A Multi-center, Two-Part, Single-Arm, Open Label, 25-Week Trial With PRO 140 in Treatment-Experienced HIV-1 Subjects
Phase: PHASE2
Conditions: HIV-1-infection
Sponsor: CytoDyn, Inc.

 
 
CytoDyn Inc.    1111 Main Street, Suite 660, Vancouver, Washington 98660   T 360.980.8524  F 360.799.5954 
 
 
Protocol Cover Page 
 
 
Protocol Title: A Multi-center, Two-Part, Single-Arm, Open Label, 25-Week Trial with PRO 140 
in Treatment-Experienced HIV-1 Subjects. 
 
Protocol Number: PRO 140_CD02_OpenLabel 
 
Version: 3.0 
 
Document Date: 11-Mar-2019 
 
NCT Number: NCT03902522 
 

CONFIDENTIAL
Page 1 of 112
 
 
 
 
 
 
 
A Multi-center, Two-Part, Single-Arm, Open Label, 25-Week Trial with 
PRO 140 in Treatment-Experienced HIV-1 Subjects. 
 
 
 
 
 
Protocol Number:
PRO 140_CD02_OpenLabel
Version: 
3.0 
Date: 
11-Mar-2019 
 
 
 
 
 
 
Sponsor:
CytoDyn, Inc.
1111 Main Street, Suite 660 
Vancouver, Washington 98660
(360) 980-8524-Work 
(360) 980-8549-Fax 
www.cytodyn.com 
 
 
 
 
 
 
 
Confidentiality Statement 
This document is a confidential communication of CytoDyn, Inc. It is provided for the conduct of 
a clinical research study. The information contained in this document is confidential and, except 
to the extent necessary to obtain informed consent or IEC/IRB approval, cannot be disclosed unless 
required by governmental regulation. Persons to whom any portion of the contents of this 
document is disclosed must be informed that the information is confidential and may not be further 
disclosed by them. 
 
 
 
 

Protocol # PRO 140_CD02_OpenLabel
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Date: 11-Mar-2019
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INVESTIGATOR’S SIGNATURE PAGE 
 
Protocol Number: 
PRO 140_CD02_OpenLabel 
Version: 
3.0 
Date: 
11-Mar-2019 
 
 
 
 
 
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_CD02_OpenLabel
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Date: 11-Mar-2019
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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 
 
Amarex Clinical Research, LLC (Amarex) 
 
20201 Century Boulevard, Suite 450 
Germantown, MD 20878 USA 
www.amarexcro.com 
 

Protocol # PRO 140_CD02_OpenLabel
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PROTOCOL SYNOPSIS 
 
Name of Sponsor: 
CytoDyn, Inc. 
Name of Study Product: PRO 140 (Humanized monoclonal antibody to CCR5) 
Protocol Number: 
PRO 140 _CD02_OpenLabel 
Therapeutic Indication: 
Human Immunodeficiency Virus Type-1 (HIV-1) Infection 
Title of Study: 
A Multi-center, Two-Part, Single-Arm, Open Label, 25-Week Trial with PRO 140 in Treatment-Experienced 
HIV-1 Subjects. 
Study Center(s): 
Up to 40 centers in the United States 
Planned Number of Subjects: 
Up to 25 subjects (or any number of subjects that can be enrolled by the time of Biologics Licence Application 
(BLA) submission for PRO 140). 
Indication for Use: 
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: 
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). 
Objectives: 
The primary objectives of the trial are to assess the efficacy, clinical safety and tolerability parameters of PRO 
140 in combination with failing ART during the initial one-week treatment period, and in combination with 
Optimized Background Therapy during the subsequent 24-week treatment period. 
Endpoints: 
Primary Efficacy Endpoint: 

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Name of Sponsor: 
CytoDyn, Inc. 
Name of Study Product: PRO 140 (Humanized monoclonal antibody to CCR5) 
Protocol Number: 
PRO 140 _CD02_OpenLabel 
Therapeutic Indication: 
Human Immunodeficiency Virus Type-1 (HIV-1) Infection 
 
Proportion of participants with ≥ 0.5 log10 reduction in HIV-1 RNA viral load from baseline at the 
end of the initial 1-week treatment period 
Secondary Endpoints: 
 
Proportion of participants with ≥ 1 log10 reduction in HIV-1 RNA viral load from baseline at the end 
of the initial 1-week treatment period 
 
Mean change from Baseline in HIV-1 RNA levels (log10 copies/mL) at the end of the initial 1-week 
treatment period 
 
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 
 
Mean change from Baseline in HIV-1 RNA levels (log10 copies/mL) at week 25 
 
Mean change from Baseline in CD4 cell count at the end of the initial 1-week treatment period 
 
Mean change from Baseline in CD4 cell count at week 25 
Safety Assessments: 
 
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 
Trial Design: 
This is a multi-center, two part study, designed to evaluate the safety and tolerability of PRO 140 in conjunction 
with existing ART (failing regimen) for one week and Optimized Background Therapy (OBT) for 24 weeks. 
The patient population for this trial are treatment-experienced HIV-infected patients with CCR5- tropic virus 
and 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 four phases: Screening, Baseline,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 

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Name of Sponsor: 
CytoDyn, Inc. 
Name of Study Product: PRO 140 (Humanized monoclonal antibody to CCR5) 
Protocol Number: 
PRO 140 _CD02_OpenLabel 
Therapeutic Indication: 
Human Immunodeficiency Virus Type-1 (HIV-1) Infection 
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, Baseline, and 
first week (Part 1) of the Treatment Phase. 
Baseline (1 week): 
Potentially eligible subjects will confirm continued eligibility one week prior to the first treatment visit. HIV 
RNA will be tested at Baseline. Subjects whose result is >400 copies/mL will be enrolled one week later. 
Subjects with results <400 copies/mL will be designated as screen failure. The Baseline Visit (T0) will take place 
within 6 weeks of the Screening Visit. 
Treatment Phase (25 weeks ± allowed windows): 
The Treatment Phase is divided into two parts: 
 
Part 1: 1-week treatment period consisting of PRO 140 along with existing ART (failing regimen)
 
Part 2: 24-week treatment period consisting of PRO 140 along with OBT
The injectable study treatment (PRO 140) will be administered starting at T1 visit and weekly there after: 
o 
by a qualified medical professional (MD, DO, PA, LPN, LVN, NP, RN, or CMA if permitted by state 
law ) or 
o 
self-administered by subjects 
Subjects will receive PRO 140 700 mg administered subcutaneously once per week. 
Note: Subjects who are currently enrolled and receiving 350 mg dose will have the option to move to the 700 
mg dose for the remainder of their participation in the trial. 
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 treatment period [PRO 140 + 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 
enrolled and receive PRO 140 for one week (Table 0-1). A visit to confirm HIV RNA continues to meet 
eligibility will be conducted one week pior to the first treatment. 
Table 0-1: One-week period [PRO 140 + existing ART] 

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Name of Sponsor: 
CytoDyn, Inc. 
Name of Study Product: PRO 140 (Humanized monoclonal antibody to CCR5) 
Protocol Number: 
PRO 140 _CD02_OpenLabel 
Study Drug 
Dosage 
Therapeutic Indication: 
Human Immunodeficiency Virus Type-1 (HIV-1) Infection 
IP 
Dosing Frequency and Amount 
Route of 
Form 
PRO 140 
Parenteral 
solution 
concentration 
175 mg/mL 
2 injections of PRO 140 (2 X 2 mL/inj.) 
at T1 visit 
Administration 
SC injection 
 
 
 
 
Part 2: 24-week treatment period [PRO 140 + OBT] 
As shown in Table 0-2, after 7 days all subjects will enter the 24-week 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. 
 
Table 0-2: 24-week treatment period [PRO 140 + OBT] 
 
 
Parenteral 
solution 
175 mg/mL 
2 injections of PRO 140 (2 X 2 mL/inj.) 
per week for up to 24 weeks (T2 – T25) 
SC injection 
 
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. 
(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 Treatment Phase Part 2. [Assessment 
Timepoint: T3 and T4 visit] 
 
< 1.0 log10 copies/mL decrease in HIV-1 RNA at or after Week 4 of Treatment Phase Part 2 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 25 of Treatment Phase Part 2. 
[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 Treatment Phase Part 2 
[Assessment Timepoint: from T3 up to T25 visit] or 
Study Drug
Dosage 
Form
IP
concentration
Dosing Frequency and Amount
Route of 
PRO 140

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*Note: This refers to “Nadir” level in the Treatment Phase which starts from T2 visit 

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Name of Sponsor: 
CytoDyn, Inc. 
Name of Study Product: PRO 140 (Humanized monoclonal antibody to CCR5) 
Protocol Number: 
PRO 140 _CD02_OpenLabel 
Therapeutic Indication: 
Human Immunodeficiency Virus Type-1 (HIV-1) Infection 
 
≥ 400 copies/mL after suppression  to  < 50 copies/mL in Treatment Phase Part 2. [Assessment 
Timepoint: from T3 up to T25 visit] 
 
Safety Follow-up Visits: 
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 Treatment Phase Part 2 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 Treatment Phase Part 2, will be followed up 
every 2 weeks for total of 4 weeks. 
Duration of Study: 
 
Screening Phase:
o 
up to 6 weeks* 
*Subject will move to Treatment Phase as soon as HIV-1 viral tropism, genotypic and phenotypic resistance 
results are available for review by Investigator, within 6 weeks of the Screening Visit. 
 
Baseline
o 
1 week 
 
Treatment Phase:
o 
25 weeks (± allowed windows) 
 
Follow-up Phase:
o 
4 weeks** (± allowed windows) 
**or up to maximum of 6 months after experiencing Treatment Failure (TF) if the treating physician does not feel 
that there is an antiretroviral regimen that will regain full viral suppression. 
 
Total Study Duration:
o 
36 weeks [Does not include additional follow-up time for treatment failure subjects] 
Inclusion Criteria: Potential subjects are required to meet all of the following criteria for enrollment into the 
study. 
1. Males and females, age ≥ 18 years 
2. Exclusive CCR5-tropic virus at Screening Visit as determined by Monogram Biosciences Trofile® Assay 

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Name of Sponsor: 
CytoDyn, Inc. 
Name of Study Product: PRO 140 (Humanized monoclonal antibody to CCR5) 
Protocol Number: 
PRO 140 _CD02_OpenLabel 
Therapeutic Indication: 
Human Immunodeficiency Virus Type-1 (HIV-1) Infection 
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) 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). 

