VRC 607-ACTG A5378: A Phase 1, Single Dose Study of the Safety and Virologic Effect of an HIV-1 Specific Broadly Neutralizing Human Monoclonal Antibody, VRC-HIVMAB080-00-AB (VRC01LS) or VRC-HIVMAB075-00-AB (VRC07-523LS), Administered Intravenously to HIV-Infected Adults.
Phase: PHASE1
Conditions: HIV-1
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Official Title: A Phase 1, Single Dose Study of the Safety and Virologic Effect of an HIV-1 Specific
Broadly Neutralizing Human Monoclonal Antibody, VRC-HIVMAB080-00-AB (VRC01LS) or
VRC-HIVMAB075-00-AB (VRC07-523LS), Administered Intravenously to HIV-Infected Adults
ClinicalTrials.gov Identifier: NCT02840474
Document Type:
• 
Redacted Final Version of the Study Protocol (Statistical Analysis Considerations located in
Section 6 of the Protocol)
• 
Redacted Final Version of IRB-approved Informed Consent
Document/Date:
• 
Protocol Version 4.0: May 29, 2018
• 
Version 4.0 IRB-approved Informed Consent

 
Version 4.0 
May 29, 2018 
 
VACCINE RESEARCH CENTER 
AIDS CLINICAL TRIALS GROUP 
 
Protocol VRC 607/ACTG A5378 
(NIH 16-I-0147) 
(DAIDS-ES ID 30089) 
 
A PHASE 1, SINGLE DOSE STUDY OF THE SAFETY AND VIROLOGIC EFFECT OF AN 
HIV-1 SPECIFIC BROADLY NEUTRALIZING HUMAN MONOCLONAL ANTIBODY, 
VRC-HIVMAB080-00-AB (VRC01LS) OR VRC-HIVMAB075-00-AB (VRC07-
523LS), ADMINISTERED INTRAVENOUSLY TO HIV-INFECTED ADULTS 
 
Study Product Provided by: 
Vaccine Research Center/NIAID/NIH, Bethesda, MD 
 
Clinical Trial Sponsored by: 
National Institute of Allergy and Infectious Diseases (NIAID) 
Vaccine Research Center (VRC) 
Bethesda, Maryland 
AIDS Clinical Trials Group (ACTG) Network 
 
IND Sponsored by: 
National Institute of Allergy and Infectious Diseases 
Division of AIDS (DAIDS) 
Bethesda, Maryland 
 
IND 130,804 - held by DAIDS 
 
 
 
 
IRB Initial Review Date: June 6, 2016 

PRODUCT: VRC01LS/VRC07-523LS 
PROTOCOL: VRC 607/A5378, VERSION 4.0 
DATE:  MAY 29, 2018 
 
Page 2 of 70 
 
A PHASE 1, SINGLE DOSE STUDY OF THE SAFETY AND VIROLOGIC EFFECT OF AN 
HIV-1 SPECIFIC BROADLY NEUTRALIZING HUMAN MONOCLONAL ANTIBODY, 
VRC-HIVMAB080-00-AB (VRC01LS) OR VRC-HIVMAB075-00-AB 
(VRC07-523LS), ADMINISTERED INTRAVENOUSLY TO HIV-INFECTED ADULTS 
 
 
SIGNATURE PAGE 
 
 
I will conduct the study in accordance with the provisions of this protocol and all applicable 
protocol-related documents. I agree to conduct this study in compliance with United States 
(US) Health and Human Service regulations (45 CFR 46); applicable U.S. Food and Drug 
Administration regulations; standards of the International Conference on Harmonization 
Guideline for Good Clinical Practice (E6); Institutional Review Board/Ethics Committee 
determinations; all applicable in-country, state, and local laws and regulations; and other 
applicable requirements (e.g., US National Institutes of Health, Division of AIDS) and 
institutional policies. 
 
 
 
 
 
Principal Investigator: _______________________________________________ 
Print/Type 
 
 
 
 
 
Signed: ___________________________________ Date: _____________ 
Name/Title 
 
 
 

PRODUCT: VRC01LS/VRC07-523LS 
PROTOCOL: VRC 607/A5378, VERSION 4.0 
DATE:  MAY 29, 2018 
 
Page 3 of 70 
TABLE OF CONTENTS 
 
Page 
SIGNATURE PAGE .................................................................................................................2 
ABBREVIATIONS ...................................................................................................................6 
PRÉCIS ......................................................................................................................................9 
 
INTRODUCTION..................................................................................................... 11 
 Rationale for the Study ................................................................................................12 
 VRC01LS and VRC07-523LS Specific Research Laboratory Assessments ...............12 
 Previous human experience .........................................................................................13 
1.3.1 
VRC01 Safety Data ..........................................................................................13 
1.3.2 
VRC01LS Safety Data ......................................................................................14 
1.3.3 
VRC07-523LS Safety Data ...............................................................................15 
1.3.4 
Antiviral Effect of VRC01 ................................................................................16 
 Pharmacokinetic Parameters ........................................................................................17 
 
