Conditions: Graft Vs Host Disease
Keywords: Allogeneic Stem Cell Transplantation
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 11
Healthy volunteers: no

Brief summary:
This is a Phase II, Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study of the Safety and Efficacy of PRO 140 for Prophylaxis of Acute Graft-Versus-Host Disease in Patients with Acute Myeloid Leukemia (AML) or Myelodysplastic Syndromes (MDS) Undergoing Allogeneic Stem-Cell Transplantation.

Detailed description:
This is a Phase II, randomized, double-blind, placebo-controlled, multi-center study to evaluate the feasibility of the use of PRO 140 as an add-on therapy to standard GVHD prophylaxis treatment for prevention of acute GVHD in adult patients with AML or MDS undergoing allogeneic HCT.

In this study, 60 subjects will be randomized to receive either PRO 140 or placebo in a 1:1 ratio (i.e., 30 subjects per arm). PRO 140 or placebo will be administered as a 350 mg subcutaneous injection on Day -3 or Day -2 prior to stem cell infusion, on the day of stem cell infusion (Day 0), and then weekly for 30 days (at Week 1, Week 2, Week 3 and Week 4) after which it will be administered every two weeks for up to 100±7 days (at Week 6, Week 8, Week 10, Week 12 and Week 14). Subjects will return to clinic for two Follow-up visits at 2 weeks after the last treatment visit, and one year after the first treatment visit.

Arms:
arm 1: In this study, 60 subjects will be randomized to receive either PRO 140 or placebo in a 1:1 ratio (i.e. 30 subjects per arm). PRO 140 or placebo will be administered as a 350 mg subcutaneous injection.

Placebo will be administered -2/-3 days before the stem cell infusion, on the day of stem cell infusion (Day 0) and thereafter on days 7, 14, 21, 28, 42, 56, 70, 84 and 98 as per the study schedule of assessments.

Each vial of the Placebo contains 5mM Histidine, 15 mM Glycine, 95 mM Sodium Chloride, 0.3% (w/v) Sorbitol, 0.005% (w/v) Polysorbate 20 at a pH of 5.5.

Each 350 mg dose of placebo consist of 2 SC injections of placebo (5mM Histidine, 15 mM Glycine, 95 mM Sodium Chloride, 0.3% (w/v) Sorbitol, 0.005% (w/v) Polysorbate 20 at a pH of 5.5) of 2 X 1 mL/inj. on opposite sides of abdomen. arm 2: In this study, 60 subjects will be randomized to receive either PRO 140 or placebo in a 1:1 ratio (i.e.,30 subjects per arm). PRO 140 or placebo will be administered as a 350 mg subcutaneous injection.

PRO 140 will be administered -2/-3 days before the stem cell infusion, on the day of stem cell infusion (Day 0) and thereafter on days 7, 14, 21, 28, 42, 56, 70, 84 and 98 as per the study schedule of assessments.

Each vial of the PRO 140 product contains 1.4 mL antibody at 175 mg/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.

Each 350 mg dose of PRO 140 will consist of 2 SC injections of PRO 140 (2 X 1 mL/inj.) on opposite sides of abdomen.

Interventions: intervention 1: PRO 140 intervention 2: Placebo
Intervention descriptions: intervention 1: PRO 140 is a humanized IgG4,κ monoclonal antibody (mAb) to the chemokine receptor CCR5. intervention 2: Placebo in parenteral solution.

Protocol document:
Prot_000.pdf: 
CONFIDENTIAL
Page 1 of 108
A Phase II, Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study of the 
Safety and Efficacy of PRO 140 for Prophylaxis of Acute Graft-Versus-Host Disease in 
Patients With Acute Myeloid Leukemia (AML) or Myelodysplastic Syndromes (MDS) 
Undergoing Allogeneic Stem-Cell Transplantation 
Protocol Number:
PRO 140_CD 03_GVHD
Version:
3.0
Date:
17 Jun 2016 
Sponsor:
CytoDyn, Inc.
1111 Main Street, Suite 660 
Vancouver, Washington 98660
(360) 980-8524-Work
(360) 980-8549-Fax
www.cytodyn.com 
Confidentiality Statement
This document is a confidential communication of CytoDyn, Inc. It is provided for the conduct 
of a clinical research study. The information contained in this document is confidential and, 
except to the extent necessary to obtain informed consent or IEC/IRB approval, cannot be 
disclosed unless required by governmental regulation. Persons to whom any portion of the 
contents of this document is disclosed must be informed that the information is confidential and 
may not be further disclosed by them. 


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PROTOCOL APPROVAL PAGE
Protocol Number:  
PRO 140_CD 03_GVHD
Version: 
 
3.0 
Date:
 
17 Jun 2016 
We, the undersigned, have reviewed this protocol and agree that it contains all relevant 
information required to meet FDA, GCP and all applicable regulatory guidelines and statutes.


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INVESTIGATOR’S SIGNATURE PAGE
Protocol Number:  
PRO 140_CD 03_GVHD
Version: 
 
3.0 
Date:
 
17 Jun 2016 
INVESTIGATOR’S SIGNATURE
I have read the protocol specified above and agree to participate in and comply with the 
procedures, as outlined herein for the conduct of this clinical trial. I also agree to comply with the 
applicable US Food and Drug Administration (FDA) regulations and Investigational Review Board 
(IRB) requirements for testing on human subjects. I agree to ensure that the requirements for 
obtaining informed consent are met.  
Principal Investigator’s Signature
Date
Print Name
Address
Site Number


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PROTOCOL SYNOPSIS
Name of Sponsor/Company: CytoDyn Inc.
Protocol Number: PRO 140_CD 03_GVHD
Investigational Product:  
PRO 140 (Humanized monoclonal antibody to CCR5) or Placebo
Indication:
Prophylaxis of Acute Graft-Versus-Host Disease (GVHD) in Patients With Acute Myeloid Leukemia (AML) 
or Myelodysplastic Syndromes (MDS) Undergoing Allogeneic Stem-Cell Transplantation
Title of Study
A Phase II, Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study of the Safety and Efficacy of 
PRO 140 for Prophylaxis of Acute Graft-Versus-Host Disease in Patients With Acute Myeloid Leukemia 
(AML) or Myelodysplastic Syndromes (MDS) Undergoing Allogeneic Stem-Cell Transplantation. 
Clinical Phase
Phase II 
Concept and Rationale
Acute myeloid leukemia (AML) is the most common acute leukemia in adults. The American Cancer Society 
estimates that in 2015, there will be 20,830 new cases of AML diagnosed in the United States, and about 
10,460 deaths from AML have been projected. AML is generally a disease of older people with average age of 
a patient with AML being 66 years. The lifetime risk of being diagnosed with AML for the average American 
man is about 1 in 227 and for the average American woman the risk is about 1 in 278. The mainstay of 
induction therapy for AML for the past 40 years has been combination chemotherapy, which has resulted in 
approximately 60-70% complete remission rate and 30-40% 5-year overall survival.
Myelodysplastic Syndromes (MDS) is a heterogeneous group of clonal malignant hematopoietic stem cell 
disorders characterized by hyper- or hypocellular marrows, peripheral blood cytopenias, and cell function 
abnormalities resulting from failure of hematopoietic differentiation. MDS has a highly variable natural 
history with a variable risk of transformation to AML. The annual incidence of MDS in the US is 10-100 per 
million but might be higher in the elderly population. 
Notwithstanding the use of combination chemotherapy for AML and MDS, these two, often related disorders 
remain the leading indications for allogeneic hematopoietic cell transplantation (HCT) in adults. 
Even though allogeneic HCT is the treatment of choice for offering the curative option to patients with AML 
with unfavorable cytogenetics or molecular mutations as well as to patients with MDS, whether it should be 
offered to all patients in first remission of AML or to all patients with MDS is contested.  
Transplantation-related mortality can be as high as 20-30%, which can counterbalance the potential 
advantages. Graft Versus Host Disease (GVHD) is one of the major causes of post-transplant morbidity and 
mortality.
Migration of donor cells, particularly T-cells, into different tissues including skin, liver and gastrointestinal 


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Name of Sponsor/Company: CytoDyn Inc.
Protocol Number: PRO 140_CD 03_GVHD
Investigational Product:  
PRO 140 (Humanized monoclonal antibody to CCR5) or Placebo
Indication:
Prophylaxis of Acute Graft-Versus-Host Disease (GVHD) in Patients With Acute Myeloid Leukemia (AML) 
or Myelodysplastic Syndromes (MDS) Undergoing Allogeneic Stem-Cell Transplantation
(GI) tract and recognition of the host histocompatibility antigens is critical in development of GVHD. Small 
molecules and monoclonal antibodies that block chemokine receptors such as CCR5, are in theory able to 
lessen the migration of donor cells into tissues. Therefore, blocking CCR5 after allogeneic HCT may reduce 
the occurrence rates of GVHD. PRO 140 is a humanized monoclonal antibody directed against CCR5. This 
study will investigate the safety and efficacy of pharmacologic inhibition of CCR5 in prevention of acute 
GVHD by administering PRO 140 as an add-on therapy to standard GVHD prophylaxis to adult patients with 
AML or MDS undergoing allogeneic HCT.
Study Objectives
The primary objective of this study is to assess the efficacy of PRO 140 compared to placebo as an add-on 
therapy to standard GVHD prophylaxis in adult patients with AML or MDS undergoing allogeneic HCT 
The secondary objective of this study is to assess safety and tolerability of PRO 140 compared to placebo 
as an add-on therapy to standard GVHD prophylaxis in adult patients with AML or MDS undergoing 
allogeneic HCT
Study Endpoints
Primary Efficacy Endpoint
Incidence of  Grade II , Grade III or Grade IV acute GVHD by Day-100 
Secondary Efficacy Endpoints
Incidence of severe and life-threatening (Grade III and Grade IV) acute GVHD by Day-100 
Incidence of organ-specific acute GVHD by Day-100 
Donor engraftment evaluated by T-cell and myeloid chimerism in peripheral blood
Neutrophil and platelet count recovery 
Changes in ECOG performance score
GVHD-free survival (GFS)
Safety Assessments
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 emergent adverse events and serious adverse events


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Name of Sponsor/Company: CytoDyn Inc.
Protocol Number: PRO 140_CD 03_GVHD
Investigational Product:  
PRO 140 (Humanized monoclonal antibody to CCR5) or Placebo
Indication:
Prophylaxis of Acute Graft-Versus-Host Disease (GVHD) in Patients With Acute Myeloid Leukemia (AML) 
or Myelodysplastic Syndromes (MDS) Undergoing Allogeneic Stem-Cell Transplantation
AML or MDS relapse rate by Day-100
Changes and shifts in laboratory measurements over time
Changes in Electrocardiogram (ECG) parameters over time
Study Design
This is a Phase II, randomized, double-blind, placebo-controlled, multi-center study to evaluate the feasibility 
of the use of PRO 140 as an add-on therapy to standard GVHD prophylaxis treatment for prevention of acute 
GVHD in adult patients with AML or MDS undergoing allogeneic HCT. 
In this study, 60 subjects will be randomized to receive either PRO 140 or placebo in a 1:1 ratio (i.e. 30 
subjects per arm). PRO 140 or placebo will be administered as a 350 mg subcutaneous injection on Day -3 or 
Day -2 prior to stem cell infusion, on the day of stem cell infusion (Day 0), and then weekly for 30 days (at 
Week 1, Week 2, Week 3 and Week 4) after which it will be administered every two weeks for up to 100±7 
days (at Week 6, Week 8, Week 10, Week 12 and Week 14). Subjects will return to clinic for two Follow-up 
visits at 2 weeks after the last treatment visit, and one year after the first treatment visit.
Planned Number of Subjects
60
Planned Number of Center(s)
Multi-center study including up to 20 sites in the US 
Inclusion Criteria
Subjects may be included in the study only if they meet all of the following inclusion criteria:   
1.
Patients diagnosed with AML or MDS per below: 
o
Patients with a history of histologically or pathologically confirmed diagnosis of AML and < 
5% blasts in the peripheral blood or bone marrow (per bone marrow aspiration and/or biopsy 
within 6 weeks prior to screening) scheduled to undergo allogeneic stem-cell transplantation
o
Patients with a histologically or pathologically confirmed diagnosis of MDS with < 10% 
blasts in the bone marrow (per bone marrow aspiration and/or biopsy within 6 weeks prior to 
screening) scheduled to undergo allogeneic stem-cell transplantation


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Name of Sponsor/Company: CytoDyn Inc.
Protocol Number: PRO 140_CD 03_GVHD
Investigational Product:  
PRO 140 (Humanized monoclonal antibody to CCR5) or Placebo
Indication:
Prophylaxis of Acute Graft-Versus-Host Disease (GVHD) in Patients With Acute Myeloid Leukemia (AML) 
or Myelodysplastic Syndromes (MDS) Undergoing Allogeneic Stem-Cell Transplantation
2.
Eastern Cooperative Oncology Group (ECOG) performance status score  2  
3.
Patients must have normal organ function as defined below: 
Males and females, age 18 and  65 years of age
Myeloablative allogeneic HCT:  
Total bilirubin  2 mg/dL (except in patients with Gilbert’s Syndrome) 
AST/ALT 
institutional upper limit of normal (except in patients with 
leukemic infiltration of liver)
Serum creatinine 
creatinine clearance  60 ml/hr 
Diffusing capacity of the lung for carbon monoxide (DLCO) > 50% predicted with no 
symptomatic pulmonary disease 
Cardiac ejection fraction  50%. If between 40-49% a cardiology consult is required
Clinically normal resting 12-lead ECG at screening visit or, if abnormal, considered 
not clinically significant by the PI
4.
Patients must have a reasonable expectation of 
5.
The donor-recipient HLA match criteria required for participation in this protocol are not research 
subjects in this study and they must meet criteria as National Marrow Donor Program (NMDP) 
donors. Procedures for selection of donors and stem cell dose will follow FDA requirements for Blood 
Products (21 CFR 640) and Human Cellular and Tissue Based Products (21 CFR 1271). The standard 
institutional practices for stem cell transplants also will be followed. The donors are:
o
HLA-Identical Sibling (6/6): Minimal typing necessary is serologic typing for class I (AB) 
and molecular typing for class II (DRB1)
o
Matched Unrelated Donor (8/8): Molecular identity at HLA A, B, C and DRB1 by high-
resolution typing
o
Matched Related and Unrelated Donor (7/8): high-resolution molecular typing at the 
following loci is required: HLA A, B, C and DRB1
6.
Both male and female patients and their partners of childbearing potential must agree to use 


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Name of Sponsor/Company: CytoDyn Inc.
Protocol Number: PRO 140_CD 03_GVHD
Investigational Product:  
PRO 140 (Humanized monoclonal antibody to CCR5) or Placebo
Indication:
Prophylaxis of Acute Graft-Versus-Host Disease (GVHD) in Patients With Acute Myeloid Leukemia (AML) 
or Myelodysplastic Syndromes (MDS) Undergoing Allogeneic Stem-Cell Transplantation
appropriate birth control methods (birth control pills, barriers, or abstinence) throughout the study 
duration (excluding women who are not of childbearing potential and men who have been sterilized). 
Females of childbearing potential must have a negative serum pregnancy test at Screening visit and 
negative urine pregnancy test prior to receiving the first dose of study drug.  
7.
Patients must understand and voluntarily sign an informed consent form 
Exclusion Criteria
Subjects will be excluded from the study if they meet one or more of the following exclusion criteria: 
1.
Patients not expected to be available for follow-up for at least 114 days after transplant
2.
Patients who have received prior allogeneic stem cell-transplantation 
3.
Patients who receive post-transplant high dose cyclophosphamide 
4.
Patients with active central nervous system (CNS) involvement by malignant cells
5.
Patients receiving other investigational drugs for GVHD. Co-enrollment in other clinical trials that do 
not include experimental GVHD therapies is allowed 
6.
Prior use of any experimental or approved CCR5 modulators including maraviroc and PRO 140  
7.
Patients with uncontrolled bacterial, viral or fungal infections including diagnosis of acute viral 
hepatitis (defined as any active infection with hepatitis A or a new diagnosis of hepatitis B or C within 
24 weeks of transplant) 
8.
Currently active second malignancy other than non-melanoma skin cancers
9.
Presence of fluid collection (ascites, pleural or pericardial effusion) that interferes with methotrexate 
clearance or makes methotrexate use contraindicated
10. Patients who are HIV positive 
11. Females who are pregnant, lactating, or breastfeeding, or who plan to become pregnant during the 
study 
12. Subjects on chronic steroid therapy 
5 mg/day within 2 weeks of screening except for inhaled, nasal, 
or topical steroids
13. Any other clinical condition that, in the Investigator's judgment, would potentially compromise study 


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Name of Sponsor/Company: CytoDyn Inc.
Protocol Number: PRO 140_CD 03_GVHD
Investigational Product:  
PRO 140 (Humanized monoclonal antibody to CCR5) or Placebo
Indication:
Prophylaxis of Acute Graft-Versus-Host Disease (GVHD) in Patients With Acute Myeloid Leukemia (AML) 
or Myelodysplastic Syndromes (MDS) Undergoing Allogeneic Stem-Cell Transplantation
compliance or the ability to evaluate safety/efficacy
Statistical Considerations
For this two arm clinical trial, it is planned to have a total of 60 subjects (30 per treatment group). The sample 
size is on the basis of clinical judgment and not based on statistical power calculation. The number of subjects 
was deemed adequate to provide clinically meaningful descriptive results consistent with study objectives.
Sample Size Determination and Rationale: 
There will be a safety interim analysis after the first 10 subjects complete the treatment or withdraw from the 
study, whichever occurs first. The data from this interim analysis will be reviewed by an independent Data 
Monitoring Committee (DMC). The DMC responsibilities will be further elaborated in the study DMC 
charter.  
Interim Analysis:  
There is no planned interim analysis for efficacy.
All data from the secondary endpoints will be summarized and tabulated according to the variable type:  
Statistical Analysis Considerations:
Continuous data summaries will include: 
o
Descriptive statistics (n, mean, standard deviation, median, minimum and maximum) will be 
presented by treatment group  
o
For inferential statistics, if the Normality assumption is met, t-test will be used and if the 
Normality assumption is not met, a non-parametric method will be used.  
Categorical data summaries 
o
Frequencies and percentages will be presented by treatment group.  
o
For inferential statistics Chi-square or fisher’s exact test will be used.
The primary analysis will be conducted on the intention-to-treat (ITT) population. The per-protocol (PP)
population will be used for supportive analysis. 
A Statistical Analysis Plan (SAP) will be developed to detail the statistical consideration and data convention 
prior to database lock.  