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Name of Sponsor: 
CytoDyn, Inc. 
Name of Study Product: PRO 140 (Humanized monoclonal antibody to CCR5) 
Protocol Number: 
PRO 140 _CD02_OpenLabel 
Therapeutic Indication: 
Human Immunodeficiency Virus Type-1 (HIV-1) Infection 
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. 
Exclusion Criteria: Potential subjects meeting any of the following criteria will be excluded from enrollment. 
1. Documented CXCR4-tropic virus or Dual/Mixed tropic (R5X4) virus as determined by HIV-1 tropism 
assay 
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. Participation in an experimental drug trial(s) within 30 days of the Screening Visit 
12. Any known allergy or antibodies to the study drug or excipients 
13. Treatment with any of the following: 

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Name of Sponsor: 
CytoDyn, Inc. 
Name of Study Product: PRO 140 (Humanized monoclonal antibody to CCR5) 
Protocol Number: 
PRO 140 _CD02_OpenLabel 
Therapeutic Indication: 
Human Immunodeficiency Virus Type-1 (HIV-1) Infection 
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. 
14. Any other clinical condition that, in the Investigator's judgment, would potentially compromise study 
compliance or the ability to evaluate safety. 
Statistical Considerations: 
Sample Size Determination and Rationale: 
Up to 25 subjects (or any number of subjects that can be enrolled by the time of BLA submission for PRO 
140) will be enrolled. The sample size is based on clinical judgement with an intention to supplement the data 
for the target BLA indication. 
Analysis Populations: 
The Intent-to-Treat (ITT) population is defined as the set of subjects who are enrolled and have received at 
least one dose of PRO 140. 
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 analysis. 
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 Safety population is defined as all subjects who received at least one dose of PRO 140. This population will 
be used for the analysis of safety parameters. 
Efficacy Analysis 
The primary analysis of primary and secondary endpoint will be conducted on the ITT population and PP 
population will be used for supportive analysis using the same analysis methodologies. 
All data collected from the study will be presented as a by-subject listing and also summarized according to the 
variable type as: 

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Name of Sponsor: 
CytoDyn, Inc. 
Name of Study Product: PRO 140 (Humanized monoclonal antibody to CCR5) 
Protocol Number: 
PRO 140 _CD02_OpenLabel 
Therapeutic Indication: 
Human Immunodeficiency Virus Type-1 (HIV-1) Infection 
 
Continuous data summaries will include number of observations, mean, standard deviation, median, 
and minimum and maximum values. 
 
Categorical data summaries will include frequency counts and percentage. 

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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_CD02 Study ......................................................................................35 
1.4.2.10 
PRO 140_CD02 Extension study ......................................................................36 
1.4.2.11 
PRO 140_CD03 Study ......................................................................................36 
1.4.2.12 
PRO140_CD03 Extension Study ......................................................................36 
1.5 
Rationale for Dose Selection ...............................................................................................40 
1.6 
Risks / Benefits Assessment ................................................................................................41 
1.6.1 Risks/Discomfort to Subjects and Precautions to Minimize Risk .......................................41 
1.6.1.1 
Risks associated with continuation of Failing Antiretroviral Treatment 
Regimen .............................................................................................................41 
1.6.1.2 
Allergic Reaction ...............................................................................................42 
1.6.1.3 
Immune Response .............................................................................................42 

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1.6.1.4 
Pregnancy ..........................................................................................................42 
1.6.1.5 
Venipuncture .....................................................................................................42 
1.6.1.6 
Risks to the Study Personnel and the Environment ...........................................42 
1.6.1.7 
Unknown Risks .................................................................................................42 
1.6.1.8 
Theoretical risk for increased severity of West Nile virus infection .................43 
1.6.2 Intended Benefit for Subjects ..............................................................................................43 
2 STUDY OBJECTIVES ..........................................................................................................44 
3 STUDY DESIGN ....................................................................................................................45 
3.1 
Study Center(s) ....................................................................................................................46 
3.2 
Study Population .................................................................................................................46 
3.3 
Eligibility Criteria ................................................................................................................46 
3.3.1 
Inclusion Criteria ...............................................................................................46 
3.3.2 
Exclusion Criteria ..............................................................................................47 
4 STUDY SCHEDULE .............................................................................................................50 
4.1 
Screening Phase ...................................................................................................................57 
4.1.1 
Pre-Screening ....................................................................................................57 
4.1.2 
Screening Visits .................................................................................................57 
4.2 
Baseline ...............................................................................................................................59 
4.3 
Treatment Phase ..................................................................................................................59 
4.3.1 
Treatment Visit (T1) - Part 1 of Treatment Phase .............................................61 
4.3.2 
Treatment Visit-2 (T2) to Treatment Visit-25 (T25) - Part 2 of Treatment Phase63 
4.3.3 
End of Treatment (EOT) Visit ...........................................................................64 
4.3.4 
Treatment Failure (TF) Visit .............................................................................65 
4.4 
Follow-up Phase ..................................................................................................................66 
4.4.1 
Follow-Up Visits ...............................................................................................66 
4.5 
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 

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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 
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 
7.11.14 
Coagulation Indices ...........................................................................................84 
7.12 Investigational Product Administration ...............................................................................84 

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7.13 Injection Site Reaction assessment ......................................................................................84 
7.14 Pain Assessment using Visual Analog Scale (VAS) ...........................................................84 
8 STATISTICAL CONSIDERATIONS .................................................................................86 
8.1 
Treatment Groups ................................................................................................................86 
8.2 
Description of Study Endpoints...........................................................................................86 
8.2.1 
Primary Endpoint...............................................................................................86 
8.2.2 
Secondary Endpoint...........................................................................................86 
8.2.3 
Safety Assessments ...........................................................................................86 
8.3 
Sample Size Determination and Rationale ..........................................................................87 
8.4 
Randomization and Blinding ...............................................................................................87 
8.5 
Interim Analysis ..................................................................................................................87 
8.6 
General Statistical Considerations .......................................................................................87 
8.6.1 
Analysis Populations .........................................................................................87 
8.6.1.1 
Intent-to-Treat Population .................................................................................87 
8.6.1.2 
Per Protocol Population .....................................................................................87 
8.6.1.3 
Safety Population ...............................................................................................87 
8.6.2 
Statistical Methods ............................................................................................88 
8.6.3 
Prognostic Factors/Covariates ...........................................................................88 
8.6.4 
Handling of Missing Data .................................................................................88 
8.7 
Data Summary .....................................................................................................................88 
8.7.1 
Subject Disposition ............................................................................................88 
8.7.2 
Demographic and Baseline Characteristics .......................................................88 
8.7.3 
Prior and Concomitant Medications ..................................................................88 
8.7.4 
Efficacy Analysis ...............................................................................................88 
8.7.4.1 
Primary Analysis ...............................................................................................88 
8.7.4.2 
Supportive Analysis ..........................................................................................89 
8.7.5 
Safety Analysis ..................................................................................................89 
8.7.5.1 
Adverse Events ..................................................................................................89 
8.7.5.2 
Tolerability Assessment ....................................................................................89 
8.7.5.3 
Clinical Laboratory Data ...................................................................................90 
8.7.5.4 
Physical Examination ........................................................................................90 
8.7.5.5 
Vital Signs .........................................................................................................90 
8.7.5.6 
ECG Examination ..............................................................................................90 
8.7.5.7 
Neurological Assessment ..................................................................................90 
9 ADVERSE EVENTS (DEFINITIONS AND REPORTING) ............................................91 

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9.1 
Adverse Event .....................................................................................................................91 
9.1.1 
Reporting of Adverse Events.............................................................................91 
9.1.2 
Impact of Study Treatment ................................................................................91 
9.1.3 
DAIDS AE Grade (Severity) Assessment .........................................................91 
9.1.4 
Causality Assessment ........................................................................................92 
9.1.5 
Treatment Given as a Result of the Event .........................................................93 
9.1.6 
Outcome Assessment ........................................................................................93 
9.1.7 
Expected / Anticipated Adverse Events ............................................................93 
9.1.8 
SC Injection-related Events ...............................................................................94 
9.2 
Serious Adverse Events (SAE) ............................................................................................94 
9.3 
Reporting of Serious Adverse Events ..................................................................................95 
9.3.1 
SAE Follow-Up .................................................................................................96 
10 DIRECT ACCESS TO SOURCE DATA/DOCUMENTATION ......................................97 
11 QUALITY CONTROL AND QUALITY ASSURANCE ...................................................98 
11.1 Monitoring Requirements ....................................................................................................98 
11.2 Acceptability of Case Report Forms (CRFs) .......................................................................98 
11.3 Modification of Protocol .....................................................................................................99 
11.4 Reporting Protocol Deviations ............................................................................................99 
12 ETHICS AND REGULATORY REQUIREMENTS .......................................................100 
12.1 Institutional Review Board/Independent Ethics Committee (IRB/IEC) ...........................100 
12.2 Investigator’s Responsibilities ...........................................................................................100 
12.3 Subject Informed Consent Requirements ..........................................................................101 
13 DATA HANDLING AND RECORD KEEPING ..............................................................102 
13.1 Recording and Collection of Data .....................................................................................102 
13.2 Clinical Data Management ................................................................................................102 
13.3 Archiving ...........................................................................................................................103 
14 PUBLICATION PLAN .......................................................................................................104 
15 REFERENCES .....................................................................................................................106 
16 APPENDIX ...........................................................................................................................108 
16.1 Appendix I: AIDS-Defining Conditions ...........................................................................108 
16.2 Appendix II: Division of AIDS Table for Grading the Severity of Adult and Pediatric 
Adverse Events (DAIDS AE Grading Table) ..............................................................................110 
16.3 Appendix III: Adverse Events of Special Interest: Injection Site Reactions....................111 

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16.4 Appendix V: Neurological Assessment ............................................................................112 
 
LIST OF TABLES 
 
Table 1-1: 
Clinical Studies with PRO 140 .............................................................................. 37 
Table 4-1: 
Schedule of Assessments – Screening and Treatment Phase ................................ 53 
Table 4-2: 
Schedule of Assessments –Follow-Up (FU) Phase ............................................... 56 
Table 4-3 
Part 1: One week period [IP (PRO 140) + existing ART] ..................................... 60 
Table 4-4 
Part 2: 24-week treatment maintenance period [PRO 140 + OBT]....................... 60 
Table 6-1: 
Investigational Product - PRO 140 at T1 visit ...................................................... 70 
Table 6-2: 
Investigational Product - PRO 140 at T2 - T25 visit ............................................. 70 
Table 9-1: 
DAIDS AE Grading Table v2 General Guidelines ............................................... 92 

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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. .................. 40 
Figure 3-1: 
Study Flow Diagram .............................................................................................. 49 
Figure 4-1: 
Study Schematic .................................................................................................... 50 
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 
BLA 
Biologics Licence Application 
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 

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Abbreviation 
Term 
GCP 
Good Clinical Practice 
HAART 
Highly Active Antiretroviral Therapy 
Hb 
Hemoglobin 
HBsAg 
Hepatitis B Surface Antigen 
HCT 
Hematocrit 
HEENT 
Head, Ears, Eyes, Nose, and Throat 
HIPAA 
Health Insurance Portability Accountability Act 
HIV 
Human Immunodeficiency Virus 
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 
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 
Amarex Clinical Research as the Contract Research Organization (CRO). 
 