STUDY PRODUCTS ................................................................................................ 17 
 VRC-HIVMAB080-00-AB..........................................................................................17 
 VRC-HIVMAB075-00-AB..........................................................................................18 
 Preclinical Safety Studies ............................................................................................18 
 Nonhuman Primate (NHP) Studies ..............................................................................19 
 
STUDY OBJECTIVES ............................................................................................. 21 
 Primary Objectives.......................................................................................................21 
 Secondary Objectives...................................................................................................21 
 Exploratory Objectives ................................................................................................21 
 
STUDY DESIGN ....................................................................................................... 21 
 Study Population ..........................................................................................................22 
4.1.1 
Inclusion Criteria .............................................................................................22 
4.1.2 
Exclusion Criteria ............................................................................................23 
 Clinical Procedures and Laboratory Assays ................................................................24 
4.2.1 
Screening..........................................................................................................24 
4.2.2 
Enrollment, Study Days and Visit Numbers .....................................................25 
4.2.3 
Administration of Study Product ......................................................................25 
4.2.4 
Solicited Adverse Events and Clinical Follow-up ...........................................26 
4.2.5 
Pharmacokinetics Procedures .........................................................................26 
4.2.6 
Schedule of Evaluations ...................................................................................27 
4.2.7 
Monitoring HIV Infection Status ......................................................................27 
4.2.8 
Concomitant Medications ................................................................................27 
 Discontinuation of Study Participation Following Product Administration ................27 
 Protocol Criteria for Pausing the Study and Resuming the Study ...............................28 
 Plan for Review of Pauses and Resuming Rules .........................................................28 

PRODUCT: VRC01LS/VRC07-523LS 
PROTOCOL: VRC 607/A5378, VERSION 4.0 
DATE:  MAY 29, 2018 
 
Page 4 of 70 
 
SAFETY AND ADVERSE EVENT REPORTING ............................................... 29 
 Adverse Events ............................................................................................................29 
 Serious Adverse Events (SAE) ....................................................................................29 
 Adverse Event Reporting to the IND Sponsor .............................................................29 
5.3.1 
Expedited Adverse Event (EAE) Reporting Criteria ........................................29 
5.3.2 
Attribution Categories .....................................................................................31 
 Reporting to the Institutional Review Board ...............................................................31 
5.4.1 
Unanticipated Problem (UP) Definition ..........................................................31 
5.4.2 
Protocol Deviation Definition..........................................................................32 
5.4.3 
Non-Compliance Definition .............................................................................32 
5.4.4 
Expedited Reporting to the IRB .......................................................................32 
5.4.5 
Annual Reporting to the IRB ............................................................................33 
 
STATISTICAL CONSIDERATIONS .................................................................... 33 
 Overview ......................................................................................................................33 
 Objectives ....................................................................................................................33 
 Size and Accrual ..........................................................................................................34 
6.3.1 
Sample Size Considerations .............................................................................34 
 Statistical Analysis .......................................................................................................35 
6.4.1 
Analysis Variables ...........................................................................................35 
6.4.2 
Baseline Demographics ...................................................................................35 
6.4.3 
Safety Analysis .................................................................................................35 
6.4.4 
Tolerability Evaluation ....................................................................................36 
6.4.5 
Analysis of effect on CD4+ and HIV Viral load ...............................................36 
6.4.6 
Pharmacokinetics Analysis ..............................................................................36 
6.4.7 
Interim Analyses...............................................................................................37 
 
PHARMACY PROCEDURES ................................................................................ 37 
 Study Products and Administration Regimen ..............................................................37 
 Vialed Study Product Storage ......................................................................................38 
7.2.1 
Temperature Excursions ..................................................................................38 
 Preparation of Study Products for Administration.......................................................38 
7.3.1 
VRC-HIVMAB080-00-AB or VRC-HIVMAB075-00-AB: Preparation for IV 
Administration..................................................................................................39 
 Labeling of Study Products ..........................................................................................40 
 Study Product Distribution/Accountability..................................................................40 
 Study Product Disposition ...........................................................................................41 
 
HUMAN SUBJECT PROTECTIONS AND ETHICAL OBLIGATIONS ......... 41 
 Informed Consent.........................................................................................................41 
 Risks and Benefits........................................................................................................41 
8.2.1 
Risks .................................................................................................................41 
8.2.2 
Benefits .............................................................................................................43 