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TABLE OF CONTENTS
TABLE OF CONTENTS ............................................................................................................26
List of Tables .................................................................................................................................31
List of Figures ...............................................................................................................................32
List of Abbreviations .....................................................................................................................33
1
INTRODUCTION..................................................................................................................36
1.1
Statement of Intent ..............................................................................................................36
1.2
Background .........................................................................................................................36
1.3
Name and Description of the Investigational Product .........................................................38
1.4
Summary of Prior Pre-Clinical And Clinical Studies .........................................................38
1.4.1
Pre-Clinical Studies with PRO 140 ...................................................................38
1.4.2
Impact of PRO 140 on homing of stem cells ....................................................39
1.4.3
Clinical Studies with PRO 140 ..........................................................................40
1.4.3.1
PRO 140 1101 Study .........................................................................................40
1.4.3.2
PRO 140 1102 Study .........................................................................................40
1.4.3.3
PRO 140 1103 Study .........................................................................................40
1.4.3.4
PRO 140 1302 Study .........................................................................................40
1.4.3.5
PRO 140 2301 Study .........................................................................................41
1.4.3.6
PRO 140 2101 Study .........................................................................................41
1.4.3.7
PRO 140-CD01 Study .......................................................................................42
1.4.3.8
PRO 140-CD01 Extension Study ......................................................................43
1.4.3.9
PRO 140-CD02 Study .......................................................................................43
1.4.3.10
PRO 140-CD03 HIV Study ...............................................................................44
1.5
Rationale for Dose Selection ...............................................................................................47
1.6
Risks / Benefits Assessment ................................................................................................47
1.6.1 Risks/Discomfort to Subjects and Precautions to Minimize Risk .......................................47
1.6.1.1
Allergic Reaction ...............................................................................................47
1.6.1.2
Immune Response .............................................................................................47
1.6.1.3
Pregnancy ..........................................................................................................47
1.6.1.4
Venipuncture .....................................................................................................48
1.6.1.5
Unknown Risks .................................................................................................48
1.6.1.6
Theoretical risk for increased severity of West Nile virus infection .................48
1.6.2 Intended Benefit for Subjects ..............................................................................................48


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2
STUDY OBJECTIVES ..........................................................................................................49
3
STUDY DESIGN ....................................................................................................................50
3.1
Study Center(s) ....................................................................................................................50
3.2
Study Population .................................................................................................................50
3.3
Eligibility Criteria ................................................................................................................50
3.3.1
Inclusion Criteria ...............................................................................................50
3.3.2
Exclusion Criteria ..............................................................................................51
4
STUDY SCHEDULE .............................................................................................................54
4.1
Screening Phase ...................................................................................................................58
4.1.1
Screening Visit ..................................................................................................58
4.2
Treatment Phase ..................................................................................................................59
4.2.1
Treatment Visit-1 (T1) ......................................................................................59
4.2.2
Treatment Visit-2 (T2) - Stem Cell Infusion (Day 0) .......................................60
4.2.3
Treatment Visit-3 to Treatment Visit-11 (T11) .................................................61
4.3
Follow-up Phase ..................................................................................................................62
4.3.1
Follow-Up Visit 1 ..............................................................................................62
4.3.2
Follow-up Visit 2...............................................................................................62
5
SUBJECT COMPLETION AND WITHDRAWAL ..........................................................63
5.1
Subject Completion .............................................................................................................63
5.2
Subject Withdrawal .............................................................................................................63
5.2.1
Data Collected for Withdrawn Subjects ............................................................63
5.3
Screen Failures ....................................................................................................................64
6
STUDY TREATMENTS .......................................................................................................65
6.1
Investigational Product Description ....................................................................................65
6.2
Investigational Product Packaging and Labeling ................................................................65
6.3
Investigational Product Storage ...........................................................................................67
6.4
Investigational Product Administration ...............................................................................67
6.5
Investigational Product Receipt and Accountability ...........................................................68
6.6
Investigational Product Disposition ....................................................................................68
7
DESCRIPTION OF PROTOCOL ASSESSMENTS AND PROCEDURES ...................69
7.1
Informed Consent ................................................................................................................69
7.2
Assessment of Eligibility .....................................................................................................69
7.2.1
Re-screening ......................................................................................................69


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7.3
Demographic Information ...................................................................................................69
7.4
Medical History ...................................................................................................................70
7.5
Prior / Concomitant Medications and Non-Study Treatments ............................................71
7.5.1
Excluded Medications and Therapies ................................................................71
7.5.2
Allowable Medications and Therapies ..............................................................71
7.6
Physical Examination ..........................................................................................................71
7.7
Electrocardiogram ...............................................................................................................72
7.8
Human Immunodeficiency Virus (HIV) Rapid Antigen Test .............................................72
7.9
Vital Signs, Height and Weight ...........................................................................................72
7.10 Eastern Cooperative Oncology Group (ECOG) Performance Status ..................................73
7.11 Clinical Laboratory Assessments ........................................................................................73
7.11.1
Routine CBC .....................................................................................................73
7.11.2
Biochemistry .....................................................................................................74
7.11.3
Population Pharmacokinetics ............................................................................74
7.11.4
Lymphocyte phenotype panel ...........................................................................74
7.11.5
T-cell and Myeloid chimerism evaluation.........................................................74
7.11.6
Anti-idiotypic antibodies to PRO 140 ...............................................................74
7.11.7
Serum pregnancy test ........................................................................................74
7.11.8
Urinalysis...........................................................................................................74
7.12 Randomization .....................................................................................................................75
7.13 PRO 140 Administration .....................................................................................................75
7.14 Standard of Care ..................................................................................................................75
7.15 Injection Site Reaction assessment ......................................................................................76
7.16 Pain Assessment using Visual Analog Scale (VAS) ...........................................................76
7.17 Acute GVHD Diagnosis ......................................................................................................77
7.18 Acute GVHD Clinical Grading and Staging .......................................................................77
7.19 Standard Institutional Practices For Stem Cell Infusion .....................................................79
7.19.1
Conditioning Regimen of Stem Cells ................................................................79
8
STATISTICAL CONSIDERATIONS .................................................................................80
8.1
Treatment Groups ................................................................................................................80
8.2
Description of Study Endpoints ..........................................................................................80
8.2.1
Primary Efficacy Endpoint ................................................................................80
8.2.2
Secondary Efficacy Endpoints ..........................................................................80
8.2.3
Safety Assessments ...........................................................................................80


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8.3
Sample Size Determination and Rationale ..........................................................................81
8.4
Randomization, Stratification and Blinding ........................................................................81
8.5
Interim Analysis ..................................................................................................................81
8.6
General Statistical Considerations .......................................................................................82
8.6.1
Analysis Populations .........................................................................................82
8.6.1.1
Intent-to-Treat Population .................................................................................82
8.6.1.2
Per Protocol Population .....................................................................................82
8.6.1.3
Safety Population ..............................................................................................82
8.6.2
Statistical Methods ............................................................................................82
8.6.3
Prognostic Factors/Covariates ...........................................................................82
8.6.4
Handling of Missing Data .................................................................................82
8.7
Data Summary .....................................................................................................................82
8.7.1
Subject Disposition............................................................................................83
8.7.2
Demographic and Baseline Characteristics .......................................................83
8.7.3
Prior and Concomitant Medications ..................................................................83
8.7.4
Administration of Study Drug ...........................................................................83
8.7.5
Efficacy Analysis ..............................................................................................84
8.7.5.1
Primary Analysis ...............................................................................................84
8.7.5.2
Supportive Analysis ..........................................................................................84
8.7.6
Safety Analysis ..................................................................................................84
8.7.6.1
Adverse Events ..................................................................................................84
8.7.6.2
Tolerability Assessment ....................................................................................85
8.7.6.3
Clinical Laboratory Data ...................................................................................85
8.7.6.4
Physical Examination ........................................................................................85
8.7.6.5
Vital Signs .........................................................................................................85
8.7.6.6
ECG Examination..............................................................................................85
8.7.6.7
AML or MDS relapse rate by Day-100 .............................................................85
9
ADVERSE EVENTS (DEFINITIONS AND REPORTING) ............................................86
9.1
Adverse Event .....................................................................................................................86
9.1.1
Reporting of Adverse Events ............................................................................86
9.1.2
Impact of Study Treatment ................................................................................86
9.1.3
CTCAE Grade (Severity) Assessment ..............................................................86
9.1.4
Causality Assessment ........................................................................................87
9.1.5
Treatment Given as a Result of the Event .........................................................88
9.1.6
Outcome Assessment ........................................................................................88
9.1.7
Expected / Anticipated Adverse Events ............................................................88


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9.1.8
SC Injection-related Events ...............................................................................89
9.1.9
Stopping Rules for PRO 140 .............................................................................89
9.1.10
Study Stopping Rules ........................................................................................89
9.2
Serious Adverse Events (SAE) ............................................................................................90
9.2.1
Reporting of SAE ..............................................................................................90
9.2.2
SAE Follow-Up .................................................................................................91
9.2.3
Pregnancy ..........................................................................................................91
10 DIRECT ACCESS TO SOURCE DATA/DOCUMENTATION ......................................92
11 QUALITY CONTROL AND QUALITY ASSURANCE ...................................................93
11.1 Monitoring Requirements ....................................................................................................93
11.2 Acceptability of Case Report Forms (CRFs) ......................................................................93
11.3 Modification of Protocol .....................................................................................................93
11.4 Reporting Protocol Deviations ............................................................................................94
12 DATA MONITORING COMMITTEE (DMC) ..................................................................95
13 ETHICS AND REGULATORY REQUIREMENTS .........................................................96
13.1 Institutional Review Board/Independent Ethics Committee (IRB/IEC) .............................96
13.2 Investigator’s Responsibilities ............................................................................................96
13.3 Subject Informed Consent Requirements ............................................................................97
14 DATA HANDLING AND RECORD KEEPING ................................................................98
14.1 Recording and Collection of Data .......................................................................................98
14.2 Clinical Data Management ..................................................................................................98
14.3 Archiving .............................................................................................................................99
15 PUBLICATION PLAN .......................................................................................................100
16 REFERENCES .....................................................................................................................102
17 APPENDICES ......................................................................................................................106
17.1 Appendix I:  Adverse Events of Special Interest: Injection Site Reactions ......................107
17.2 Appendix II: Common Terminology Criteria for Adverse Events v4.03 ..........................108


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LIST OF TABLES
Table 1-1:
Clinical Studies with PRO 140 .............................................................................. 45
Table 4-1:
Schedule of Assessments ....................................................................................... 55
Table 6-1:
Investigational Product - PRO 140/Placebo at Treatment visits ........................... 65
Table 7-1:
ECOG Performance Status .................................................................................... 73
Table 7-2:
GVHD Staging ...................................................................................................... 78
Table 7-3:
CONSENSUS GVHD Grading (Przepiorka D, et al., 1995) ................................ 78
Table 7-4:
CIBMTR GVHD Index (Rowlings et al., 1997) ................................................... 78
Table 9-1: 
CTCAE v4.03 General Guidelines ........................................................................ 87


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LIST OF FIGURES
Figure 3-1: 
Study Flow Diagram ............................................................................................. 53
Figure 6-1:
Investigational Product - Vial Label ..................................................................... 66
Figure 6-2:
Investigational Product - Syringe Label ................................................................ 66
Figure 6-3:
Investigational Product - Kit Label ....................................................................... 67
Figure 7-1:
Sample Visual Analog Scale ................................................................................. 76
Figure 7-2:
Clinical Acute GVHD Assessment ....................................................................... 77


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LIST OF ABBREVIATIONS
Abbreviation
Term
AE
Adverse Event
ALT
Alanine Transaminase
AML
Acute Myeloid Leukemia
ANC
Absolute Neutrophil Count 
AST
Aspartate Transaminase
AUC
Area Under Curve 
C 
Celsius
CBC
Complete Blood Count 
CCR5
C-C chemokine receptor type 5
CFR
Code of Federal Regulations 
CHO
Chinese Hamster Ovary
cm 
Centimeter
Cmax
Maximal Concentration
CNS
Central Nervous System
CRF
Case Report Form
CR
Complete remission
CRO
Contract Research Organization
CS
Clinically Significant
CTCAE
Common Terminology Criteria for Adverse Events 
DLCO
Lung Diffusion Capacity Testing
DMC
Data Monitoring Committee
DNA
Deoxyribonucleic acid
DO
Doctor of Osteopathic Medicine
ECG
Electrocardiogram
ECOG
Eastern Cooperative Oncology Group
eCRF
Electronic Case Report Form
Emax
Maximum drug effect
et al
et aliae; Latin for "and others"
F 
Fahrenheit
FDA
U.S. Food and Drug Administration 
FDP
Fixed Dose Procedure
FU
Follow-Up
GCP
Good Clinical Practice


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Abbreviation
Term
GI
Gastrointestinal
GVHD
Graft Versus Host Disease
HCT
Hematopoietic Cell Transplantation 
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 
HLA
Human Leukocyte Antigen  
IA
Interim Analysis
IB
Investigator’s Brochure
IBMTR
International Bone Marrow Transplant Registry 
ICF
Informed Consent Form 
ICH
International Conference on Harmonization 
iDMC
Independent Data Monitoring Committee
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
LVEF
Left Ventricular Ejection Fraction
LVN
Licensed Vocational Nurse
mAb
Monoclonal Antibody
MD
Doctor of Medicine
MDS
Myelodysplastic Syndromes 
MedDRA
Medical Dictionary for Regulatory Activities
mg
Milligram


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Abbreviation
Term
mL
Milliliter
mm
Millimeter
MRD
HLA-Mismatched Related Donor
MUD
HLA-Matched Unrelated Donor 
MUGA
Multi Gated Acquisition Scan
MW
Molecular Weight
NCS
Not Clinically Significant
NMDP
National Marrow Donor Program 
NP
Nurse Practitioner
PA
Physician Assistant
PBSC
Peripheral Blood Stem Cell
PI
Principal Investigator
PK
Pharmacokinetics
PP
Per Protocol
QA
Quality Assurance
QC
Quality Control 
RBC
Red Blood Cells 
RN
Registered Nurse
SAE
Serious Adverse Event
SAP
Statistical Analysis Plan
SC
Subcutaneous 
SD
Standard Deviation 
SOP
Standard Operating Procedure 
SOS
Sinusoidal Obstruction Syndrome 
TBI
Total Body Irradiation 
TEAE
Treatment Emergent Adverse Events
USA
United States of America
VAS
Visual Analogue Scale 
WBC
White Blood Cells 
WHO
World Health Organization 