1.2 
THE PROBLEM STATEMENT 
Though substantial progress has been made over the past two decades in the development of 
effective and well tolerated combination antiretroviral regimens, nearly 25% of patients receiving 
Highly Active Antiretroviral Therapy (HAART) are not virologically suppressed due to various 
reasons. Recent data suggest that most virologic failure on first-line regimens occurs because of 
either pre-existing (transmitted) drug resistance or suboptimal adherence.   Patient- and regimen-
related factors play a crucial role in determining whether an antiretroviral regimen is successful 
or result in virologic failure [Office of AIDS Research Advisory Council, 2014]. 
In general, drug resistance can be considered a core issue in patients with limited treatment options. 
However, there are other known factors apart from drug resistance (such as incomplete adherence, 
medication intolerance, pharmacokinetic issues, etc.) which also contribute to limiting treatment 
options in constructing a new regimen for patients who experience treatment failure. New agents 
and drug classes (e.g., integrase inhibitors, fusion inhibitors and CCR5 antagonists) are necessary 
to keep up with ongoing viral mutations in an attempt to prevent viral replication and transmission 
[Tang MW, 2012][Gulick RM, 2008][Moyle G, 2008]. The availability of an effective 
maintenance regimen would benefit a subset of HIV-1 infected persons who are challenged by 
transferred resistance, medication adherence and/or chronic nucleoside toxicity. 
PRO 140 is a promising new antiretroviral agent that does not have any cross-resistance with drugs 
from other classes. Although PRO 140 would require subcutaneous (SC) administration, its 
favorable pharmacokinetics allows for weekly dosing. The purpose of this study is to exhibit 
antiviral activity of PRO 140 in combination with other antiretroviral agents for treatment of 
antiretroviral-experienced persons infected with CCR5-tropic HIV-1 virus. 

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1.3 
NAME AND DESCRIPTION OF THE INVESTIGATIONAL PRODUCT 
PRO 140 is a humanized IgG4, monoclonal antibody (mAb) to the C-C chemokine receptor type 
5 (CCR5), under development as a therapy for human immunodeficiency virus (HIV) infection. 
PRO 140 binds to the N terminus (Nt) and the extracellular loop 2 (ECL2) domain of the CCR5 
cell surface receptor that HIV-1 uses to gain entry to a cell. PRO 140 binding to CCR5 blocks viral 
entry by interfering with the final phase of viral binding to the cell surface prior to fusion of the 
viral and cell membranes. PRO 140 has been administered intravenously or subcutaneously to 
174 HIV-1 infected individuals in Phase I/II studies of safety, tolerability, pharmacokinetics and 
pharmacodynamics [Jacobson JM, 2010][Jacobson JM, 2010]. The drug has been well tolerated 
following administration of single doses of 0.5 to 5 mg/kg or up to three weekly doses of up to 324 
mg. Single subcutaneous doses of 324 mg have resulted in drops in plasma HIV-1 RNA levels of 
approximately 1.0 log10. Repetitive weekly administration of this dose of PRO 140 has been 
associated with drops in plasma HIV-1 RNA levels of approximately 1.5 log10. Serum 
concentrations of PRO 140 above the IC50 for clinical isolates of HIV-1 are maintained for at least 
2 weeks following a single dose of 324 mg. Plasma HIV-1 RNA levels rise to baseline levels as 
PRO 140 is cleared from the plasma and, presumably, other compartments. 
 
1.4 
SUMMARY OF PRIOR PRE-CLINICAL AND CLINICAL STUDIES 
1.4.1 Pre-Clinical Studies with PRO 140 
In vitro and in vivo preclinical studies have been conducted to determine the pharmacokinetic, 
immunogenicity, and toxicity profiles of PRO 140 following IV and SC administration. Several 
acute and chronic toxicity studies have been conducted to support the clinical development plan. 
Acute toxicity of PRO 140 was evaluated in New Zealand rabbits, following IV administration of 
5 or 15 mg/kg. Chronic toxicity was evaluated in cynomolgus monkeys following biweekly 
administration of IV doses up to 10 mg/kg for six months and biweekly administration of various 
SC doses up to 50 mg/kg for 24 weeks. The drug was generally well tolerated. Biweekly 
administration of IV doses up to 10 mg/kg for six months resulted in minimum to mild lymphoid 
hyperplasia in assorted lymph nodes and spleen, which was considered an expected immune 
response to a foreign protein. Biweekly administration of SC doses up to 50 mg/kg for 24 weeks 
resulted in minimum injection-site reactions (minimal, multifocal, mononuclear cell infiltrates in 
the subcutis), which were considered due to an inflammatory response to the injected antigen. 
Monkeys tolerated treatment with PRO 140 for 24 weeks without evidence of local or systemic 
toxicity. PRO 140 caused no mortality, cageside observations, in-life injection-site observations, 
or gross pathologic findings. Chronic treatment with PRO 140 did not affect body weight, food 
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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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1.4.2.4 PRO 140 1302 Study 
This initial proof-of-concept study was a randomized, double-blind, placebo-controlled study in 
subjects with early-stage, asymptomatic HIV infection, only CCR5 HIV-1 detectable, and no 
antiretroviral therapy for 12 weeks. Subjects (n=39) were randomized to receive a single IV 
injection of placebo or PRO 140 at doses of 0.5, 2, or 5 mg/kg. Subjects were monitored for 
antiviral effects, safety and PRO 140 pharmacokinetics (PK) for 58 days. 
The study enrolled 31 males and 8 females. The median age, CD4+ cell count and HIV-1 RNA at 
baseline were 40.3 years, 484cells/μL and 26,900 copies/mL, respectively. The baseline 
characteristics were similar for all treatment groups. 
PRO 140 demonstrated potent, rapid, prolonged and dose-dependent antiviral activity (Figure 
1-1 and Figure 1-2). A single 5mg/kg dose reduced viral loads by 1.83 log10 on average (Figure 1-
2). These reductions represent the largest antiviral effects reported after just one dose of any HIV-
1 drug [Jacobson JM, 2008]. In the 5 mg/kg group, mean viral load reductions of greater than 1 
log10 were sustained for 2-3 weeks post-treatment (Figure 1-2). 
Figure 1-1: PRO 140 1302 Study: Mean of the maximum (nadir) log10 reductions in HIV 
RNA 
 
 
 
2 
 
 
1.5  
 
 
1 
 
 
0.5 
 
 
0 
placebo
0.5 mg/kg 
2 mg/kg 
5 mg/kg 
1.83
1.2
0.58
0.39
Mean Maximum Log 10 
Reduction in HIV RNA 

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Figure 1-2: 
PRO 140 1302 Study: Mean log10 reductions in HIV RNA over time 
 
 
0. 5 
Pl acebo 
0. 5 mg/ kg 
2 mg/ kg 
5 mg/ kg 
 
 
 
0. 0 
 
 
 
- 0. 5 
 
 
 
- 1. 0 
 
 
 
- 1. 5 
 
 
 
- 2. 0 
0 
10 
20 
30 
40 
50 
60 
St udy Day 
 
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 
+++
++
++
+
+++
+++
+++
+++
+++
+ p ≤ 0.01 
++ p ≤ 0.001 
+++ p ≤ 0.0001 
Mean Log 10 C hange i n H I V - 1 R N A 

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(AUC∞) values were 11.1, 74.3 and 278 mg x day/L for the 0.5, 2 and 5 mg/kg groups. The mean 
serum half-life was 3.5-3.9 days in the two highest dose groups. In addition, PRO 140 significantly 
masked CCR5 on circulating lymphocytes for 2-4 weeks [Jacobson JM, 2008]. The PK and 
receptor occupancy data were broadly consistent with the duration of antiviral effects. 
Figure 1-3: PRO 140 1302 Study: PRO 140 serum concentrations following a single 
intravenous injection in HIV- infected individuals. 
 
0 .5 m g/k g 
2 m g /k g 
5 m g /k g 
30 0 .0 
10 0 .0 
 
 
 
10 .00 
 
 
 
1 .00 
 
 
 
0 .10 
 
0 .03 
0 
5 
10 
15 
20 
25 
30  
Study Day 
 
The figure illustrates the mean serum concentrations over time by treatment group. The error bars 
depict standard deviations. The mean serum half-lives were 3.9 days and 3.5 days in the 2 mg/kg 
and 5 mg/kg dose groups, respectively. 
Intravenous PRO 140 was generally well tolerated. No drug-related serious events or dose- limiting 
toxicity was observed. The most common adverse events (headache, lymphadenopathy, diarrhea, 
and fatigue) were observed at similar frequencies across the placebo and PRO 140 dose groups. 
There was no significant effect on QTc interval intervals or other electrocardiographic parameters, 
and there were no remarkably laboratory findings. There was no loss or depletion of CD4+ or 
CCR5+ cells from the circulation. At the 5 mg/kg dose, there was a trend towards increased CD4+ 
cell counts from baseline, with mean changes of +129, +96 and +83 cells/μL observed on days 8, 
15, and 22, respectively. 
PRO 140  Se ru m Conc entrati ong,/mL 

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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 
 
324mg Days 1,8,15 
2 
 
 
1.5 
 
 
1 
 
 
0.5 
 
 
0 
1.65
1.37
0.58
0.23
Mean Maximum Log10 Reduction in HIV RNA 

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Figure 1-6: 
PRO 140 2101 Study: Mean change from baseline in HIV-1 RNA (Log10 
copies/mL) over Time (ITT Subjects) 
 
0.5 
 
 
 
0.0 
 
 
 
-0.5 
 
 
 
-1.0 
 
 
 
-1.5 
 
1 
8 
15 
22 
29 
36 
43 
50 
57 
64 
                          
                       Study Day 
 
Treatment 
 
 
Subcutaneous PRO 140 was generally well tolerated both locally and systemically. There was no 
obvious dose-related pattern of toxicity. The most common adverse events (diarrhea, headache, 
lymphadenopathy and hypertension) were mild to moderate and self-resolving. These events are 
common in HIV infection and were reported with similar frequencies in the placebo and PRO 140 
treatment groups. Administration-site reactions were mild, transient, and observed in a fraction of 
subjects. There was a trend towards increased CD4+ cell counts in subjects treated with PRO 140 
(Figure 1-7). Based on its encouraging antiviral and tolerability profiles and the convenience of 
weekly self-administration, SC PRO 140 has been selected for further clinical development. 
 
 
 
 
 
 
 
 
 
 
 
 
Placebo 
162mg Days 1,8,15 
324mg Days 1,15 
324mg Days 1,8,15 
Mean Log10 Change in HIV-1 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 
Stu d y Da y 
 
125 
100 
75 
50 
25 
0 
-25 
-50 
 
 
1 8 15 22 29 36 43 50 57 64 
Stu d y Da y 
 
 
 
 
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 
 
 
 
 
Me d i a n Ch a n g e i n CD4 + Ce 
Me d i a n Ch a n g e i n CD4 + Ce l l s 

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in HIV-1 infected patients (with exclusive CCR5-tropic virus). Participants in this study were 
experienced HIV-infected individuals who were virologically suppressed on combination 
antiretroviral therapy. Consenting patients were shifted from combination antiretroviral regimen 
to PRO 140 monotherapy for 12 weeks. 
Forty (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 

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time of virologic failure) enrolled in the study. 
 
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. 
This clinical study is currently ongoing. 
1.4.2.9 PRO 140_CD02 Study 
PRO 140_CD02 study (double blind, placebo controlled, 50 subjects, multi-center) seeks to 
evaluate the efficacy, safety, and tolerability of PRO 140 in combination with existing ART 
(failing regimen) for one week and Optimized Background Therapy (OBT) for 24 weeks in 
patients infected with HIV-1. The study population includes 50 treatment-experienced HIV- 
infected adult patients with CCR5-tropic virus who demonstrates evidence of HIV-1 replication 
despite ongoing antiretroviral therapy with documented history of genotypic or phenotypic 
resistance to at least one ART drug within two drug classes. 
In double-blind treatment period, virally non-suppressed subjects will be randomized and treated 
with either PRO 140 or Placebo in combination with the failing ART regimen for 7 days. The 
primary efficacy endpoint is proportion of participants with ≥ 0.5 log10 reduction in HIV-1 RNA 
viral load from baseline at the end of the 7 day functional monotherapy period. 