PRODUCT: VRC01LS/VRC07-523LS 
PROTOCOL: VRC 607/A5378, VERSION 4.0 
DATE:  MAY 29, 2018 
 
Page 5 of 70 
 Institutional Review Board ..........................................................................................43 
 Protocol Registration ...................................................................................................43 
 Participant Confidentiality ...........................................................................................44 
8.5.1 
Loss or Destruction of Samples, Specimens or Data .......................................44 
 Plan for Use and Storage of Biological Samples .........................................................44 
8.6.1 
Use of Samples, Specimens and Data ..............................................................44 
8.6.2 
Storage and Tracking of Blood Samples and Other Specimens ......................44 
 Participant Identification and Enrollment of Study Participants .................................45 
8.7.1 
Participation of Children .................................................................................45 
8.7.2 
Participation of Site Employees .......................................................................45 
 Compensation ..............................................................................................................46 
 Safety Monitoring ........................................................................................................46 
 
ADMINISTRATIVE AND LEGAL OBLIGATIONS .......................................... 46 
 Protocol Amendments and Study Termination ............................................................46 
 Study Documentation and Storage ...............................................................................46 
 Study Monitoring, Data Collection and Data Sharing .................................................47 
9.3.1 
Study Monitoring .............................................................................................47 
9.3.2 
Data Collection ................................................................................................47 
9.3.3 
Data Sharing ....................................................................................................48 
 Language ......................................................................................................................48 
 Policy Regarding Research-Related Injuries ...............................................................48 
 Multi-site Management ................................................................................................48 
 
REFERENCES .......................................................................................................... 49 
APPENDIX I ......................................................................................................................... 51 
APPENDIX II ........................................................................................................................ 63 
APPENDIX III ...................................................................................................................... 65 
APPENDIX IV ...................................................................................................................... 72 
 

PRODUCT: VRC01LS/VRC07-523LS 
PROTOCOL: VRC 607/A5378, VERSION 4.0 
DATE:  MAY 29, 2018 
 
Page 6 of 73 
 
ABBREVIATIONS 
 
Abbreviation
Term
ACTG
AIDS Clinical Trials Group
ADA
anti-drug antibody
ADL 
activities of daily living 
AE
adverse event
AIDS
Acquired Immunodeficiency Syndrome
ALP
alkaline phosphatase
ALT 
alanine aminotransferase
AoU 
Assessment of Understanding
ARV
antiretroviral
AST
aspartate aminotransferase
AUC
area under the curve 
β-HCG
human chorionic gonadotropin 
BMI
body mass index
CBC 
complete blood count
CCR5 
CC family of chemokines, receptor type 5
CL 
clearance 
CHO
Chinese Hamster Ovary
Cmax
maximum concentration 
CRPMC
Clinical Research Products Management Center
CRS
cytokine release syndrome 
cGMP
current Good Manufacturing Practice 
DAERS
DAIDS Adverse Experience Reporting System 
DAIDS
Division of AIDS
DAIDS MO  
DAIDS Medical Officer
DAIDS PRO
DAIDS Protocol Registration Office  
DHHS
Department of Health & Human Services
DNA
deoxyribonucleic acid
DSMB
Data and Safety Monitoring Board
EAE 
expedited adverse event
EC 
ethics committee
EC50 
half-maximal effective concentration
EDTA
Ethylenediaminetetraacetate
ELISA
enzyme-linked immunosorbent assay
Env
envelope
EOI
end of infusion
F 
bioavailability

PRODUCT: VRC01LS/VRC07-523LS 
PROTOCOL: VRC 607/A5378, VERSION 4.0 
DATE:  MAY 29, 2018 
 
Page 7 of 73 
Abbreviation
Term
FDA 
Food and Drug Administration 
GCP
Good Clinical Practice
GLP
Good Laboratory Practice
GLT 
(green) lithium heparin tube 
HIV 
human immunodeficiency virus
HLA 
human leukocyte antigen
HRPP 
Human Research Protections Program
IB 
Investigator’s Brochure 
ICF
Informed Consent Form
IgG1 
Immunoglobulin G1
IND 
investigational new drug application
IRB
Institutional Review Board
ISM 
Independent Safety Monitor 
IV 
intravenous
kg 
kilogram
L 
liter 
LIMS
Laboratory Information Management System 
z
terminal slope of concentration vs time profile 
MAb
monoclonal antibody 
mcg 
microgram
mcL
microliter 
mg 
milligram 
mL
milliliter
mM, mmol
millimole
MO
Medical Officer 
MSD
Meso Scale Discovery 
NIAID
National Institute of Allergy and Infectious Diseases
NIH 
National Institutes of Health
NIH CC 
National Institutes of Health Clinical Center
NHP 
non-human primate 
NVITAL
NIAID Vaccine Immune T-Cell and Antibody Laboratory 
OHRP
Office for Human Research Protections
PBMC 
peripheral blood mononuclear cells
PBS 
phosphate buffered saline
PCR
polymerase chain reaction
PI
Principal Investigator
PK 
pharmacokinetic
PSRT
Protocol Safety Review Team
Q 
inter-compartmental clearance