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1
INTRODUCTION
1.1
STATEMENT OF INTENT
The design, conduct and reporting of this trial shall be conducted in compliance with the 
protocol, International Conference on Harmonization/Good Clinical Practice (ICH/GCP), and all 
appropriate regulatory requirements. Investigator(s) participating in this study will have 
documented training in GCP. Independent monitoring of the trial will be accomplished utilizing 
Amarex Clinical Research as the Contract Research Organization (CRO).
1.2
BACKGROUND
Acute myeloid leukemia (AML) is the most common acute leukemia in adults. The American 
Cancer Society estimates that in 2015, there will be 20,830 new cases of AML diagnosed in the 
United States, and about 10,460 deaths from AML have been projected. AML is generally a 
disease of older people with average age of a patient with AML being 66 years. The lifetime risk 
of being diagnosed with AML for the average American man is about 1 in 227 and for the 
average American woman the risk is about 1 in 278. The mainstay of induction therapy for AML 
for the last 40 years has been combination chemotherapy with cytarabine and an anthracycline 
and sometimes with a third agent, which has resulted in approximately 60-70% complete 
remission rate and 30-40% 5-year overall survival. 
Myelodysplastic Syndromes (MDS) is a heterogeneous group of clonal malignant hematopoietic 
stem cell disorders characterized by hyper- or hypocellular marrows, peripheral blood 
cytopenias, and cell function abnormalities resulting from failure of hematopoietic 
differentiation. It has a highly variable natural history with a variable risk of transformation to 
AML. The annual incidence of MDS in the US is 10-100 per million but might be higher in 
elderly.
Although chemotherapeutic agents including DNA methyltransferase inhibitors are used for 
treatment of AML and MDS, these two, often related, malignant disorders are the leading 
indications for allogeneic hematopoietic cell transplantation (HCT) in adults. The ability of the 
immune system to eliminate residual AML blasts or dysfunctional stem-cells in MDS has been 
demonstrated in the context of allogeneic stem cell transplantation with myeloablative as well as 
non-myeloablative conditioning regimens. 
Even though allogeneic HCT is the treatment of choice for offering the curative option to 
patients with AML with unfavorable cytogenetics or molecular mutations as well as to patients 
with MDS, whether it should be offered to all patients in first remission of AML or to all patients 
with MDS is contested.  


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It is true that allogeneic HCT has the lowest risk of relapse of all therapeutic options for patients 
with AML and MDS, but transplantation-related mortality can be as high as 20-30%, which can 
counterbalance the potential advantages. The equilibrium between the increased anti-leukemic 
efficacy of allogeneic HCT and the risk of non-relapse mortality depends on many factors 
including the disease risk category, recipient age, donor type, and comorbidities.  
In allogeneic HCT, even after histocompatibility matching, risk of recognizing the recipient cells 
as “foreign” by the donor cells exist. When this recognition happens, an immunological response 
is initiated by donor T-cells reacting against the recipient antigens. This phenomenon is known 
as the Graft Versus Host Disease (GVHD). GVHD is one of the major causes of post-transplant 
morbidity and mortality.
Novel conditioning regimens and immunosuppressive strategies for treatment of GVHD can and 
have extended the pool of patients eligible for transplantation at the same time as reducing toxic 
effects in these patients, however GVHD still remains as a significant complication for 
allogeneic HCT patients. 
GVHD is categorized into two classes, acute and chronic, based on the timing of the onset after 
the transplant. Acute GVHD generally occurs within the first 100 days after the transplantation 
and often involves the skin, liver and the GI tract. Chronic GVHD occurs after 100 days post-
transplant and can persist for several years.  
There are two commonly used systems for grading of GVHD including the Glucksberg grade (I-
IV) and the International Bone Marrow Transplant Registry (IBMTR) grading system (A-D)
(Przepiorka D, et al., 1995, Rowlings, PA et al., 1997, Cahn JY et al., 2005). For the purpose of 
this study Glucksberg grading will be used (see section 7.18).  
The current standard for initial GVHD therapy is methylprednisolone alone or in combination
with immunosuppressive drugs, however, only 20-30 % of patients achieve complete responses
(Deeg et al., 2001), where a complete response is a complete resolution of GVHD. The response 
to treatment of GVHD declines with increasing severity of the condition. Sixty to 95% of Grade 
II patients show some response to the ‘standard of care,’ but that declines to 15 to 40% for Grade 
III and to 0%-6% for Grade IV (Przepiorka et al., 1995). Failure of first line therapy of acute 
GVHD is a significant factor for poor 2-year survival: 10% survival rate for non-responders and 
54% in responders (Pavletic et al., 1999).  
A number of additional immunosuppressive drugs have been tested for the treatment of acute
GVHD, but neither anti-thymocyte globulins (ATG), CD5-immunotoxins, Interleukin-1 (IL-1) 
antagonists nor monoclonal antibodies such as anti-IL-2 receptors and others have demonstrated 
an ability to control GVHD or improve overall patient survival (Martin et al., 1991; Remberger 
et al., 2001; Martin et al., 1996; Antin et al., 2002, Anasetti et al., 1994). Thus, development of 
new therapeutic agents and strategies are required to improve prophylaxis and management of 
acute GVHD and to decrease the toxicities of the immunosuppressive regimens.  


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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 prophylactic agent for Acute Graft-Versus-Host Disease 
(GVHD).
Migration of donor cells, particularly T-cells, into different tissues including skin, liver and GI 
tract is critical in development of acute GVHD. Small molecules and monoclonal antibodies that 
block chemokine receptors such as CCR5, are in theory able to lessen the migration of donor 
cells into tissues. Therefore, blocking CCR5 after allogeneic stem cell transplantation may 
reduce the occurrence rates of GVHD. PRO 140 is a humanized monoclonal antibody directed 
against CCR5. This study will investigate the safety and efficacy of pharmacologic inhibition of 
CCR5 in prevention of acute GVHD by administering PRO 140 to adult patients with AML or 
MDS undergoing allogeneic HCT. 
1.4
SUMMARY OF PRIOR PRE-CLINICAL AND CLINICAL STUDIES
1.4.1
Pre-Clinical Studies with PRO 140
In vitro and in vivo preclinical studies have been conducted to determine the pharmacokinetic, 
immunogenicity, and toxicity profiles of PRO 140 following IV and SC administration. Several 
acute and chronic toxicity studies have been conducted to support the clinical development plan.  
Acute toxicity of PRO 140 was evaluated in New Zealand rabbits, following IV administration 
of 5 or 15 mg/kg. Chronic toxicity was evaluated in cynomolgus monkeys following biweekly 
administration of IV doses up to 10 mg/kg for six months and biweekly administration of 
various SC doses up to 50 mg/kg for 24 weeks. The drug was generally well tolerated. Biweekly 
administration of IV doses up to 10 mg/kg for six months resulted in minimum to mild 
lymphoid hyperplasia in assorted lymph nodes and spleen, which was considered an expected 
immune response to a foreign protein. Biweekly administration of SC doses up to 50 mg/kg for 
24 weeks resulted in minimum injection-site reactions (minimal, multifocal, mononuclear cell 
infiltrates in the subcutis), which were considered due to an inflammatory response to the 
injected antigen. Monkeys tolerated treatment with PRO 140 for 24 weeks without evidence of 
local or systemic toxicity. PRO 140 caused no mortality, cageside observations, in-life 
injection-site observations, or gross pathologic findings. Chronic treatment with PRO 140 did 
not affect body weight, food consumption, hematology, clinical chemistry or coagulation 
parameters.
Both IV and SC administration resulted in elimination half-lives of approximately 200 hours, 
and overall exposure increased with increasing doses. Following SC administration of PRO 140 
in monkeys, the maximal concentration (Cmax) was achieved within 56 hours and bioavailability 
for PRO 140 after SC dosing was approximately 70%. 


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1.4.2
Impact of PRO 140 on homing of stem cells 
From a previous in vitro study with PRO 140 (Insel et al., 2015) and from published research on 
the CCR5 (Robertson et al., 2006; Hutter et al., 2009), in addition to the discussions with the 
Key Opinion Leaders associated with this study, the evidence strongly suggests that binding of 
CCR5 by PRO 140 does not interfere with stem cell homing to the bone marrow given that: 
iii)
CCR5 does not seem to play a significant role in stem cell homing to the bone 
marrow, which is the target site in the treatment for acute myeloid leukemia and 
myelodysplastic syndromes;
iv)
Complete absence of functional CCR5 does not preclude homing of stem cells to the 
bone marrow, which is the target site in the treatment for acute myeloid leukemia and 
myelodysplastic syndromes; therefore, a similar outcome is expected from cells 
expressing CCR5 and bound to PRO 140. 
The in vitro study with PRO 140 (Insel et al., 2015) evaluated the antagonist/agonist activity of 
PRO 140 downstream of CCR5 binding in human CD4+ cells. Specifically, the study measured 
the levels of cAMP upon treatment of CD4+/CCR5+ human T-cells with G-protein-coupled 
receptor (GPCR) effectors and inhibitors in combination with PRO 140. The rationale was that, 
since CCR5 is a GPCR, a differential response in cAMP production or degradation would be 
observed in PRO 140, if it does interfere with CCR5 function in the context of G-protein-
mediated modulation of cAMP and all associated downstream signaling pathways. The study 
concluded that PRO 140 does not interfere with the rolipram-activated synthesis of cAMP, but it 
does antagonize the RANTES-activated degradation of cAMP. Previous in vitro data from 
Progenics suggest that PRO 140 inhibits calcium transients downstream of CCR5 binding. 
Overall, these observations suggest that PRO 140 interferes with some but not all G-protein-
dependent signaling pathways downstream of CCR5 binding. 
The published study by Robertson et al. (Robertson et al., 2006) provides preclinical data 
suggesting that CCR5 is not involved in homing of stem cells to the bone marrow. This is 
evidenced by lower levels of CCR5 mRNA in cells homing to the bone marrow, compared to 
those homing to the thymus. Also, treatment with pertussis toxin (CXCR4 inhibitor) drastically 
reduced the number of cells homing to the thymus but did not alter the number of cells homing 
to the bone marrow. Finally, bone marrow cells lacking CCR5 showed no significant 
impairment in homing to either organ. 
Furthermore, the published study by Hutter et al. (Hutter et al., 2009) refers to an HIV-1-
positive subject who was treated for acute myeloid leukemia with two courses of allogeneic 
stem cell transplantation with CD34+ peripheral blood stem cells from an HLA-identical donor 
who was homozygous for CCR5-delta-32 (non-functional CCR5). In both instances, the 
treatment resulted in successful engraftment, suggesting that the absence of functional CCR5 


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receptors does not preclude stem cell homing.
1.4.3
Clinical Studies with PRO 140
Current human experience with PRO 140 consists of seven completed and two ongoing clinical 
trials, mostly on healthy subjects or HIV-1 positive subjects. These studies are summarized in 
Table 1-1. In all clinical trials, the majority of adverse events (AEs) have been 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. 
1.4.3.1
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 to healthy subjects 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. Seventy- five percent (75%) of subjects reported TEAEs, most of 
which were deemed unrelated to study treatment by the investigator. 
1.4.3.2
PRO 140 1102 Study 
For PRO 140 1102, the majority of AEs, other than injection-site reactions, were considered mild 
and possibly related to drug administration. The majority of injection-site reactions were 
considered mild, self-resolving, and definitely related to drug administration. PRO 140 derived 
from Chinese Hamster Ovary (CHO) cells and administered at 100 mg/mL was generally well 
tolerated in healthy, normal volunteers. Overall, PRO 140 administered SC using Autoject® 2 
appeared better tolerated than manual injection.
1.4.3.3
PRO 140 1103 Study  
In PRO 140-1103, administration of PRO 140 at 350 mg using Autoject® 2 appeared well 
tolerated. Manual injections, on the other hand, were associated with a greater number of AEs. 
There did not appear, however, to be any substantial difference in subject perception of pain or 
discomfort related to site of drug administration. No anti-PRO 140 antibodies were detected in 
any subjects in this study. There was a tendency of higher exposure associated with SC 
administration of PRO 140 at 350 mg in the abdomen and the thigh. A higher number of AEs 
were associated with injections in the arm. Based on these observations, thigh and abdominal 
administration of PRO 140 were preferred over arm injection. 
1.4.3.4
PRO 140 1302 Study
The initial proof-of-concept study was a randomized, double-blind, placebo-controlled study in 
subjects with early-stage, asymptomatic HIV infection, only R5 HIV-1 detectable, and no 
antiretroviral therapy for 12 weeks. Subjects (n=39) were randomized to receive a single IV


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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.  
PRO 140 demonstrated potent, rapid, prolonged and dose-dependent antiviral activity.
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 intervals or other electrocardiographic 
parameters, and there were no remarkably laboratory findings.  
1.4.3.5
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. 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.  
1.4.3.6
PRO 140 2101 Study 
A subcutaneous (SC) form of PRO 140 was tested in HIV-infected subjects. The trial was a 
randomized, double-blind, placebo-controlled study in subjects (n=44) with early-stage, 
asymptomatic HIV infection, only R5 HIV-1 detectable, and no antiretroviral therapy for 12 
weeks (Thompson, 2009). Placebo (n=10) and three PRO 140 doses were examined: 162 mg 
weekly for three weeks (n=11), 324 mg weekly for three weeks (n=11), and 324 mg biweekly 
(every other week) for two doses (n=12). Subjects were followed for 44 days after the final dose.  
Potent, dose-dependent and highly statistically significant antiviral activity was observed. The 
trial established the first antiviral proof of concept for a long-acting, self-administrable drug for 
HIV-1 infection (Thompson, 2009).
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 


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140 treatment groups. Administration-site reactions were mild, transient, and observed in a 
fraction of subjects.  
1.4.3.7
PRO 140-CD01 Study
PRO 140_CD01 study (open-label, 40 subjects, multi-center) evaluated the efficacy, safety, and 
tolerability of PRO 140 monotherapy (350 mg subcutaneous injection weekly for up to 12 
weeks) for the maintenance of viral suppression following substitution of antiretroviral therapy 
in HIV-1 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 
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 R5-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 


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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.  
This clinical study is complete and results are pending publication.  
1.4.3.8
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 
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. Results for 
PhenoSense® Entry Assay, ADA and PK assessments and Serum Concentration of ART Drugs 
for the ongoing CD01-Extension study are expected to be available in 2017.   
This clinical study is currently ongoing.
1.4.3.9
PRO 140-CD02 Study
PRO 140_CD02 study (double blind, placebo controlled, 150 subjects, multi-center) seeks to 
evaluate the efficacy, safety, and tolerability of PRO 140 in combination with either existing 
ART (failing regimen) or Optimized Background Therapy (OBT) in patients infected with HIV-
1.  The study population includes 150 adult patients with a documented history of genotypic or 
phenotypic resistance to ART drugs within one or more drug classes who demonstrate evidence 
of HIV-1 replication despite ongoing antiretroviral therapy and have limited treatment options.  


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The options may be limited as a result of drug antiviral class cross-resistance, documented 
treatment intolerance, potential for hypersensitivity to one or more ART drugs, or potential drug 
interactions with treatment for co-morbid conditions. 
In Part 1 of 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 until HIV-1 genotypic drug resistance assay results are available to construct an OBT.  The 
primary efficacy endpoint is proportion of participants with 
-1 RNA 
viral load from baseline at the end of the 7 day functional monotherapy period. 
In Part 2 of double-blind treatment period, subjects will continue treatment with either PRO 140 
or Placebo in combination with OBT for an additional 3 weeks until HIV-1 co-receptor tropism 
assay results are available, at which time subjects will move into the 24-week open-label period.  
During the 24-week open-label period, subjects infected with only CCR5-tropic HIV-1 will 
receive PRO 140 + OBT, whereas subjects infected with D/M- or CXCR4-tropic HIV-1 will 
receive OBT alone during the 24-week open-label treatment period.   
This clinical study is currently ongoing.  
1.4.3.10 PRO 140-CD03 HIV Study
PRO 140_CD03 study (open-label, 300 subjects, multi-center) seeks to evaluate the treatment 
strategy of using PRO 140 SC as long-acting single-agent maintenance therapy for 48 weeks in 
virologically suppressed subjects with CCR5-tropic HIV-1 infection. This clinical study is ready 
to start, pending approval. 






