) days from last visit 
• 
T5 (Fifth Treatment Administration): 7(± 3) days from last visit 
• 
T6 (Sixth Treatment Administration): 7(± 3) days from last visit 
• 
T7 (Seventh Treatment Administration): 7(± 3) days from last visit 
• 
T8 (Eighth Treatment Administration): 7(± 3) days from last visit 


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• 
T9 (Ninth Treatment Administration): 7(± 3) days from last visit 
• 
T10 (Tenth Treatment Administration): 7(± 3) days from last visit 
• 
T11 (Eleventh Treatment Administration): 7(± 3) days from last visit 
• 
T12 (Twelfth Treatment Administration): 7(± 3) days from last visit 
• 
T13 (Thirteenth Treatment Administration): 7(± 3) days from last visit 
• 
T14 (Fourteenth Treatment Administration): 7(± 3) days from last visit 
• 
T15 (Fifteenth Treatment Administration): 7(± 3) days from last visit 
• 
T16 (Sixteenth Treatment Administration): 7(± 3) days from last visit 
• 
T17 (Seventeenth Treatment Administration): 7(± 3) days from last visit 
• 
T18 (Eighteenth Treatment Administration): 7(± 3) days from last visit 
• 
T19 (Nineteenth Treatment Administration): 7(± 3) days from last visit 
• 
T20 (Twentieth Treatment Administration): 7(± 3) days from last visit 
• 
T21 (Twenty-first Treatment Administration): 7(± 3) days from last visit 
• 
T22 (Twenty-second Treatment Administration): 7(± 3) days from last visit 
• 
T23 (Twenty-third Treatment Administration): 7(± 3) days from last visit 
• 
T24 (Twenty-fourth Treatment Administration): 7(± 3) days from last visit 
• 
T25 (Twenty-fifth Treatment Administration): 7(± 3) days from last visit 
• 
End of Treatment (EOT) Visit – 7(± 3) days from last treatment 
• 
Treatment Failure (TF) Visit – Only if treatment failure occurs during the Treatment Phase 
 
4.2.1 Treatment Visit (T1) - Part 1 of Treatment Phase 
The following assessments will be performed at the first treatment visit, unless otherwise 
specified: 
Pre-Treatment 
• Confirmation of eligibility criteria by reviewing test results and other criteria assessments 
performed at Screening Visit (see section 7.2 ) 
• Neurological assessment (see section 7.9) 
• Symptom-directed physical examination (see section 7.7), 
• Change in concomitant medications (see section 7.5) 
• Any changes in medical history since Screening Visit (see section 7.4), 
• Collection of Blood Specimens (see section 7.11) for 


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o Plasma HIV-1 RNA level 
o TruCount T Assay 
o PK sample for PRO 140 
o Anti-idiotypic antibodies to PRO 140 
o Serum concentration of ART drugs 
o HIV Drug Resistance Assay 
 Note: Blood sample for Plasma HIV-1RNA level, TruCount T Assay and HIV-1 Drug 
Resistance Assay will be collected at SV, T1, T2, T3, T7, T11, T15, T19, T23, EOT and 
TF visits. 
 Note: PK sample for PRO 140 and Anti-idiotypic antibodies to PRO 140 will be 
performed at T1, T7, T15, EOT and TF visits 
 Note: Serum concentration for ART will be performed at T1, T7, T15, visits, EOT and 
TF visits, as well as any Unscheduled Visit within the Treatment Phase as per 
discretion of the Investigator. 
• Urine Pregnancy Test (see section 7.11.6) 
• Randomization (see section 7.12) 
Administration of study treatment [PRO 140 or placebo] 
Study treatment will be administered weekly as a subcutaneous injection in the abdomen. 
Subjects will receive the study treatment delivered as two 1 mL injections on opposite sides of the 
abdomen. 
Note: All study treatments (PRO 140 or placebo) must be administered by a qualified medical 
professional (MD, DO, PA, LPN, LVN, NP, or RN) or self-administered by subjects depending 
on the study visit week. 
Post-Treatment 
• Injection Site Reaction Assessment (see section 7.14) 
 Note: To assess injection site reactions, the investigator will use the DAIDS AE 
grading table (refer to section 17.3). 
• Assessment of Adverse Events (AE) (see section 9) 
• Vital Signs (see section 7.10) will be assessed within 15 minutes of study treatment 
administration. 


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Note: Investigator should determine the Optimized background therapy (OBT) regimen based on 
genotypic and/or phenotypic results obtained during Screening Phase and provide the appropriate 
prescription to the study subject at Treatment Visit 1 (T1). 
OBT is a standard-of-care regimen comprised of 3 or more antiretroviral agents selected by the 
investigator based on treatment history and genotypic and/or phenotypic assessments. The use of 
another experimental agent (e.g., ibalizumab) to create a viable HIV suppressive OBT regimen in 
certain subjects with severely limited approved and available therapeutic options will be allowed 
with the prior approval from sponsor. 
4.2.2 Treatment Visit-2 (T2) to Treatment Visit-25 (T25) - Part 2 of Treatment Phase 
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 7.7), 
• Neurological Assessment (see section 7.9) 
 Note: Neurological assessment will be performed at T3, T7, T11, T15, T19, T23 visits 
• Vital Signs (see section 7.10) 
 Note: Post-treatment vital signs will be assessed within 15 minutes following study 
treatment administration when performed inside clinic. 
• Collection of Blood Specimens (see section 7.11) for 
o Plasma HIV-1 RNA level 
o TruCount T Assay 
o HIV-1 Drug Resistance Assay 
o PK sample for PRO 140 
o Serum concentration of ART drugs 
o Anti-idiotypic antibodies to PRO 140 
 Note: Blood sample for Plasma HIV-1RNA level, TruCount T Assay, and HIV-1 Drug 
Resistance Assay will be performed at SV, T1, T2, T3, T7, T11, T15, T19, T23, EOT 
and TF visits 
 Note: PK sample for PRO 140 and Anti-idiotypic antibodies to PRO 140 will be 
performed at T1, T7, T15, EOT and TF visits 


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 Note: Serum concentration for ART will be performed at T1, T7, T15, visits, EOT and 
TF visits, as well as any Unscheduled Visit within the Treatment Phase as per 
discretion of the investigator. 
 
• Study Treatment Administration (PRO 140) 
• Injection Site Reaction Assessment (see section 7.14) 
 Note: To assess injection site reactions, the investigator will use the DAIDS AE 
grading table (refer to section 17.3). 
• Subject-perceived Injection Site Pain Assessment (see section 7.15) 
 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. 
4.2.3 End of Treatment (EOT) Visit 
The following assessments will be performed for subjects who do not experience treatment failure 
at any time during the Treatment Phase: 
• Assess for any Adverse Events and changes in Concomitant medications (see section 9 
and 7.5), 
• Complete Physical Examination (see section 7.7), 
• Vital Signs (see section 7.10), 
• Neurological Assessment (see section 7.9), 
• Subject-perceived Injection Site Pain Assessment (see section 7.15), 
• Collection of Blood Specimens (see section 7.11) for 
o Plasma HIV-1 RNA level 
o TruCount T Assay 
o Complete Blood Count 
o Biochemistry 
o Anti-idiotypic antibodies to PRO 140 
o PK sample for PRO 140 
o Serum Conc. of ART Drugs 


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4.2.4 Treatment Failure (TF) Visit 
Treatment failure is defined in terms of virologic non-response and virologic rebound in Part 2 of 
the Treatment Phase: 
(1) Virologic non-response is defined as two consecutive viral load results of: 
• <0.5 log10 copies/mL decrease in HIV-1 RNA at Day 7 of the Open-Label Treatment 
Period. [Assessment Timepoint:T3 visit] 
• <1 log10 copies/mL decrease in HIV-1 RNA at or after Week 4 of the Open-Label 
Treatment Period unless HIV-1 RNA <400 copies/mL. [Assessment Timepoint: from T6 
up to T25 visit] 
• Confirmed plasma HIV-1 RNA levels ≥400 copies/mL at Week 24 of the Open-Label 
Treatment Period. [Assessment Timepoint: T25 visit] 
(2) Virologic rebound is defined as two consecutive viral load results of: 
≥1.0 log10 copies/mL increase in plasma HIV-1 RNA above nadir level* in the Open- 
Label Treatment Period [Assessment Timepoint: from T3 up to T25 visit] or 
*Note: This refers to “Nadir” level in the Open-Label Treatment Phase which starts from 
T2 visit. 
• ≥400 copies/mL after suppression to <50 copies/mL in the Open-Label Treatment Period. 
[Assessment Timepoint: from T3 up to T25 visit] 
 
The following assessments will be performed for subjects who experience treatment failure at any 
time during the Treatment Phase: 
• Assess for any Adverse Events and changes in Concomitant medications (see section 9 
and 7.5), 
• Complete Physical Examination (see section 7.7), 
• Vital Signs (see section 7.10), 
• Neurological Assessment (see section 7.9), 
• Subject-perceived Injection Site Pain Assessment (see section 7.15), 
• Collection of Blood Specimens (see section 7.11) for 
o Plasma HIV-1 RNA level 
o TruCount T Assay 
o Complete Blood Count 
o Biochemistry 


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o HIV Drug Resistance Assay 
o HIV PhenoSense Entry® Assay 
o HIV Trofile® Assay 
o Anti-idiotypic antibodies to PRO 140 
o PK sample for PRO 140 
o Serum Conc. of ART drugs 
o Blood sample collection for Exploratory/Confirmatory analysis 
• Change in Optimized Background Therapy based on genotypic and phenotypic results 
obtained at TF visit. 
 
4.3 
FOLLOW-UP PHASE 
The duration of follow-up depends on whether subject experiences treatment failure. 
• Subjects who experience treatment failure within Open-Label Treatment Phase will be 
followed up every 4 weeks until viral suppression is achieved (i.e., plasma HIV-1 RNA 
levels below level of detection) or up to a maximum of 6 months after cessation of therapy 
if the treating physician does not feel that there is an antiretroviral regimen that will regain 
full viral suppression. 
• Subjects who do not experience treatment failure at the end of Open-Label Treatment 
Phase, will be followed up every 2 weeks for total of 4 weeks. 
4.3.1 Follow-Up Visits 
The following assessments will be performed at each follow-up visit, unless otherwise specified: 
• Assess for any Adverse Events and changes in Concomitant medications (see section 9 
and 7.5), 
• Symptom-directed physical examination (see section 7.7), 
• Vital Signs (see section 7.10), 
• Collection of Blood Specimens (see section 7.11) for 
o Plasma HIV-1 RNA level 
o TruCount T Assay 
o Anti-idiotypic antibodies to PRO 140 (only at Treatment Failure - FU1 and Non 
Treatment Failure - FU2) 


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4.4 
UNSCHEDULED VISITS 
In the event that the patient returns to clinic at a time other than a regularly scheduled study visit, 
the visit will be regarded as an unscheduled visit. Assessments at unscheduled visits are at the 
discretion of the Investigator. 


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5 
SUBJECT COMPLETION AND WITHDRAWAL 
 
5.1 
SUBJECT COMPLETION 
 
• A subject who completes the Open-Label Treatment Phase (without treatment failure) 
and 4-week Non-Treatment Failure Follow-Up Phase will be considered as having 
completed the study. 
• A subject who experiences treatment failure during the Treatment Phase, undergoes the 
Treatment Failure (TF) Visit assessments and is followed up until viral suppression is 
achieved or up to a maximum of 6 months after experiencing treatment failure if the 
treating physician does not feel that there is an antiretroviral regimen that will regain 
full viral suppression will be considered as having completed the study. 
 
5.2 
SUBJECT WITHDRAWAL 
 
A subject who enters the Treatment Phase but does not complete the study, as defined in Section 
5.1, is considered to have prematurely withdrawn from the Study. 
All subjects have the right to withdraw at any point during treatment without prejudice to future 
care. It will be documented whether or not each subject completed the clinical study. If for any 
subject, study treatment or observations were discontinued, the reason(s) will be recorded. 
The Investigator can discontinue a subject at any time if it is considered medically necessary. 
In addition, subjects WILL be withdrawn from the study, in consultation with the Medical 
Monitor and the Investigator, if any of the following are met: 
• A subject is significantly non-compliant with the requirements of the protocol. 
• The investigator determines that it is in the best interest of the subject. 
• Subject chooses to withdraw or is withdrawn due to an adverse event 
• A subject becomes pregnant 
Note: The pregnancy will be followed to term for safety follow-up. Relevant safety 
information collected after the study has completed will be reported as supplemental 
information. 
• Discontinuation of study by Sponsor 
Premature withdrawal from the study MAY occur if, in consultation with the Medical Monitor 
and the Investigator, any of the following are met: 
• A subject is treated with a prohibited medication. 