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During the 24-week open-label period, all subjects will receive PRO 140 along with OBT. 
 
1.4.2.10 PRO 140_CD02 Extension study 
PRO 140_CD02 Extension study (open label, 50 subjects, multi-center) seeks to evaluate the 
long term efficacy, safety and tolerability of PRO 140 weekly injection in combination with 
Optimized Background Therapy (OBT) in patients infected with HIV-1. The study population 
includes 50 treatment-experienced HIV-infected adult patients with CCR5-tropic virus who 
successfully completed PRO 140_CD02 study and continue to demonstrate HIV-1 viral 
suppression. 
This clinical study is currently ongoing. 
 
1.4.2.11 PRO 140_CD03 Study 
PRO 140_CD03 study (open-label, two-arm comparator, 500 subjects, multi-center) seeks to 
evaluate the treatment strategy of using PRO 140 SC as long-acting single-agent maintenance 
therapy versus continuing combination ART for 48 weeks in virologically suppressed subjects 
with CCR5-tropic HIV-1 infection. 
The first ~150 eligible subjects were enrolled to receive PRO 140 350mg SC weekly injection in 
a single-arm study. Subsequently, next ~150 subjects were randomized 1:1 to PRO 140 350mg 
(Group A) or PRO 140 525mg (Group B). An additional ~200 subjects will be randomized 1:1 to 
PRO 140 525mg (Group B) or PRO 140 700mg (Group C). This clinical study is currently ongoing. 
1.4.2.12 PRO140_CD03 Extension Study 
PRO 140_CD03 Extension study (open label, 300 subjects, multi-center) seeks to evaluate the 
long term efficacy, safety and tolerability of PRO 140 weekly injection as long-acting single- 
agent maintenance therapy versus continuing combination ART in patients infected with HIV-1. 
The study population includes treatment-experienced HIV-infected adult patients with CCR5- 
tropic virus who successfully completed PRO 140_CD03 study and continue to demonstrate 
HIV-1 viral suppression. 
This clinical study is currently ongoing. 

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

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Protocol 
Number 
 
Phase 
No. of Subjects 
(Planned/Analyzed) 
 
Doses 
Cell line used to 
make 
PRO-140 
Subject 
Population 
 
Comments 
PRO 140 
_CD01 
2b 
40/40 
350 mg SC 
weekly dose 
for 12 Weeks 
of 
Monotherapy 
(total 
treatment 
duration 14 
Weeks) 
CHO 
HIV-1 
positive 
Generally well tolerated, no drug-related SAEs, 
weekly dose demonstrated favorable tolerability, 
and potent, long-acting, dose-dependent antiviral 
activity. Results are pending publication. 
PRO 140 
_CD01- 
Extension 
2b 
16/16 
350 mg SC 
weekly 
monotherapy 
dose 
CHO 
HIV-1 
positive 
This clinical study is currently ongoing. 
PRO 140 
_CD02 
2b/3 
50/52 
350 mg SC or 
placebo + 
ART for 1 
week, then 
350mg SC 
weekly + OBT 
for 24 weeks 
CHO 
HIV-1 
positive 
This clinical study has been completed 
PRO 140 
_CD02- 
Extension 
2b/3 
50/TBD 
350 mg SC 
weekly + OBT 
CHO 
HIV-1 
positive 
This clinical study is currently ongoing. 
PRO 140 
_CD03 
2b/3 
500/TBD 
350 mg SC 
weekly dose 
for up to 48 
weeks of 
monotherapy 
CHO 
HIV-1 
positive 
This clinical study is currently ongoing.. 

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Protocol 
Number 
 
Phase 
No. of Subjects 
(Planned/Analyzed) 
 
Doses 
Cell line used to 
make 
PRO-140 
Subject 
Population 
 
Comments 
PRO 140 
_CD03- 
Extension 
2b/3 
300/TBD 
350 mg SC 
weekly 
monotherapy 
dose 
CHO 
HIV-1 
positive 
This clinical study is currently ongoing. 

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1.5 
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. 
Majority of subjects receiving 350 mg weekly SC dosing in monotherapy setting experienced virologic 
failure in CD01-Extension study. Review of PRO 140 clinical data to date with 350mg SC weekly 
dosing, suggests no evidence of emergence of viral isolates with reduced susceptibility to PRO 140, 
no altered viral tropism or anti-PRO 140 antibodies formation suggesting the most likely cause of viral 
rebound is inadequate dosing to fully cover CCR5 receptor populations. Based on pharmacologic 
modeling studies, we anticipate that the 700mg dose will result in a lower fraction of study participants 
with trough levels below that which will ‘uncoat’ a significant number of CD4 cells (i.e., less than a 
certain multiple of the IC50 or IC90 for PRO 140). 
 
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 700mg 
SC injection) 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 700mg SC injection) to the failing regimen may not be 
effective in achieving a reduction in viral load for all subjects. Such cases could lead to an 

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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 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 

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As with all research there is the remote possibility of risks that are unknown or that cannot be 
foreseen based on current information. 
1.6.1.8 Theoretical risk for increased severity of West Nile virus infection 
Individuals who lack a functional CCR5 gene are at increased risk for severe infection by West 
Nile virus [Thompson, 2009] Because of this, treatment with CCR5 co-receptor antagonists poses 
a theoretical risk for increased severity of West Nile virus infection. However, this concern is 
mitigated by several factors. First, no increased risk was observed for individuals who possess one 
functional and one non-functional CCR5 gene, indicating that an intermediate amount of CCR5 is 
sufficient for defense against West Nile virus [Thompson, 2009]. Second, use of CCR5 co-receptor 
antagonists is unlikely to completely abrogate CCR5 function, and there has been no association 
reported to date between CCR5 co-receptor use and severe West Nile virus. Additionally, PRO 
140 weakly antagonizes the natural activity of CCR5 and thus is less likely to adversely affect 
immune function. Furthermore, this has not been established to be a risk with maraviroc, the anti-
CCR5 drug already FDA-approved for the treatment of HIV. 
Collectively, the experience with both IV and SC, simulation modeling and the recent confirmation 
that a higher concentration of PRO 140 synthesized using a highly efficient CHO cell line can be 
conveniently and safely administered has resulted in the design of the current study. 
 
1.6.2 INTENDED BENEFIT FOR SUBJECTS 
This study provides an opportunity for subjects to have 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 efficacy, clinical safety and tolerability parameters of PRO 
140 in reducing HIV-1 viral load in patients on their current ART (failing regimen) during the 1- 
week treatment period, and in combination with Optimized Background Therapy during the 
subsequent 24-week treatment period. 
The primary efficacy endpoint is proportion of participants with ≥ 0.5 log10 reduction in HIV-1 
RNA viral load from baseline at the end of the initial 1-week treatment period. 
The secondary efficacy endpoints will be proportion of participants with ≥ 1 log10 reduction in 
HIV-1 RNA viral load from baseline at the end of the initial 1-week treatment period, mean change 
from Baseline in HIV-1 RNA levels (log10 copies/mL) at the end of the initial 1-week treatment 
period, 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, mean change from Baseline in 
HIV-1 RNA levels (log10 copies/mL) at week 25, mean change from Baseline in CD4 cell count 
at the end of 1-week treatment period, and mean change from Baseline in CD4 cell count at week 
25. 
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 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 classes, or two drug classes with limited treatment options. 
The study is divided into four phases: Screening, Baseline,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 Baseline visit is to confirm HIV RNA continues to meet eligibility and will be conducted 
one week pior to the first treatment. 
The Treatment phase is divided into two parts: 
 Part 1: One-week treatment period consisting of PRO 140 along with existing ART (failed 
regimen). 
 Part 2: 24-week treatment period consisting of 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 Treatment Phase Part 1, all subjects will enter 
the 24-week treatment period (Part 2).   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 Treatment Phase Part 2 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. 
Note: Subjects who are currently enrolled and receiving 350 mg dose will have the option to move 
to the 700 mg dose for the remainder of their participation in the trial. 

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3.1 
STUDY CENTER(S) 
Up to 40 centers in the United States 
 
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. 
 
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. Participation in an experimental drug trial(s) within 30 days of the Screening Visit 
12. Any known allergy or antibodies to the study drug or excipients 
13. 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 
14. 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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Yes 
No
No
Yes
 
 
 
 
 
 
 
 
 
Figure 3-1: 
Study Flow Diagram 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 Week 
(PRO 140 + Existing 
ART) 
(Existing ART) 
24 Weeks (PRO 140 + OBT) 
TREATMENT PHASE 
T1 to T25 Visits 
BASLELINE 
SCREENING PHASE 
FOLLOW UP PHASE 
4 Weeks (or up to 6 Months in subjects who 
experienced treatment failure) 
Up to 1 Week 
Up to 6 Weeks 
25 Weeks 
 
 
 
 
 
 
 
 

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4 
STUDY SCHEDULE 
As shown in Figure 4-1, this study is divided into three phases: Screening, Treatment and 
Follow-up. 
Figure 4-1: 
Study Schematic 
 
Baseline 
Up to 1 week 
 
 
T0 Visit 
1 Wk Treatment Period 
 
 
 
 
 
 
 
 
 
 
 
 
 
Regimen. 
 
 
 
 
 
 
 
 
Subject to continue on 
Failing ART Regimen 
 
*Optimized background therapy (OBT) is chosen on the basis of a 
subject’s resistance test results and treatment history. 
 
 
 
 
*or up to maximum of 
6 months after 
experiencing 
Treatment Failure 
(TF) if the treating 
physician does not 
feel that there is an 
antiretroviral regimen 
that will regain full 
viral suppression. 
 