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1.5
RATIONALE FOR DOSE SELECTION
For this proof of concept study with the indication of GVHD, the dose of 350 mg administered 
SC was chosen in light of dosages used in previous and ongoing human studies on HIV 
indication (especially PRO140-CD01 and PRO 140-CD02). Table 1-1 provides the summaries of 
clinical studies completed or ongoing using PRO 140. The dose of 350 mg weekly used in these 
studies was well tolerated with no dose limiting toxicities (DLT). The results of this study will 
determine the next steps to be taken in terms of dose selection to further develop PRO 140 for 
the indication of GVHD.  
1.6
RISKS / BENEFITS ASSESSMENT
PRO 140 or placebo will be administered as add-on therapy to the standard GVHD prophylaxis 
treatments, thus there is no risk of discontinuing anti-GVHD therapy.
1.6.1
RISKS/DISCOMFORT TO SUBJECTS AND PRECAUTIONS TO MINIMIZE RISK
1.6.1.1
Allergic Reaction
PRO 140 belongs to the monoclonal antibody class of drugs. Monoclonal antibodies are 
sometimes associated with allergic reactions (fatigue, diarrhea, fever, vomiting, headache, 
nausea, pain at the site of injection, low blood pressure, rash, itching, and chills) or flu-like 
reactions such as fever, chills, and aches. These events are usually of short duration if they occur 
at all. Severe allergic reactions, however, can be life-threatening. Although anaphylaxis has not 
been observed in prior trials of PRO 140, infusion of proteins always carries with it the 
theoretical risk for anaphylactic shock. Accordingly, whenever PRO 140 is administered to 
subjects, there should be available and in place the procedures required to manage anaphylactic 
shock. 
1.6.1.2
Immune Response
People 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. 
1.6.1.3
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).  


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1.6.1.4
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. 
1.6.1.5
Unknown Risks
As with all research there is the remote possibility of risks that are unknown or that cannot be 
foreseen based on current information.  
1.6.1.6
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 other FDA-approved anti-CCR5 drug already. 
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 is a proof of concept study for the purpose of evaluating safety and efficacy of PRO 140 for 
further clinical testing in acute GVHD indication. The most significant limitation with the 
current GVHD prophylaxis treatments has been the necessity and challenge of continued 
adherence to the medications, along with relatively high risk of occurring GVHD. This study 
provides opportunity to the subjects to have supervised SC treatments with PRO 140 as an add-
on to their current GVHD prophylaxis regimen. Subjects participating in the present add-on 
therapy study will contribute to the development of a drug which has the potential to become a
treatment option for them and others in the future. 


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2
STUDY OBJECTIVES 
The primary objective of this study is to assess the efficacy of PRO 140 compared to placebo as 
an add-on therapy to standard GVHD prophylaxis in adult patients with AML or MDS 
undergoing allogeneic HCT.
The secondary objective of this study is to assess safety and tolerability of PRO 140 compared to 
placebo as an add-on therapy to standard GVHD prophylaxis in adult patients with AML or 
MDS undergoing allogeneic HCT. 
Study Endpoints
Primary Efficacy Endpoint 
Incidence of Grade II, Grade III or Grade IV acute GVHD by Day-100
Secondary Efficacy Endpoints 
Incidence of severe and life-threatening (Grade III and Grade IV) acute GVHD by Day-
100
Incidence of organ-specific acute GVHD by Day-100
Donor engraftment evaluated by T-cell and myeloid chimerism in peripheral blood
Neutrophil and platelet count recovery
Changes in ECOG performance score
GVHD-free survival (GFS)
Safety Assessments
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 emergent adverse events and serious adverse events
AML or MDS relapse rate by Day-100 
Changes and shifts in laboratory measurements over time
Changes in Electrocardiogram (ECG) parameters over time


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3
STUDY DESIGN
3.1
STUDY CENTER(S) 
Approximately up to 20 centers in the United States will enroll patients in this study.
3.2
STUDY POPULATION
This study will recruit 60 subjects with Acute Myeloid Leukemia (AML) or Myelodysplastic 
Syndromes (MDS) undergoing allogeneic stem-cell transplantation. 
3.3
ELIGIBILITY CRITERIA
3.3.1
Inclusion Criteria
Subjects must meet all of the following criteria to be included in the study: 
1. Patients diagnosed with AML or MDS per below: 
o
Patients with a history of histologically or pathologically confirmed diagnosis of 
AML and < 5% blasts in the peripheral blood or bone marrow (per bone marrow 
aspiration and/or biopsy within 6 weeks prior to screening) scheduled to undergo 
allogeneic stem-cell transplantation
o
Patients with a histologically or pathologically confirmed diagnosis of MDS with 
< 10% blasts in the bone marrow (per bone marrow aspiration and/or biopsy 
within 6 weeks prior to screening) scheduled to undergo allogeneic stem-cell 
transplantation
2. Eastern Cooperative Oncology Group (ECOG) performance status score  2  
3. Patients must have normal organ function as defined below: 
Males and females, age 18 and  65 years of age
Myeloablative allogeneic HCT: 
Total bilirubin 2 mg/dL (except in patients with Gilbert’s Syndrome)
AST/ALT 
with leukemic infiltration of liver)
Serum creatinine 
 60 ml/hr 
Diffusing capacity of the lung for carbon monoxide (DLCO) > 50% 
predicted with no symptomatic pulmonary disease 
Cardiac ejection fraction 
50%. If between 40-49% a cardiology consult 
is required


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Clinically normal resting 12-lead ECG at screening visit or, if abnormal, 
considered not clinically significant by the PI
4. Patients must have a reasonable expectation of 
5. The donor-recipient HLA match criteria required for participation in this protocol are not 
research subjects in this study and they must meet criteria as National Marrow Donor 
Program (NMDP) donors. Procedures for selection of donors and stem cell dose will 
follow FDA requirements for Blood Products (21 CFR 640) and Human Cellular and 
Tissue Based Products (21 CFR 1271). The standard institutional practices for stem cell 
transplants also will be followed. The donors are:
o
HLA-Identical Sibling (6/6): Minimal typing necessary is serologic typing for 
class I (AB) and molecular typing for class II (DRB1)
o
Matched Unrelated Donor (8/8): Molecular identity at HLA A, B, C and DRB1 by 
high-resolution typing 
o
Matched Related and Unrelated Donor (7/8): high-resolution molecular typing at 
the following loci is required: HLA A, B, C and DRB1 
6. Both male and female patients and their partners of childbearing potential must agree to 
use appropriate birth control methods (birth control pills, barriers, or abstinence) 
throughout the study duration (excluding women who are not of childbearing potential 
and men who have been sterilized). Females of childbearing potential must have a 
negative serum pregnancy test at Screening visit and negative urine pregnancy test prior 
to receiving the first dose of study drug.  
7. Patients must understand and voluntarily sign an informed consent form 
3.3.2
Exclusion Criteria
Subjects meeting any of the following criteria will be excluded from the study: 
1. Patients not expected to be available for follow-up for at least 114 days after transplant 
2. Patients who have received prior allogeneic stem cell-transplantation
3. Patients who receive post-transplant high dose cyclophosphamide 
4. Patients with active central nervous system (CNS) involvement by malignant cells
5.
Patients receiving other investigational drugs for GVHD. Co-enrollment in other clinical 
trials that do not include experimental GVHD therapies is allowed


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6. Prior use of any experimental or approved CCR5 modulator including maraviroc and 
PRO 140  
7. Patients with uncontrolled bacterial, viral or fungal infections including diagnosis of 
acute viral hepatitis (defined as any active infection with hepatitis A or a new diagnosis 
of hepatitis B or C within 24 weeks of dosing) 
8. Currently active second malignancy other than non-melanoma skin cancers
9. Presence of fluid collection (ascites, pleural or pericardial effusion) that interferes with 
methotrexate clearance or makes methotrexate use contraindicated
10. Patients who are HIV positive
11. Females who are pregnant, lactating, or breastfeeding, or who plan to become pregnant 
during the study 
12. Subjects on chronic steroid therapy 
5 mg/day within 2 weeks of screening except for 
inhaled, nasal, or topical steroids 
13. 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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4
STUDY SCHEDULE
This research study is divided into three study phases: 
(1) Screening Phase
(2)
(Screening to T1 Visit) begins with signing of Informed Consent and 
lasts up to 4 weeks (28 days). 
Treatment Phase
(3)
(up to 14 weeks ± allowed windows). Eligible subjects will be 
randomized and receive up to 11 study treatments (PRO 140 or placebo), given on Day -3
or Day -2 prior to stem cell infusion, on the day of stem cell infusion (Day 0), and then 
weekly for 30 days (at Week 1, Week 2, Week 3 and Week 4) after which it will be 
administered every two weeks for up to 98 days (at Week 6, Week 8, Week 10, Week 12 
and Week 14).
Follow-Up Phase
Procedures to be performed during each of these study phases are described below and provided 
as a Schedule of Assessments in
 (up to one year). Subjects who have completed the Treatment phase or 
who have withdrawn from the study will be followed-up at 2 weeks after the last 
treatment visit and one year after first treatment visit. 
Table 4-1.


Unscheduled Visit


Unscheduled Visit




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4.1
SCREENING PHASE
4.1.1
Screening Visit
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 two-digit Study 
Center number (01, 02 or 03….) 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. 01-
001 or 02-001).  
Subject Screening # :
XX
-
YYY
XX=Study Center
YYY=Subject Numeric ID
All study centers will be instructed to maintain the study-specific pre-screening, screening and 
enrollment logs at their sites. If a subject initially fails to meet inclusion/exclusion criteria and is 
later reconsidered for participation, the subject will be re-consented and assigned a new 
screening number at the time of re-screening. Subjects who fail their first screening attempt may 
be re-screened a maximum of once and may be enrolled if they are found to meet all inclusion 
and no exclusion criteria when re-screened.
Once the ICF has been signed, screening procedures and information will be obtained to confirm 
subject eligibility, including: 
1. Medical history (section 7.4),
2. Subject demographics (section 7.3), 
3. Physical examination (section 7.6), 
4. Vital Signs (section 7.9),
5. Body Weight & Height measurements (section 7.9) 
6. Eastern Cooperative Oncology Group (ECOG) performance status (section 7.10) 
7. Prior and current medications review (section 7.5), 
8. Electrocardiogram (ECG) (section 7.7)
9. Collection of Blood Specimens for: 
o
Complete Blood Count (CBC) w/diff (section 7.11.1) 


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o
Biochemistry (section 7.11.2) 
o
Serum pregnancy test, for female subjects of childbearing potential (section 
7.11.7). Childbearing potential is defined as someone who is not surgically sterile 
or is not more than one year past complete cessation of menstrual cycles.
10. Collection of Urine Specimen for Urinalysis (section 7.11.8)
11. HIV rapid antigen testing (section 7.8) 
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
For consented subjects 
, 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, and the reason for screen failure. No additional information 
will be required for subjects who fail screening.  
who meet eligibility criteria
Eligible subjects that are not enrolled within 28 days of Screening Visit will have screening lab 
assessments repeated to reconfirm eligibility.
, all required screening information 
will be transcribed onto the appropriate page of the eCRF.
4.2
TREATMENT PHASE
Subjects who meet all eligibility criteria, as per data gathered from Screening Visit and who stay 
eligible for the study are to be randomized and treated. 
4.2.1
Treatment Visit-1 (T1) 
Treatment Visit 1 (T1) will happen -2/-3 days prior to the transplant. The following assessments 
will be performed at the T1. 
Confirmation of eligibility criteria by reviewing test results and other criteria 
assessments performed at the Screening Visit (section 
Pre-Treatment
7.2 ) 
Any changes in concomitant medications (section 7.5) 
Any changes in medical history since Screening Visit (section 7.4),
ECOG performance status (section 7.10) 
12. ECG (section 7.7), 


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Collection of Blood Specimens for: 
o
CBC w/diff (section 7.11.1) 
o
Serum Biochemistry (section 7.11.2) 
Randomization (see section 7.12) 
All eligible subjects who are randomized will receive either PRO 140 350 mg or placebo as
subcutaneous injection in the abdomen. A total of 350 mg (175 mg/mL) is delivered as two 1 mL 
injections on opposite sides of the abdomen. The study treatment (PRO 140 or placebo SC 
injections) will be administered by a licensed medical professional (MD, DO, PA, LPN, LVN, 
NP, or RN).
Administration of Study treatment (PRO 140 or Placebo)
Injection Site Reaction Assessment (see section 
Post-Treatment
7.15) 
Note: To assess injection site reactions, refer to the investigator injection site 
reaction table (refer to section 17.1).
Injection Site Pain Assessment (VAS) (section 7.16) 
Vital Signs (see section 7.9) will be assessed within 15 minutes of study treatment 
administration.
Assessment of Adverse Events (AE) (see section 9) 
4.2.2
Treatment Visit-2 (T2) - Stem Cell Infusion (Day 0) 
The following assessments will be performed on Treatment Visit-2: 
Assess for any Adverse Events and changes in Concomitant medications (section 
9 and 7.5) 
Physical examination (section 7.6)
Vital Signs (section 7.7) 
Collection of Blood Specimens for  
o
CBC (section 7.11.1) 
o
Lymphocyte Phenotype Panel (section 7.11.4) 
Study Treatment Administration (PRO 140 or Placebo) (section 7.13) 


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Stem cell infusion will be conducted post-study treatment administration (as per 
institutional guidelines; see section 7.19) 
Diagnosis and Grading of GVHD (section 7.17 and 7.18) 
Injection Site Reaction Assessment (section 7.15) 
Note: To assess injection site reactions, refer to the investigator injection site 
reaction table (refer to section 17.1).
Injection Site Pain Assessment (VAS) (section 7.16) 
4.2.3
Treatment Visit-3 to Treatment Visit-11 (T11) 
The following assessments will be performed at each visit, unless otherwise specified:
Assess for any Adverse Events and changes in Concomitant medications (section 
9 and 7.5),
Diagnosis and Grading of GVHD (section 7.17 and 7.18) 
Physical examination (section 7.6) (at T8, T11)  
Vital Signs (section 7.9), (at T4, T6, T7, T8, T9, T10, T11) 
ECOG performance status (section 7.10) (at T4, T7, T9, T11) 
ECG (section 7.7) (at T6, T9, T11) 
Collection of Blood Specimens for: 
o
CBC w/diff (section 7.11.1) 
o
Serum biochemistry (section 7.11.2) (at T4, T6, T7, T8, T9, T10, T11) 
o
Serum pregnancy test, for female subjects of childbearing potential (section 
7.11.7) (at T7 and T11) 
o
Anti-idiotypic antibodies to PRO 140 (section 7.11.6) (at T7 and T11) 
o
Lymphocyte Phenotype Panel (section 7.11.4) (at T4, T6, T8 and T11) 
o
T-cell and myeloid chimerism (section 7.11.5) (at T6, T8 and T11)  
Collection of Urine Specimen for Urinalysis (section 7.11.8) (at T7 and T11) 
Study Treatment Administration (PRO 140 or Placebo) (section 7.13) 
Injection Site Reaction Assessment (section 7.15) 


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Note: To assess injection site reactions, refer to the investigator injection site 
reaction table (refer to section 17.1).
Injection Site Pain Assessment (VAS) (section 7.16) 
4.3
FOLLOW-UP PHASE
4.3.1
Follow-Up Visit 1
The follow-up visit 1 will occur two (2) weeks after the last treatment visit. The following 
assessments will be performed at the follow-up visit 1, unless otherwise specified:
Assess for any Adverse Events and changes in Concomitant medications (section 
9 and 7.5),
Vital Signs (section 7.9),
ECOG performance status (section7.10) 
Collection of Blood Specimens  for 
o
CBC w/diff (section 7.11.1) 
o
Serum biochemistry (section 7.11.2)
ECG (section 7.7) 
Grading GVHD – skin, gut, liver (section 7.17) 
4.3.2
Follow-up Visit 2
The follow-up visit 2 will occur one year after the first treatment visit. The following 
assessments will be performed at the follow-up visit 2, unless otherwise specified:
Assess for any Adverse Events and changes in Concomitant medications (section 
9 and 7.5),
Vital Signs (section 7.7),
Collection of Blood Specimens for: 
o
T-cell and myeloid chimerism (section 7.11.5). 