PRODUCT: VRC01LS/VRC07-523LS 
PROTOCOL: VRC 607/A5378, VERSION 4.0 
DATE:  MAY 29, 2018 
 
Page 8 of 73 
Abbreviation
Term
QA 
quality assurance 
RE 
regulatory entity 
RSC
Regulatory Support Center
SAE
serious adverse event
SC 
subcutaneous
SHIV
simian-human immunodeficiency virus 
SSRI
selective serotonin reuptake inhibitor
SST 
serum separator tube
TCR 
tissue cross reactivity
T½
half-life 
Tmax
time of maximal concentration (Cmax)
UNAIDS
Joint United Nations Programme on HIV/AIDS
UP 
unanticipated problem 
USP
United States Pharmacopeia 
VCMP 
Vaccine Clinical Materials Program
Vd 
volume of distribution 
VRC 
Vaccine Research Center
WBC 
white blood cell
WT
Wild Type
 
 

PRODUCT: VRC01LS/VRC07-523LS 
PROTOCOL: VRC 607/A5378, VERSION 4.0  
DATE:  MAY 29, 2018 
 
 
Page 9 of 73 
PRÉCIS 
 
VRC 607/A5378: 
A Phase 1, Single Dose Study of the Safety and Virologic Effect of an HIV-1 Specific 
Broadly Neutralizing Human Monoclonal Antibody, VRC-HIVMAB080-00-AB 
(VRC01LS) or VRC-HIVMAB075-00-AB (VRC07-523LS), Administered 
Intravenously to HIV-Infected Adults. 
Study Design:   
Open-label, single dose study to examine safety, tolerability, pharmacokinetics and 
virologic impact of VRC01LS or VRC07-523LS in HIV-infected viremic adults. 
Study Hypotheses: 
This is the first study of VRC01LS or VRC07-523LS in HIV-infected viremic adults. 
The primary hypothesis is that both VRC01LS and VRC07-523LS will be safe for 
intravenous administration to HIV-1-infected adults. The secondary hypothesis is that 
VRC01LS and VRC07-523LS will be detectable in human sera with a definable half-
life. Part A (VRC01LS) of the study has completed enrollment. 
Product Description:  
VRC-HIVMAB080-00-AB (VRC01LS) and VRC-HIVMAB075-00-AB are human 
MAbs targeted to the CD4+ binding site of HIV-1. Both MAbs are modifications of 
the VRC01 MAb (which has been shown to be safe and to have antiviral activity in 
human studies) with the addition of the “LS”, a 2-amino acid mutation designed to 
improve the half-life of the antibody. There are no changes to the Fab binding sites. 
These MAbs were developed and manufactured by VRC/NIAID/NIH under cGMP at 
the VRC Vaccine Pilot Plant operated under contract by the Vaccine Clinical 
Materials Program (VCMP), Leidos Biomedical Research, Inc., Frederick, MD. Vials 
are provided at 100 mg/mL.  
Participants: 
HIV-1-infected viremic adults; 18-70 years of age. 
Study Plan: 
This study will assess VRC01LS or VRC07-523LS administered at 40 mg/kg IV in 
HIV-infected viremic participants. Participants will enroll in one of two parts: Part A 
(VRC01LS) and Part B (VRC07-523LS). Enrollment into Part A (VRC01LS) is 
complete. Part B enrollment will include 7 participants (up to 10 participants may be 
enrolled in the event that there are participants who do not complete the sampling 
schedule) who will receive VRC07-523LS. Safety lab samples, HIV viral load, CD4+ 
count, PK samples, and blood samples for human anti-VRC01LS antibody (Part A) 
and human anti-VRC07-523LS antibody (Part B) detection will be drawn at baseline 
and intervals throughout the study. Participants will keep a daily diary of 
reactogenicity symptoms for 3 days after study product administration and will be 
queried at each study visit for adverse events. Participants in Part B will be strongly 
encouraged to initiate 3-drug ART (prescribed by their primary HIV clinician; not 
study-provided) any time after completing day 14 study evaluations. 
 
Results from Part A and Part B may be analyzed, published, and presented separately 
since they involve two different MAbs. 
 
 
 

PRODUCT: VRC01LS/VRC07-523LS 
PROTOCOL: VRC 607/A5378, VERSION 4.0  
DATE:  MAY 29, 2018 
 
 
Page 10 of 73 
 
 
VRC 607/A5378 Study Schema 
Parts 
Participants 
Product 
Administration Schedule 
Day 0 
Part A 
(Enrollment complete)
7 
VRC01LS 
40 mg/kg IV 
Part B 
7 
VRC07-523LS 
40 mg/kg IV 
Total* 
14 
 
*The expected enrollment is 14 participants (i.e., a minimum of 7 participants in each part). However, up to 20 participants 
(i.e., 10 participants in each part) may be enrolled in the event that there are participants who do not complete the sampling 
schedule, if additional PK evaluations are needed, or if additional participants are needed for safety evaluations. 
 
Study Duration:   
Participants will be followed for 48 weeks after study product administration. 
 