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• Major protocol violation 
 
5.2.1 Discontinuation of Study Treatment 
Discontinuation of study treatment (PRO 140) and continuation of HAART as per standard of 
care is recommended if: 
• Subject experiences treatment failure 
Defined in terms of virologic non-response and virologic rebound in the Open-Label 
Treatment Phase (Part 2) of the study: 
(1) Virologic non-response is defined as two consecutive viral load results of: 
• <0.5 log10 copies/mL decrease in HIV-1 RNA at Day 7 of the Open-Label 
Treatment Period. [Assessment Timepoint:T3 visit] 
• <1 log10 copies/mL decrease in HIV-1 RNA at or after Week 4 of the Open-Label 
Treatment Period unless HIV-1 RNA <400 copies/mL. [Assessment Timepoint: 
from T6 up to T25 visit] 
• Confirmed plasma HIV-1 RNA levels ≥400 copies/mL at Week 24 of the Open- 
Label Treatment Period. [Assessment Timepoint: T25 visit] 
(2) Virologic rebound is defined as two consecutive viral load results of: 
• ≥1.0 log10 copies/mL increase in plasma HIV-1 RNA above nadir level* in the 
Open-Label Treatment Period [Assessment Timepoint: from T3 up to T25 visit] or 
*Note: This refers to “Nadir” level in the Open-Label Treatment Phase which starts from T2 
visit 
• ≥400 copies/mL after suppression to <50 copies/mL in the Open-Label Treatment 
Period. [Assessment Timepoint: from T3 up to T25 visit] 
 
Note: Subjects will be allowed to continue PRO 140 with existing OBT regimen while 
waiting for new regimen to be constructed by the Investigator. 
 
• Develops AIDS-defining conditions as specified in Appendix I (Section 17.1) under which 
subject is unable to continue treatment with study drug (PRO 140), or subject require 
treatment with prohibited concomitant medications. 
• Shows signs or symptoms of clinically significant immunosuppression 
• Subject or the subject’s clinician wishes to adjust OBT (except in the event of toxicity 
management). 
• Subject becomes pregnant. 


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5.2.2 Data Collected for Withdrawn Subjects 
Patients may withdraw from the study or discontinue study treatment at any time; 
however, CytoDyn is dedicated to minimizing missing data in this study. It is therefore 
suggested that all patients, regardless of whether they continue to receive study treatment, 
continue within the study. 
Investigators considering discontinuing study treatment should contact the medical monitor 
prior to such discontinuation. Patients who have study treatment discontinued will continue 
to be followed, per protocol, whenever possible. Patients who have study treatment 
discontinued due to a serious adverse event will be followed until resolution or stabilization of 
the event. 
In the event that a subject is withdrawn from the study at any time due to an adverse event or 
serious adverse event (SAE), the procedures stated in Section 9.1.1 or 9.3, respectively must be 
followed. 
Every attempt should be made to collect follow-up information. The reason for withdrawal from 
the study will be recorded in the source documents and on the appropriate page of the eCRF. 
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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The pharmacy manual provides the criteria regarding vial acceptance or rejection, as well as 
instructions for the preparation of the IP syringes to be used to administer drug. 
 
6.3 
INVESTIGATIONAL PRODUCT STORAGE 
Study drug will be shipped at 2°C to 8°C (refrigerated [36°F to 46°F]) to the investigator’s site. 
Upon receipt at the site, the responsible site staff or pharmacist should verify the integrity of the 
vials. Study drug should be stored at 2°C to 8°C (refrigerated [36°F to 46°F]). The contents of the 
vial should appear as a clear to opalescent, colorless to yellow solution; fine translucent particles 
may be present. This is normal. 
The investigator must maintain an accurate record of the shipment, storage, and dispensing of the 
study drug in a drug accountability log. An accurate record including the date and amount of 
study drug dispensed 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 or placebo will be provided to the administering personnel in single-use syringes 
prepared from vials of study drug stored at 2-8°C at the site pharmacy prior to use. Each of two 
syringes is filled to deliver 1.0 mL of study drug. 
Equivalent volumes of study drug will be administered subcutaneously on opposite sides of the 
abdomen. 
A 25-guage needle should be used to remove IP from vial and for administration to subjects. 
IP should be administered slowly over 15 seconds per mL. IP should not be kept in syringe for 
longer than 60 minutes. 
Following each SC delivery of drug, careful examination will be made to assess the appearance of 
any study drug Injection Site Reactions (ISRs) as described in Section 17.3. 
All doses of study drug will be prepared by either the credentialed pharmacist or qualified 
medical professional and will be administered as SC injection by a qualified medical professional 
(MD, DO, PA, LPN, LVN, NP, or RN) or self-administered by subjects depending on the study 
visit week. 
Note: It is preferred that the same injection site be used throughout the study. At the same time, it 
is not recommended to inject the study drug into areas where skin shows signs of a previous 


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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 
includes each quantity dispensed, identification of the staff member/subject to whom dispensed, 
the date of dispensing, the intended study participant, and the identification of the preparer. All 
used and unused study kits will be retained by the investigational site until drug accountability 
can be confirmed by study CRA during the monitoring visits. Instructions will be provided by 
Sponsor regarding final disposition of all study drug in compliance with applicable regulations. 
 
6.6 
INVESTIGATIONAL PRODUCT DISPOSITION 
All drug supplies are to be used only for this protocol and not for any other purpose. The 
investigator must not destroy any drug labels or any partially used or unused drug supply until 
instructed by the Sponsor. At the conclusion of the study and as appropriate during the course of 
the study, the investigator will return all used and unused drug containers and drug labels to the 
drug distributor as directed by the Sponsor. A copy of the completed drug disposition form will be 
sent to CytoDyn, Inc. or to its designee. 


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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 T1 Visit (prior to treatment administration), the Investigator 
must assess a subject’s continued suitability and eligibility for the trial. The Inclusion and 
Exclusion criteria of this Protocol are described in Sections 3.3.1 and 3.3.2. If the subject is not 
suitable or eligible for the trial then the subject will be a screen failure. 
 
7.3 
DEMOGRAPHIC INFORMATION 
For the purposes of this study, demographic information will include: 
• Dates of ICF signature 
• Date of birth 
• Gender 
• Race (American Indian/Alaskan Native, Asian, Black/African American, Native 
Hawaiian/Pacific Islander, Caucasian, or other) 
• 
Ethnicity (Hispanic/Latino or Not Hispanic/Latino) 
 
7.4 
MEDICAL HISTORY 
A medical history will be recorded during the Screening Phase and will include: 


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• All ongoing medical conditions 
• Disease history (HIV), history of substance abuse, social history, blood transfusion history 
and any past surgeries 
• All previously resolved medical conditions related to HIV or which are relevant in the 
judgment of the Investigator 
• Any prior medical conditions that have resolved within the last year 
Events that emerge prior to the first treatment (T1) will be recorded in the medical history and not 
as AEs. Aside from being used to determine subject eligibility, this information will permit the 
Investigator to record the nature, duration and severity of any ongoing baseline medical 
conditions prior to the patient’s receiving investigational product (IP) treatment. 
Medical histories will be recorded using the body system categories outlined below: 
• Cardiovascular 
• 
Lymphatic 
• Respiratory 
• 
Hematologic 
• Gastrointestinal 
• 
Immunologic 
• Renal 
• 
Dermatologic 
• Hepatic 
• 
Psychiatric 
• Neurological 
• 
Genitourinary 
• Endocrine 
• 
Other 
 
For each relevant history, the following will be documented: 
• Disease/disorder/condition 
• Date of diagnosis 
• History status (resolved or ongoing) 
 
7.5 
HIV HISTORY 
A detailed HIV history will be recorded during the Screening Phase and will include: 
• Date of diagnosis 
• Most recent viral load and CD4 count 
• Nadir CD4 and peak viral load, if known 
• ART-related history 


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o Current and previous ART regimens 
o Date of initiation of ART 
o Reasons for changes in ART 
o Previous adverse drug reactions, including hypersensitivity reactions to prior 
therapies 
o Challenges with adherence to therapy 
o History of drug resistance, if known 
o Opportunistic infections, malignancies, and previous adverse reactions to drugs 
used for opportunistic infections prophylaxis 
 
7.6 
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 
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 


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prescribed. If concomitant medications are started during the study, the indication for the 
concomitant medication should be considered an AE. 
7.6.1 Excluded Medications and Therapies 
1. Use of Maraviroc or any other CCR5 antagonist 
2. Use of oral or parenteral corticosteroids (>5 mg/day) is NOT allowed during the study, with 
the following exceptions: 
o Use of chronic systemic corticosteroids at replacement doses (e.g., < 5mg/day prednisone) 
AND use of inhaled, nasal, or topical steroids are allowed. 
o Use of short course of systemic corticosteroids (Medrol pack) after T2 will only be 
allowed with prior approval from the sponsor. 
3. Use of radiation or cytotoxic chemotherapy, immunosuppressants and immunomodulating 
agents (e.g., interleukins, interferons) or agents with known anti-HIV activity (i.e., 
hydroxyurea, foscarnet) are NOT allowed during the study. 
4. Use of any non-FDA approved/investigational therapy 
 
7.6.2 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. 
 
7.7 
PHYSICAL EXAMINATION 
The complete physical examination will include routine examinations for the following: 
• General Appearance 
• Head, Ears, Eyes, Nose, Throat (HEENT) 
• Lymph Nodes 
• Heart/Cardiovascular abnormalities 
• Respiratory 
• Abdomen 
• Genitourinary 
• Musculoskeletal and Extremities 
• Neurologic abnormalities Dermatologic abnormalities 


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• 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 Screening Visit (SV), End of 
Treatment (EOT) Visit, and at Treatment Failure (TF) Visit. Only symptom-directed physical 
examination will be performed at treatment and follow-up visits conducted within the clinic, and 
at unscheduled visits within the Treatment and Follow-up Phases. 
 
7.8 
ELECTROCARDIOGRAM 
A 12-lead ECG will be conducted at the Screening Visit (SV) results will be evaluated by the 
Investigator. The following parameters will be recorded: ventricular rate (beats per minute), PR 
interval (msec), QRS interval (msec), QT interval (msec), and QTc interval (msec). Additionally, 
the investigator will record the overall results of the ECG reading as either normal or abnormal, 
and as either not clinically significant or clinically significant. If abnormalities are observed, each 
will be recorded. 
 
7.9 
NEUROLOGICAL ASSESSMENT 
Neurological assessment will be performed by the Principal Investigator (or delegated personnel) 
or a Neurologist at Treatment Visits 1, 3, 7, 11, 15, 19 and 23 (T1, T3, T7, T11, T15, T19, T23), 
End of Treatment (EOT) and at Treatment Failure (TF) Visit. 
The neurological assessment tool is based on the three question survey used by Simioni et al. 
[Simioni S, 2010]. Refer to section 17.4 for further details. Additional assessment modalities can 
be used for further assessment as per Investigator’s discretion. 
 
7.10 VITAL SIGNS (INC. HEIGHT AND WEIGHT) 
Vital signs will be collected at all study visits performed at the clinic. Vital signs collected during 
the Treatment Phase will be performed post-treatment, assessed within 15 minutes following 
study treatment administration. 
The following vital signs will be collected at all visits, unless otherwise stated: 
• Height (at Screening Visit) 
• Weight (at SV, EOT and TF visits) 
• BMI (derived from the height and weight measurements; at SV, EOT and TF visits) 


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• Seated blood pressure (taken after the subject has been seated for at least 5 minutes) 
• Heart Rate 
• Respiration Rate 
• Temperature 
 
7.11 CLINICAL LABORATORY ASSESSMENTS 
Blood and urine samples will be collected according to the time points in the schedule of 
assessments for analysis of the following parameters: 
7.11.1 Routine CBC 
• Frequency of testing: At Screening Visit, End of Treatment Phase Visit or Treatment 
Failure Visit 
• Includes hemoglobin, hematocrit (HCT), red blood cell (RBC) count, white blood cell 
(WBC) count, WBC differential count (%), absolute neutrophils count and platelets count. 
7.11.2 Biochemistry 
• Frequency of testing: At Screening Visit, End of Treatment Phase Visit or Treatment 
Failure Visit 
• Biochemistry profile includes assessment of 
Hepatic function indicators: total and direct bilirubin, alkaline phosphatase, aspartate 
aminotransferase (AST), alanine aminotransferase (ALT), total protein, LDH 
Renal function indicators: BUN, creatinine 
Electrolytes: sodium, potassium, chloride, calcium and bicarbonate 
Other: glucose (random), cholesterol (total) 
7.11.3 PK sample for PRO 140 
 Frequency of testing: At the T1, T7, T15, EOT and TF visits. 
 
7.11.4 Anti-idiotypic antibodies to PRO 140 
• Frequency of sample collection*: At the T1, T7, T15, EOT and TF visits in addition to 
Treatment Failure Follow-up Visit 1 (TF-FU1) and Non-Treatment Failure Follow-up 
Visit 2 (NTF-FU2) 
*Note: Sera will be collected from study subjects and stored at -80oC for future analysis. 