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5
SUBJECT COMPLETION AND WITHDRAWAL
5.1
SUBJECT COMPLETION
A subject who completes the 14-week Treatment Phase and 2-week Follow-Up Phase will be 
considered as having completed the study. 
5.2
SUBJECT WITHDRAWAL
A subject who is randomized 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
A subject is significantly non-compliant with the requirements of the protocol. 
be withdrawn from the study, in consultation with the Medical 
Monitor and the Investigator, if any of the following are met: 
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 specified in section 
9.1.9
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
A subject is treated with a prohibited medication
occur if, in consultation with the Medical Monitor 
and the Investigator, any of the following are met: 
Major protocol violation 
5.2.1
Data Collected for Withdrawn Subjects
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


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discontinued due to a serious adverse event will be followed until resolution or stabilization
of the event.
In the event that a subject is withdrawn from the study at any time due to an adverse event or 
serious adverse event (SAE), the procedures stated in Section 9.1.1 or 9.2.1, respectively must be 
followed. 
Every attempt should be made to collect follow-up information. The reason for withdrawal from 
the study will be recorded in the source documents and on the appropriate page of the eCRF. 
Before a subject is identified as lost-to-follow up, the site should make all reasonable efforts to 
contact the subject. These attempts must be documented and should include at a minimum one 
phone call and one certified letter. 
5.3
SCREEN FAILURES
A subject who has signed a consent form, has been assigned a screening number, but is not 
randomized is classified as a screen failure. Subject number, demographics and reason for screen 
failure will be recorded.
If a subject initially fails to meet inclusion/exclusion criteria and is later reconsidered for 
participation, the subject will be re-consented and assigned a new screening number at the time 
of re-screening. Subjects who fail their first screening attempt may be re-screened only one more 
time (i.e., up to two screenings) and may be enrolled if they are found to meet all inclusion and 
no exclusion criteria at the subsequent screening visit.


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6
STUDY TREATMENTS 
6.1
INVESTIGATIONAL PRODUCT DESCRIPTION
PRO 140 is a humanized IgG4,
monoclonal antibody (mAb) to the chemokine receptor CCR5.
PRO 140 is provided at a concentration of 175 mg/mL and is intended for SC route of 
administration.
Kits will be labeled with a unique identification number. Each kit used during the Treatment 
Phase will contain two vials of PRO 140 or Placebo for SC injection. One milliliter (1 mL) of 
PRO 140 or placebo solution will be drawn from each vial and loaded into the syringe. A total of 
350 mg (175 mg/mL) of PRO 140 or placebo is delivered as two 1 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 175 mg/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. 
Each vial of the Placebo contains 5mM Histidine, 15 mM Glycine, 95 mM Sodium Chloride, 
0.3% (w/v) Sorbitol, 0.005% (w/v) Polysorbate 20 at a pH of 5.5. 
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.
Table 6-1 provides the unit strength, dosing frequency and mode of administration for the study 
drug.
Table 6-1: 
Investigational Product - PRO 140/Placebo at Treatment visits 
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 1 mL/inj.) 
on opposite sides of abdomen
SC injection
Placebo
Parenteral 
solution
0 mg/mL
2 injections of placebo (2 X 1 mL/inj.) 
on opposite sides of abdomen 
SC injection
6.2
INVESTIGATIONAL PRODUCT PACKAGING AND LABELING
The contents of each vial are described in section 6.1. PRO 140 and placebo kits will be labeled 
with information such as: study protocol #; fill volume; concentration; storage condition; a “use 


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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 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 
Protocol: PRO 140_CD 03_GVHD                Kit No.  xxx
Subject No. _________              
Single use 3 mL vial contains 1.4 mL of PRO 140 (175 
mg/mL) or placebo solution for subcutaneous injection
Store at 2oC to 8oC (36oF to 46oF)
USE AS PER STUDY PROTOCOL
Caution: New Drug – Limited by Federal (or United States) 
Law to Investigational Use
CytoDyn Inc., Vancouver, WA, USA
Protocol: PRO 140_CD 03_GVHD                 Kit No.  xxx
Subject No. _________              
Single use 3 mL vial contains 1.4 mL of PRO 140 (175 
mg/mL) or placebo solution for subcutaneous injection
Store at 2oC to 8oC (36oF to 46oF)
USE AS PER STUDY PROTOCOL
Caution: New Drug – Limited by Federal (or United States) 
Law to Investigational Use
CytoDyn Inc., Vancouver, WA, USA
Figure 6-2: 
Investigational Product - Syringe Label
Protocol: PRO 140_CD 03_GVHD                                                 Contents of Kit No. xxx
This syringe contains 1 mL PRO 140 (175 mg/mL) or placebo solution for subcutaneous injection
USE AS PER STUDY PROTOCOL
Caution: New Drug – Limited by Federal (or United States) Law to Investigational Use
CytoDyn Inc., Vancouver, WA, USA


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Figure 6-3: 
Investigational Product - Kit Label
Protocol: PRO 140_CD 03_GVHD                                                          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) or placebo solution for subcutaneous 
injection
Store at 2oC to 8oC (36oF to 46oF)
USE AS PER STUDY PROTOCOL
Caution: New Drug – Limited by Federal (or United States) Law to Investigational Use
CytoDyn Inc., Vancouver, WA, USA
The study pharmacy manual provides the criteria regarding vial acceptance or rejection, as well 
as instructions for the preparation of the filled syringes to be used to administer drug.  
6.3
INVESTIGATIONAL PRODUCT STORAGE
Study drug will be shipped at 2°C to 8°C (refrigerated [36°F to 46°F]) to the study 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. Possible presence of fine 
translucent particles is normal.
The site 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 study 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.  


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A 25-guage needle should be used to remove IP from vial and for administration of IP to 
subjects. IP should be administered slowly over 15 seconds per mL. 
Following each SC delivery of drug, careful examination will be made to assess the appearance 
of any study drug Injection Site Reactions (ISRs) as described in section 17.1.
All doses of study drug will be prepared by the credentialed pharmacist and will be administered 
as SC injection by a licensed medical professional (MD, DO, PA, LPN, LVN, NP, or RN).
Note
6.5
INVESTIGATIONAL PRODUCT RECEIPT AND ACCOUNTABILITY
: 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(s). It is advised to change the injection site if any previous injection site 
reaction remains unresolved. 
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 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. 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 the Sponsor or 
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 randomization), 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. Screen failure subjects may be re-entered 
into the study at a later time and re-screened. 
7.2.1
Re-screening
If a subject initially fails to meet inclusion/exclusion criteria, and is later reconsidered for 
participation, the subject will be re-consented and 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.
7.3
DEMOGRAPHIC INFORMATION
For the purposes of this study, demographic information will include: 
Date of birth
Gender


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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: 
All ongoing medical conditions
Baseline diagnosis requiring stem cell transplant, including AML or MDS 
Date of diagnosis 
Any prior medical conditions that have resolved within the last year  
Events that emerge prior to the first treatment (T1) administration 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 onset/diagnosis 
History status (resolved or ongoing) 
Date of resolution, if applicable 


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7.5
PRIOR / CONCOMITANT MEDICATIONS AND NON-STUDY TREATMENTS 
A complete history of current 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 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 
prescribed. If concomitant medications are started during the study, the indication for the 
concomitant medication should be recorded as an AE if it meets the criteria.
7.5.1
Excluded Medications and Therapies
Cyclophosphamide and CCR5 inhibitors other than PRO 140 (ex. maraviroc) are prohibited 
during this study. 
7.5.2
Allowable Medications and Therapies
All other medications/therapies that are not otherwise prohibited and, in the judgment of the 
Investigator, are required for proper medical care of the subject may be prescribed. 
7.6
PHYSICAL EXAMINATION
The complete physical examination will include routine examinations for the following:


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Head, Ears, Eyes, Nose, Throat (HEENT) 
Abnormalities of the extremities
Neurologic abnormalities
Heart/cardiovascular abnormalities
Musculoskeletal abnormalities
Dermatologic abnormalities
Any other body system for which an abnormality is noted and which, in the opinion of 
the Investigator, is relevant to the safety of the subject or could impact safety or efficacy 
results for the subject; i.e., the abnormality is clinically significant (CS).
Each abnormality will be recorded and the Investigator will record an assessment of its clinical 
significance. After administration of the first dose of study treatment, each physical exam 
abnormality that is considered to be clinically significant will be recorded as an AE.
7.7
ELECTROCARDIOGRAM
12-lead ECG will be conducted and 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. Each treatment-
emergent abnormality that is considered to be clinically significant will be recorded as an AE.
Each ECG should be signed by a physician. 
7.8
HUMAN IMMUNODEFICIENCY VIRUS (HIV) RAPID ANTIGEN TEST
Test should be performed per the site standard kits and procedures. The result reports will need 
to be reviewed and signed by the Investigator. 
7.9
VITAL SIGNS, HEIGHT AND WEIGHT
Vital signs collected during the Treatment Phase will be performed post-treatment, assessed 
within 15 minutes following study treatment administration. Height and weight will be assessed 
only at Screening and unscheduled visits.   
The following will be collected:
Height and weight; BMI will be calculated using high and weight measurements




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recovery will be defined as an increase in absolute neutrophil count (ANC) to 
greater than 500/µL on 2 consecutive days. The date of neutrophil recovery will 
be defined as the day of the first count above the threshold.  
7.11.2 Biochemistry
Biochemistry profile includes assessment of: 
Hepatic function indicators: total and direct bilirubin, alkaline phosphatase (ALP),
aspartate aminotransferase (AST), alanine aminotransferase (ALT), total protein, Lactate 
dehydrogenase (LDH) 
Renal function indicators: Blood Urea Nitrogen (BUN), creatinine
Electrolytes: sodium, potassium, chloride, calcium and bicarbonate 
Other:
7.11.3 Population Pharmacokinetics 
 glucose (random), cholesterol (total) 
Blood samples will be collected and evaluated per the study schedule of assessments.
7.11.4 Lymphocyte phenotype panel
Lymphocyte phenotype panel will be performed and evaluated per the study schedule of 
assessments. 
7.11.5 T-cell and Myeloid chimerism evaluation
T-cell and myeloid chimerism tests will be evaluated per the institutional standards. 
7.11.6 Anti-idiotypic antibodies to PRO 140 
The first samples for anti-idiotypic antibodies for PRO 140 may be collected at the T1 
prior to first dose of PRO 140 
*Note: Sera will be collected from study subjects and stored at -80oC for future analysis.
7.11.7 Serum pregnancy test 
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.
7.11.8 Urinalysis
Urine samples will be tested for color, appearance, specific gravity, pH, protein, glucose, 
occult blood, ketones, RBC, WBC, epithelial cells, bacteria, casts, crystals


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All laboratory reports will be reviewed by the Investigator.
Post-treatment abnormal results that are considered by the Investigator to be clinically significant 
will be recorded as adverse events. If the Investigator judges it necessary, testing may be 
repeated in order to make the determination of clinical significance. Validated, quality-controlled 
laboratory data will be transferred to the main database for analyses.
7.12 RANDOMIZATION
Subjects who are eligible to participate in the trial will be randomized to one of the treatment 
groups via IWRS (Interactive Web Based Randomization System) at the T1 Visit prior to IP 
administration. The randomization will be central and will use mixed block size of 2 and 4 with a 
1:1 ratio of Active Treatment to Control Treatment to ensure even distribution of Active and 
Control subjects. A randomization plan that details the stratification and randomization will be 
developed. 
7.13 PRO 140 ADMINISTRATION
PRO 140 will be administered -2/-3 days before the stem cell infusion, on the day of stem cell 
infusion (Day 0) and thereafter on days 7, 14, 21, 28, 42, 56, 70, 84 and 98 as per the study 
schedule of assessments (Table 4-1).
Refer to section 6.4 for details on the procedure of PRO 140 administration. 
7.14 STANDARD OF CARE 
For the purpose of this study, the combination regimen of tacrolimus plus methotrextate per 
below will be considered as standard of care (Ratanatharathorn et al., 1998 and Ruutu et al., 
2014): 
For tacrolimus the starting dose of 0.02-0.03 mg/kg/day will be initiated on day -1 of 
transplant by continuous IV infusion to target whole blood levels of tacrolimus between 5 
and 10 ng/ml. The route of administration will be converted from IV to oral at the ratio of 1:3 
to 1:4 when patients are able to tolerate oral intake. When a patient is switched from IV to 
oral tacrolimus, the target for blood levels of tacrolimus will be kept at approximately 10 
ng/ml. For dose modifications institutional standards will be followed.
For methotrexate the initial dose will be a minimum of 5 mg/m2 on day +1 after the 
transplant. Three additional doses of minimum 5 mg/m2 are given on days +3, +6 and +11 
after the transplant. The day +11 dose is omitted in case of any toxicity of grade II or higher. 
The drug is given as bolus IV injection. For dose modifications institutional standards will be 
followed.  




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7.17 ACUTE GVHD DIAGNOSIS
GVHD diagnosis will be confirmed by biopsies of organs involved per the institutional 
standards, when the clinical features are consistent with GVHD. The diagnosis and biopsy results 
must be confirmed by the PI on the source documents and entered into the eCRF.  
7.18 ACUTE GVHD CLINICAL GRADING AND STAGING
Acute GVHD grading and staging will be performed by the Investigator as per procedures 
described in the Technical Manual of Procedures version 3.0 and dated 19 March 2013 (Blood 
and Marrow Transplant Clinical Trials Network): 
Assessment of the clinical acute GVHD using the form Clinical Acute GHVD (see Figure
7-2);
Assessment of the GVHD staging using the GVHD Staging table (see Table 7-2);
Assessment of the GVHD grading using the GVHD Grading Scale (see Table 7-3);
Assessment of the GHVD index using the CIBMTR GHVD Index (see Table 7-4).
Figure 7-2: 
Clinical Acute GVHD Assessment


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Table 7-2: 
GVHD Staging
Table 7-3: 
CONSENSUS GVHD Grading (Przepiorka D, et al., 1995) 
Table 7-4: 
CIBMTR GVHD Index (Rowlings et al., 1997) 


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7.19 STANDARD INSTITUTIONAL PRACTICES FOR STEM CELL INFUSION
Procedures for selection of donors and stem cell dose will follow FDA requirements for Blood 
Products (21 CFR 640) and Human Cellular and Tissue Based Products (21 CFR 1271). The 
standard institutional practices for cell transplants will also be followed including the use of G-
CSF, irradiations and infection prophylaxis. The inclusion criteria for peripheral blood stem cell 
(PBSC) donors are detailed in section 3.3.1 of this study. 
The sources of stem cells to be used in this study will consist only of bone marrow and 
peripheral blood. The cord blood will be excluded as graft source to avoid confound incidence of 
GVHD. Minimum recommended doses for each of stem cells source will be as follows: 
Bone marrow: minimum of 2 x 106 CD34+ cells/kg of recipient’s body weight;
Peripheral blood: minimum of 2 x 106 CD34+ cells/kg of recipient’s body weight. 
7.19.1 Conditioning Regimen of Stem Cells
For the purpose of this study, only myeloablative conditioning regimens will be used. Total Body 
Irradiation (TBI) and chemotherapy conditioning regimens can be used in concordance with the 
clinical site’s standard procedures. The clinical sites should use chemotherapy with or without 
TBI with the minimum cumulative dosages mentioned below: 
TBI at 1200 cGy;  
Cyclophosphamide at 120 mg/kg; 
Etoposide at 60 mg/kg; 
Melphalan at 100 mg/m2; 
Busulfan at 12 mg/kg; 
Fludarabine at 160 mg/m2; 
In case that TBI is used with combination of Busulfan and fludarabine, the minimum dose of 
TBI will be 400 cGy.