 
(1) Screening Phase: This phase lasts up to 6 weeks, consists of Screening Visit (SV) and 
begins with signing of Informed Consent. Assessments performed during this phase 
determine the subject’s final eligibility for study participation. First treatment will be 
administered within 42 days of Screening Visit. 
All subjects will continue taking their existing ART (failed regimen) during the Screening 
Phase and first week of the Treatment Phase (Part 1). 
(2) Baseline: The Baseline (T0) visit will take place within 6 weeks of the Screening Visit, 
as soon as HIV-1 viral tropism, genotypic and/or phenotypic resistance results are available 
for review by Investigator.   HIV RNA and TruCount Assay will be performed to ensure 
continued eligibility prior to the first Treatment Visit (T1). 
(3) Treatment Phase: Subjects will receive up to 25 treatments, given approximately every 
week (window period of ±3 days) or until treatment failure is experienced, whichever 
comes first. 
The first Treatment Visit (T1) will take place within one week of the T0 visit. 
The injectable study treatment (PRO 140) will be administered by a qualified medical 
 
Existing 
ART only 
PRO 140 700 mg weekly S.C. Inj. + Optimized background therapy* 
(OBT) 
End of Study 
(Safety Follow- 
Up Visit) 
 
Treatment 
Phase 
25 weeks 
24 Wk Treatment Period 
T2 to T25 Visits 
Follow-Up
Phase 
4 weeks OR until 
viral suppression 
is achieved* 
T1 Visit 
 
PRO 140 700 mg + 
Existing ART 
 
  
 
 
Screening 
Phase 
Up to 6 weeks 
Screening Visit 
 
 
HIV-Infected 
patient 
population: 
Treatment- 
experienced 
Patients who are 
failing on their 
current ART 

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professional (MD, DO, PA, LPN, LVN, NP,RN, or CMA if permitted by state law) or 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. 
Any time during Treatment Period Part 2, 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 
Part 2 of the Treatment Phase 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 Treatment Period Part 
2. [Assessment Timepoint:T3 visit] 
 <1 log10 copies/mL decrease in HIV-1 RNA at or after Week 4 of Treatment Period 
Part 2 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 25 of the 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 
Treatment Period Part 2 [Assessment Timepoint: from T3 up to T25 visit] or 
*Note: This refers to “Nadir” level in the Treatment Phase which starts from T2 
visit 
 ≥400 copies/mL after suppression to <50 copies/mL in Treatment Period Part 2. 
[Assessment Timepoint: from T3 up to T25 visit] 
(4) Follow-Up Phase: The duration of follow-up depends on whether or not subject has 
experienced treatment failure during Treatment Period Part 2. 
 Subjects who experience treatment failure within Treatment Period Part 2 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. 

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 Subjects who do not experience treatment failure at the end of Treatment Period Part 
2, will be followed up every 2 weeks for total of 4 weeks. 
Procedures to be performed during each of these study phases are described below and provided 
as a Schedule of Assessments in Table 4-1 and Table 4-2. 

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Table 4-1: 
Schedule of Assessments – Screening and Treatment Phase 
 
 
 
Procedure/Assessments 
 
Screeni 
ng Visit
Treatment Phase (26 weeks) 
 
In case of 
Treatment 
Failure 
ART 
only 
(1 week)
IP + ART 
(1 week) 
IP + OBT 
(24 weeks) 
 
Visit
 
SV 
 
T0 
T1
 
T2 
 
T3 
 
T4-6 
 
T7 
 
T8 - 10 
 
T11 
 
T12-14 
 
T15 
 
T16-18 
 
T19 
 
T20-22 
 
T23 
 
T24-25 
 
EOT 
 
TF 
(Pre-
Rx) 
(Post-
Rx) 
 
 
Window Period
 
 
Within 6 
weeks of 
the 
Screening 
visit 
 
 
Within 1 week 
±3 days since T0 
 
1 week 
±3 days 
since last 
treatment
 
1 week 
±3 days 
since last 
treatment 
 
1 week 
±3 days 
since last 
treatment
 
1 week 
±3 days 
since last 
treatment
 
1 week 
±3 days 
since last 
treatment
 
1 week 
±3 days 
since last 
treatment
 
1 week 
±3 days 
since last 
treatment
 
1 week 
±3 days 
since last 
treatment
 
1 week 
±3 days 
since last 
treatment 
 
1 week 
±3 days 
since last 
treatment
 
1 week 
±3 days 
since last 
treatment 
 
1 week 
±3 days 
since last 
treatment 
 
1 week 
±3 days 
since last 
treatment 
 
1 week 
±3 days 
since last 
treatment 
 
Informed Consent[1] 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Eligibility Evaluation[2] 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Subject Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical History[3] 
X 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HIV History 
X 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical Examination 
X 
 
X[4]  
X[4] 
X[4] 
 
X[4] 
 
X[4] 
 
X[4] 
 
X[4] 
 
X[4] 
 
X 
X 
Neurological Examination[5]  
 
X 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
Vital Signs[6] 
X 
 
 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
Body Mass Index 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
ECG 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Complete Blood Count[7] 
X 
 
 
 
 
 
 
X 
 
 
 
X 
 
 
 
 
 
X 
X 
Biochemistry[8] 
X 
 
 
 
 
 
 
X 
 
 
 
X 
 
 
 
 
 
X 
X 
Coagulation Indices[9] 
X 
 
 
 
 
 
 
X 
 
 
 
X 
 
 
 
 
 
X 
X 
Serum Pregnancy Test[10] 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urinalysis[11] 
X 
 
 
 
 
 
 
X 
 
 
 
X 
 
 
 
 
 
X 
X 
HBsAg 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Plasma HIV-1 RNA level 
X 
X 
X 
 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
TruCount T assay[12] 
X 
X 
X 
 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
PK conc. to PRO 140[13] 
 
 
X 
 
 
 
 
X 
 
 
 
X 
 
 
 
 
 
X 
X 

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Procedure/Assessments 
 
Screeni 
ng Visit
Treatment Phase (26 weeks) 
 
In case of 
Treatment 
Failure 
ART 
only 
(1 week)
IP + ART 
(1 week) 
IP + OBT 
(24 weeks) 
 
Visit
 
SV 
 
T0 
T1
 
T2 
 
T3 
 
T4-6 
 
T7 
 
T8 - 10 
 
T11 
 
T12-14 
 
T15 
 
T16-18 
 
T19 
 
T20-22 
 
T23 
 
T24-25 
 
EOT 
 
TF 
(Pre-
Rx) 
(Post-
Rx) 
 
 
Window Period
 
 
Within 6 
weeks of 
the 
Screening 
visit 
 
 
Within 1 week 
±3 days since T0 
 
1 week 
±3 days 
since last 
treatment
 
1 week 
±3 days 
since last 
treatment 
 
1 week 
±3 days 
since last 
treatment
 
1 week 
±3 days 
since last 
treatment
 
1 week 
±3 days 
since last 
treatment
 
1 week 
±3 days 
since last 
treatment
 
1 week 
±3 days 
since last 
treatment
 
1 week 
±3 days 
since last 
treatment
 
1 week 
±3 days 
since last 
treatment 
 
1 week 
±3 days 
since last 
treatment
 
1 week 
±3 days 
since last 
treatment 
 
1 week 
±3 days 
since last 
treatment 
 
1 week 
±3 days 
since last 
treatment 
 
1 week 
±3 days 
since last 
treatment 
 
Serum conc. of ART 
Drugs[14] 
 
 
X 
 
 
 
 
X 
 
 
 
X 
 
 
 
 
 
X 
X 
Urine Pregnancy Test[10] 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pre-enrollment Eligibility 
 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PRO 140 + Existing ART 
Regimen 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PRO 140 + OBT 
Administration 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Injection Site Reaction 
Assessment[15] 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Injection Site Pain 
Assessment (VAS)[16] 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
HIV-1 Trofile® Assay[17] 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
HIV-1 Drug Resistance 
Assay[18] 
X 
 
X 
 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
X 
HIV-1 PhenoSense® Entry 
Assay[19] 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Anti-idiotypic antibodies to 
PRO 140 
 
 
X 
 
 
 
 
X 
 
 
 
X 
 
 
 
 
 
X 
X 
Blood sample collection for 
exploratory analysis[20] 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Adverse Events 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant Medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 

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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 (i.e.,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] Injection Site Reaction Assessment as assessed by Investigator (or designee) at each treatment visit that occurs in the clinic. 
[16] 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 that occurs in the clinic. 
[17] Monogram Biosciences Trofile® DNA and RNA 
[18] 
Monogram Biosciences PhenoSense® GT and Gensosure Archive (and PhenoSense Integrase and GeneSeq Integrase testing, if applicable) 
[19] Monogram Biosciences HIV-1 PhenoSense® Entry assay with AMD3100 (CXCR4 inhibitor drug), Maraviroc and PRO 140 (CCR5 inhibitor drugs). 
[20] Quest Diagnostics HIV-1 Coreceptor Tropism with Reflex to Ultradeep Sequencing and/or HIV-1 Proviral Tropism 

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Table 4-2: 
Schedule of Assessments –Follow-Up (FU) Phase 
(a) Subjects who do NOT experience treatment failure 
 
Procedure/Assessments 
Follow-Up Visit -1 
Follow-Up Visit -2 
 
NTF-FU1 
NTF-FU2 
Window Period
2 weeks 
(±3 days) after EOT visit 
4 weeks 
(±3 days) after EOT visit 
Physical Examination 
X[1] 
X[1] 
Vital Signs 
X 
X 
Plasma HIV-1 RNA level 
X 
X 
TruCount T assay 
X 
X 
Adverse Events 
X 
X 
Concomitant Medications 
X 
X 
Anti-idiotypic Antibodies to PRO 140 
 
X 
[1] 
Symptom-directed physical examination 
 
 
(b) Subjects who experience treatment failure 
 
Procedure/Assessments 
Follow-Up Visit -1 
Follow-Up Visit -2 
Follow-Up Visit -3[1] 
 
TF-FU1 
TF-FU2 
TF-FU3 
Window Period
4 weeks 
(±7 days) after TF visit 
8 weeks 
(±7 days) after TF 
12 weeks
(±7 days) after TF 
Physical Examination 
X[2] 
X[2] 
X[2] 
Vital Signs 
X 
X 
X 
Plasma HIV-1 RNA level 
X 
X 
X 
TruCount T assay 
X 
X 
X 
Adverse Events 
X 
X 
X 
Concomitant Medications 
X 
X 
X 
Anti-idiotypic Antibodies to PRO 140 
X 
 
 
[1] 
 Subject will be followed up till the viral suppression is achieved or up to a maximum of 6 months after experiencing 
Treatment Failure (TF) if the treating physician does not feel that there is an antiretroviral regimen that will regain full 
viral suppression. 
[2] 
Symptom-directed physical examination 

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4.1 
SCREENING PHASE 
4.1.1 Pre-Screening 
Sites are encouraged to pre-screen subjects for study inclusion, evaluating HIV-1 RNA prior to 
performing a full screening visit. 
 
The subject will sign and date the pre-screening informed consent form (ICF) prior to any study- 
related pre-screening procedures. A unique identification number (pre-screening number) will be 
assigned to each subject who has provided written pre-screening informed consent. The pre- 
screening number will incorporate a three-digit Study Center number (PS201, PS202, PS203….) 
and a two-digit numeric ID assigned in successive order of consenting to pre-screening procedures 
after signing the pre-screening ICF at each center, beginning with 001 at each site (e.g. PS201-01 
or PS202-01). 
 
Once the pre-screening ICF has been signed, the following procedures and information will be 
obtained to confirm pre- eligibility including: 
• Review of prior medical records for ART history and resistance to ART drugs 
• Blood sample collection for HIV-1 RNA and TruCount assay 
 
A pre-screening log will be maintained to capture the following information: 
• Pre-screening number 
• Patient initials 
• Date pre-screened 
• Initial eligibility 
• Date of re-consent (for the full consent form) or reason for ineligibility 
 
4.1.2 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

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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 
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. 