 

PRODUCT: VRC01LS/VRC07-523LS 
PROTOCOL: VRC 607/A5378, VERSION 4.0  
DATE:  MAY 29, 2018 
 
 
Page 11 of 73 
 INTRODUCTION 
The global incidence of new human immunodeficiency virus (HIV) infections peaked in the mid-
1990s. The incidence of new infections in 2014 is reported by Joint United Nations Programme on 
HIV/AIDS (UNAIDS) as 2 million new cases, down from 2.9 million in 2005, with an estimated 
global total of 36.9 million people living with HIV. The reduction of HIV incidence is due to 
multiple factors that include prevention and treatment programs. The decrease in incidence is an 
encouraging trend, but the scope and cost of the epidemic remains of great global concern. The 
wider availability of antiretroviral (ARV) treatment, mother to child transmission prevention 
programs, and a diverse array of other prevention programs have all contributed to turning the tide 
of the epidemic [1]. Each effective form of prevention and treatment is a welcome public health 
measure.  
The National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health 
(NIH) is committed to the development of safe, effective methods to prevent and treat HIV 
infection and AIDS worldwide. In this regard, the Vaccine Research Center (VRC), NIAID, 
Division of AIDS (DAIDS), NIAID, and AIDS Clinical Trials Group (ACTG) are collaborating to 
evaluate the potential clinical uses of HIV-specific broadly neutralizing human monoclonal 
antibodies (MAb) [2, 3, 4].  
The VRC, NIAID, NIH developed VRC01LS and VRC07-523LS, highly potent and broadly 
neutralizing HIV-1 human MAbs targeted against the HIV-1 CD4+ binding site [5]. The predecessor 
of VRC01LS and VRC07-523LS, VRC01, is in clinical trials under IND 113611 for prevention 
indication and under IND 126001 and IND 126664 for therapeutic indication. VRC01 was 
originally discovered in a subject infected with HIV-1 for more than 15 years and whose immune 
system controlled the virus without anti-retroviral therapy [6]. The VRC01 sequence was modified 
by site-directed mutagenesis to increase its binding affinity for the neonatal Fc receptor (FcRn) and 
the resulting antibody was designated VRC01LS. The LS designation specifies methionine to 
leucine (L) and asparagine to serine (S) (M428L/N434S, referred to as LS) changes within the C-
terminus of the heavy chain constant region far outside of the antigen-binding site [7]. Other than 
the two amino acid difference, VRC01LS is identical to VRC01. VRC01LS has an extended half-
life in both serum and mucosal tissue compared to VRC01, persists at higher concentrations in 
mucosal tissues, and has demonstrated improved protection against primate simian-human 
immunodeficiency virus (SHIV) infection [5]. VRC01LS is currently in clinical trials in HIV 
uninfected adults under IND 125494 for its HIV prevention indication. The VRC07 (wild-type) 
heavy chain was identified by 454 deep sequencing based on its similarity to the VRC01 MAb and 
paired with the VRC01 (wild-type) light chain. The mutations that together define the 523 
designations are a glycine to histidine mutation at residue 54 of the heavy chain, a deletion of the 
first two amino acids, glutamate and isoleucine, from the light chain, and a valine to serine mutation 
at the third amino acid residue of the light chain. The LS designation specifies methionine to leucine 
(L) and asparagine to serine (S) (M428L/N434S, referred to as LS) changes within the C-terminus 
of the heavy chain constant region. Like VRC01LS, the LS mutation of VRC07-523LS was 
introduced by site-directed mutagenesis to increase the binding affinity for the neonatal Fc-receptor 
(FcRn), resulting in increased recirculation of functional IgG [5, 7], thus increasing plasma half-life. 