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7.11.5 Serum pregnancy test 
• Frequency of testing: At 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. 
7.11.6 Urine pregnancy test 
• Frequency of testing: At Treatment Visit 1 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. 
7.11.7 Plasma HIV-1 RNA level and TruCount T Assay 
• Frequency of testing: At SV, Treatment Visits 1, 2, 3, 7, 11, 15, 19 and 23, as well as EOT 
and TF visits. In addition, blood sample will also be collected at all Treatment Failure 
Follow-up (TF-FU) Visits or Non-Treatment Failure Follow-up (NTF-FU) 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% 
7.11.8 HIV-1 Trofile® Assay 
• Includes: 
a. Trofile® RNA Assay 
b. Trofile® DNA Assay 
Trofile® RNA is the primary assay used to assess HIV-1 co-receptor tropism status. 
However, Trofile® DNA can be used at the discretion of the Investigator when last 
recorded viral load is less than 1000 copies/mL. 
• 
Frequency of testing: At SV and TF visits 
 
7.11.9 HIV-1 Drug Resistance Assay 
• Includes: 
a. PhenoSense® GT 


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b. PhenoSense Integrase and GeneSeq Integrase testing 
PhenoSense® GT is a combination resistance test for three classes of antiretroviral drugs 
(i.e., nucleoside/nucleotide, non-nucleoside, and protease inhibitors), that provides both 
phenotypic and genotypic results from the same blood sample (viral load ≥500 copies/ml). 
PhenoSense Integrase and GeneSeq Integrase testing will be additionally performed if 
subject has past exposure to an integrase or in cases where complex drug resistance 
patterns is known or suspected. 
• Frequency of sample collection: At SV, T1, T2, T3, T7, T11, T15, T19, T23 and TF 
Samples for PhenoSense® GT (and PhenoSense Integrase and GeneSeq Integrase testing, 
if collected) during visits T1, T2, T3, T7, T11, T15, T19, and T23 will be stored at Lab and 
will be analyzed only if subject experiences Treatment Failure. 
7.11.10 HIV-1 PhenoSense® Entry assay 
• Frequency of testing: At SV and TF visits 
• With AMD3100 (CXCR4 inhibitor drug), Maraviroc and PRO 140 (CCR5 inhibitor 
drugs). 
7.11.11 Serum Concentration of ART drugs 
• Frequency of sample collection: At Treatment Visits 1, 7, 15, EOT and TF. 
• Sample collected at T1 visit is to identify serum concentration for ART drugs (failing 
regimen) at the time of first study dose while sample collected at T7, T15, EOT and TF 
visit is to confirm subject compliance to OBT regimen during Part 2 of the Treatment 
Phase. 
7.11.12 Blood sample collection for Exploratory/Confirmatory analysis 
• Includes: 
a. HIV-1 Coreceptor Tropism with Reflex to Ultradeep Sequencing or 
b. HIV-1 Proviral Tropism 
The Quest Diagnostics HIV-1 coreceptor tropism test begins with standard Sanger 
sequencing of the third variable (V3) loop of the HIV-1 gene, the primary determinant of 
viral tropism. The next-generation DNA sequencing (ultradeep sequencing [UDS]) is 
performed if standard sequencing detects only CCR5 virus. HIV-1 Coreceptor Tropism, 
Proviral DNA test is used when the plasma viral load is <1000 copies/mL. 
• Frequency of testing: At SV and TF visits 


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7.11.13 Urinalysis 
• Frequency of testing: At the Screening Visit 
• Urine samples will be tested for color, appearance, specific gravity, pH, protein, glucose, 
occult blood, ketones, leukocyte esterase, nitrite, bilirubin, urobilinogen, and microscopic 
examination of urine sediment 
All laboratory reports will be reviewed by the Investigator. 
Post-treatment abnormal results that are considered by the Investigator to be clinically significant 
will be recorded as adverse events. If the Investigator judges it necessary, testing may be repeated 
in order to make the determination of clinical significance. Validated, quality-controlled 
laboratory data will be transferred to the main database for analyses. 
 
7.12 RANDOMIZATION 
Subjects who are eligible to participate in the trial will be randomized to one of the treatment 
groups via IWRS (Interactive Web Based Randomization System) at the T1 Visit prior to IP 
administration. The randomization will be central and will use mixed block size of 2 and 4 with a 
1:1 ratio of Active Treatment to Control Treatment to ensure even distribution of Active and 
Control subjects. 
Prior to randomization, subjects will be stratified based on degree of ART drug resistance as 
follows: 
• Resistance to ART drugs within three drug classes. 
• Resistance to ART drugs within two drug classes with limited treatment option. 
Centers will be limited to a maximum enrollment of 10 randomized subjects, unless the site is 
audited and passes the audit. This ceiling is imposed to ensure that the data from a single center 
does not unduly influence the outcome of the efficacy analysis. 
 
7.13 INVESTIGATIONAL PRODUCT ADMINISTRATION 
Refer to Section 6.4 for details. 
 
7.14 INJECTION SITE REACTION ASSESSMENT 
At each treatment visit that occurs at the clinical site, an injection site reaction assessment will be 
made for the current and previous injection sites. Injection site reaction assessments are recorded 
by the Investigator (or designee) starting after the first injection is given. Refer to sections 9.1.8 
and 17.3 for more details. 


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7.15 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). 
This assessment will be performed each time subjects arrive to the clinic for the study visit. 
Beginning at Treatment Visit 2, 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. 
 
 
Figure 7-1:  Visual Analog Scale 
 


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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 comparator study, PRO 140 versus placebo. All eligible subjects will receive a single 
dose of study treatment [PRO 140 or placebo SC injection] within 6 weeks of Screening Visit, 
followed by PRO 140 as a 350 mg subcutaneous injection weekly for up to 24 weeks. 
 
8.2 
DESCRIPTION OF STUDY ENDPOINTS 
8.2.1 Primary Efficacy Endpoints 
The primary efficacy endpoint for this study is proportion of participants with a ≥ 0.5 log10 
reduction in HIV-1 RNA viral load from baseline at the end of the 1-week double-blind treatment 
period. 
8.2.2 Secondary Efficacy Endpoints 
There are multiple secondary endpoints to be assessed in this study, to maintain the trial-wise 
Type I error rate at 0.05, a closed test procedure will be used for the secondary endpoints. The 
order of the endpoints will be as follows: 
1. Proportion of participants with ≥ 0.5 log10 reduction in HIV-1 RNA viral load from 
baseline at the end of the 1-week double-blind treatment period, stratified to each group: 
a. resistance to ART drugs within three drug classes, 
b. resistance to ART drugs within two drug classes with limited treatment option. 
2. Proportion of participants with ≥ 1 log10 reduction in HIV-1 RNA viral load from baseline 
at the end of the 1-week double-blind treatment period for all patients and within each 
stratum 
3. Mean change from Baseline in HIV-1 RNA levels (log10 copies/mL) at the end of the 1- 
week double-blind treatment period for all patients and within each stratum 
4. Percentage of participants achieving HIV-1 RNA < 400 copies/mL at week 25 for all 
patients and within each stratum 
5. Percentage of participants achieving HIV-1 RNA < 50 copies/mL at week 25 for all 
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6. Mean change from Baseline in HIV-1 RNA levels (log10 copies/mL) at week 25 for all 
patients and within each stratum 
7. Mean change from Baseline in CD4 cell count at the end of the 1-week double-blind 
treatment period for all patients and within each stratum 
8. Mean change from Baseline in CD4 cell count at week 25 for all patients and within each 
stratum 
8.2.3 Safety Assessments 
Safety measurements will include: 
• Emergence of Dual/Mixed (D/M)- and CXCR4-tropic virus in patients who had exclusive 
CCR5-tropic virus at study entry. 
• Tolerability of repeated subcutaneous administration of PRO 140 as assessed by study 
participants (using Visual Analogue Scale) and by investigator-evaluation of injection site 
reactions. 
• Frequency of treatment-related adverse events resulting in study drug discontinuation 
• Frequency of Grade 3 or 4 adverse events as defined by the DAIDS Adverse Event scale 
• Frequency of treatment–emergent serious adverse events 
 
8.3 
SAMPLE SIZE DETERMINATION AND RATIONALE 
For this two arm clinical trial, it is planned to have a total of 50 subjects (25 per treatment group) 
randomized and complete the clinical trial. 
The nQuery 6.01 is used for this sample size calculation. The sample size calculation is based on 
the assumption that the proportion of participants with ≥ 0.5 log10 reduction in HIV-1 RNA viral 
load from baseline at Week 1 during the double-blind treatment period is 90% for the PRO 140 
group vs 35% for the Placebo group. 
Note: Response rate of 90% is estimated for the PRO 140 group on the basis of results from 
PRO140 2101 study wherein 90% of participants with CCR5-tropic virus achieved ≥ 0.5 log10 
reduction in HIV-1 RNA viral load in one week from baseline. 
Under the above assumptions, 25 subjects per treatment group will be required to meet the Type I 
error rate of 0.05 and more than 90% power; for a total of 50 subjects for the clinical trial. 
 
8.4 
RANDOMIZATION AND BLINDING 
This trial is a two part treatment phase study with a one-week randomized, double-blind, placebo- 
controlled period, followed by a 24-week open label, single arm treatment period. 


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Randomization will be conducted via a Web based system, and the process for the blinding 
requirements will be outlined in the study randomization plan. Resistance to ART drugs at the 
time of randomization will be used as a stratification factor to ensure balance between each 
treatment group in this stratum. 
 
8.5 
INTERIM ANALYSIS 
An efficacy Interim Analysis (IA) will be conducted when 40 randomized subjects complete the 
1-week randomized part of the study or early terminated, whichever comes first. The main 
purpose of this efficacy IA is to conduct a sample size re-estimation based on the double blind 
data. 
In addition there will be a regular safety review for the trial from the beginning and at 
approximately six month intervals thereafter, based on enrollment. The safety review includes 
data for AEs, SAEs, labs, ECGs, vital signs, and all other safety related variables identified per 
the DMC Charter. No inferential statistics will be conducted for the safety interim analysis 
tabulation of the data. 
All the interim data will be monitored by an independent DMC to ensure patient safety and to 
assess efficacy. 
To protect the integrity of the blinded data, the IA will be conducted based on a Standard 
Operating Procedure for Interim Analysis that has a well-established firewall to protect the 
integrity of the trial. The details of the IA, including the below bullet points, are included in the 
Statistical Analysis Plan (SAP) for the study. 
• The goals of the IA 
• IA procedures for data preparation 
• IA procedures conduct of the analysis 
• Data to be shared with the DMC 
• Information to be shared with the sponsor after the IA 
• The stopping rule 
• Protection of Type I error rate and adjustments 
 
8.6 
GENERAL STATISTICAL CONSIDERATIONS 
8.6.1 Analysis Populations 
8.6.1.1 Intent-to-Treat Population 
The Intent-to-Treat (ITT) population is defined as the set of subjects who are randomized and 
have received at least one dose of PRO 140 or placebo. 


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Subjects who discontinue from the study prior to their first post-baseline assessment will be 
included in the ITT population and analyzed as non-responders in the primary efficacy analysis. 
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 or 
placebo after randomization. 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 
including details of appropriate statistical tests to examine underlying assumptions. 
8.6.3 Prognostic Factors/Covariates 
There are no pre-planned covariates analyses of the data from this study. 
 
8.6.4 Handling of Missing Data 
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 population of the primary and secondary endpoints. 
 
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 ITT population. 
The primary efficacy endpoint for this study is proportion of participants with a ≥ 0.5 log10 or 
greater reduction in HIV-1 RNA viral load from baseline at the end of the 1-week double-blind 
treatment period. 
Logit model will be used to compare the primary endpoint between the treatment groups. The 
details will be presented in the Statistical Analysis Plan (SAP). 
The secondary efficacy endpoints are: 
• Proportion of participants with ≥ 0.5 log10 reduction in HIV-1 RNA viral load from 
baseline at the end of the 1-week double-blind treatment period, stratified to each group: 
a. resistance to ART drugs within three drug classes 
b. resistance to ART drugs within two drug classes with limited treatment option. 
• Proportion of participants with ≥ 1 log10 reduction in HIV-1 RNA viral load from baseline 
at the end of the 1-week double-blind treatment period for all patients and within each 
stratum 
• Mean change from Baseline in HIV-1 RNA levels (log10 copies/mL) at the end of the 1- 
week double-blind treatment period for all patients and within each stratum 
• Percentage of participants achieving HIV-1 RNA < 400 copies/mL at week 25 for all 
patients and within each stratum. (The lower 95% confidence interval will be at least 85%) 
• Percentage of participants achieving HIV-1 RNA < 50 copies/mL at week 25 for all 
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• Mean change from Baseline in HIV-1 RNA levels (log10 copies/mL) at week 25 for all 
patients and within each stratum 
• Mean change from Baseline in CD4 cell count at the end of the 1-week double-blind 
treatment period for all patients and within each stratum 
• Mean change from Baseline in CD4 cell count at week 25 for all patients and within each 
stratum 
All data from the secondary endpoints will be summarized and tabulated according to the variable 
type: 
• Continuous data summaries will include: 
o Number of observations, mean, standard deviation, median, and minimum and 
maximum values. 
o Analysis of Covariance (ANCOVA) will be used for between group comparisons, if 
Normality assumption is not met non-parametric methods (e.g., Wilcoxon test) will be 
considered. 
o Paired t-test will be used for within group comparisons; if Normality assumption is not 
met Wilcoxon signed rank sum test will be used. 
• Categorical data summaries will include: 
o Frequency counts and percentages. 
o Logit model will be used for inferential statistics. 
8.7.4.2 Supportive Analysis 
To assess the consistency of the Primary Analysis results, supportive analysis will be conducted 
using the PP 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 assessments. 
For continuous variables data will be summarized using n, mean, Standard Deviation (SD), 
minimum and maximum values. For categorical variables data will be summarized using 
frequency and percentage. 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: 


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• 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. 
 
8.7.5.7 Neurological Assessment 
All neurological assessment findings will be listed and any abnormality will be summarized. 