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8
STATISTICAL CONSIDERATIONS
This section presents general information about statistical considerations and concepts such as 
randomization, sample size, and a brief discussion on analysis methodology, as well as some 
data conventions. Detailed descriptions of the statistical analysis methods and data conventions 
that will be used in this study will be in a separate document; i.e., the Statistical Analysis Plan 
(SAP).
8.1
TREATMENT GROUPS 
This is a placebo-controlled study. The following treatment groups will be assessed: 
Group
Description
Active Treatment
Standard GVHD prophylaxis + PRO140  
Control Treatment 
Standard GVHD prophylaxis + Placebo 
8.2
DESCRIPTION OF STUDY ENDPOINTS 
8.2.1
Primary Efficacy Endpoint 
Incidence of Grade II, Grade III or Grade IV acute GVHD by Day-100
8.2.2
Secondary Efficacy Endpoints 
Incidence of severe and life-threatening (Grade III and Grade IV) acute GVHD by Day-
100
Incidence of organ-specific acute GVHD by Day-100
Effect of PRO 140 or Placebo on donor engraftment by T-cell and myeloid chimerism in 
peripheral blood
Effect of PRO 140 or Placebo on neutrophil and platelet count recovery
Changes in ECOG performance score
GVHD-free survival (GFS)
8.2.3
Safety Assessments
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 emergent adverse events and serious adverse events


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AML or MDS relapse rate by Day-100 
Changes and shifts in laboratory measurements over time 
Changes in Electrocardiogram (ECG) parameters over time
8.3
SAMPLE SIZE DETERMINATION AND RATIONALE
For this two arm clinical trial, it is planned to have a total of 60 subjects (30 per treatment 
group). The sample size is on the basis of clinical judgment and not based on statistical power 
calculation. The number of subjects was deemed adequate to provide clinically meaningful 
descriptive results consistent with study objectives.
8.4
RANDOMIZATION, STRATIFICATION AND BLINDING
This is a double-blind, multi-center randomized clinical trial. The randomization will be central 
and will use mixed blocks of 2 and 4 with a 1:1 ratio of Active to Control to ensure even 
distribution of Active and Control subjects.  
Randomization will be conducted via a Web based system, and the process for the blinding
requirements will be outlined in the study randomization plan. To decrease the effect of HLA-
Matched Unrelated Donor (MUD) vs HLA-Mismatched Related Donor (MRD) as a confounding 
factor in this study, the donor source will be used as a stratification factor. This stratification will 
allows us to achieve a balanced randomization scheme with more reliable interpretation.
8.5
INTERIM ANALYSIS 
There will be a safety interim analysis after the first 10 subjects complete the treatment or 
withdraw from the study, whichever occurs first. The data from this interim analysis will be 
reviewed by an independent Data Monitoring Committee (DMC). The DMC responsibilities will 
be further elaborated in the study DMC charter.  
There is no planned interim analysis for efficacy. 
To protect the integrity of the blinded data, the IA will be conducted based on a Standard 
Operating Procedure for Interim Analysis that has a well-established firewall to protect the 
integrity of the trial.  The details of the IA, including the below bullet points, are included in the 
Statistical Analysis Plan (SAP) for the study. 
The goals of the IA
IA procedures for data preparation  
IA procedures for conduct of the analysis 
Data to be shared with the DMC


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Information to be shared with the sponsor after the IA
The stopping rule 
Protection of Type I error rate and adjustments 
8.6
GENERAL STATISTICAL CONSIDERATIONS 
8.6.1
Analysis Populations  
8.6.1.1
Intent-to-Treat Population
The Intent-to-Treat (ITT) population is defined as the set of subjects who are randomized to PRO 
140 or placebo. The ITT population will be the primary analysis population for the analysis of 
primary and secondary endpoints. 
8.6.1.2
Per Protocol Population
The Per Protocol (PP) population is defined as the set of subjects who meet the ITT population 
requirements, and were not associated with a major protocol violation. This population will be 
identified before the database lock. The PP population will be the supportive analysis population 
for the analysis of primary and secondary endpoints. 
8.6.1.3
Safety Population 
The Safety population is defined as all subjects who received at least one dose of PRO 140 or 
placebo after randomization. This population will be used for the analysis of safety parameters. 
8.6.2
Statistical Methods 
All collected study data will be presented in subject data listings. Statistical analyses will be 
performed using SAS® for Windows, version 9.3 or later.  
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 methods that will be detailed in the SAP for the 
ITT population of the primary and secondary endpoints.  
8.7
DATA SUMMARY
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.


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All statistical tests will be 2-sided and a 0.05% significance level will be used throughout the 
analyses.
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, HIV rapid antigen test, etc.) will 
be summarized using appropriate descriptive statistics.
Medical history of the subjects will also be provided as a by-subject listing and included as a 
baseline characteristic.  
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 CRFs will be coded to matching Anatomic Therapeutic 
Classification (ATC) codes using World health Organization (WHO) drug dictionary. 
Summaries will be prepared using the coded terms. All prior and concomitant medications 
recorded in the eCRFs will also be listed.
8.7.4
Administration of Study Drug
All the data from administration of study drug will be summarized and/or listed appropriately.  


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8.7.5
Efficacy Analysis 
8.7.5.1
Primary Analysis 
The primary analysis will be conducted on the ITT population.  
The primary efficacy endpoint for this study is the incidence of 
acute GVHD by Day -
100.
Chi-square/ Fisher’s exact test will be used to compare the primary endpoint between the 
treatment groups. 
All data from the secondary endpoints will be summarized and tabulated according to the 
variable type: 
Continuous data summaries will include:  
o
Descriptive statistics (n, mean, standard deviation, median, minimum and maximum) 
will be presented by treatment group  
o
For inferential statistics, if the Normality assumption is met, t-test will be used and if
the Normality assumption is not met, a non-parametric method will be used. 
Categorical data summaries 
o
Frequencies and percentages will be presented by treatment group. 
o
For inferential statistics Chi-square or fisher’s exact test will be used.
8.7.5.2
Supportive Analysis  
To assess the consistency of the Primary Analysis results, supportive analysis will be conducted 
using the Per Protocol (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. 
8.7.6
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. 
8.7.6.1
Adverse Events 
Adverse events will be coded using Medical Dictionary for Regulatory Activities (MedDRA). 
TEAEs are defined as events with an onset on or after the first treatment. TEAEs will be 
summarized by treatment group, System Organ Class, and preferred term. The following TEAE 
summaries will be provided: 


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Overall TEAEs
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.
8.7.6.2
Tolerability Assessment
All data from tolerability assessments of repeated subcutaneous administration of PRO 140 as 
assessed by study participants (using Visual Analogue Scale) and by investigator-evaluation of 
injection site reactions will be summarized.
8.7.6.3
Clinical Laboratory Data 
All laboratory values will be listed. Laboratory measurements will also be summarized. 
8.7.6.4
Physical Examination  
All physical examination findings will be listed and any abnormality will be summarized. 
8.7.6.5
Vital Signs 
All vital sign assessment findings will be listed and summarized. 
8.7.6.6
ECG Examination  
All ECG examination findings will be listed and any abnormality will be summarized. 
8.7.6.7
AML or MDS relapse rate by Day-100  
AML or MDS relapse rate by Day-100 will be presented. 


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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 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 and continue 
up until the final study visit (i.e. up to the Follow-up visit). All events will be followed to 
resolution or until 30 days after the subject completes the study. A final assessment of outcome 
will be made at that time.
All AEs must be recorded in the subject’s medical records and on the eCRFs. AEs will be 
reported using customary medical terminology along with the following information: the onset 
and end dates, whether the event is considered to be a SAE (see section 9.2), the impact the event 
had on study treatment (see section 9.1.2 ), the CTCAE grade (intensity) of the event (see section 
9.1.3), the causality of the event (see section 9.1.4), whether treatment was given as a result of 
the event (see section 9.1.5), and the outcome of the event (see section 9.1.6).
9.1.2
Impact of Study Treatment
The impact the event had on the study treatment will be assessed as either: none, study treatment 
interrupted, study treatment discontinued, or not applicable. The “not applicable” assessment will 
be used only when the subject is no longer in the treatment phase of the protocol, or if the 
outcome of the event was “death”.
9.1.3
CTCAE Grade (Severity) Assessment
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. To assess severity, the 


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investigator will use the guidelines outlined in CTCAE v4.03. The general guidelines for 
assessing 
the 
AE 
grade 
appear 
below. 
Full 
guidelines 
may 
be 
obtained 
at 
http://evs.nci.nih.gov/ftp1/CTCAE. 
Table 9-1:  
CTCAE v4.03 General Guidelines 
Grade
Description
Grade 1
Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated.
Grade 2
Moderate; minimal, local, or noninvasive intervention indicated; limiting age-
appropriate instrumental activities of daily living (ADL)*.
Grade 3
Severe or medically significant but not immediately life-threatening; hospitalization
or prolongation of hospitalization indicated; disabling; limiting self care ADL†.
Grade 4
Life-threatening consequences; urgent intervention indicated.
Grade 5
Death related to AE.
*Instrumental ADL refer to preparing meals, shopping for groceries or clothes, using the telephone, managing 
money, etc.
†Self care ADL refer to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and 
not bedridden.
-Common Terminology Criteria for Adverse Events (CTCAE), v4.03: June 14, 2010
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, pruritis, 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, pruritis, rash, nausea, 
tingling, and hypertension.  
SC Injection-site reactions thought to be directly related to the injection are considered to be AEs 
of special interest, and a separate guideline for the acquisition of data related to this AE of 
special interest is provided in section 17.1.
9.1.9
Stopping Rules for PRO 140  
Subjects who develop Grade 1 or Grade 2 adverse events will continue 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 or higher adverse events per below, or experience graft failure 
or relapse the study treatment will be permanently discontinued: 
Grade 3 or higher liver toxicity not attributable to other causes such as infection, GVHD 
or Sinusoidal Obstruction Syndrome (SOS); 
Grade 3 or higher toxicity which is assessed by the investigator to be definitely, probably 
or possibly related to the study drug; 
Graft failure or relapse;
9.1.10 Study Stopping Rules
Upon occurrence of any of the following events, data will be reviewed by the Data Monitoring 
Committee (DMC):
1.
Occurrence of a Grade 4 toxicity or two (2) occurrences of Grade 3 toxicities that are 
assessed to be definitely, probably or possibly study drug-related by the treating 
investigator;
2.
Occurrence of more than 20 percent mortality by day +100; 
3.
Occurrence of more than 5 percent graft failures by day +100; 
4.
Occurrence of 5 or more of the first 10 subjects experiencing acute Grade II-IV 
GVHD.


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The DMC will make a recommendation to the study investigators, who, in consultation with the 
sponsor will decide whether to stop enrollment in the study. 
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
Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered a serious adverse device effect when, based upon 
appropriate medical judgment, they may jeopardize the subject and may require medical 
or surgical intervention to prevent one of the outcomes listed in this definition. 
9.2.1
Reporting of SAE 
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 
The
 Medical Monitor may request additional supporting documentation as it becomes 
available, such as lab reports, ECG reports, discharge summary, hospital notes, etc.  
The Investigator is also responsible for reporting all SAEs to the appropriate Institutional Review 
Board (IRB) in accordance with local laws and regulations. The Investigator is responsible for 
maintaining documentation in the study file that indicates the IRB has been properly notified. 


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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)). 
9.2.2
SAE Follow-Up
All subjects experiencing an SAE, including the discontinued subjects, must be closely followed 
until sufficient information is obtained to indicate a return to normal status or until the event 
stabilizes at a level acceptable to the investigator (i.e., recovery, return to baseline status, no 
further improvement expected, or death). 
For each SAE indicated as an unresolved event on the initial report, regardless of whether the 
subject completed the study or withdrew, the site should submit a follow-up report with updated 
information. 
9.2.3
Pregnancy
If a pregnancy occurs in a subject or partner of a male subject during the study, it must also be 
reported to CytoDyn, Inc. Any pregnant subject must be followed up by the Investigator or 
designee until the child is born. Any complication experienced through the end of the pregnancy 
should be considered as an adverse event (AE), and should be recorded, and if it meets the
seriousness criteria, it must be reported CytoDyn, Inc/designated CRO promptly. 


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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, ulcer 
images, quality of life questionnaire, etc. 
Site inspections serve to verify strict adherence to the protocol and the accuracy of the data being 
entered on the case report forms, in accordance with federal regulations. A Monitoring Log will 
be maintained at each study site which the monitor will sign, date and state the type of visit. 
The Investigator should be aware that the study site and subject records may be inspected by the 
Sponsor and or representatives of the designated CRO, FDA or other regional regulatory 
authority. 
11.2
ACCEPTABILITY OF CASE REPORT FORMS (CRFS) 
Electronic CRFs must be completed for each subject who has signed an informed consent form. 
For subjects who are screen failures, this would be limited to the screen failure eCRF page. All 
source documents and eCRFs will be completed as soon as possible after the subject's visit. 
Corrections to data on the eCRFs will be documented. The Investigator will review eCRFs to 
indicate that, to his/her knowledge, they are complete and accurate. Electronic CRFs will be 
reviewed by the Sponsor’s or designated CRO’s monitor, who will make a decision as to their 
acceptability. 
11.3
MODIFICATION OF PROTOCOL
The Investigator will not modify or alter this protocol without first obtaining the concurrence of 
the Sponsor. Approval by the Investigator’s IRB must also be obtained prior to implementation of 
the change, with two exceptions: 


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1. When necessary to eliminate apparent immediate hazard to the subject; or 
2. When the modification does not involve the subject’s participation in the trial. 
An amendment may also require modification of the informed consent form. The Investigator will 
provide an approval letter for the amendment and revised informed consent form, if applicable, to 
the Sponsor. An amendment must be in writing and it must be dated by both the Sponsor and the 
Investigator. If necessary, the Sponsor will submit protocol amendments to FDA and other 
appropriate regulatory authorities and notify other Investigators using this protocol. 
11.4 REPORTING PROTOCOL DEVIATIONS
The Investigator is obligated to follow the protocol without departure from the requirements 
written in the protocol. If the Investigator deviates from the protocol requirements, the Sponsor 
will make the determination as to whether the subject will continue in the study. The Sponsor also 
has the right to discontinue the subject for protocol violations. The IRB may also have to be 
contacted if safety to the subject or if the scientific soundness of the study is involved. All 
protocol deviations must be documented in the eCRFs.


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12
DATA MONITORING COMMITTEE (DMC) 
A Data Monitoring Committee (DMC), independent of the study operations will be established to 
consider safety data generated during the study and to make recommendations about IA data. The 
details of the DMC responsibilities will be included in the DMC charter. The DMC charter will be 
developed and operated in adherence to the current FDA guidance on DSMC (Establishment and 
Operation of Clinical Trial Data Safety Monitoring Committees [March 2006]). The DMC 
meetings will take place at least once after the IA, and at other time-points as determined by the 
DMC charter, if necessary. In addition to the pre-specified time-points, the DMC may also decide 
to schedule a meeting whenever they decide a review of emergent safety data is warranted. The 
charter will detail the roles and responsibilities of the DMC members once they have been 
appointed. The study data will be provided to the Committee members in the form of a data 
report. Meetings to discuss the data will be held in person or by teleconference, based on the 
DMC Chair’s decision. The meetings will be in two stages: an “open stage” which will involve 
discussion on general aspects of the trial, and a “closed stage” between the DMC members only. 
The remit of the DMC will be primarily to assess the safety aspects of the trial.