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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 
BASELINE 
The Baseline (T0) visit will be performed for subjects who have met all eligibility criteria within 
6 weeks of the Screening Visit, as soon as HIV-1 viral tropism, genotypic and/or phenotypic 
resistance results are available for review by Investigator. HIV RNA and TruCount Assay will be 
performed to ensure continued eligibility prior to the first Treatment Visit (T1). Subjects who have 
an HIV RNA result >400 copies/mL will be enrolled at the T1 visit. Subjects who have an HIV 
RNA result <400 copies/mL will be designated as screen failure. 
The following assessments will be performed at the T0 visit: 
 Change in concomitant medications (see section 7.5) 
 Collection of Blood Specimens (see section 7.11) for 
o Plasma HIV-1 RNA level 
o TruCount T Assay 
 
4.3 
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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Eligible subjects will receive up to 25 treatments injections, given once per week (± 3 days) or until 
treatment failure, whichever occurs first. Eligible subjects will receive PRO 140 700mg 
administered as two subcutaneous injections within the first week of the Treatment Phase, followed 
by two subcutaneous injections of PRO 140 700mg, given once per week (± 3 days) for up to 24 
weeks. 
Treatment Phase is divided into two parts: 
 Part 1: One-week treatment period [PRO 140 + failing ART]Part 2: 24-week treatment 
period [PRO 140 + OBT] 
Note: A confirmatory HIV RNA test will be completed one week prior to initiation of treatment 
with PRO 140. 
As shown in Table 4-3, enrolled subjects will have IP along with failing ART for one week. 
Table 4-3 Part 1: One week period [IP (PRO 140) + existing ART] 
 
Study Drug 
Dosage 
Form 
IP 
concentration 
Dosing Frequency and Amount 
Route of 
Administration 
PRO 140 
Parenteral 
solution 
175 mg/mL 
2 injections of PRO 140 (2 X 2 mL/inj.) 
at T1 visit 
SC injection 
 
As shown in Table 4-4, all enrolled subjects will receive PRO 140 along with optimized background 
therapy (OBT) for up to 24 weeks after completing the initial 7-day treatment period. 
Table 4-4      Part 2: 24-week treatment maintenance period [PRO 140 + OBT] 
 
Study Drug 
Dosage 
Form 
IP 
concentration 
Dosing Frequency and Amount 
Route of 
Administration 
PRO 140 
Parenteral 
solution 
175 mg/mL 
2 injections of PRO 140 (2 X 2 mL/inj.) 
per week for up to 24 weeks (T2 – T25) 
SC injection 
The study treatment (PRO 140 SC injections) will be administered by a qualified medical 
professional (MD, DO, PA, LPN, LVN, NP, RN, or CMA if permitted by state law ) or self- 
administered by subjects depending on the study visit week. 
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. 
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 

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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. 
 
 
4.3.1 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 
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. 

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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) 
Administration of study treatment [PRO 140] 
Study treatment will be administered weekly as a subcutaneous injection in the abdomen. 
Subjects will receive the study treatment delivered as two 1 mL injections on opposite sides of the 
abdomen. 
Note: All study treatments (PRO 140) must be administered by a qualified medical professional 
(MD, DO, PA, LPN, LVN, NP, RN, or CMA if permitted by state law ) or self-administered by 
subjects depending on the study visit week. 
Post-Treatment 
 Injection Site Reaction Assessment (see section 7.13) 
 Note: To assess injection site reactions, the investigator will use the DAIDS AE grading 
table (refer to section 16.3). 
 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. 
4.3.2 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 7.13) 
 Note: To assess injection site reactions, the investigator will use the DAIDS AE grading 
table (refer to section 16.3). 
 Subject-perceived Injection Site Pain Assessment (see section 7.14) 
 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. 
4.3.3 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 7.14), 
 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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4.3.4 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 Treatment Phase Part 2. 
[Assessment Timepoint:T3 visit] 
 <1 log10 copies/mL decrease in HIV-1 RNA at or after Week 4 of Treatment Phase Part 2 
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 Treatment Phase 
Part 2. [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 Treatment 
Phase Part 2 [Assessment Timepoint: from T3 up to T25 visit] or 
*Note: This refers to “Nadir” level in Treatment Phase Part 2 which starts from T2 visit. 
 ≥400 copies/mL after suppression to <50 copies/mL in Treatment Phase Part 2. 
[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 7.14), 
 Collection of Blood Specimens (see section 7.11) for 
o Plasma HIV-1 RNA level 
o TruCount T Assay 
o Complete Blood Count 
o Biochemistry 
o HIV Drug Resistance Assay 
o HIV PhenoSense Entry® Assay 
o HIV Trofile® Assay 

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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. 
 
4.4 
FOLLOW-UP PHASE 
The duration of follow-up depends on whether subject experiences treatment failure. 
 Subjects who experience treatment failure within Treatment Phase Part 2 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 Treatment Phase Part 2, will 
be followed up every 2 weeks for total of 4 weeks. 
4.4.1 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) 
 
4.5 
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 Treatment Phase Part 2 (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 Treatment Phase Part 2. 
[Assessment Timepoint:T3 visit] 
 <1 log10 copies/mL decrease in HIV-1 RNA at or after Week 4 of Treatment Phase 
Part 2 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 Treatment 
Phase Part 2. [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 Treatment 
Phase Part 2 [Assessment Timepoint: from T3 up to T25 visit] or 
*Note: This refers to “Nadir” level in Treatment Phase Part 2 which starts from T2 visit 
 ≥400 copies/mL after suppression to <50 copies/mL in Treatment Phase Part 2. 
[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 16.1) under which 
subject is unable to continue treatment with study drug (PRO 140), or subject require treatment 
with prohibited concomitant medications. 
 Shows signs or symptoms of clinically significant immunosuppression 
 Subject or the subject’s clinician wishes to adjust OBT (except in the event of toxicity 
management). 
 Subject becomes pregnant. 

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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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6 
STUDY TREATMENT 
 
6.1 
INVESTIGATIONAL PRODUCT DESCRIPTION 
PRO 140 is a humanized IgG4, monoclonal antibody (mAb) to the chemokine receptor CCR5. 
PRO 140 is provided at a concentration of 175 mg/mL and is intended for SC route of 
administration. 
Kits will be labeled with a unique identification number. Each kit used during Part 1 and Part 2 of 
the Treatment Phase will contain two vials of PRO 140 for SC injection. One milliliter (1 mL) of 
PRO 140 solution will be drawn from each vial and loaded into the syringe. A total of 700 mg (175 
mg/mL) of PRO 140 is delivered as two 2 mL injections administered subcutaneously on opposite 
sides of the abdomen. One study injection kit will be assigned per subject per treatment visit. 
Each vial of the PRO 140 product contains ~1.4 mL antibody at 175mg/ml in a buffer containing 
5 mM L-histidine, 15.0 mM glycine, 95 mM sodium chloride, 0.3% (w/v) sorbitol, 0.005% (w/v) 
polysorbate 20 (Tween 20®), and sterile water for injection, at pH of 5.5. 
 
 
 
Table 6-1 and Table 6-2 provide the unit strength, dosing frequency and mode of administration 
for the study drug. 
 
Table 6-1: 
Investigational Product - PRO 140 at T1 visit 
 
Study Drug 
Dosage 
Form 
IP 
concentration 
Dosing Frequency and Amount 
Route of 
Administration 
 
PRO 140 
Parenteral 
solution 
 
175 mg/mL 
2 injections of PRO 140 (2 X 2mL/inj.) 
per week on opposite sides of abdomen at T1 
visit 
 
SC injection 
 
Table 6-2: 
Investigational Product - PRO 140 at T2 - T25 visit 
 
Study Drug 
Dosage 
Form 
IP 
concentration 
Dosing Frequency and Amount 
Route of 
Administration 
 
PRO 140 
Parenteral 
solution 
 
175 mg/mL 
2 injections of PRO 140 (2 X 2mL/inj.) 
per week on opposite sides of abdomen 
for up to 24 weeks (T2 – T25) 
 
SC injection 
Note: 1 mL injection will be drawn from 1.4 mL solution in a vial. Remaining 0.4 mL medication 
will be discarded appropriately from each vial. 

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Note: Patients with low body fat percentages may find subcutaneous injections uncomfortable. In 
such cases, PRO 140 700 mg can be injected as four 175mg/ml injections of 1 mL each and/or can 
be placed at different areas other than abdomen as per discretion of the Investigator. 
 
6.2 
INVESTIGATIONAL PRODUCT PACKAGING AND LABELING 
Study drug will be prepared by Ajinomoto Althea, Inc. and will be packaged, labeled, and shipped 
by Sherpa Clinical Packaging, LLC. 
The contents of each vial are described in Section 6.1. PRO 140 kits will be labeled with information 
such as: study protocol #; fill volume; concentration; storage condition; a “use as per study 
protocol” statement; a cautionary statement; sponsor’s name and address; and the kit number. 
Below are representative samples of the Investigational Product, Fixed Dose Procedure (FDP) 
individual vial ( 
Figure 6-1), syringe label (Figure 6-2), and kit labels (Figure 6-3) designated for use in this clinical 
protocol. Each kit contains two labeled vials and two syringe labels. 
 
Figure 6-1: 
Investigational Product - Vial Label 
Part 1: One-week treatment period (T1) 
Protocol: PRO 140_CD02 
Kit No. xxx 
Subject No.   
 
Single use 3 mL vial contains 1.4 mL of PRO 140 (175 
mg/mL) solution for subcutaneous injection 
Store at 2oC to 8oC (36oF to 46oF) 
USE AS PER STUDY PROTOCOL 
Caution: New Drug – Limited by Federal (or United States) 
Law to Investigational Use 
CytoDyn Inc., Vancouver, WA, USA 
Protocol: PRO 140_CD02 
Kit No. xxx 
Subject No.   
 
Single use 3 mL vial contains 1.4 mL of PRO 140 (175 
mg/mL) solution for subcutaneous injection 
Store at 2oC to 8oC (36oF to 46oF) 
USE AS PER STUDY PROTOCOL 
Caution: New Drug – Limited by Federal (or United States) 
Law to Investigational Use 
CytoDyn Inc., Vancouver, WA, USA 

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Part 2: 24-week treatment period (T2 – T25) 
 
Protocol: PRO 140_CD02 
Kit No. xxx 
Subject No.   
 