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9 
ADVERSE EVENTS (DEFINITIONS AND REPORTING) 
The Investigator is responsible for the detection and documentation of events meeting the criteria 
and definition of an AE or SAE, as provided in this protocol. During the study when there is a 
safety evaluation, the Investigator or site staff will be responsible for detecting, documenting, and 
reporting AEs and SAEs as detailed in this section of the protocol. 
 
9.1 
ADVERSE EVENT 
An adverse event (AE) is defined as any unfavorable or unintended sign, symptom, or disease that 
occurs or is reported by the subject to have occurred, or a worsening of a pre-existing condition. 
An AE may or may not be related to the study treatment. 
AEs will be elicited through direct questioning and subject reports. Any abnormalities in visit 
evaluations, physical examination findings or laboratory results that the Investigator believes are 
clinically significant to the research subject and that occurred after initiation of the first study 
treatment will be reported as AEs. Abnormal findings that are NOT clinically significant (NCS) 
should not be recorded as an AE. 
9.1.1 Reporting of Adverse Events 
Report initiation for all AEs and SAEs will begin at the time of the first treatment visit and 
continue up until the final study visit (i.e. up to NTF-FU2 for subject who do not experience 
virologic failure or until viral suppression is achieved for subjects who experience virologic 
failure). All events will be followed to resolution or until 30 days after the subject completes the 
study. A final assessment of outcome will be made at that time. 
All AEs must be recorded in the subject’s medical records and on the eCRFs. AEs will be 
reported using customary medical terminology along with the following information: the onset 
and end dates, whether the event is considered to be a SAE (see Section 9.2), the impact the event 
had on study treatment (see Section 9.1.2 ), the DAIDS AE grade (intensity) of the event (see 
Section 9.1.3), the causality of the event (see Section 9.1.4), whether treatment was given as a 
result of the event (see Section 9.1.5), and the outcome of the event (see Section 9.1.6). 
9.1.2 Impact of Study Treatment 
The impact the event had on the study treatment will be assessed as either: none, study treatment 
interrupted, study treatment discontinued, or not applicable. The “not applicable” assessment will 
be used only when the subject is no longer in the treatment phase of the protocol, or if the 
outcome of the event was “death”. 
9.1.3 DAIDS AE Grade (Severity) Assessment 




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known response pattern to treatment with the study treatment. 
3. Possibly related: This category applies to those AEs which, after careful medical 
consideration at the time they are evaluated, are judged unlikely but cannot be ruled out 
with certainty to the study treatment. An AE may be considered possible if or when (must 
have two): (1) it follows a reasonable temporal sequence from administration of the study 
treatment. (2) It could not readily have been produced by subject’s clinical state, 
environmental or toxic factors, or other therapies administered to the subject. (3) 
Disappears or is decreased upon discontinuation of the study treatment. (4) It follows a 
known response pattern to treatment with the study treatment. 
4. Remotely related: In general this category can be considered applicable to those AEs 
which, after careful medical consideration at the time they are evaluated, are judged likely 
to be unrelated to the study treatment. An AE may be considered unlikely if or when (must 
have two): (1) it does not follow a reasonable temporal sequence from administration of 
the study treatment. (2) It could not readily have been produced by subject’s clinical state, 
environmental or toxic factors, or other therapies administered to the subject. (3) 
Disappears or is decreased upon discontinuation of the study treatment. (4) It does not 
follow a known response pattern to treatment with the study treatment. 
5. Unrelated: This category applies to those AEs which, after careful consideration at the 
time they are evaluated, are clearly and incontrovertibly due to extraneous causes (disease, 
environment, etc.) and determined with certainty to have no relationship to the study 
treatment. 
9.1.5 Treatment Given as a Result of the Event 
The event impact in terms of treatment provided will be as either: none, medication administered, 
non-medication therapy administered, surgery, or other (with a specification). 
9.1.6 Outcome Assessment 
The outcome of the event will be assessed as either: resolved, resolved with sequelae, ongoing, or 
death. Only one AE per subject is allowed to have an outcome assessment as “death.” If there are 
multiple causes of death for a given subject, only the primary cause of death will have an outcome 
of death. 
9.1.7 Expected / Anticipated Adverse Events 
The most common potential study drug-related adverse reaction reported is mild headache. Other 
adverse events likely to be related to the drug include mild to moderate diarrhea, nausea, and 
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9.1.8 SC Injection-related Events 
SC and IV injections of concentrated protein materials can be associated with injection-related 
AEs that impact the ability to safely and successfully deliver the drug. Local injection-site 
reactions may include pain/discomfort, induration, erythema, nodules/cysts, pruritus, ecchymosis, 
etc. For SC injections, bleeding, absorption of the drug, leakage of drug, and induration at the 
local injection site can be additional complications. Other AEs that are common to monoclonal 
antibody-based therapies are chills, headache, backache, malaise, fever, pruritus, rash, nausea, 
tingling, and hypertension. 
SC injection-related events will be monitored according to the guidelines provided in Section 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) 
 
• Requires subject hospitalization or prolongs existing hospitalization 
 
• Results in persistent or significant disability/incapacity 
 
• Is a congenital anomaly/birth defect 


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Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered a serious adverse event when, based upon appropriate medical 
judgment, they may jeopardize the subject and may require medical or surgical intervention to 
prevent one of the outcomes listed in this definition. 
If a pregnancy occurs in a subject or partner of a male subject during a clinical study this must 
also be reported to CytoDyn, Inc. The Investigator should discuss the case with the Medical 
Monitor. Any pregnant subject must be followed up by the Investigator or designee until the child 
is born. Any AEs of the subject during pregnancy, that meets serious criteria, must be 
documented and reported CytoDyn, Inc. Participants who become pregnant will be entered into 
the Antiretroviral Pregnancy Registry (http://www.apregistry.com). 
 
9.3 
REPORTING OF SERIOUS ADVERSE EVENTS 
The Investigator is required to report all SAEs that occur during the time period specified in 
Section 9.1.1. Once the Investigator becomes aware of an SAE, he/she must report the SAE to 
Safety Department within 24 hours: 
 
The 
Medical Monitor may request additional supporting documentation as it becomes 
available, such as lab reports, ECG reports, discharge summary, hospital notes, etc. 
The Investigator is also responsible for reporting all SAEs to the appropriate Institutional Review 
Board (IRB) in accordance with local laws and regulations. The Investigator is responsible for 
maintaining documentation in the study file that indicates the IRB has been properly notified. 
Under 21 CFR 312.32(c), the sponsor is required to notify FDA and all participating investigators 
in an IND safety report (i.e., 7- or 15-day expedited report) of potentially serious risks from 
clinical trials or any other source as soon as possible, but no later than 15 calendar days after the 
sponsor receives the safety information and determines that the information qualifies for 
reporting. Participating investigators include all investigators to whom the sponsor is providing 
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9.3.1 SAE Follow-Up 
All subjects experiencing an SAE, including the discontinued subjects, must be closely followed 
until sufficient information is obtained to indicate a return to normal status or until the event 
stabilizes at a level acceptable to the investigator (i.e., recovery, return to baseline status, no 
further improvement expected, or death). 
For each SAE indicated as an unresolved event on the initial report, regardless of whether the 
subject completed the study or withdrew, the site should submit a follow-up report with updated 
information. 


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10 DIRECT ACCESS TO SOURCE DATA/DOCUMENTATION 
Subjects will be identified on eCRFs by a unique subject identification number and on source 
documents by name and date of birth. No personal identifier will be used in any publication or 
communication used to support this research study. The subject identification number will be 
used if it becomes necessary to identify data specific to a single subject. 
The monitors, auditors, personnel authorized by the Sponsor, the local IRB, and the FDA are 
eligible to review medical and research records related to this study as a part of their 
responsibility to protect human subjects in clinical research and will be given direct access to 
source data and documentation (e.g., medical charts/records, printouts etc.) for source data 
verification, provided that subject confidentiality is maintained in accordance with local 
requirements. Access to electronic medical records may be governed by institution policy and 
each site will be required to ensure access while remaining compliant with institutional 
requirements. 


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11 QUALITY CONTROL AND QUALITY ASSURANCE 
 
11.1 MONITORING REQUIREMENTS 
In an effort to fulfill the obligations outlined in 21 Code of Federal Regulations (CFR) Part 312 
and ICH guidelines which requires the Sponsor to maintain current personal knowledge of the 
progress of a study, the Sponsor's designated monitor will visit the center(s) during the study as 
well as maintain frequent telephone and written communication. The Investigator will permit the 
Sponsor to monitor the study as frequently as is deemed necessary and provide access to medical 
records to ensure that data are being recorded adequately, that data are verifiable and that protocol 
adherence is satisfactory. 
The Investigator will permit representatives of the Sponsor and/or designated CRO to inspect all 
eCRFs and corresponding study subject original medical records (source documents) at regular 
intervals throughout the study. Subject original medical records and other relevant data must be 
available to support all data recorded in the eCRF. In addition to the original medical records, 
these data may include but are not limited to, study, laboratory and diagnostic reports, 
neurological examination results, etc. 
Site inspections serve to verify strict adherence to the protocol and the accuracy of the data being 
entered on the case report forms, in accordance with federal regulations. A Monitoring Log will 
be maintained at each study site which the monitor will sign, date and state the type of visit. 
The Investigator should be aware that the study site and subject records may be inspected by the 
Sponsor and or representatives of the designated CRO, FDA or other regional regulatory 
authority. 
For the IA, a cut-off date for data collection and monitoring will be determined and sites will be 
requested to provide current information up to the cut-off date. 
11.2 ACCEPTABILITY OF CASE REPORT FORMS (CRFS) 
Electronic CRFs must be completed for each subject who has signed an informed consent form. 
For subjects who are screen failures, this would be limited to the screen failure eCRF page. All 
source documents and eCRFs will be completed as soon as possible after the subject's visit. 
Corrections to data on the eCRFs will be documented. The Investigator will review eCRFs to 
indicate that, to his/her knowledge, they are complete and accurate. Electronic CRFs will be 
reviewed by the Sponsor’s or designated CRO’s monitor, who will make a decision as to their 
acceptability. 


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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. 
The DMC will monitor the safety of the trial from the beginning and at approximately six month 
intervals thereafter based on enrollment. The DMC will also assess the study for futility once all 
the randomized subjects complete the 1-week randomized part of the study or early terminated, 
whichever comes first. The DMC will consist of at least three independent members (including 
clinicians with expertise in HIV disease, a neurologist or psychiatrist and at least one 
biostatistician) and will review all safety signals including number of virologic non-response 
and virologic rebounds, unexpected AEs, all related AEs, all SAEs, and all deaths during the 
Treatment and Follow-Up Phases. 
All expedited safety reports will be provided in real time to the DMC chair upon being reported 
to FDA. At each meeting, the DMC will be authorized to unblind the study upon unanimous 
vote in the event of any concerns about safety or lack of efficacy. Unblinded CRO personnel, 
separate and independent of the blinded CRO personnel, will supply the DMC with all 
necessary tables and listings to perform their independent review. 
The Sponsor will be invited to attend open sessions where data remain blinded, but will not attend 
closed sessions where data are discussed in more detail with potential unblinding. The DMC will 
make the following recommendations at each 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 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. 


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


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


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16 REFERENCES 
Demeter LM Shafer RW, Meehan PM, Holden-Wiltse J, Fischl MA, Freimuth WW, Para 
MF, Reichman RC. Delavirdine susceptibilities and associated reverse transcriptase mutations in 
human immunodeficiency virus type 1 isolates from patients in a phase I/II trial of delavirdine 
monotherapy (ACTG 260). Antimicrob.Agents Chemother.. - 2000. - Vol. 44. - pp. 794-797. 
Gulick RM Lalezari J, Goodrich J, Clumeck N, DeJesus E, Horban A, Nadler J, Clotet B, 
Karlsson A, Wohlfeiler M, Montana JB, McHale M, Sullivan J, Ridgway C, Felstead S, 
Dunne MW, van der Ryst E, Mayer H. Maraviroc for Previously Treated Patients with R5 
HIV-1 Infection NEJM. - October 2, 2008. - Vol. 359 : 14. - pp. 1429-1441. 
Jacobson JM Lalezari JP, Thompson MA, Fichtenbaum CJ, Saag MS, Zingman BS, 
D'Ambrosio P, Stambler N, Rotshteyn Y, Marozsan AJ, Maddon PJ, Morris SA, Olson WC. 
study of the CCR5 monoclonal antibody PRO 140 administered intravenously to HIV-infected 
adults. Antimicrob Agents Chemother.. - 2010. - Vol. 54. - pp. 4137-42.. 
Jacobson JM Saag MS, Thompson MA, Fischl MA, Liporace R, Reichman RC, Redfield 
RR, Fichtenbaum CJ, Zingman BS, Patel MC, Murga JD, Pemrick SM, D'Ambrosio P, 
Michael M, Kroger H, Ly H, Rotshteyn Y, Buice R, Morris SA, Stavola JJ, Maddon PJ, 
Kremer AB, Ols Antiviral activity of single-dose PRO 140, a CCR5 monoclonal antibody, in 
HIV-infected adults. J Infect Dis.. - 2008. - Vol. 198. - pp. 1345-52.. 
Jacobson JM Thompson MA, Lalezari JP, Saag MS, Zingman BS, D'Ambrosio P, Stambler 
N, Rotshteyn Y, Marozsan AJ, Maddon PJ, Morris SA, Olson WC. Anti-HIV-1 activity of 
weekly or biweekly treatment with subcutaneous PRO 140, a CCR5 monoclonal antibody. J 
Infect Dis.. - 2010. - Vol. 201. - pp. 1481-7. 
Marozsan A. J., T. Parsons, W. Huang, E. Stawiski, J. M. Whitcomb, P. J. Maddon, and W. 
C. Olson. Clonal analysis of HIV-1 co-receptor tropism change following treatment with PRO 
140, a CCR5 monoclonal antibody. 48th Annual ICAAC / IDSA 46th Annual Meeting. - 
Washington, DC. : [s.n.], 2008. - Vols. Abstract H-1218. 
Moyle G Gatell J, Perno CF, Ratanasuwan w, Schechter M, Tsoukas C Potential for new 
antiretrovirals to address unmet needs in the management of HIV-1 infection. AIDS Patient Care 
STDS. - 2008. - pp. 459-471. 
Nishikawa M Takashima K, Nishi T, Furuta RA, Kanzaki N, Yamamoto Y et al. Analysis of 
binding sites for the new small-molecule CCR5 antagonist TAK-220 on human CCR5. 
Antimicrob Agents Chemother. - 2005. - Vol. 49(11). - pp. 4708-4715.. 
Office of AIDS Research Advisory Council AIDSinfo Guidelines for the Use of Antiretroviral 
Agents in HIV-1-Infected Adults and Adolescents [Online] AIDS Info. - Nov 13, 2014. - Dec 29, 
2014. - http://aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf. 
Richman D. D., D. Havlir, J. Corbeil, D. Looney, C. Ignacio, S. A. Spector, J. Sullivan, S. 
Cheeseman, K. Barringer, D. Pauletti. Nevirapine resistance mutations of human 
immunodeficiency virus type 1 selected during therapy. J Virol.. - 1994. - Vol. 68. - pp. 1660- 
1666.. 