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13
ETHICS AND REGULATORY REQUIREMENTS
This study is to be conducted in accordance with the specifications of this protocol and in 
accordance with principles consistent with Declaration of Helsinki, GCP, 21 CFR Part 312, ICH 
E6, HIPAA regulations in 45 CFR Part 164 (US only), and the Belmont Principles of respect for 
persons, beneficence, and justice. Procedures for selection of donors and stem cell dose will 
follow FDA requirements for Blood Products (21 CFR 640) and Human Cellular and Tissue 
Based Products (21 CFR 1271). No protocol changes will be implemented without the prior 
review and approval of the IRB, except when the modification does not involve the subject’s 
participation in the trial or where it may be necessary to eliminate an immediate hazard to a 
research subject. In the latter case, the change will be reported to the IRB as soon as possible, 
according to IRB regulations.  
Additionally, all study products used in this study are manufactured, handled and stored in 
accordance with applicable GMP and the products provided for this study will be used only in 
accordance with this protocol. 
13.1 INSTITUTIONAL REVIEW BOARD/INDEPENDENT ETHICS COMMITTEE (IRB/IEC)
The Principal Investigator at the site will provide the Institutional Review Board/Independent 
Ethics Committee (IRB/IEC) with all appropriate materials as required by their IRB/IEC, 
including but not limited to the clinical study protocol, informed consent form, and any 
advertising materials. The study will not be initiated until the IRB/IEC provides written approval 
of the aforementioned documents and until approval documents have been obtained by the 
Principal Investigator and Sponsor or Sponsor designee. The Investigator will not participate in 
the decision. If the Investigator is an IRB or IEC member, documentation must be provided 
indicating recusal from the approval process. Appropriate reports on the progress of this study by 
the Principal Investigator will be made to the IRB/IEC as required by local and applicable 
government regulations and in agreement with policy established by the Sponsor. The 
Investigator is required to maintain an accurate and complete record of all written correspondence 
to and received from the IRB/IEC, and must agree to share all such documents and reports with 
the Sponsor. 
No changes from the final approved protocol will be initiated without the IRB/IEC’s prior written 
approval or favorable opinion of a written amendment, except when necessary to eliminate 
immediate hazards to the subjects or when the modification does not involve the subject’s 
participation in the trial. 
13.2 INVESTIGATOR’S RESPONSIBILITIES


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


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14
DATA HANDLING AND RECORD KEEPING
14.1 RECORDING AND COLLECTION OF DATA
The primary source document for this study will be the subject's medical records. If separate 
research records are maintained by the Investigator(s), the medical records and the research 
records will be considered the source documents for the purposes of auditing the study.  
Applicable source data will be manually transcribed to the approved eCRFs. The Investigator is 
ultimately responsible for the accuracy of the data transcribed on the forms. All source documents 
and eCRFs will be completed as soon as possible after the subject's visit. 
The Investigator will review eCRFs to indicate that, to his/her knowledge, they are complete and 
accurate. Designated source documents will be signed and dated by the appropriate study 
personnel. The Investigator must agree to complete and maintain source documents and eCRFs 
for each subject participating in the study. 
All research data will be entered, either electronically or manually, into a computerized database. 
The clinical database will be designed by the clinical data manager in accordance with 21 CFR 
Part 11 and based on protocol requirements defined by the Sponsor in association with the Lead 
Investigator.  
The Investigator will maintain a confidential list of study subjects that will include each subject’s 
study number, name, date of birth, and unique hospital identification number if applicable. This 
list will be kept by the Investigator and will not be collected by the Sponsor. A notation will be 
made in the subject’s case history/medical chart that he/she is participating in a clinical study and 
has provided a signed and dated ICF as well as a release for protected health information as 
required by local policies. The Investigator must also maintain a separate screening log of all the 
subjects screened for participation in the study; it should include gender, age, eligibility status, 
reason for ineligibility, if applicable; and study allocated subject number, if applicable.  
14.2 CLINICAL DATA MANAGEMENT
The Sponsor and/or designated CRO will be responsible for the processing and quality control 
(QC) of the data. Data management will be carried out as described in the Sponsor’s or CRO’s 
standard operating procedures (SOPs) for clinical studies. 
The handling of data, including data QC, will comply with regulatory guidelines (e.g., ICH E6 
GCP, and local regulations where applicable) and the Sponsor’s or the CRO’s SOPs as well as 
provisions of the study-specific Data Management Plan.


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


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


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


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16
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198, 234-240. 
Chen YH, D. D. (2004). Increasing the sample size when the unblinded interim result is 
promising. 23(7), 1023-38. 
Coleridge Smith PD, T. P. (1988). Causes of venous ulceration: a new hypothesis. 296, 1726-
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Cullum N, F. A. (2000). Compression bandages and stockings in the treatment of venous ulcers. 
CD000265 . Cochrane Database Syst Rev .
Danon D, M. J. (1997). Treatment of human ulcers by application of macrophages prepared from 
a blood unit. 32(6), 633-41. 


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de Laat EH, S. o. (2005). Pressure ulcers: diagnostics and interventions aimed at wound-related 
complaints: a review of the literature. 14(4), 464-72. 
Demeter LM, S. R.-W. (2000). 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. , 44, 794-797. 
Falanga V, M. D.-Y. (1998). Rapid healing of venous ulcers and lack of clinical rejection with an 
allogeneic cultured human skin equivalent. Human Skin Equivalent Investigators Group. 134(3),
293-300. 
Guarnera G, T. G. (2007). Pain and quality of life in patients with vascular leg ulcers: an Italian 
multicentre study. 16(8), 347-51. 
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maintenance strategy: an observational study. AIDS , 26, 2345-50. 
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NEJM , 359 (14), 1429-1441. 
Gutmann C, C. A. (2010). Randomized controlled study demonstrating failure of LPV/r 
monotherapy in HIV: the role of compartment and CD4-nadir. AIDS , 24, 2347-2354. 
Hankin CS, K. J. (2012). Clinical and cost efficacy of advanced wound care matrices for venous 
ulcers. 18(5), 375-84. 
Hutter, G.(2009). Long-term control of HIV by CCR5 delta32/delta32 stem-cell transplantation. N
Engl J Med, 360(7), 692-698. 
Insel, P., Franco, A. (2015). Evaluation of Antagonist/Agonist Activity of PRO 140 Downstream 
of CCR5 Binding Using Human CD4+ Cells. Sponsor commissioned study.
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intravenously to HIV-infected adults. Antimicrob Agents Chemother. , 54, 4137-42. 
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antibody, in HIV-infected adults. J Infect Dis. , 198, 1345-52. 
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Marozsan, A. J. (2008). 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,
Abstract H-1218. Washington, DC. 
Meynard JL, B. V. (2010). Lopinavir/ritonavirmonotherapy versus current treatment continuation 
for maintenance therapy of HIV-1infection: the KALESOLO trial. J Antimicrob Chemother. , 65,
2436-2444. 


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Moltó J, S. J. (2007). Lopinavir/ritonavir monotherapy as a simplification strategy in routine 
clinical practice. J Antimicrob Chemother. (60), 436-439. 
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Nunes EP, S. d. (2009). Monotherapy with Lopinavir/Ritonavir as maintenance after HIV-1 viral 
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by application of activated macrophage suspension. 13(3), 237-42. 
Przepiorka D, Weisdorf D, et al. (1995). 1994 Consensus Conference on Acute GVHD Grading. 
Bone Marrow Transplant. 15 (6): 825-828.  
Pulido F, A. J.-G.-E. (2008). Lopinavir-ritonavir monotherapy versus lopinavir-ritonavir and two 
nucleosides for maintenance therapy of HIV. AIDS , 22, F1-9. 
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hematopoietic cells to the postnatal thymus. Exp Hematol, 34(3), 308-319.  
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HIV-1 reverse transcriptase. N.Engl.J Med. , 329, 1065-1072. 
Shai A, H. S. (2005). Direct triggers for ulceration in patients with venous insufficiency. 44(12),
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Shukla D, T. A. (2005). Pain in acute and chronic wounds: a descriptive study. 51(11), 47-51. 
Simioni S, C. M. (2010). Cognitive dysfunction in HIV patients despite long-standing suppression 
of viremia. 24, 1243-1250. 
Tang MW, S. R. (2012). HIV-1 Antiretroviral Resistance: Scientific Principles and Clinical 
Applications. Drugs , e1-e25. 


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Technical Manual of Procedures version 3.0 dated March 19, 2103, Blood and Marrow 
Transplant Clinical Trials Network.
Thompson MA, A. J. (2012). Antiretroviral Treatment of Adult HIV Infection: 2012 
Recommendations of the International Antiviral Society–USA Panel. JAMA , 308, 387-402. 
Thompson, M. L. (2009). Weekly and bi-weekly subcutaneous PRO 140 demonstrates potent, 
sustained antiviral activity. 16th Conference on Retroviruses and Opportunistic Infections,
Abstract #571a. Montreal QE, Canada,. 
Zuloff-Shani A, A. A.-Z. (2010). Hard to heal pressure ulcers (Stage III-IV): Efficacy of injected 
activated macrophage suspension as compared with standard of care (SOC) treatment controlled 
trial. 51(3), 268-71. 
Zuloff-Shani A, D. D. (Submitted for publication). Treatment of infected wounds following 
saphenous vein harvesting for coronary bypass surgery by injection of activated macrophage 
suspension. 
Ruutu T, Gratwohl A, De Witte T, et al. Prophylaxis and treatment of GVHD: EBMT–ELN 
working group recommendations for a standardized practice. Bone Marrow Transplant. 2014 
Feb;49(2):319 


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17
APPENDICES


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17.1 APPENDIX I:  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.  
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 
hours treatment
Generalized itching 
causing inability to 
perform usual 
social and
functional 
activities
N/A
Bleeding
Initial bleed that 
does not exceed
bandage and 
spontaneously 
stops
Bleeding that 
exceeds bandage 
and spontaneously 
stops 
Continued bleeding 
that requires 
change of dressing 
and alternative 
injection site
N/A
Absorption of drug
Minor elevation of 
skin at injection 
site but no leakage 
of injection 
material
Leakage at
injection site 
ceases with 
decrease in
injection rate 
Leakage at
injection site that 
does not cease with 
decrease in
injection rate


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

SAP_001.pdf: 




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TABLE OF CONTENTS 
 
Section   
Page 
LIST OF ABBREVIATIONS ................................................................................................. 5 
1. 
INTRODUCTION ............................................................................................................... 6 
2. 
PROTOCOL DESIGN AND OBJECTIVES ........................................................................ 6 
2.1 
Study Objectives ...................................................................................................... 6 
2.2 
Design Overview ...................................................................................................... 7 
2.3 
Study Duration ......................................................................................................... 9 
2.4 
Study Treatments ...................................................................................................... 9 
2.4.1 
Treatment Groups ........................................................................................ 9 
2.4.2 
Randomization and Blinding ........................................................................ 9 
3. 
STUDY ASSESSMENTS/ ENDPOINTS .............................................................................. 9 
3.1.1 
Primary Efficacy Endpoint ........................................................................... 9 
3.1.2 
Secondary Efficacy Endpoints ...................................................................... 9 
3.1.3 
Safety Assessments .................................................................................... 10 
4. 
SAMPLE SIZE DETERMINATION AND RATIONALE, STATISTICAL POWER, 
AND SIGNIFICANCE LEVEL .......................................................................................... 10 
5. 
INTERIM ANALYSIS ....................................................................................................... 10 
5.1.1 
Procedures ................................................................................................ 11 
5.1.2 
Data and Information Provided to DMC ...................................................... 11 
5.1.3 
DMC Recommendation .............................................................................. 11 
5.1.4 
Type I Error Rate Adjustment ..................................................................... 11 
6. 
ANALYSIS POPULATIONS ............................................................................................. 11 
6.1 
Intent-to-Treat Population ....................................................................................... 11 
6.2 
Per Protocol Population ........................................................................................... 11 
6.3 
Safety Population ................................................................................................... 12 
7. 
DATA CONVENTION AND RELATED DEFINITIONS .................................................. 12 
7.1 
Baseline Definition ................................................................................................. 12 
7.2 
Duplicate Data ....................................................................................................... 12 
7.3 
Handling of Missing Data ........................................................................................ 12 
7.4 
Sensitivity Analysis ................................................................................................ 12 
7.5 
Multicenter Clinical Trials ....................................................................................... 12 
7.6 
Multiple Comparisons and Type I Error Rate Multiplicity adjustments ........................ 12 
7.7 
Covariates and Prognostic Factors ............................................................................ 12 
7.8 
Stratification Factors ............................................................................................... 13 
7.9 
Standard Calculations ............................................................................................. 13 
7.9.1 
Age .......................................................................................................... 13 
7.9.2 
Height ...................................................................................................... 13 
7.9.3 
Weight ...................................................................................................... 13 
7.9.4 
Body Mass Index (BMI)............................................................................. 13 
7.9.5 
Definition and Duration of Platelet Recovery ............................................... 14 
7.9.6 
Definition and Duration of Neutrophil Recovery .......................................... 14 
7.9.7 
Duration of GVHD-Free Survival (GFS) ..................................................... 14 
8. 
STATISTICAL METHODS ............................................................................................... 15 


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8.1 
Summarizing and Tabulating the Collected Data ....................................................... 15 
8.1.1 
Subject Disposition and Withdrawals .......................................................... 15 
8.1.2 
Protocol Deviations ................................................................................... 15 
8.1.3 
Demographics and Baseline Characteristics ................................................. 16 
8.1.4 
Prior and Concomitant Medications ............................................................ 16 
8.1.5 
Treatment Administration ........................................................................... 16 
8.2 
Analysis of Efficacy Data ........................................................................................ 16 
8.2.1 
Primary Endpoint ...................................................................................... 16 
8.2.2 
Secondary Endpoints ................................................................................. 17 
8.3 
Supportive Analysis ................................................................................................ 18 
8.4 
Analysis of Safety Data ........................................................................................... 18 
8.4.1 
Adverse Events ......................................................................................... 18 
8.4.2 
Tolerability of repeated subcutaneous administration as assessed by Visual 
Analogue Scale ......................................................................................... 19 
8.4.3 
Clinical Laboratory Evaluations .................................................................. 19 
8.4.4 
Physical Examination ................................................................................. 20 
8.4.5 
Vital Signs ................................................................................................ 20 
8.4.6 
ECG Assessment ....................................................................................... 20 
8.4.7 
AML or MDS relapse rate by Day-100 ........................................................ 20 
8.4.8 
PK ............................................................................................................ 20 
8.4.9 
Anti-idiotypic antibodies ............................................................................ 20 
8.4.10 
Injection Site Reactions .............................................................................. 20 
9. 
APPENDIX 1: SCHEDULE OF ASSESSMENTS .............................................................. 21 
10. 
APPENDIX 2 – PLANNED TLG ....................................................................................... 24 
10.1 
Planned by-subject listings ...................................................................................... 24 
10.2 
Planned Summary Tables ........................................................................................ 25 
11. 
VERSION HISTORY ........................................................................................................ 26 
12. 
REFERENCES .................................................................................................................. 27 


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LIST OF ABBREVIATIONS 
Abbreviation 
Term 
AE 
AML 
Adverse Event 
Acute Myeloid Leukemia 
ATC 
Anatomic Therapeutic Classification  
CFR 
Code of Federal Regulations 
CRF 
Case Report Form 
CRO 
Contract Research Organization 
DMC 
Data Monitoring Committee 
ECG 
Electrocardiogram 
eCRF 
Electronic Case Report Form 
FDA 
U.S. Food and Drug Administration 
FU 
Follow-Up 
GCP 
GVHD 
Good Clinical Practice 
Graft-versus-host disease 
HIV 
Human Immunodeficiency Virus 
IA 
Interim Analysis 
ICH 
International Conference on Harmonization 
iDMC 
Independent Data Monitoring Committee 
IP 
Investigational Product 
IRB 
Institutional Review Board 
ITT 
MDS 
Intent-to-treat 
Myelodysplastic Syndromes 
MedDRA 
Medical Dictionary for Regulatory Activities 
PI 
Principal Investigator 
PP 
Per Protocol 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SD 
Standard Deviation 
SOP 
Standard Operating Procedure 
TEAE 
Treatment Emergent Adverse Events 
VAS 
Visual Analogue Scale 
 
 
 
 
 
 


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1. 
INTRODUCTION 
This Statistical Analysis Plan describes the planned analyses and reporting for the clinical trial 
protocol PRO 140_CD03_GVHD, sponsored by CytoDyn Inc.  The reader of this Statistical 
Analysis Plan (SAP) is encouraged to review the complete protocol and amendments as this plan 
contains only a limited overview of protocol information.  The main objective of this plan is to 
provide details pertaining to statistical methodology, data conventions, and processes used for the 
analysis of data from this trial.  
The format and content of this Statistical Analysis Plan are structured to provide sufficient detail to 
meet the requirements specified by the International Conference on Harmonization (ICH) E9: 
Guidance on Statistical Principles in Clinical Trials.  All work planned and presented in this 
Statistical Analysis Plan will follow the ethical guidelines published by the American Statistical 
Association (ASA). 
The following documents and references [1-6], were reviewed in preparation of this Statistical 
Analysis Plan: 
• Version 3.0, protocol 17 June 2016 
• US Federal Register, Department of Health and Human Services, FDA, Guidance on Statistical 
Principles for Clinical Trials (1998) 
• ASA Ethical Guidelines for Statistical Practice (1999) 
• The Royal Statistical Society: Code of Conduct (1993) 
• ICH Guidance on the Structure and Content of Clinical Study Reports (ICH E3, 1996) 
• ICH Guideline on General Considerations for Clinical Trials (ICH E8, 1997) 
• ICH Guidance on the Statistical Principles for Clinical Trials (ICH E9, 1997) 
 
2. 
PROTOCOL DESIGN AND OBJECTIVES 
2.1 Study Objectives 
The primary objective of this study is to assess the efficacy of PRO 140 compared to placebo as an 
add-on therapy to standard GVHD prophylaxis in adult patients with AML or MDS undergoing 
allogeneic HCT. 
The secondary objective of this study is to assess safety and tolerability of PRO 140 compared to 


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placebo as an add-on therapy to standard GVHD prophylaxis in adult patients with AML or MDS 
undergoing allogeneic HCT. 
2.2 Design Overview 
This is a Phase II, randomized, double-blind, placebo-controlled, multi-center study to evaluate the 
feasibility of the use of PRO 140 as an add-on therapy to standard GVHD prophylaxis treatment for 
prevention of acute GVHD in adult patients with AML or MDS undergoing allogeneic HCT. 
In this study, 60 subjects will be randomized to receive either PRO 140 or placebo in a 1:1 ratio (i.e. 
30 subjects per arm). PRO 140 or placebo will be administered as a 350 mg subcutaneous injection 
on Day -3 or Day -2 prior to stem cell infusion, on the day of stem cell infusion (Day 0), and then 
weekly for 30 days (at Week 1, Week 2, Week 3 and Week 4) after which it will be administered 
every two weeks for up to 100±7 days (at Week 6, Week 8, Week 10, Week 12 and Week 14). 
Subjects will return to clinic for two Follow-up visits at 2 weeks after the last treatment visit, and 
one year after the first treatment visit. 
The study will have three phases: Screening Phase, Treatment Phase and Follow-up Phase as shown 
in the study flow diagram Figure 2-1. 
 