Single use 3 mL vial contains 1.4 mL of PRO 140 (175 
mg/mL) solution for subcutaneous injection 
Store at 2oC to 8oC (36oF to 46oF) 
USE AS PER STUDY PROTOCOL 
Caution: New Drug – Limited by Federal (or United States) 
Law to Investigational Use 
CytoDyn Inc., Vancouver, WA, USA 
Protocol: PRO 140_CD02 
Kit No. xxx 
Subject No. _  
 
Single use 3 mL vial contains 1.4 mL of PRO 140 (175 
mg/mL) solution for subcutaneous injection 
Store at 2oC to 8oC (36oF to 46oF) 
USE AS PER STUDY PROTOCOL 
Caution: New Drug – Limited by Federal (or United States) 
Law to Investigational Use 
CytoDyn Inc., Vancouver, WA, USA 
 
Figure 6-2: 
Investigational Product - Syringe Label 
Part 1: One-week treatment period (T1) 
 
 
 
Part 2: 24-week treatment period (T2 – T25) 
 
Protocol: PRO 140_CD02
Contents of Kit No. xxx
This syringe contains 1 mL PRO 140 (175 mg/mL) solution for subcutaneous 
injection 
 
USE AS PER STUDY PROTOCOL 
 
Caution: New Drug – Limited by Federal (or United States) Law to 
Investigational Use 
 
CytoDyn Inc., Vancouver, WA, USA
Protocol: PRO 140_CD02
Contents of Kit No. xxx
This syringe contains 1 mL PRO 140 (175 mg/mL) solution for subcutaneous 
injection 
 
USE AS PER STUDY PROTOCOL 
 
Caution: New Drug – Limited by Federal (or United States) Law to 
Investigational Use 
 
CytoDyn Inc., Vancouver, WA, USA

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Figure 6-3: 
Investigational Product - Kit Label 
Part 1: One-week treatment period (T1) 
 
 
 
Part 2: 24-week treatment period (T2 – T25) 
 
 
Protocol: PRO 140_CD02
Kit No. xxx
Site No. 
Subject No.  
This kit contains 2 single-use vials
 
Each 3 mL vial contains 1.4 mL of PRO 140 (175 mg/mL) solution for 
subcutaneous injection 
 
Store at 2oC to 8oC (36oF to 46oF) 
USE AS PER STUDY PROTOCOL 
Caution: New Drug – Limited by Federal (or United States) Law to Investigational 
Use 
 
CytoDyn Inc., Vancouver, WA, USA
Protocol: PRO 140_CD02
Kit No. xxx
Site No. 
Subject No.  
This kit contains 2 single-use vials
 
Each 3 mL vial contains 1.4 mL of PRO 140 (175 mg/mL) solution for 
subcutaneous injection 
 
Store at 2oC to 8oC (36oF to 46oF) 
USE AS PER STUDY PROTOCOL 
Caution: New Drug – Limited by Federal (or United States) Law to Investigational 
Use 
 
CytoDyn Inc., Vancouver, WA, USA

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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 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. 
Note: Patients with low body fat percentages may find subcutaneous injections uncomfortable. In 
such cases, PRO 140 700 mg can be injected as four 175mg/ml injections of 1 mL each and/or can 
be placed at different areas other than abdomen as per discretion of the Investigator. 
Following each SC delivery of drug, careful examination will be made to assess the appearance of 
any study drug Injection Site Reactions (ISRs) as described in Section 16.3. 
All doses of study drug will be prepared by either the credentialed pharmacist or qualified medical 
professional and will be administered as SC injection by a qualified medical professional 

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(MD, DO, PA, LPN, LVN, NP, RN, or CMA if permitted by state law) or self-administered by 
subjects depending on the study visit week. 
Note: It is preferred that the same injection site be used throughout the study. At the same time, it 
is not recommended to inject the study drug into areas where skin shows signs of a previous 
injection site reaction. It is advised to change the injection site if any previous injection site reaction 
remains unresolved. 
 
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 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 16.4 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, T7, T15 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, T7, T15, 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, T12, EOT and TF.
 Urine samples will be tested for color, appearance, specific gravity, pH, protein, glucose, 
occult blood, ketones, leukocyte esterase, nitrite, bilirubin, urobilinogen, and microscopic 
examination of urine sediment
7.11.14 Coagulation Indices 
 
Frequency of testing: At the Screening Visit, T12, EOT and TF.
 
Prothrombin time (PT) and International Normalized Ratio (INR)
 
 
All laboratory reports will be reviewed by the Investigator. 
Post-treatment abnormal results that are considered by the Investigator to be clinically significant 
will be recorded as adverse events. If the Investigator judges it necessary, testing may be repeated 
in order to make the determination of clinical significance. Validated, quality-controlled laboratory 
data will be transferred to the main database for analyses. 
 
7.12 INVESTIGATIONAL PRODUCT ADMINISTRATION 
Refer to Section 6.4 for details. 
 
7.13 INJECTION SITE REACTION ASSESSMENT 
At each treatment visit that occurs at the clinical site, an injection site reaction assessment will be 
made for the current and previous injection sites. Injection site reaction assessments are recorded 
by the Investigator (or designee) starting after the first injection is given. Refer to sections 9.1.8 
and 16.3 for more details. 
 
7.14 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 

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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 an open label study. All eligible subjects will receive study treatment within 6 weeks of 
Screening Visit, followed by weekly subcutaneous injections of study treatment for up to 24 weeks. 
 
8.2 
DESCRIPTION OF STUDY ENDPOINTS 
8.2.1 Primary Endpoint 
The primary endpoint for this study is proportion of participants with a ≥ 0.5 log10 reduction in HIV-
1 RNA viral load from baseline to the end of the initial 1-week treatment period. 
8.2.2 Secondary Endpoint 
The secondary endpoints will be as follows: 
1. Proportion of participants with ≥ 1 log10 reduction in HIV-1 RNA viral load from baseline 
to the end of the initial 1-week treatment period 
2. Mean change from Baseline in HIV-1 RNA levels (log10 copies/mL) to the end of the 
initial 1-week treatment period 
3. Percentage of participants achieving HIV-1 RNA < 400 copies/mL at week 25 
4. Percentage of participants achieving HIV-1 RNA < 50 copies/mL at week 25 
5. Mean change from Baseline in HIV-1 RNA levels (log10 copies/mL) at week 25 
6. Mean change from Baseline in CD4 cell count at the end of the initial 1-week treatment 
period 
7. Mean change from Baseline in CD4 cell count at week 25 
 
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 

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 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 
Up to 25 subjects (or any number of subjects that can be enrolled by the time of BLA submission 
for PRO 140) will be enrolled in this study. The sample size is based on clinical judgement with an 
intention to supplement the data for the target BLA indication. 
 
8.4 
RANDOMIZATION AND BLINDING 
No randomization or blinding requirement. 
 
8.5 
INTERIM ANALYSIS 
No interim analysis planned for this study. 
 
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 enrolled and have 
received at least one dose of PRO 140. 
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 safety 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. 
8.6.1.3 Safety Population 
The Safety population is defined as all subjects who received at least one dose of PRO 140. This 
population will be used for the analysis of safety parameters. 

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8.6.2 Statistical Methods 
All collected study data will be presented in subject data listings. Statistical analyses will be 
performed using SAS® for Windows, version 9.4 or later. 
A SAP will be developed and approved before the database is locked. The SAP will present the 
detailed statistical methodology to be used in analyzing the efficacy and safety data from this trial 
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. 
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 

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The primary analysis will be conducted on the ITT population. 
All data from the primary and secondary endpoints will be summarized and tabulated according 
to the variable type: 
 Continuous data summaries will include: 
Number of observations, mean, standard deviation, median, and minimum and 
maximum values. 
 Categorical data summaries will include: 
o Frequency counts and percentages. 
 
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: 
 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. 

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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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The investigator will carefully evaluate the comments of each subject and the response to treatment 
in order to judge the true nature and severity of the AE. The question of the relationship of AEs to 
study drug should be determined by the investigator after thorough consideration of all available 
facts. To assess severity, the investigator will use the DAIDS AE grading table (for adverse events 
as well as any injection site reactions refer to Section 16.2 and Section 16.3). 
The general guidelines for assessing the AE grade appear below. Full guidelines may be obtained 
at http://rsc.tech- 
res.com/Document/safetyandpharmacovigilance/DAIDS_AE_Grading_Table_v2_NOV2014. 
 
Table 9-1: 
DAIDS AE Grading Table v2 General Guidelines 
 
Grade 
Description 
Grade 1 
indicates a mild event 
Grade 2 
indicates a moderate event 
Grade 3 
indicates a severe event 
Grade 4 
indicates a potentially life-threatening event 
Grade 5 
Death related to AE. 
DAIDS AE Grading Table Version 2.0- November 2014 
 
9.1.4 Causality Assessment 
Adverse events will be assigned a relationship (causality) to the study treatment. The Principal 
Investigator (PI) must review each AE and make the determination of relationship of the event to 
the study treatment. Relationship of AEs to study treatment will be classified as follows: 
1. Definitely related: This category applies to those AEs that the Investigator feels are 
incontrovertibly related to the study treatment. An AE may be assigned an attribution of 
definitely related if or when it meets all of the following criteria: (1) it follows a reasonable 
temporal sequence from administration of the study treatment; (2) it could not be reasonably 
explained by the known characteristics of the subject’s clinical state, environmental or toxic 
factors, or other modes of therapy administered to the subject; (3) it follows a known 
response pattern to treatment with the study treatment. 
2. Probably related: This category applies to those AEs which, after careful medical 
consideration at the time they are evaluated, are felt with a high degree of certainty to be 
related to the study treatment. An AE may be considered probable if or when (must have 
three): (1) it follows a reasonable temporal sequence from administration of the study 
treatment. (2) It could not readily have been produced by subject’s clinical state, 
environmental or toxic factors, or other therapies administered to the subject. (3) Disappears 
or is decreased upon discontinuation of the study treatment. (4) It follows a 

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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 
fatigue. 

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9.1.8 SC Injection-related Events 
SC and IV injections of concentrated protein materials can be associated with injection-related AEs 
that impact the ability to safely and successfully deliver the drug. Local injection-site reactions may 
include pain/discomfort, induration, erythema, nodules/cysts, pruritus, ecchymosis, etc. For SC 
injections, bleeding, absorption of the drug, leakage of drug, and induration at the local injection 
site can be additional complications. Other AEs that are common to monoclonal antibody-based 
therapies are chills, headache, backache, malaise, fever, pruritus, rash, nausea, tingling, and 
hypertension. 
SC injection-related events will be monitored according to the guidelines provided in Section 16.2 
(Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events [DAIDS 
AE Grading Table]). Injection-site reactions thought to be directly related to the injection are 
considered to be AEs of special interest, and a separate guideline for the acquisition of data 
related to this AE of special interest is provided in Section 16.3. 
For subjects who develop grade 1 or grade 2 events, continue therapy as per protocol. If a subject 
chooses to discontinue study treatment, the site should notify the protocol team leadership, and 
encourage the subject to complete any remaining study visits until the toxicity resolves. 
For subjects who develop grade 3 events following study drug injection, the subject should be 
reevaluated closely until the AE returns to Grade ≤2, at which time study treatment may be 
reintroduced at the discretion of the site investigator. If the same Grade 3 AE recurs following the 
next administration of study drug, study treatment must be permanently discontinued. Subjects 
experiencing Grade 3 AEs requiring permanent discontinuation of study treatment should be 
followed closely for resolution of the AE to Grade ≤ 2 and the team leadership must be notified. 
Subjects with Grade 3 asymptomatic laboratory abnormalities in cholesterol, creatine kinase (CK) 
or triglycerides may continue study treatment. 
For grade 4 events permanently discontinue therapy. 
 