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Saag M. S., E. A. Emini, O. L. Laskin, J. Douglas, W. I. Lapidus, W. A. Schleif, R. J. 
Whitley, C. Hildebrand, V. W. Byrnes, J. C. Kappes. A short-term clinical evaluation of L- 
697,661, a non-nucleoside inhibitor of HIV-1 reverse transcriptase. N.Engl.J Med.. - 1993. - Vol. 
329. - pp. 1065-1072.. 
Simioni S Cavassini M, Annoni J, Abraham AR, Bourquin I, Schiffer V, Calmy A, Chave J, 
Giacobini E, Hirschel B, Du Pasquier RA Cognitive dysfunction in HIV patients despite long- 
standing suppression of viremia.. - 2010. - Vol. 24. - pp. 1243-1250. 
Tang MW Shafer RW HIV-1 Antiretroviral Resistance: Scientific Principles and Clinical 
Applications Drugs. - 2012. - pp. e1-e25. 
Thompson M., Lalezari, J., Saag, M., Jacobson, J., Zingman, B., Stambler, N., D'Ambrosio, 
P., Maddon, P., Olson, W., and Morris, S. Weekly and bi-weekly subcutaneous PRO 140 
demonstrates potent, sustained antiviral activity. 16th Conference on Retroviruses and 
Opportunistic Infections. - Montreal QE, Canada, : [s.n.], 2009. - Vol. Abstract #571a. 


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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/DAIDS_AE_Grading_Table_v2_NOV2014.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 
Pain without 
Pain without 
Pain without 
touching or pain 
touching or pain 
touching or pain 
touching or pain 
when area is 
when area is 
when area is 
when area is 
touched: no or 
touched limiting 
touched causing 
touched causing 
minimal limitation 
use of limb OR 
inability to perform 
inability to perform 
of use of limb 
causing greater 
usual social and 
basic self-care 
than minimal 
functional 
function OR 
interference with 
activities 
hospitalization 
usual social and 
(other than 
functional 
emergency room 
activities 
visit) indicated for 
management of 
pain/tenderness 
Characterization of 
Erythema OR 
Erythema OR 
Ulceration OR 
Necrosis 
the injection site, if 
induration of 5x5 
induration OR 
secondary infection 
(involving dermis 
not normal 
cm - 9x9 cm (or 25 
Edema >9 cm any 
OR Phlebitis or 
and deeper tissue) 
cm2-81 cm2) 
diameter (or >81 
Sterile abscess OR 
cm2) 
drainage 
Pruritus associated 
Itching localized to 
Itching beyond the 
Generalized itching 
N/A 
with injection 
injection site AND 
injection site but 
causing inability to 
relieved 
not generalized OR 
perform usual 
spontaneously or 
itching localized to 
social and 
<48 hours of 
injection site 
functional 
treatment 
requiring ≥48 
activities 
hours treatment 
Bleeding 
Initial bleed that 
Bleeding that 
Continued bleeding 
N/A 
does not exceed 
exceeds bandage 
that requires 
bandage and 
and spontaneously 
change of dressing 
spontaneously 
stops 
and alternative 
stops 
injection site 
Absorption of drug 
Minor elevation of 
Leakage at 
Leakage at 
skin at injection 
injection site 
injection site that 
site but no leakage 
ceases with 
does not cease with 
of injection 
decrease in 
decrease in 
material 
injection rate 
injection rate 


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

SAP_001.pdf: 
 
 
STATISTICAL ANALYSIS PLAN 
FOR PROTOCOL PRO 140_CD 02 
 
 
Sponsor: 
 
CytoDyn, Inc. 
1111 Main Street, Suite 660 
Vancouver, Washington 
98660 
(360) 980-8524-Work 
(360) 980-8549-Fax 
www.cytodyn.com 
Protocol Number: 
PRO 140_CD 02 
Protocol Title: 
A Multi-center, Randomized, Double-blind, Placebo- 
controlled Trial, Followed by Single-arm Treatment of PRO 
140 in Combination With Optimized Background Therapy in 
Treatment-Experienced HIV-1 Subjects 
Protocol Date / Version: 
9.0 / 08 Jan 2018 
 
 
Plan Version: 
SAP - Version 3.0 
Plan Date: 
09 Feb 2018 
 
 
 
 
 
 
 
--- confidential--- 


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Protocol Number: 
PRO 140_CD 02 
Protocol 
Version/Date: 
Version 9.0 / 08 Jan 2018 
Protocol Name: 
A Multi-center, Randomized, Double-blind, Placebo- 
controlled Trial, Followed by Single-arm Treatment of 
PRO 140 in Combination With Optimized Background 
Therapy in Treatment-Experienced HIV-1 Subjects 
Sponsor: 
CytoDyn, Inc. 
1111 Main Street, Suite 660 
Vancouver, Washington 98660 
SAP Version: 
SAP - Version 3.0 
SAP Date: 
09 Feb 2018 
 
 
 
 
I have read and approve the Statistical Analysis Plan specified above and agree with its 
content: 
 


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TABLE OF CONTENTS 
 
Section 
Page 
LIST OF ABBREVIATIONS ............................................................................................................ 5 
1. 
INTRODUCTION ........................................................................................................................... 7 
2. 
PROTOCOL DESIGN AND OBJECTIVES................................................................................. 7 
2.1 
Study Objectives ................................................................................................................. 7 
2.2 
Design Overview ................................................................................................................. 8 
2.3 
Study Duration ................................................................................................................. 12 
2.4 
Study Treatments .............................................................................................................. 12 
2.4.1 
Treatment Groups .............................................................................................. 12 
2.4.2 
Randomization and Blinding .............................................................................. 12 
3. 
STUDY ASSESSMENTS/ ENDPOINTS .................................................................................... 13 
3.1 
Primary Efficacy Endpoint ............................................................................................... 13 
3.2 
Secondary Efficacy Endpoints .......................................................................................... 13 
3.3 
Safety Assessments .......................................................................................................... 14 
4. 
SAMPLE SIZE DETERMINATION AND RATIONALE, STATISTICAL POWER, 
AND SIGNIFICANCE LEVEL ................................................................................................... 14 
5. 
INDEPENDENT DATA MONITORING COMMITTEE (IDMC) .......................................... 15 
5.1 
Interim Safety Reviews .................................................................................................... 15 
5.2 
Interim Efficacy Review .................................................................................................. 15 
5.2.1 
Data Snapshot .................................................................................................... 16 
5.2.2 
Metrics to be Calculated for the IA .................................................................... 16 
5.2.3 
Conditional Power (CP) ..................................................................................... 17 
5.2.4 
Protection of integrity of the trial ....................................................................... 17 
5.2.5 
Rules and Method for Increasing Sample Size ................................................... 17 
5.2.6 
Data Provided to IDMC ..................................................................................... 18 
5.2.7 
Stopping Rule ..................................................................................................... 18 
5.2.8 
Information Provided to Sponsor by IDMC ....................................................... 19 
5.2.9 
Protection of Type I Error Rate .......................................................................... 19 
6. 
ANALYSIS POPULATIONS ...................................................................................................... 19 
6.1 
Intent-to-Treat Population ................................................................................................ 19 
6.2 
Per Protocol Population .................................................................................................... 19 
6.3 
Safety Population ............................................................................................................. 20 
7. 
DATA CONVENTION AND RELATED DEFINITIONS ........................................................ 20 
7.1 
Baseline Definition ........................................................................................................... 20 
7.2 
Duplicate Data .................................................................................................................. 20 
7.3 
Handling of Missing Data ................................................................................................ 20 
7.4 
Multicenter Clinical Trials................................................................................................ 20 
7.5 
Multiple Comparisons and Type I Error Rate Multiplicity adjustments ........................... 20 
7.6 
Covariates and Prognostic Factors .................................................................................... 20 
7.7 
Stratification Factors ........................................................................................................ 21 
7.8 
Subgroups and Exploratory Analysis ............................................................................... 21 


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7.9 
Standard Calculations ........................................................................................................ 21 
7.9.1 
Age...................................................................................................................... 21 
7.9.2 
Height ................................................................................................................. 21 
7.9.3 
Weight ................................................................................................................ 21 
7.9.4 
Body Mass Index (BMI) ..................................................................................... 21 
8. 
STATISTICAL METHODS ......................................................................................................... 21 
8.1 
Summarizing and Tabulating the Collected Data .............................................................. 22 
8.1.1 
Subject Disposition and Withdrawals.................................................................. 22 
8.1.2 
Protocol Deviations ............................................................................................. 22 
8.1.3 
Demographics and Baseline Characteristics ........................................................ 23 
8.1.4 
Prior and Concomitant Medications .................................................................... 23 
8.1.5 
Anti-Retroviral Therapy (ART)........................................................................... 23 
8.1.6 
Optimized Background Therapy (OBT) .............................................................. 23 
8.1.7 
Treatment Administration ................................................................................... 24 
8.2 
Analysis of Efficacy Data .................................................................................................. 24 
8.2.1 
Primary Endpoint ................................................................................................ 24 
8.2.2 
Secondary Endpoints ........................................................................................... 24 
8.3 
Analysis of Safety Data ..................................................................................................... 26 
8.3.1 
Adverse Events .................................................................................................... 26 
8.3.2 
Clinical Laboratory Evaluations .......................................................................... 27 
8.3.3 
Urine and Serum Pregnancy Test ........................................................................ 27 
8.3.4 
Physical Examination .......................................................................................... 27 
8.3.5 
Vital Signs .......................................................................................................... 28 
8.3.6 
Tolerability Assessment ....................................................................................... 29 
8.3.7 
ECG Assessment ................................................................................................. 30 
8.3.8 
Neurological Assessment .................................................................................... 30 
8.3.9 
Tropism and Drug Resistance from Monogram Biosciences ............................... 31 
8.3.10 
Tropism from Quest Diagnostics ........................................................................ 31 
8.3.11 
Anti-Idiotypic Antibodies to Pro 140 .................................................................. 31 
8.3.12 
PK Concentration of PRO140 ............................................................................. 31 
8.3.13 
Serum Concentration of ART Drugs ................................................................... 31 
8.3.14 
Notification and Outcome Pregnancy .................................................................. 31 
9. 
APPENDIX 1: SCHEDULE OF ASSESSMENTS ...................................................................... 32 
10. 
APPENDIX 2 – PLANNED TLG ................................................................................................. 37 
10.1 
Planned by-subject listings ................................................................................................ 37 
10.2 
Planned Summary Tables .................................................................................................. 38 
11. 
REFERENCES .............................................................................................................................. 39 


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LIST OF ABBREVIATIONS 
 
Abbreviation 
Term 
AE 
Adverse Event 
AIDS 
ANCOVA 
ART 
Acquired Immune Deficiency Syndrome 
Analysis of Covariance 
Anti Retroviral Therapy 
ASA 
ATC 
BMI 
BP 
American Statistical Association 
Anatomic Therapeutic Classification 
Body Mass Index 
Blood Pressure 
CFR 
Code of Federal Regulations 
CRF 
Case Report Form 
CRO 
CS 
Contract Research Organization 
Clinically Significant 
DAIDS 
Division of AIDS 
DMC 
Data Monitoring Committee 
ECG 
Electrocardiogram 
eCRF 
EOT 
Electronic Case Report Form 
End of Treatment 
FDA 
U.S. Food and Drug Administration 
FU 
Follow-Up 
GCP 
HEENT 
Good Clinical Practice 
Head, Ears, Eyes, Nose, Throat 
HIV 
Human Immunodeficiency Virus 
IA 
Interim Analysis 
ICH 
International Conference on Harmonization 
IP 
Investigational Product 
IRB 
Institutional Review Board 
ITT 
Intent-to-treat 
MedDRA 
MoCA 
OBT 
Medical Dictionary for Regulatory Activities 
Montreal Cognitive Assessment 
Optimized Background Therapy 
PI 
Principal Investigator 
PP 
PT 
Per Protocol 
Preferred Term 
SAE 
Serious Adverse Event 