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2.3 Study Duration 
A subject will be in this trial at maximum of around 56 weeks.   
• Screening Phase: up to 4 weeks (28 days). 
• Treatment Phase: up to 14 weeks ± allowed windows (up to 14 treatments). 
• Follow-up Phase: up to one year after first treatment visit (T1), approx. 38 weeks from 
end of treatment visit]. 
2.4 Study Treatments  
2.4.1 Treatment Groups 
This is a placebo-controlled study. The following treatment groups will be assessed: 
• Active Treatment Group: Standard GVHD prophylaxis + PRO140 
• Control Treatment Group: Standard GVHD prophylaxis + Placebo 
2.4.2 Randomization and Blinding 
This is a double-blind, multi-center randomized clinical trial. The randomization will be central and 
will use mixed blocks of 2 and 4 with a 1:1 ratio of Active to Control to ensure even distribution of 
Active and Control subjects.  
Randomization will be conducted via a Web based system, and the process for the blinding 
requirements will be outlined in the study randomization plan. To decrease the effect of HLA-
Matched Unrelated Donor (MUD) vs HLA-Mismatched Related Donor (MRD) as a confounding 
factor in this study, the donor source will be used as a stratification factor. This stratification will 
allows us to achieve a balanced randomization scheme with more reliable interpretation. 
3. STUDY ASSESSMENTS/ ENDPOINTS 
There are multiple efficacy endpoints and assessments in this trial.  These are partitioned in the 
primary and secondary endpoints.   
3.1.1 Primary Efficacy Endpoint 
• Incidence of ≥ Grade II acute GVHD by Day-100 
3.1.2 Secondary Efficacy Endpoints 
• Incidence of severe and life-threatening (Grade III and Grade IV) acute GVHD by Day-100 
• Incidence of organ-specific acute GVHD by Day-100 


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• Donor engraftment evaluated by T-cell and myeloid chimerism in peripheral blood 
• Neutrophil and platelet count recovery 
• Changes in ECOG performance score 
• GVHD-free survival (GFS) 
3.1.3 Safety Assessments 
Safety will be assessed by the below evaluations:  
• 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 emergent adverse events and serious adverse events 
• AML or MDS relapse rate by Day-100 
• Changes and shifts in laboratory measurements over time 
• Changes in Electrocardiogram (ECG) parameters over time 
4. SAMPLE SIZE DETERMINATION AND RATIONALE, STATISTICAL POWER, AND 
SIGNIFICANCE LEVEL 
For this two arm clinical trial, it is planned to have a total of 60 subjects (30 per treatment group). 
This is a proof of concept study, and sample size is on the basis of clinical judgment and not based 
on statistical power calculation. The number of subjects was deemed adequate to provide clinically 
meaningful descriptive results consistent with study objectives. Based on literature review, the 
incidence of GVHD in ablative transplant population range from 40-60%. Assuming that the 
control incidence of GVHD is 50% and that of the Active group is 15%, a sample size of 30 
subjects per group produces a two-sided 95% CI for the difference in proportions with a width of 
0.44 (i.e.,95% CI of  0.13 – 0.57). 
5. INTERIM ANALYSIS  
There will be a safety interim analysis after the first 10 subjects complete the treatment phase or 
withdraw from the study, whichever occurs first. The data from this interim analysis will be 
reviewed by an independent Data Monitoring Committee (DMC). The DMC responsibilities will be 
further elaborated in the study DMC charter.  
There is no planned interim analysis for efficacy. 


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5.1.1 Procedures 
• Cut-off dates for review of eCRFs, data cleaning, and analysis will be established based on 
an estimated target date of the first ten (10) treated subject completing pre-defined treatment 
period or withdraw from the study.  
• All data received by the cutoff date will be entered, validated, queries generated and 
resolved or pending queries documented.  
• Data snapshot will be taken for the safety analysis.  
• The statistician will generate planned data and information for the DMC, as described 
below.  
5.1.2 Data and Information Provided to DMC 
The DMC will receive: AEs, SAEs, labs, ECGs, vital signs, and all other safety related variables 
identified per the DMC Charter.  
5.1.3 DMC Recommendation 
The DMC will make a recommendation to the study investigators, who, in consultation with the 
CytoDyn, Inc., will decide whether to stop enrollment in the study. 
5.1.4 Type I Error Rate Adjustment 
 
There will be no impact on Type I error rate due to the safety interim analysis for this Phase 2 
study.  
6. ANALYSIS POPULATIONS  
6.1 Intent-to-Treat Population 
The Intent-to-Treat (ITT) population is defined as the set of subjects who are randomized to PRO 
140 or placebo. The ITT population will be the primary analysis population for the analysis of 
primary and secondary endpoints. 
6.2 Per Protocol Population 
The Per Protocol (PP) population is defined as the set of subjects who meet the ITT population 
requirements, and were not associated with a major protocol violation. This population will be 
identified before the database lock. The PP population will be the supportive analysis population for 


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the analysis of primary and secondary endpoints. 
6.3 Safety Population 
The Safety population is defined as all subjects who received at least one dose of PRO 140 or 
placebo after randomization. This population will be used for the analysis of safety parameters. 
7. 
DATA CONVENTION AND RELATED DEFINITIONS   
7.1 Baseline Definition 
For all parameters, baseline will be defined as the last available value before treatment.   
7.2 Duplicate Data  
For unplanned duplicate data within a protocol-specified visit, the last measured value will be used 
for the analysis.  If it is not possible to identify the “last measured value” the average of the 
duplicate values will be used.  
No data will be excluded.  All collected data will be listed.  
7.3 Handling of Missing Data  
There will be no imputation of missing data for the analysis of efficacy and safety variables for this 
Phase II study.  
7.4 Sensitivity Analysis  
For the analysis of the primary endpoint, a tipping point analysis will be conducted to assess the 
robustness of the results of the primary analysis and the impact of missing data.   
7.5 Multicenter Clinical Trials  
Multi-center study including up to 20 sites in the US. 
7.6 Multiple Comparisons and Type I Error Rate Multiplicity adjustments 
There is no need to adjust for multiplicity in this Phase II study.  
7.7 Covariates and Prognostic Factors 
There are no pre-planned covariates analyses of the data from this study. 






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8. STATISTICAL METHODS 
All data collected during this study will be presented in subject data listings. All statistical analyses 
will be performed using SAS® for Windows, version 9.4 or later.    
8.1 Summarizing and Tabulating the Collected Data  
All data collected will be summarized according to the variable type:  
• Continuous data summaries will include:  
o Descriptive statistics (n, mean, standard deviation, median, minimum and maximum) 
will be presented by treatment group  
o For inferential statistics, if the Normality assumption is met, t-test will be used and if the 
Normality assumption is not met, a non-parametric method will be used.  
• Categorical data summaries  
o Frequencies and percentages will be presented by treatment group.  
o For inferential statistics Chi-square or fisher’s exact test will be used. 
• Time-dependent data: Kaplan Meier methods will be used to analyze time dependent data 
and to depict the time to event data. 
8.1.1 Subject Disposition and Withdrawals 
There will be a detailed accounting of all subjects that signed the informed consent to participate in 
this trial.  The following will be summarized:   
• The number of subjects who signed the informed consent 
• The number of subjects who are screen failures 
• The number of subjects who are treated  
• The number of subjects who completed the study  
• The number of subjects who discontinued  
Reasons for discontinuation will also be summarized.  
In addition, there will also be a listing of all discontinued subjects, which will provide the clinical 
trial center and the specific reason for discontinuation.   
8.1.2 Protocol Deviations 
The deviations occurring during the clinical trial will be summarized descriptively according to the 
following categories: 


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• Entrance criteria deviation 
• Withdrawal criteria deviation  
• Received wrong treatment or incorrect dose 
• Received an excluded medication  
• All other deviations  
Additionally a by-subject listing of all deviations will also be prepared.   
8.1.3 Demographics and Baseline Characteristics 
Demographics and baseline characteristics (i.e., Age, Gender, etc.) will be summarized using 
appropriate descriptive statistics. 
Medical history of the subjects will also be provided as a by-subject listing and included as a 
baseline characteristic.  
8.1.4 Prior and Concomitant Medications 
Prior and concomitant medications will be summarized for the Safety population. All prior and 
concomitant medications recorded in the CRFs will be coded to match Anatomic Therapeutic 
Classification (ATC) codes using the most recent version of World health Organization (WHO) 
drug dictionary.  
Summaries will be prepared using the coded terms. All prior and concomitant medications recorded 
in the eCRFs will also be listed. 
8.1.5 Treatment Administration  
All the data from administration of study drug will be summarized and/or listed appropriately.  
8.2 Analysis of Efficacy Data 
The primary analysis will be conducted on the ITT population. The Per Protocol (PP) population 
will be used as a supportive analysis. 
8.2.1 Primary Endpoint  
The primary efficacy endpoint for this study is the incidence of ≥ Grade II acute GVHD by Day -
100. 


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Chi-square/ Fisher’s exact test will be used to compare the primary endpoint between the treatment 
groups.  
8.2.2 Secondary Endpoints 
All data from the secondary endpoints will be summarized as follows: 
8.2.2.1  Incidence of severe and life-threatening (Grade III and Grade IV) acute GVHD by 
Day-100 
The number and percentages of subjects with severe and life-threatening (Grade III and Grade IV) 
acute GVHD by Day-100 will be presented.  Chi-square/ Fisher’s exact test will be used to compare 
the incidence between the treatment groups. 
8.2.2.2 Incidence of organ-specific acute GVHD by Day-100  
The number and percentages of subjects with organ-specific acute GVHD by Day-100 will be 
presented by organ category. Chi-square/ Fisher’s exact test will be used to compare the incidence 
between the treatment groups. 
8.2.2.3 Donor engraftment evaluated by T-cell and myeloid chimerism in peripheral blood  
 The number and percentages of subjects with donor engraftment failure evaluated by T-cell and 
myeloid chimerism in peripheral blood will be presented by different treatment groups. The 
definition of donor engraftment failure is presented in Section 7.9.8. Chi-square/ Fisher’s exact test 
will be used to compare the incidence of donor engraftment failure. 
8.2.2.4 Neutrophil and platelet count recovery  
The number and percentages of subjects with neutrophil and platelet count recovery will be 
presented. The definition of neutophil and platelet count recovery is presented in Sections 7.9.5 and 
7.9.6, respectively. Chi-square/ Fisher’s exact test will be used to compare the incidence of 
neutrophil recovery and of platelet recovery between treatment groups.  
8.2.2.5 Changes in ECOG performance score 
The raw and change from baseline in ECOG performance score will be summarized for each 
assessment scheduled visit (i.e., Screening visit, Treatment Visits 1, 4, 7, 9, 11, Follow-up Visit 1 


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and Unscheduled Visit(s)). Descriptive statistics (n, mean, standard deviation, median, minimum 
and maximum) will be presented by treatment group. If the Normality assumption is met, t-test will 
be used to compare the mean of ECOG performance score between the treatment groups and if the 
Normality assumption is not met, a non-parametric method will be used. 
8.2.2.6 GVHD-free survival (GFS) 
GFS will be defined as the elapsed time between the date of transplant until GVHD related death. 
Duration of GVHD-free survival will be measured as in Section 7.9.7.  
GVHD-free survival will be compared between the treatment groups using Log-rank test and 
Kaplan-Meier methods will be used to depict the survival curves. 
 
8.3 Supportive Analysis  
The PP population will be used for the supportive analysis.  
To assess the consistency of the Primary Analysis results, supportive analysis will be conducted 
using the Per Protocol (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. 
8.4 Analysis of Safety Data 
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.  
8.4.1 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: 
• Overall TEAEs 
• TEAEs by severity grade 


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• TEAEs by relationship to study treatment. 
In addition, separate summaries of SAEs, and AEs resulting in discontinuation of study treatment 
will be presented. 
8.4.2 Tolerability of repeated subcutaneous administration as assessed by Visual Analogue Scale 
All data from tolerability assessments of repeated subcutaneous administration of PRO 140 as 
assessed by study participants (using Visual Analogue Scale, as presented in Figure 8-1: Visual 
Analog Scale below) and by investigator-evaluation of injection site reactions will be summarized 
using n, mean, Standard Deviation (SD), minimum and maximum values.  
 
Figure 8-1: 
Visual Analog Scale 
 
 
8.4.3 Clinical Laboratory Evaluations 
The changes in laboratory values will be summarized descriptively for each visit. Changes will be 
calculated relative to the values collected at baseline.  
o Serum chemistry  
o Complete blood count (CBC)  
o Urinalysis  
Laboratory data will be summarized as appropriate to the variable type.    
• For continuous data, summaries will include the number of observations, mean, standard 
deviation, median, minimum and maximum values.   
• For categorical data, frequency counts and percentages will be used.   


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For change from baseline summaries, subjects with an undefined change from baseline, because of 
missing data, will be excluded. All available laboratory data will be included in individual subject 
listings.     
8.4.4 Physical Examination  
Physical examination results will be listed and summarized in terms of the number and percentage 
of subjects with abnormal and normal findings at the scheduled protocol assessment visit. 
8.4.5 Vital Signs  
Vital sign results (systolic and diastolic blood pressure, heart rate, respiration rate and temperature) 
will be summarized descriptively for each scheduled protocol visit. Changes will be calculated 
relative to the assessments at baseline.  For change from baseline summaries, subjects with an 
undefined change from baseline, because of missing data, will be excluded. 
8.4.6 ECG Assessment 
ECG results will be listed and summarized in terms of the number and percentage of subjects with 
abnormal and normal findings at the scheduled protocol assessment visit. Additionally, descriptive 
statistics will be tabulated for the reported ventricular rate (beats per minute), PR interval (msec), 
QRS interval (msec), QT interval (msec), and QTc interval (msec) values along with changes from 
baseline at each visit. Subjects with missing data for a given time point will not contribute to the 
tabulations for that time point.  
8.4.7 AML or MDS relapse rate by Day-100 
AML or MDS relapse rate by Day-100 will be summarized and present by treatment groups. 
8.4.8 PK 
PK results will be descriptively summarized for each scheduled protocol visit.  
 
8.4.9 Anti-idiotypic antibodies 
Anti-idiotypic antibodies will be descriptively summarized and presented by treatment groups.  
 
8.4.10 Injection Site Reactions  
All data from injection site reaction assessments of the repeated subcutaneous administration of 
PRO 140 will be descriptively summarized. 


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9. APPENDIX 1: SCHEDULE OF ASSESSMENTS  
TABLE 1: 
SCHEDULE OF ASSESSMENTS  
 
 
 
 


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TABLE 1: 
SCHEDULE OF ASSESSMENTS– CONTINUED FROM PREVIOUS PAGE  
 
 
 
 
 


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


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


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11. 
VERSION HISTORY  
Final version 1.0 based on the information from Protocol v3.0 (19Jun2016) 
 
 
 


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12. 
REFERENCES 
1. ASA. (1999) Ethical Guidelines for Statistical Practice. Prepared by the Committee on 
Professional Ethics, August 7, 1999.  
2. The Royal Statistical Society: Code of Conduct (1993). 
3. E8 General Considerations for Clinical Trials, ICH Guidance, Federal Register, 1997. 
4. E9 Statistical Principles for Clinical Trials, ICH Guideline, Federal Register, 1997 
5. Guideline for the Format and Content of the Clinical and Statistical Section of an 
Application, 1988. 
6. Guideline for Industry:  Structure and Content of Clinical Study Reports (ICH E3), July 
1996.