9.2 
SERIOUS ADVERSE EVENTS (SAE) 
A SAE is defined as any AE that: 
 Results in death 
 
 Is life threatening (the subject is at immediate risk of dying from the AE) 
 
 Requires subject hospitalization or prolongs existing hospitalization 
 
 Results in persistent or significant disability/incapacity 
 
 Is a congenital anomaly/birth defect 

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Important medical events that may not result in death, be life-threatening, or require hospitalization 
may be considered a serious adverse event when, based upon appropriate medical judgement, 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 Amarex 
Safety Department within 24 hours: 
 
CRO Medical Monitor 
Attn: Shide Badri, MD 
Amarex LLC 
20201 Century Boulevard, Suite 450 
Germantown, MD 20874 
Email: saereporting@amarexcro.com 
Phone: +1 (240) 454-6844 
Fax: +1 (240) 454-6602 
The Amarex Medical Monitor may request additional supporting documentation as it becomes 
available, such as lab reports, ECG reports, discharge summary, hospital notes, etc. 
The Investigator is also responsible for reporting all SAEs to the appropriate Institutional Review 
Board (IRB) in accordance with local laws and regulations. The Investigator is responsible for 
maintaining documentation in the study file that indicates the IRB has been properly notified. Under 
21 CFR 312.32(c), the sponsor is required to notify FDA and all participating investigators in an 
IND safety report (i.e., 7- or 15-day expedited report) of potentially serious risks from clinical trials 
or any other source as soon as possible, but no later than 15 calendar days after the sponsor receives 
the safety information and determines that the information qualifies for reporting. Participating 
investigators include all investigators to whom the sponsor is providing drug under any of its INDs 
or under any investigator’s IND (21 CFR 312.32(c)(1)). 

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9.3.1   SAE Follow-Up 
All subjects experiencing an SAE, including the discontinued subjects, must be closely followed 
until sufficient information is obtained to indicate a return to normal status or until the event 
stabilizes at a level acceptable to the investigator (i.e., recovery, return to baseline status, no further 
improvement expected, or death). 
For each SAE indicated as an unresolved event on the initial report, regardless of whether the 
subject completed the study or withdrew, the site should submit a follow-up report with updated 
information. 

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

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11 QUALITY CONTROL AND QUALITY ASSURANCE 
 
11.1 MONITORING REQUIREMENTS 
In an effort to fulfill the obligations outlined in 21 Code of Federal Regulations (CFR) Part 312 and 
ICH guidelines which requires the Sponsor to maintain current personal knowledge of the progress 
of a study, the Sponsor's designated monitor will visit the center(s) during the study as well as 
maintain frequent telephone and written communication. The Investigator will permit the Sponsor 
to monitor the study as frequently as is deemed necessary and provide access to medical records to 
ensure that data are being recorded adequately, that data are verifiable and that protocol adherence 
is satisfactory. 
The Investigator will permit representatives of the Sponsor and/or designated CRO to inspect all 
eCRFs and corresponding study subject original medical records (source documents) at regular 
intervals throughout the study. Subject original medical records and other relevant data must be 
available to support all data recorded in the eCRF. In addition to the original medical records, these 
data may include but are not limited to, study, laboratory and diagnostic reports, neurological 
examination results, etc. 
Site inspections serve to verify strict adherence to the protocol and the accuracy of the data being 
entered on the case report forms, in accordance with federal regulations. A Monitoring Log will be 
maintained at each study site which the monitor will sign, date and state the type of visit. 
The Investigator should be aware that the study site and subject records may be inspected by the 
Sponsor and or representatives of the designated CRO, FDA or other regional regulatory authority. 
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 ETHICS AND REGULATORY REQUIREMENTS 
This study is to be conducted in accordance with the specifications of this protocol and in 
accordance with principles consistent with Declaration of Helsinki, GCP, 21 CFR Part 312, ICH 
E6, HIPAA regulations in 45 CFR Part 164 (US only), and the Belmont Principles of respect for 
persons, beneficence, and justice. No protocol changes will be implemented without the prior 
review and approval of the IRB, except when the modification does not involve the subject’s 
participation in the trial or where it may be necessary to eliminate an immediate hazard to a research 
subject. In the latter case, the change will be reported to the IRB as soon as possible, according to 
IRB regulations. 
Additionally, all study products used in this study are manufactured, handled and stored in 
accordance with applicable GMP and the products provided for this study will be used only in 
accordance with this protocol. 
 
12.1 INSTITUTIONAL REVIEW BOARD/INDEPENDENT ETHICS COMMITTEE (IRB/IEC) 
The Principal Investigator at the site will provide the Institutional Review Board/Independent 
Ethics Committee (IRB/IEC) with all appropriate materials as required by their IRB/IEC, including 
but not limited to the clinical study protocol, informed consent form, and any advertising materials. 
The study will not be initiated until the IRB/IEC provides written approval of the aforementioned 
documents and until approval documents have been obtained by the Principal Investigator and 
Sponsor or Sponsor designee. The Investigator will not participate in the decision. If the 
Investigator is an IRB or IEC member, documentation must be provided indicating recusal from 
the approval process. Appropriate reports on the progress of this study by the Principal Investigator 
will be made to the IRB/IEC as required by local and applicable government regulations and in 
agreement with policy established by the Sponsor. The Investigator is required to maintain an 
accurate and complete record of all written correspondence to and received from the IRB/IEC, and 
must agree to share all such documents and reports with the Sponsor. 
No changes from the final approved protocol will be initiated without the IRB/IEC’s prior written 
approval or favorable opinion of a written amendment, except when necessary to eliminate 
immediate hazards to the subjects or when the modification does not involve the subject’s 
participation in the trial. 
 
12.2 INVESTIGATOR’S RESPONSIBILITIES 
The Investigators are responsible for performing the study in full accordance with the protocol 
and the current revision of the Declaration of Helsinki, the Good Clinical Practice: Consolidated 
Guideline, approved by the ICH, and any applicable national and local laws and regulations. 

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Information regarding any study centers participating in this study that cannot comply with these 
standards will be documented. 
 
12.3 SUBJECT INFORMED CONSENT REQUIREMENTS 
Written and oral information about the study in a language understandable by the subject will be 
given to all subjects by the Investigator and/or designee. Written informed consent will be obtained 
from each subject before any procedures or assessments that would not otherwise be required for 
the care of the subject are done and after the aims, methods, anticipated benefits, potential hazards, 
and insurance arrangements in force are explained and the subject has been given sufficient time to 
ask questions and consider participation in the study. It will also be explained to the subjects that 
they are free to refuse entry into the study and free to withdraw from the study at any time without 
prejudice to future treatment. It is permissible for a third person (e.g., a family member) to be 
present during the explanation of the study. 
The written Informed Consent Form ICF is to be in compliance with CFR 21 Part 50.27 and GCP 
guidelines. The Sponsor and/or designated CRO will approve the ICF and all amendments to the 
ICF prior to submission to the IRB/IEC. A copy of the ICF to be used will be submitted by the 
Investigator to the IRB/IEC for review and approval prior to the start of the study. Each study site 
must provide the Sponsor with an unsigned copy of IRB/IEC-approved ICF along with applicable 
documentation to support this approval. The original signed ICF is retained in the subject's study 
records, and a copy is provided to the subject. A second copy may be filed in the subject’s medical 
record, if allowed by institutional policy. 

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13 DATA HANDLING AND RECORD KEEPING 
 
13.1 RECORDING AND COLLECTION OF DATA 
The primary source document for this study will be the subject's medical record. If separate research 
records are maintained by the Investigator(s), the medical record and the research records will be 
considered the source documents for the purposes of auditing the study. 
Applicable source data will be manually transcribed to the approved eCRFs. The Investigator is 
ultimately responsible for the accuracy of the data transcribed on the forms. All source documents 
and eCRFs will be completed as soon as possible after the subject's visit. 
The Investigator will review eCRFs to indicate that, to his/her knowledge, they are complete and 
accurate. Designated source documents will be signed and dated by the appropriate study personnel. 
The Investigator must agree to complete and maintain source documents and eCRFs for each 
subject participating in the study. 
All research data will be entered, either electronically or manually, into a computerized database. 
The clinical database will be designed by the clinical data manager in accordance with 21 CFR Part 
11 and based on protocol requirements defined by the Sponsor in association with the Lead 
Investigator. 
The Investigator will maintain a confidential list of study subjects that will include each subject’s 
study number, name, date of birth, and unique hospital identification number if applicable. This list 
will be kept by the Investigator and will not be collected by the Sponsor. A notation will be made 
in the subject’s case history/medical chart that he/she is participating in a clinical study and has 
provided a signed and dated ICF as well as a release for protected health information as required 
by local policies. The Investigator must also maintain a separate screening log of all the subjects 
screened for participation in the study; it should include gender, age, eligibility status, reason for 
ineligibility, if applicable; and study allocated subject number, if applicable. 
 
13.2 CLINICAL DATA MANAGEMENT 
The Sponsor and/or designated CRO will be responsible for the processing and quality control (QC) 
of the data. Data management will be carried out as described in the Sponsor’s or CRO’s standard 
operating procedures (SOPs) for clinical studies. 
The handling of data, including data QC, will comply with regulatory guidelines (e.g., ICH E6 
GCP, and local regulations where applicable) and the Sponsor’s or the CRO’s SOPs as well as 
provisions of the study-specific Data Management Plan. 

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13.3 ARCHIVING 
All study documentation at the Investigator site and Sponsor site will be archived in accordance 
with ICH GCP E6 and the Sponsor’s quality standards and SOPs. 
The Investigator will maintain all research records, reports, and case history reports for a period 
of two years after regulatory approval of the investigational product. If no application is filed or if 
the application is not approved, records must be maintained for two years after all investigations 
have been completed, terminated or discontinued and the FDA has been notified. 
These documents should be retained for a longer period however, if required by the applicable 
regulatory requirements or if needed by Sponsor or its authorized representative (as per GCP 
5.5.11). 
At the completion of the study, details of the archival process must be provided to the Sponsor. 
Study records are subject to inspection by applicable health and regulatory agencies at any time. 
Records to be retained by the Investigator include, but are not restricted to: 
 Source data and the primary records upon which they are based (e.g., subject’s progress 
notes, adverse event data, test results, and any other diagnostic procedures required to 
evaluate the progress of the study) 
 Completed CRFs 
 Signed protocols and protocol amendments 
 Laboratory results, ranges, and certifications 
 Product (e.g., IP supplies) and accountability records 
 Study personnel signature log 
 Monitoring logs 
 Correspondence to and from the Sponsor, designee and IRB 
 Investigator and sub-investigator CVs 
 Signed informed consent and protected health information consent forms 
 Subject screening and enrollment log 
 SAE reports 
 IRB approval and re-approval letters 
 Other documents pertaining to the conduct of the study 
These documents must be maintained and kept on file by the Investigator so that the conduct of the 
study can be fully documented and monitored. 
At the completion of the study, details of the archival process must be provided to the Sponsor. 
Study records should not be transferred from site or destroyed without prior written agreement 
between the Sponsor and the study Investigator. 

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

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

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

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

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

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 Toxoplasmosis of brain, onset at age >1 month† 
 Wasting syndrome attributed to HIV 
 
* Only among children aged <13 years. (CDC. 1994 Revised classification system for human immunodeficiency 
virus infection in children less than 13 years of age. MMWR 1994;43[No. RR-12].) 
† Condition that might be diagnosed presumptively. 
§ Only among adults and adolescents aged >13 years. (CDC. 1993 Revised classification system for HIV infection 
and expanded surveillance case definition for AIDS among adolescents and adults. MMWR 1992;41[No. RR-17].) 
 
 
Source: http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5710a2.htm 

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16.2 APPENDIX II: DIVISION OF AIDS TABLE FOR GRADING THE SEVERITY OF ADULT AND 
PEDIATRIC ADVERSE EVENTS (DAIDS AE GRADING TABLE) 
http://rsc.tech- 
res.com/Document/safetyandpharmacovigilance/DAIDS_AE_Grading_Table_v2_NOV2014.pdf 

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

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