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Abbreviation 
Term 
SAP 
SC 
Statistical Analysis Plan 
Subcutaneous 
SD 
SOC 
Standard Deviation 
System Organ Class 
SOP 
SV 
Standard Operating Procedure 
Screening Visit 
TEAE 
TF 
Treatment Emergent Adverse Events 
Treatment Failure 
VAS 
Visual Analogue Scale 
VF 
Virologic Failure 
WHO 
World Health Organization 


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1. 
INTRODUCTION 
This Statistical Analysis Plan describes the planned analyses and reporting for the clinical trial 
protocol PRO 140 _CD02, sponsored by CytoDyn Inc. The reader of this Statistical Analysis Plan 
(SAP) is encouraged to review the complete protocol and amendments as this plan contains only a 
limited overview of protocol information. The main objective of this plan is to provide details 
pertaining to statistical methodology, data conventions, and processes used for the analysis of data 
from this trial. 
The format and content of this Statistical Analysis Plan are structured to provide sufficient detail to 
meet the requirements specified by the International Conference on Harmonization (ICH) E9: 
Guidance on Statistical Principles in Clinical Trials. All work planned and presented in this 
Statistical Analysis Plan will follow the ethical guidelines published by the American Statistical 
Association (ASA). 
The following documents and references [1-6], were reviewed in preparation of this Statistical 
Analysis Plan: 
• Version 9.0, protocol 08 Jan 2018 
• US Federal Register, Department of Health and Human Services, FDA, Guidance on Statistical 
Principles for Clinical Trials (1998) 
• ASA Ethical Guidelines for Statistical Practice (1999) 
• The Royal Statistical Society: Code of Conduct (1993) 
• ICH Guidance on the Structure and Content of Clinical Study Reports (ICH E3, 1996) 
• ICH Guideline on General Considerations for Clinical Trials (ICH E8, 1997) 
• ICH Guidance on the Statistical Principles for Clinical Trials (ICH E9, 1997) 
 
 
2. 
PROTOCOL DESIGN AND OBJECTIVES 
2.1 Study Objectives 
 
The primary objective is to assess the efficacy, clinical safety and tolerability parameters of PRO 
140 compared to placebo in reducing HIV-1 viral load in patients on their current ART (failing 
regimen) during the one week double-blind treatment period. 


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The secondary objectives are to assess the efficacy, clinical safety and tolerability parameters of 
PRO 140 in combination with optimized background therapy in patients during the 24-week single- 
arm, open-label treatment period. 
2.2 Design Overview 
 
This is a Phase 2b/3, multi-center, two part study, designed to evaluate the efficacy, safety, and 
tolerability of PRO 140 in conjunction with existing ART (failing regimen) for one week and 
Optimized Background Therapy (OBT) for 24 weeks respectively. The patient population for this 
trial are treatment-experienced HIV-infected patients with CCR5-tropic virus and demonstrates 
evidence of HIV-1 replication despite ongoing antiretroviral therapy with documented genotypic or 
phenotypic resistance to ART drugs within three drug classes (or within two drug classes with 
limited treatment option). 
 
The study is divided into three phases: Screening, Treatment and Follow-up. 
 
Screening Phase (up to 6 weeks): 
 
This phase is designed to determine whether subjects are eligible to proceed to the Treatment Phase 
of the study. This phase consists of a series of assessments designed to determine eligibility. A 
written informed consent from the subject will be obtained by the Investigator or suitably qualified 
individual before the performance of any protocol-specific procedure. 
All subjects will continue taking their existing ART (failing regimen) during the Screening Phase 
and first week of the Treatment Phase. 
Treatment Phase (25 weeks ± allowed windows): 
 
The Treatment Phase is divided into two parts: 
• Part 1: 1-week randomized, double-blind, placebo-controlled period consisting of two 
treatment arms along with existing ART (failing regimen) 
• Part 2: 24-week single-arm, open-label treatment period with all subjects receiving PRO 
140 along with OBT 
The first Treatment Visit will take place within 6 weeks of the Screening Visit. 
The injectable study treatment (PRO 140 or placebo) will be administered: 


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o by a qualified medical professional (MD, DO, PA, LPN, LVN, NP, or RN) or 
o self-administered by subjects 
Note: Study treatment injections at T1, T2, T3, T7, T11, T15, T19 and T23 must be administered at 
clinic. The remaining study treatment injections may be self-administered by subjects outside the 
clinic. 
Part 1: One-week double-blind, placebo-controlled period [IP (PRO 140 or Placebo) + 
existing ART] 
Part 1 of treatment phase begins with an evaluation of results of laboratory samples collected at the 
Screening Visit. All subjects who fail to meet eligibility criteria will be considered screen failures 
and exit the study without further evaluation. Subjects who meet all eligibility criteria, as per data 
gathered from Screening Visit, will be randomized to one of two treatment arms for one week. 
Consenting patients will be randomized 1:1 to one of two treatment arms for one week: 
 
• Group A: PRO140 350mg weekly SC Inj. + existing ART 
 
• Group B: Placebo weekly SC Inj. + existing ART 
 
Part 2: 24-week single-arm, open-label treatment period [PRO 140 + OBT] 
After 7 days all subjects will enter the 24-week single-arm, open-label treatment period. During 
this period, all subjects will receive PRO 140 SC injection and Optimized Background Therapy. 
Optimized background therapy (OBT) is a standard-of-care regimen comprised of 3 or more 
antiretroviral agents selected by the investigator based on treatment history and genotypic and/or 
phenotypic assessments. OBT regimen will be initiated after completing one week of randomized, 
double-blind placebo-controlled period. 
Study participants will be regularly monitored for viral load following initiation of PRO 140, and 
will cease weekly study treatment injections should they experience treatment failure. 
Subjects who experience treatment failure at any point during the Treatment Phase will undergo the 
Treatment Failure (TF) Visit assessments and then return in 4 weeks (± allowed window) for the 
Safety Follow-up Visit. 
Treatment failure is defined in terms of virologic non-response and virologic rebound in the Open- 
Label Treatment Phase of the study. 


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(1) Virologic non-response is defined as two consecutive viral load results of: 
• < 0.5 log10 copies/mL decrease in HIV-1 RNA at Day 7 of the Open-Label Treatment 
Period. [Assessment Timepoint: T3 and T4 visit] 
• < 1.0 log10 copies/mL decrease in HIV-1 RNA at or after Week 4 of the Open-Label 
Treatment Period unless HIV-1 RNA <400 copies/mL [Assessment Timepoint: from T6 up to 
T25 visit]. 
• Confirmed plasma HIV-1 RNA levels ≥ 400 copies/mL at Week 24 of the Open-Label 
Treatment Period. [Assessment Timepoint: T25 and EOT visit] 
(2) Virologic rebound is defined as two consecutive viral load results of: 
• ≥ 1.0 log10 copies/mL increase in plasma HIV-1 RNA above nadir level* in the Open-Label 
Treatment Period [Assessment Timepoint: from T3 up to T25 visit] or 
*Note: This refers to “Nadir” level in the Open-Label Treatment Phase which starts from 
T2 visit 
• ≥ 400 copies/mL after suppression to < 50 copies/mL in the Open-Label Treatment Period. 
[Assessment Timepoint: from T3 up to T25 visit] 
Safety Follow-up Visit: 
 
Duration of the Follow-up Phase is determined upon whether or not subject has experienced 
treatment failure during the Open-Label Treatment Phase. 
• Subjects who experience treatment failure within Open-Label Treatment Phase will be 
followed up every 4 weeks until viral suppression is achieved (i.e., plasma HIV-1 RNA 
levels below level of detection) or up to a maximum of 6 months after cessation of therapy 
if the treating physician does not feel that there is an antiretroviral regimen that will regain 
full viral suppression. 
• Subjects who do not experience treatment failure at the end of Open-Label Treatment Phase, 
will be followed up every 2 weeks for total of 4 weeks. 
All assessments are described in the protocol Table 4-1: Schedule of Assessments – Screening and 
Treatment Phase, and in the Appendix 1 of this SAP. 






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of randomization will be used as a stratification factor to ensure balance between each treatment 
group in this stratum. 
 
3. STUDY ASSESSMENTS/ ENDPOINTS 
There are multiple efficacy endpoints and assessments in this trial. These are partitioned in the 
primary and secondary endpoints. 
3.1 Primary Efficacy Endpoint 
The primary efficacy endpoint for this study is proportion of participants with a ≥ 0.5 log10 
reduction in HIV-1 RNA viral load from baseline at the end of the 1-week double-blind treatment 
period. 
3.2 Secondary Efficacy Endpoints 
There are multiple secondary endpoints to be assessed in this study, to maintain the trial-wise Type 
I error rate at 0.05, a closed test procedure will be used for the secondary endpoints. The order of 
the endpoints will be as follows: 
1. Proportion of participants with ≥ 0.5 log10 reduction in HIV-1 RNA viral load from baseline 
at the end of the 1-week double-blind treatment period, stratified to each group: 
a. resistance to ART drugs within three drug classes, 
b. resistance to ART drugs within two drug classes with limited treatment option. 
 
2. Proportion of participants with ≥ 1 log10 reduction in HIV-1 RNA viral load from baseline at 
the end of the 1-week double-blind treatment period for all patients and within each stratum 
3. Mean change from Baseline in HIV-1 RNA levels (log10 copies/mL) at the end of the 1- 
week double-blind treatment period for all patients and within each stratum 
4. Percentage of participants achieving HIV-1 RNA < 400 copies/mL at week 25 for all 
patients and within each stratum 
5. Percentage of participants achieving HIV-1 RNA < 50 copies/mL at week 25 for all patients 
and within each stratum 
6. Mean change from Baseline in HIV-1 RNA levels (log10 copies/mL) at week 25 for all 
patients and within each stratum 


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7. Mean change from Baseline in CD4 cell count at the end of the 1-week double-blind 
treatment period for all patients and within each stratum 
8. Mean change from Baseline in CD4 cell count at week 25 for all patients and within each 
stratum 
3.3 Safety Assessments 
Safety measurements will include: 
• Emergence of Dual/Mixed (D/M)- and CXCR4-tropic virus in patients who had exclusive 
CCR5-tropic virus at study entry. 
• Tolerability of repeated subcutaneous administration of PRO 140 as assessed by study 
participants (using Visual Analogue Scale) and by investigator-evaluation of injection site 
reactions. 
• Frequency of treatment-related adverse events resulting in study drug discontinuation 
• Frequency of Grade 3 or 4 adverse events as defined by the DAIDS Adverse Event scale 
• Frequency of treatment–emergent serious adverse events 
 
 
4. SAMPLE SIZE DETERMINATION AND RATIONALE, STATISTICAL POWER, AND 
SIGNIFICANCE LEVEL 
For this two arm clinical trial, it is planned to have a total of 50 subjects (25 per treatment group) 
randomized and complete the clinical trial. 
The nQuery 6.01 is used for this sample size calculation. The sample size calculation is based on 
the assumption that the proportion of participants with ≥ 0.5 log10 reduction in HIV-1 RNA viral 
load from baseline at Week 1 during the double-blind treatment period is 90% for the PRO 140 
group vs 35% for the Placebo group. 
Note: Response rate of 90% is estimated for the PRO 140 group on the basis of results from 
PRO140 2101 study wherein 90% of participants with CCR5-tropic virus achieved ≥ 0.5 log10 
reduction in HIV-1 RNA viral load in one week from baseline. 
Under the above assumptions, 25 subjects per treatment group will be required to meet the Type I 
error rate of 0.05 and more than 90% power; for a total of 50 subjects for the clinical trial. 


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5. INDEPENDENT DATA MONITORING COMMITTEE (IDMC) 
An independent data monitoring committee (IDMC) will be convened for this study and will act in 
an advisory capacity to the Sponsor with respect to safeguarding the interests of study subjects, 
assessing interim safety and efficacy data, and for monitoring the overall conduct of the study. 
The membership criteria and other details of the IDMC are described in a separate IDMC Charter. 
 
5.1 Interim Safety Reviews 
 
The IDMC will convene from the beginning and at approximately six month intervals thereafter, 
based on enrollment to evaluate the overall progress of the study, perform reviews of safety data to 
assess the risk of the trial and provide recommendations to the sponsor accordingly. 
The safety review includes data for AEs, SAEs, labs, ECGs, vital signs, and all other safety related 
variables identified per the DMC Charter. No inferential statistics will be conducted for the safety 
interim analysis tabulation of the data. 
The DMC will receive: all safety signals including number of virologic non-response and virologic 
rebounds, unexpected AEs, all related AEs, all SAEs, and all deaths during the Treatment and 
Follow-Up Phases. 
 