PRODUCT: VRC01LS/VRC07-523LS 
PROTOCOL: VRC 607/A5378, VERSION 4.0  
DATE:  MAY 29, 2018 
 
 
Page 12 of 73 
In this study, VRC01LS or VRC07-523LS will be evaluated in HIV-1 infected participants for a 
potential treatment indication.  
 RATIONALE FOR THE STUDY  
The VRC considers the potential clinical uses for broadly neutralizing MAb in three broad areas: 1) 
prevention of transmission from HIV-1 infected mothers to newborn and breastfeeding infants, 2) 
prevention of HIV infection by sexual transmission, and 3) therapeutic application in HIV-1 
infected individuals. This last application will be the focus of this study for a potential application 
of VRC01LS or VRC07-523LS in the management of HIV-1 infected people. The increased half-
life and persistence of VRC01LS and VRC07-523LS at higher concentrations in mucosal tissues 
correlate with improved protection against SHIV infection in vivo in animal studies, suggesting a 
potential clinical application for the prevention or treatment of HIV-1 infection in humans. In this 
study, we will monitor the viral load and pharmacokinetics and pharmacodynamics of VRC01LS or 
VRC07-523LS among HIV-1 infected viremic adults to determine whether a therapeutic effect is 
present following the administration of one dose.  
 VRC01LS AND VRC07-523LS SPECIFIC RESEARCH LABORATORY ASSESSMENTS 
Research assays designed to characterize the investigational product rather than assess the health of 
the participants are described below. 
Laboratory assessments in the Phase 1 studies of the VRC01LS or the VRC07-523LS MAb include 
pharmacokinetics, assessment for the development of anti-VRC01LS or anti-VRC07-523LS 
antibody following exposure to the study products, and functional capacity (neutralization) of the 
MAbs following infusion.  
Study product (VRC01LS or VRC07-523LS) concentration for the PK analysis in this Phase 1 
study will be measured by an ELISA on a Beckman Biomek based automation platform. The MAb 
is coated onto Immulon-4hXB microtiter plates overnight at 4°C at a concentration of 3.5 mg/mL. 
Plates are washed and blocked (10% FBS in PBS) for 2 hours at room temperature. Duplicate serial 
3-fold dilutions covering the range of 100-24300 of the test sample are incubated 2 hours at 37°C 
followed by Horseradish Peroxidase-labeled goat anti-human antibody (1 hour, 37°C), and TMB 
substrate (15 minutes, room temperature). Color development is stopped by addition of sulfuric acid 
and plates are read within 30 minutes at 450 nm via the Molecular Devices Paradigm plate reader. 
The 4-parameter logistic curve regression of a standard curve of the MAbs covering the range from 
0.031 to 1.0 mcg/mL is utilized in this assay to quantitate the sample concentrations based upon the 
average of sample dilutions within the range of the assay.   
Assessment for development of anti-VRC01LS or anti-VRC07-523LS antibodies in participants 
will be performed using the Meso Scale Discovery (MSD) platform based on 
electrochemiluminescence. The developed anti-drug antibody (ADA) assay uses the biotin-labeled 
VRC01LS or VRC07-523LS immobilized on a streptavidin-coated MSD plate as the capture 
molecule, and the SULFO-TAG labeled VRC01LS or VRC07-523LS as the reporter molecule. This 
assay is independent of the anti-VRC01LS or VRC07-523LS antibody isotype and permits the 

PRODUCT: VRC01LS/VRC07-523LS 
PROTOCOL: VRC 607/A5378, VERSION 4.0  
DATE:  MAY 29, 2018 
 
 
Page 13 of 73 
detection of both high and low affinity antibodies. Additional testing may be conducted with 
VRC01-based assay if positive ADA is detected to VRC01LS or VRC07-523LS. 
Depending upon the concentrations measured in collected specimens, further evaluation of the 
research samples to assess for functional capacity to neutralize HIV may be conducted by an in 
vitro cell-based virus neutralization assay using the pseudotyped viruses [8, 9, 10]. 
As an exploratory evaluation, participants may be evaluated for their IgG1 allotypes to determine 
the potential for theoretical allotype-specific effects on the VRC01LS pharmacokinetics, such as 
reduced half-life or anti-drug antibody response [11, 12, 13]. Coded stored samples may be used for 
evaluation of the genetic sequence of the immunoglobulin heavy chain constant region allotype. 
 PREVIOUS HUMAN EXPERIENCE 
VRC01LS and VRC07-523LS are very similar to their predecessor, VRC01. VRC01 was tested in 
two phase 1 clinical trials, VRC 601 (in HIV-1 infected adults) and VRC 602 (in healthy adults) 
(see Section 1.3.1) at the VRC. VRC01LS and VRC07-523LS are currently being evaluated in 
clinical trials in healthy adults at the VRC, NIH, Bethesda, MD. Initial safety data for VRC01LS 
(data from VRC 606) and VRC07-523LS (data from VRC 605) is summarized below 
1.3.1 VRC01 Safety Data  
Evaluations of the highly neutralizing antibody VRC01 as an investigational drug began in humans 
in September 2013. As of the beginning of January 2017, more than 840 adults have received 1 or 
more study product administrations of VRC01 in a dose range from 1 to 40 mg/kg through 
intravenous (IV) administration and at 5 mg/kg through subcutaneous (SC) administration. VRC01 
has been tested in 27 HIV-infected adults in the VRC 601 study [14], in 29 and 84 healthy adults in 
VRC 602 [15] and HVTN 104 studies, respectively (IND 113611). Under IND 126001 in 2015, 
studies were initiated in HIV-1 infected adults to evaluate the safety and virological effect of 
VRC01 administration during acute HIV infection (RV398), during a brief analytical treatment 
interruption in chronically infected individuals (A5340), and the effect on the HIV reservoir 
(A5342).  
Cumulatively across all studies to date (January 10, 2017), there have been no serious adverse 
events (SAEs) related to VRC01 that required expedited safety reporting to the US Food and Drug 
Administration (FDA) or other regulatory authorities, and no study safety pauses for adverse events 
(AEs). A non-serious AE of urticaria was submitted to regulatory authorities as a safety report 
because urticaria, at the grade 3 severity, was not reported in the Investigator’s Brochure (IB) 
(Version 6.0, dated October 5, 2016). As of May 10, 2018, no SAEs related to VRC01 have been 
reported across all studies (communication from DAIDS). 
SC administrations of VRC01 in adults have been associated with mild local reactions during 
product administration including some pruritus, redness, and swelling. Symptoms generally resolve 
within a few minutes to a few hours after completion of product administration. In adults, 
erythema/induration reactions were reported rarely; the largest observed diameter for erythema or 
induration events during infusions ranged up to about 9 cm.   

PRODUCT: VRC01LS/VRC07-523LS 
PROTOCOL: VRC 607/A5378, VERSION 4.0  
DATE:  MAY 29, 2018 
 
 
Page 14 of 73 
In VRC 602, 2 out of 5 subjects who received a 5 mg/kg SC dose of VRC01 reported mild pain 
during product administration that resolved within 5-7 minutes. In VRC 606, 2 out of 2 subjects 
who received a 5 mg/kg SC dose of VRC01 reported moderate pain during product administration 
that resolved within 0-2 minutes. One (1) subject in VRC 601 (5 mg/kg SC) reported mild nausea 
during VRC01 SC administration. 
Most subjects experienced mild systemic reactogenicity or none at all. The systemic symptoms 
most commonly reported were malaise/fatigue, myalgias, and headaches. Of the 3 subjects who 
reported severe systemic reactogenicity in the HVTN 104 study, 2 had concurrent viral infections, 
and 1 had malaise lasting 1 day.  
Additional information on solicited reactogenicity in other studies can be found in the IB. Overall, 
the solicited local and systemic signs and symptoms following administration of VRC01 have 
generally been none to mild.   
Adverse events attributed to VRC01 study product administration on the basis of temporal 
relationship that have not resulted in study product discontinuation include transient laboratory 
abnormalities (aspartate aminotransferase [AST], alanine aminotransferase [ALT], and creatinine 
elevation; decreased neutrophil count), diarrhea, herpes zoster, urticaria, dizziness, and pruritus at 
the administration site. Adverse events attributed to study product administration (VRC01 or 
placebo) on the basis of temporal relationship for which the schedule of study product 
administration was discontinued include one subject (placebo recipient) with mild chest discomfort 
and one subject with a mild generalized, pruritic, papular rash. The participant with rash had 
received a loading IV dose of VRC01 and 2 weeks later received another VRC01 dose by SC 
injection. Symptoms developed 3 days after the 2nd dose and had resolved by the next day. Both 
AEs resolved without clinical sequela. An HVTN 104 subject who experienced syncope a few hours 
after the IV infusion of VRC01 was also discontinued from the product administration schedule, 
although the event was assessed as unrelated.  
In the P1112 study in infants, VRC01 has been very well tolerated when administered SC in either 
of the two single dose cohorts (Group 1 and Group 2) and in the monthly dose group (Group 3). 
There have been no systemic reactions to VRC01; local reactions (induration and/or erythema) have 
been mild and self-limiting. 
Overall, VRC01 administration in the dose range from 1 to 40 mg/kg IV and at 5 mg/kg SC have 
been assessed as well-tolerated and safe for further evaluation [14, 15]. Refer to the current IB for a 
more updated information about the safety of VRC01.  
1.3.2 VRC01LS Safety Data 
Evaluation of VRC01LS began in the VRC 606 study in healthy adults in November 2015.  The 
safety and PK data for the first 37 subjects who received administrations of VRC01LS were 
published in 2018 [16].  
In summary, VRC01Ls administrations have been generally well tolerated when delivered IV or 
SC, and there were no SAEs or dose-limiting toxicity. Post-administration symptoms were mild or 