5.2 Interim Efficacy Review 
 
An efficacy Interim Analysis (IA) is planned to be conducted when at least 40 patients have been 
randomized and completed the 1-week double-blind treatment period of the study or early 
terminated, whichever comes first. 
The procedures for this IA will be based on a standard operating procedure (SOP) that has a well- 
established firewall to protect the integrity of the trial. The IA will be performed by an independent 
un-blinded statistician, who is not otherwise associated with the conduct of this trial. 
The main objectives of this IA are: 
 
• 
To evaluate the safety of PRO140. 
• 
Sample size re-assessment to evaluate the final sample size needed to proceed with the 
study. 


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This meeting will be held by telephone and arranged by the IDMC Executive Secretary at the 
request of the IDMC Chairperson and in conjunction with Sponsor. IDMC interim analyses meeting 
will be in three sessions: an “open session”, a “closed session”, and another “open session” for 
recommendations unless otherwise specified by the Chairperson. 
5.2.1 Data Snapshot 
a. Cutoff dates for collection of eCRFs, data querying, database lock and analysis will be 
established based on an estimated target date of when 40 of the subjects completed 1-week 
double-blind treatment period. 
b. All data received by the cutoff date will be entered, validated, queries generated and 
resolved or pending queries documented. 
c. Snapshot of the dataset will be taken for the IA. This snapshot will not contain the treatment 
assignments (i.e., will be blinded). 
d. The locked data snapshot will be saved in a drive to which only the independent statistician 
responsible for the IA has access. 
e. The randomization code to un-blind the data will be delivered to the independent statistician 
by the randomization code generator. 
f. The independent statistician will merge the randomization code with the validated data and 
will generate the planned statistical analyses for the IA. 
 
5.2.2 Metrics to be Calculated for the IA 
Using the validated data with the unblinded treatment allocations, the independent statistician will 
calculate the following metrics: 
1. The proportion of subjects with a ≥ 0.5log10 or greater reduction in HIV-1 RNA viral load 
from baseline at the end of the 1-week double-blind treatment period in the PRO140 group 
(Pa) the observed number of subjects in the group 
2. The proportion of subjects with a ≥ 0.5log10 or greater reduction in HIV-1 RNA viral load 
from baseline at the end of the 1-week double-blind treatment period in the Placebo group 
(Pc) the observed number of subjects in the group 
3. The difference in rates of HIV-1 RNA viral load reduction between the treatment groups 
(Pa – Pc) 
4. The Conditional Power (CP) of the trial at the time of the IA (Chen YH, 2004). (The method 
for this calculation is provided in Section 5.2.3). 
5. The revised sample size requirement based on this IA (The rule and method for sample size 


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recalculation and p-value adjustment are provided in the below sections). 
5.2.3 Conditional Power (CP) 
The CP will be calculated according to the below formula (Chen YH, 2004) using the HIV-1 RNA 
viral load reduction rates in the PRO140 and Placebo groups 
 
CP(f1,z1) = Φ { z1 / ೦𝑓𝑓1 (1 − 𝑓𝑓1) – za / ೦(1 − 𝑓𝑓1) } 
Where: 
• CP(f1,z1) is the conditional power at the IA 
• Φ{.} is the cumulative distribution function of a standard Normal distribution (μ=0, σ2 = 
1) 
• f1 is the fraction of patients enrolled and used in the interim analysis before decision of 
increasing the sample size (𝑓𝑓1 = ( na + nc ) / N0 , where na and nc are the number of 
subjects used for the interim analysis in the PRO140 & Placebo groups, respectively, 
and N0 is the original sample size) 
• zα is the upper α quintile for standard Normal distribution 
• z1 is the standardized Normal, since the original sample size is based on proportions the 
z-score will be obtained from the following formula: 
z1 = (Pa– Pc) / ೦[𝑃𝑃𝑎𝑎 (1 − 𝑃𝑃𝑎𝑎) / 𝑛𝑛𝑎𝑎 + 𝑃𝑃𝑐𝑐 (1 − 𝑃𝑃𝑐𝑐) / 𝑛𝑛𝑐𝑐 ] 
Where: 
• Pa = the number of subjects with a ≥ 0.5log10 or greater reduction in HIV-1 
RNA viral load from baseline in the Active group divided by the number of 
subjects in Active group (i.e., na) 
• na = the number of subjects in the Active group used in the IA 
• Pc= the number of subjects with a ≥ 0.5log10 or greater reduction in HIV-1 
RNA viral load from baseline in the Control group, divided by number of 
subjects in the Control group (i.e., nc) 
• nc= the number of subjects in the Control group used in the IA 
• a = the Active group 
• c = the Control group 
5.2.4 Protection of integrity of the trial 
This IA will be conducted under strict SOP to protect the integrity of the trial. Only masked 
summary data specifically for basic baseline characteristics, conditional power and safety 
summaries will be released only to the IDMC members. 
5.2.5 Rules and Method for Increasing Sample Size 
 
Rule: Regardless of the size of the CP at IA, the original sample size will not be reduced nor will 
the trial be stopped early. 


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The sample size for the study will be adjusted only if the Interim Analysis CP is less than 80%. The 
adjustment would be an increase in the sample size in order to bring the CP to at least 80% up to a 
maximum increment of 70 subjects using the observed difference at the time of the interim analysis. 
The sample size will be maintained as the original sample size, if the CP is larger than or equal to 
80%. 
 
Method: This sample size recalculation will be made by adjusting the f2 in the CP equation below, 
until the CP is 80%. 
CP(f2, Z) = Φ { – Zα / ೦(1 − 𝑓𝑓2) + Z / ೦𝑓𝑓2 (1 − 𝑓𝑓2) } 
Where: 
• CP(f2, Z) is the CP at the IA to be increased to 80% by adjusting f2 
• f2 is the fraction of patients enrolled and used in the IA before decision of 
increasing the sample size relative to the new sample in the adjusted trial. It 
is defined as: 
f2 = ( na + nc ) / (N0 + nadded ) 
• Φ{.}, Zα , Z, na , nc and N0 are the same as those defined above 
 
The number of subjects to be added to the trial is then calculated from the f2 that yields the CP of 
80% as follows: 
 
nadded = ( na + nc – N0*f2 ) / f2 
5.2.6 Data Provided to IDMC 
 
The IDMC will receive a statistical report. The details on the content of the report are described in 
the IDMC Charter. 
All expedited safety reports will be provided in real time to the DMC chair upon being reported to 
FDA. At each meeting, the DMC will be authorized to unblind the study upon unanimous vote in 
the event of any concerns about safety or lack of efficacy. Unblinded CRO personnel, separate and 
independent of the blinded CRO personnel, will supply the DMC with all necessary tables and 
listings to perform their independent review. 
 
 
5.2.7 Stopping Rule 
There will be no intention to stop the study based on the efficacy interim results; however, the 
DMC may stop the study at any time based on review of safety data such as incidence of treatment 


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failure (i.e., virologic non-response and virologic rebound) in the open-label phase of the study. 
 
 
 
5.2.8 Information Provided to Sponsor by IDMC 
 
The IDMC will make recommendations to sponsor on the sample size adjustment and any safety 
concerns. 
5.2.9 Protection of Type I Error Rate 
 
Adjustments are made to protect the trial-wise Type I error rate due to Interim Analysis and 
potential increase in the sample size after the IA. To preserve the Type I error rate, the following 
steps will be followed: 
a. If the statistical power is larger than 50%, then the sample size will be adjusted 
upward and no Type I error rate adjustment will be made to the final analysis (Chen 
YH, 2004). 
b. If the statistical power is less than 50%, the Type I error rate will be inflated and 
statistical adjustment will be made to the final analysis if the decision to increase 
the sample size is made. That is, the observed p-value, as well as the point estimate 
of the response rates, and the 95% CIs will be based on [Proschan Liu, Hunsberger, 
2003]: 
p-value =2*{1- T2(n1+n2 - 1) (|z1 + z2|/√2)}, 
Response rate for each treatment group: Ŝ = (√n1 ×Ŝ1 + √n2 ×Ŝ2)/(√n1 + √n2), 
95% Confidence Intervals= (Ŝ -2 tα/2 2(n1+n2 - 1)σ, Ŝ +2 tα/2 2(n1+n2 - 1)σ) 
where n1, is the sample size in the treatment group before interim analysis and n2 is the sample size in treatment group 
after the interim analysis; T2(n1+n2 - 1) ( . ) is t distribution with 2 (n1+ n2-1) degrees of freedom. The Ŝ1 is the 
responder rate of the n1 observation before the interim analysis and Ŝ2 is the responder rate of the n2 observation after 
the interim analysis. The (√n1 + √n2)σ is the observed pooled standard deviation before and after the interim analysis. 
 
6. ANALYSIS POPULATIONS 
6.1 Intent-to-Treat Population 
The Intent-to-Treat (ITT) population is defined as the set of subjects who are randomized and have 
received at least one dose of PRO 140 or placebo. This population will be used as a primary 
analysis population for the primary and secondary endpoints. 
6.2 Per Protocol Population 
The Per Protocol (PP) population is defined as the set of subjects who meet the ITT population 


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requirements, and were not associated with a major protocol violation. This population will be 
identified before the database lock. This analysis using this population will be supportive. 
6.3 Safety Population 
The Safety population is defined as all subjects who received at least one dose of PRO 140 or 
placebo after randomization. This population will be used for the analysis of safety parameters. 
 
7. 
DATA CONVENTION AND RELATED DEFINITIONS 
7.1 Baseline Definition 
 
For all parameters, baseline will be defined as the last available value before treatment. 
 
7.2 Duplicate Data 
 
For unplanned duplicate data within a protocol-specified visit, the last measured value will be used 
for the analysis. If it is not possible to identify the “last measured value” the average of the 
duplicate values will be used. 
No data will be excluded. All collected data will be listed. 
 
7.3 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 multiple imputation methods for the ITT population 
of the primary and secondary endpoints. 
7.4 Multicenter Clinical Trials 
 
This is a multicenter clinical trial that includes up to 60 centers in the United States. 
 
7.5 Multiple Comparisons and Type I Error Rate Multiplicity adjustments 
 
For the primary endpoint only one hypothesis will be tested, hence there is no adjustment for Type I 
error rate. 
For the secondary endpoints, the closed test procedure will be used to protect the trial-wise error 
rate. The order of the endpoints is specified in Section 3.2. 
7.6 Covariates and Prognostic Factors 


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Age (years) = integer of[(date of informed consent – date of birth)/ 365.25+ 0.5] 
 
There are no pre-planned covariates analyses of the data from this study. 
7.7 Stratification Factors 
Resistance to ART drugs at the time of randomization will be used as a stratification factor to 
ensure balance between each treatment group in this stratum. 
7.8 Subgroups and Exploratory Analysis 
All planned subgroups by the stratification factor that are part of secondary endpoints will be 
summarized. Any additional subgroup/ exploratory analyses may be conducted as post hoc 
analyses. 
 
7.9 Standard Calculations 
7.9.1 Age 
Age will be calculated as the number of completed years between the date of informed consent and 
the subject’s birth date. 
 
7.9.2 Height 
For summary purposes height will be expressed in centimeters. Entries made in inches will be 
converted to centimeters using the formula noted below. 
 
7.9.3 Weight 
For summary purposes weight will be expressed in kilograms. Entries made in pounds will be 
converted to kilograms using the formula noted below. 
 
7.9.4 Body Mass Index (BMI) 
BMI will be calculated using height (in cm) and weight (in kg) according to the formula noted 
below. 
 
 
8. STATISTICAL METHODS 
All data collected during this study will be presented in subject data listings. All statistical analyses 
BMI (kg/m2) = weight (kg) / [[height (cm)/100]2] 
Weight (kg) = Weight (lb)/ 2.2046 
Height (cm) = Height (in)*2.54 


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will be performed using SAS® for Windows, version 9.4 or later. 
 
8.1 Summarizing and Tabulating the Collected Data 
All data collected will be summarized according to the variable type: 
o Continuous data summaries will include number of observations, mean, standard 
deviation, median, and minimum and maximum values. 
o Categorical data summaries will include frequency counts and percentages. 
8.1.1 Subject Disposition and Withdrawals 
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. 
There will be a detailed accounting of all subjects that signed the informed consent to participate in 
this trial. The following will be summarized: 
• The number of subjects who signed the informed consent 
• The number of subjects who are screen failures 
• The number of subjects who are randomized for the first part of the study 
• The number of subjects who are randomized but not treated 
• The number of subjects who are treated 
• The number of subjects who completed the double blind treatment phase 
• The number of subjects who completed both treatment phases 
• The number of subjects who completed the follow up phase 
• The number of subjects who discontinued 
Reasons for discontinuation will also be summarized. 
In addition, there will also be a listing of all discontinued subjects, which will provide the clinical 
trial center and the specific reason for discontinuation. 
8.1.2 Protocol Deviations 
The deviations occurring during the clinical trial will be summarized descriptively according to the 
following categories: 


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• Entrance criteria deviation 
• Withdrawal criteria deviation 
• Received wrong treatment or incorrect dose 
• Received an excluded medication 
• All other deviations 
Additionally a by-subject listing of all deviations will also be prepared. 
 
8.1.3 Demographics and Baseline Characteristics 
Demographics and baseline characteristics (i.e., Age, Gender, Time since HIV diagnosis, Viral load 
at Screening Visit, Tropism, etc.) will be summarized and/or listed, descriptively for the Safety 
Population. 
Medical history of the subjects will also be provided as a by-subject listing. 
 
8.1.4 Prior and Concomitant Medications 
Prior and concomitant medications will be summarized for the Safety Population. All prior and 
concomitant medications recorded in the eCRFs will be coded to generic term and all matching 
Anatomic Therapeutic Classification (ATC) codes using WHO Drug. Summaries will be prepared 
using the coded terms. All prior and concomitant medications recorded in the eCRFs will also be 
listed. 
8.1.5 Anti-Retroviral Therapy (ART) 
Anti-retroviral therapy will be summarized for the Safety Population. All such 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 anti-retroviral therapy recorded in the eCRFs will also be listed. 
8.1.6 Optimized Background Therapy (OBT) 
Optimized background therapy will be summarized for the Safety Population. All such 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 optimized background therapy recorded in the eCRFs will also be listed. 


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8.1.7 Treatment Administration 
All treatment PRO-140 administration data will be listed. In addition, the number and percentage of 
the subjects who received PRO-140 injection along with the summary of volume of injection will 
be presented for the safety population for each week during the treatment period. 
8.2 Analysis of Efficacy Data 
 
8.2.1 Primary Endpoint 
 
The primary efficacy endpoint for this study is proportion of participants with a ≥ 0.5log10 or 
greater reduction in HIV-1 RNA viral load from baseline at the end of the 1-week double-blind 
treatment period. 
The number and percentage of subjects with a ≥ 0.5log10 or greater reduction in HIV-1 RNA viral 
load from baseline will be presented for the two treatment groups. Fisher’s Exact test will be used 
to test the primary endpoint if the count in any cell (of the contingency table) is less than 5; 
otherwise Chi-Square test will be used assess the difference in the primary endpoint between 
treatment groups. In addition, the odds ratio and its 95% CI will also be presented. 
 
 
8.2.2 Secondary Endpoints 
 
There are multiple secondary endpoints to be assessed in this study, to maintain the trial-wise Type 
I error rate at 0.05, a closed test procedure will be used for the secondary endpoints. The order of 
the secondary endpoints will be as discussed in the below sections: 
 
8.2.2.1 Proportion of participants with ≥ 0.5 log10 reduction in HIV-1 RNA viral load from 
baseline at the end of the 1-week double-blind treatment period 
Similar analysis methods used for the primary endpoint specified in Section 8.2.1.1 will be used to 
analyze the below subgroups: 
a. resistance to ART drugs within three drug classes 
b. resistance to ART drugs within two drug classes with limited treatment option. 


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8.2.2.2 Proportion of participants with ≥ 1 log10 reduction in HIV-1 RNA viral load from 
baseline at the end of the 1-week double-blind treatment period 
 
The number and percentage of subjects with a ≥ 1log10 or greater reduction in HIV-1 RNA viral 
load from baseline will be presented for the two treatment groups. Fisher’s Exact test will be used 
to test the endpoint if the count in any cell (of the contingency table) is less than 5; otherwise Chi- 
Square test will be used assess the difference in the endpoint between treatment groups. In 
addition, the odds ratio and its 95% CI will also be presented. 
 
 
8.2.2.3 Mean change from Baseline in HIV-1 RNA levels (log10 copies/mL) at the end of the 1- 
week double-blind treatment period 
 
The raw and change from baseline in HIV-1 RNA levels (log10 copies/mL) at the end of the 1-week 
double-blind treatment period will be summarized by treatment group for the first week during the 
double-blind treatment phase. For change from baseline summaries, subjects with an undefined 
change from baseline, because of missing data, will be excluded. The change from baseline in 
HIV-1 RNA levels will be compared between the two groups using Analysis of Covariance 
(ANCOVA) with the stratification factor (i.e., Resistance to ART drugs at the time of 
randomization) included in the model. 
 
8.2.2.4 Percentage of participants achieving HIV-1 RNA < 400 copies/mL at week 25 
 
The number and percentages of subjects achieving HIV-1 RNA < 400 copies/mL at week 25 will be 
presented. 
 
8.2.2.5 Percentage of participants achieving HIV-1 RNA < 50 copies/mL at week 25 
 
The number and percentages of subjects achieving HIV-1 RNA < 50 copies/mL at week 25 will be 
presented. 
 
8.2.2.6 Mean change from Baseline in HIV-1 RNA levels (log10 copies/mL) at week 25 
 
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summarized for each week during the treatment phase. For change from baseline summaries, 
subjects with an undefined change from baseline, because of missing data, will be excluded. 
 
8.2.2.7 Mean change from Baseline in CD4 cell count at the end of the 1-week double-blind 
treatment period 
 
The raw and change from baseline in CD4 cell count at the end of the 1-week double-blind 
treatment period will be summarized by treatment group for the first week during the double-blind 
treatment phase. For change from baseline summaries, subjects with an undefined change from 
baseline, because of missing data, will be excluded. The change from baseline in CD4 cell count 
will be compared between the two groups using Analysis of Covariance (ANCOVA) with the 
stratification factor (i.e., Resistance to ART drugs at the time of randomization) included in the 
model. 
 
8.2.2.8 Mean change from Baseline in CD4 cell count at week 25 
 
The raw and change from baseline in CD4 cell count at week 25 will be summarized for each week 
during the treatment phase. For change from baseline summaries, subjects with an undefined 
change from baseline, because of missing data, will be excluded. 
 
8.3 Analysis of Safety Data 
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. 
8.3.1 Adverse Events 
Adverse events will be classified by system organ class (SOC) and preferred term (PT) according to 
the most recent MedDRA dictionary. 
All Treatment Emergent Adverse Events (TEAEs) will be summarized by treatment group, by 
System Organ Class and Preferred Term. TEAEs are defined as events with an onset on or after the 
first treatment administration. The following TEAE summaries will be provided, using frequency 
counts and percentages: 


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• Overall (i.e., regardless of severity or relationship to treatment) 
 
• By impact of study treatment (none, study treatment interrupted, study treatment 
discontinued, or not applicable1) 
• By severity grade (mild, moderate, severe, life threatening or death for SAEs) 
 
• By relationship to study treatment (definitely related, probably related, possibly related, 
remotely related or unrelated) 
In addition, separate summaries of SAEs, and AEs resulting in discontinuation of study treatment 
will be presented. 
Unless otherwise specified, at each level of subject summarization, a subject will be counted only 
once. If there is more than one occurrence of an event, the event of the worst severity or the worst- 
case relationship category will be summarized. 
 
8.3.2 Clinical Laboratory Evaluations 
Blood and urine samples will be collected according to the time points in the schedule of 
assessments for analysis. All available results of the clinical laboratory evaluations (e.g., Routine 
CBC, Biochemistry, etc.) will be listed and summarized by treatment group. 
8.3.3 Urine and Serum Pregnancy Test 
All the results for serum pregnancy test will be presented as a by-subject listing. 
 
8.3.4 Physical Examination 
The complete physical examination will include routine examinations for the following: 
 
• 
General Appearance 
 
• 
Head, Ears, Eyes, Nose, Throat (HEENT) 
 
• 
Lymph Nodes 
 
• 
Heart/Cardiovascular abnormalities 
 
 
1 The “not applicable” assessment will be used only when the subject is no longer in the treatment phase of the protocol, 
or if the outcome of the event was “death”. 


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• 
Respiratory 
 
• 
Abdomen 
 
• 
Genitourinary 
 
• 
Musculoskeletal and Extremities 
 
• 
Neurologic abnormalities Dermatologic abnormalities 
 
• 
Any other body system for which an abnormality is noted and which, in the opinion of the 
Investigator, is relevant to the safety of the subject or could impact safety or efficacy results 
for the subject; i.e., the abnormality is clinically significant (CS). 
Each abnormality will be recorded and the Investigator will record an assessment of its clinical 
significance. 
The complete physical examination will be conducted at the Screening Visit (SV), End of 
Treatment (EOT) Visit, and at Treatment Failure (TF) Visit. Only symptom-directed physical 
examination will be performed at treatment and follow-up visits conducted within the clinic, and at 
unscheduled visits within the Treatment and Follow-up Phases. 
All physical examination findings will be listed and/or summarized by treatment group. 
 
 
8.3.5 Vital Signs 
Vital signs will be collected at all study visits performed at the clinic. Vital signs collected during 
the Treatment Phase will be performed post-treatment, assessed within 15 minutes following study 
treatment administration. 
The following vital signs will be collected at all visits, unless otherwise stated: 
 
• Height (at Screening Visit) 
 
• Weight (at SV, EOT and TF visits) 
 
• BMI (derived from the height and weight measurements; at SV, EOT and TF visits) 
 
• Seated blood pressure (taken after the subject has been seated for at least 5 minutes) 
 
• Heart Rate 


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• Respiration Rate 
 
• Temperature 
 
All vital sign assessment findings will be listed and summarized. 
Tabulations of raw data and change from baseline values will be presented by time point and 
treatment group for each vital sign parameter [i.e., pulse (beats/min), temperature (0C), systolic BP 
(mmHg), diastolic BP (mmHg)]. For change from baseline summaries, subjects with an undefined 
change from baseline, because of missing data, will be excluded. 
8.3.6 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. 
 
8.3.6.1 Injection Site Reaction Assessment 
 
At each treatment visit that occurs at the clinical site, an injection site reaction assessment will be 
made for the current and previous injection sites. Injection site reaction assessments are recorded by 
the Investigator starting after the first injection is given. 
All data from the injection site reaction assessments of the repeated subcutaneous administration of 
PRO 140 will be descriptively summarized by treatment group. 
 
8.3.6.2 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). This assessment 
will be performed each time subjects arrive to the clinic for the study visit. 
Beginning at Treatment Visit 2, 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 


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to the point that the patient marks. 
 
All data from the VAS assessment of the repeated subcutaneous administration of PRO 140 will be 
summarized descriptively by treatment group. 
Figure 8-1:   Visual Analog Scale 
 
 
 
8.3.7 ECG Assessment 
A 12-lead ECG will be conducted at the Screening Visit (SV) results will be evaluated by the 
Investigator. The following parameters will be recorded: ventricular rate (beats per minute), PR 
interval (msec), QRS interval (msec), QT interval (msec), and QTc interval (msec). Additionally, 
the investigator will record the overall results of the ECG reading as either normal or abnormal, and 
as either not clinically significant or clinically significant. If abnormalities are observed, each will 
be recorded. 
All ECG examination findings will be listed and any abnormality will be summarized. 
 
8.3.8 Neurological Assessment 
Neurological assessment will be performed by the Principal Investigator (or delegated personnel) or 
a Neurologist at Treatment Visits 1, 3, 7, 11, 15, 19 and 23 (T1, T3, T7, T11, T15, T19, T23), End 
of Treatment (EOT) and at Treatment Failure (TF) Visit. 
The neurological assessment tool is based on the three question survey used by Simioni et al. 
(Simioni S, 2010). Refer to section 17.4 in Protocol for further details. Additional assessment 
modalities can be used for further assessment as per Investigator’s discretion 
All neurological assessment findings will be listed and any abnormality will be summarized by 
treatment group. 


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8.3.9 Tropism and Drug Resistance from Monogram Biosciences 
All Trofile® assay data from Monogram Biosciences will be presented as a by-subject listing. 
 
8.3.10 Tropism from Quest Diagnostics 
All tropism data from Quest diagnostics will be presented as a by-subject listing. 
 
8.3.11 Anti-Idiotypic Antibodies to Pro 140 
Anti-idiotypic antibodies to PRO 140 will be performed at T1, T7, T15, EOT and TF visits. All data 
will be presented as by-subject listings. 
8.3.12 PK Concentration of PRO140 
PK sample for PRO 140 will be taken at T1, T7, T15, EOT and TF visits. All data will be presented 
as by-subject listings. 
8.3.13 Serum Concentration of ART Drugs 
All serum concentration of ART drugs will be presented as a by-subject listing. 
 
8.3.14 Notification and Outcome Pregnancy 
All the results for Notification and Outcome Pregnancy will be presented as a by-subject listing. 












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10. APPENDIX 2 – PLANNED TLG 
10.1 Planned by-subject listings 
DISPOSITION/WITHDRAWALS (LISTINGS 16.2.1.X) 
ELIGIBILTY AND PROTOCOL DEVIATIONS (LISTINGS 16.2.2.X) 
EXCLUDED SUBJECTS (LISTINGS 16.2.3.X) 
DEMOGRAPHICS, 
POPULATION, 
AND 
BASELINE 
CHARACTERISTICS 
(LISTINGS 16.2.4.X) 
TREATMENT ADMINISTRATION LISTINGS (LISTINGS 16.2.5.X) 
EFFICACY RESPONSE DATA (LISTINGS 16.2.6.X) 
ADVERSE EVENT DATA (LISTINGS 16.2.7.X) 
SAFETY DATA (LISTINGS 16.2.8.1.X) 


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


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11. 
REFERENCES 
1. ASA. (1999) Ethical Guidelines for Statistical Practice. Prepared by the Committee on 
Professional Ethics, August 7, 1999. 
2. The Royal Statistical Society: Code of Conduct (1993). 
3. E8 General Considerations for Clinical Trials, ICH Guidance, Federal Register, 1997. 
4. E9 Statistical Principles for Clinical Trials, ICH Guideline, Federal Register, 1997 
5. Guideline for the Format and Content of the Clinical and Statistical Section of an 
Application, 1988. 
6. Guideline for Industry: Structure and Content of Clinical Study Reports (ICH E3), July 
1996.