PRODUCT: VRC01LS/VRC07-523LS 
PROTOCOL: VRC 607/A5378, VERSION 4.0  
DATE:  MAY 29, 2018 
 
 
Page 15 of 73 
moderate for local and systemic reactogenicity. Mild malaise and myalgia were the most common 
solicited AEs reported by 10 and 6 subjects, respectively. The most frequent local reaction was 
pain/tenderness at the injection site, reported by 14 subjects (2 for IV and 12 for SC administration) 
at a maximum severity being mild and moderate by 1 subject for SC product administration. 
Observations during product administration included brief reactions of local pain and/or stinging 
sensations at SC administration sites (15 of 18 subjects, 83.3%) that resolved within 2-5 minutes 
after injection. These reactions were consistent with known risks of injections and did not meet 
criteria for reporting as AEs as defined by the Table for Grading Severity of Adverse Events 
(Appendix IV). No systemic symptoms were reported during product administration.  
Six (6) AEs were assessed as possibly related to VRC01LS administration and all were mild in 
severity. Two (2) reports of diarrhea, 1 in Group 1 (5 mg/kg, IV, subject 01606101) and 1 in Group 
5 (5 mg/kg x 3 times, SC, subject 01606501), occurred on the day of VRC01LS administration and 
resolved the same day. One (1) Group 2 subject (5 mg/kg, SC, subject 01606201) experienced 
lightheadedness on the day following administration, and symptoms resolved within 24 hours. One 
(1) AE in Group 5 (5 mg/kg x 3 times, SC, subject 01606506) pertained to an injection site reaction 
with hyperpigmentation that resolved 14 days post administration. Two (2) AEs in Group 5 (5 
mg/kg x 3 times, SC, subject 01606508) were due to elevated ALT levels (56 and 69 IU/L) on day 
14 post injection and both resolved within 15 days after onset. No subject had a positive HIV 
enzyme immunoassay (EIA) response during the study. 
As of January 17, 2018, 7 viremic participants were enrolled in Part A of VRC 607/A5378 and 
received one infusion of VRC01LS at 40 mg/kg IV as planned and are in follow-up. During 
VRC01LS administrations, no local or systemic reactogenicity was reported. All 7 participants 
reported maximal solicited local reactogenicity as “none” on a 3-day diary card. As to systemic 
solicited reactogenicity, one participant reported mild symptoms of headache, chills, and nausea that 
resolved within 7-11 days after product administration. No SAEs were reported; all unsolicited AEs 
were Grade 1 (mild) or Grade 2 (moderate) and assessed as unrelated to study product. 
Refer to the IB for more details on the VRC01LS safety data. 
1.3.3 VRC07-523LS Safety Data 
As of January 15, 2018, the VRC 605 study is fully enrolled. Twenty-five (25) of 26 subjects 
received at least 1 dose of VRC07-523LS (12 SC and 25 IV administrations). One subject withdrew 
from the study prior to receiving the study product. There have been no SAEs and no study safety 
pauses for AEs. Overall, 15 of 25 subjects who received the product (60%) have had at least 1 AE 
with the maximum severity being Grade 1 for 7 subjects and Grade 2 for 6 subjects, Grade 3 for 1 
subject and Grade 4 for 1 subject. The Grade 3 AE was for an elevated creatinine 56 days after the 
last product administration. This was most likely related to dehydration following exercise. The 
creatinine value was determined to be a Grade 3 based on the DAIDS Grading Table parameter of 
an increase of 1.5 to 2 times the baseline value, which was still well within the institutional normal 
range. The Grade 4 AE was for elevated liver enzymes likely related to starting a concomitant 
medication, fluoxetine, known to cause hepatoxicity, and not related to VRC07-523LS. VRC07-
523LS administrations were discontinued for this subject due to the concomitant illness. While the 

PRODUCT: VRC01LS/VRC07-523LS 
PROTOCOL: VRC 607/A5378, VERSION 4.0  
DATE:  MAY 29, 2018 
 
 
Page 16 of 73 
subject was being followed for safety, liver enzymes tests fluctuated again after starting citalopram, 
which reinforced that the event was most likely caused by an underlying sensitivity to selective 
serotonin reuptake inhibitor (SSRI) medications. This Grade 4 laboratory abnormality was not 
considered life-threatening as it was not clinically significant as there was no hospitalization, 
jaundice, coagulopathy, bleeding, or ascites. Six (6) mild or moderate AEs were assessed as related 
to study product including mild dizziness, 4 occasions of infusion reactions (1 mild and 3 moderate, 
reported for 2 subjects), and mild abdominal pain. All AEs assessed as related to the study product 
have resolved without residual effects.  
Two (2) subjects developed infusion reactions shortly after IV product administration. Symptoms 
were typical of infusion reactions observed with other MAbs [17]. No atypical symptoms or delayed 
symptoms were seen. Specifically, one subject enrolled in the 40 mg/kg IV group experienced a 
moderate infusion reaction with chills, rigors, fever, myalgia, and headache beginning 15 minutes 
after completion of the infusion. The subject was treated with acetaminophen and ibuprofen. All 
symptoms resolved within 12 hours. Another subject in the 20 mg/kg IV group experienced 3 
separate infusion reactions (n=2 moderate, n=1 mild) after each product infusion. The subject 
experienced nausea, chills, rigors, malaise, tachycardia, headache, myalgia, and arthralgia. 
Symptoms began 15 minutes to 1 hour after completion of each product administration and 
completely resolved within 12 hours. The subject was treated with acetaminophen and ibuprofen.  
Overall, product administrations have been generally well tolerated with no unexpected reactions.  
For solicited local reactions in the week after VRC07-523LS administrations, one of 17 subjects 
(5.9%) who received the product by IV administration reported mild bruising at the administration 
site, and 5 of 8 subjects (62.5%) who received the product SC reported mild pain/tenderness at the 
injection site [Investigator’s Brochure, Version 4.0, dated February 26, 2018; VRC07-523LS VRC-
HIVMAB075-00-AB CONFIDENTIAL 45]. 
For solicited systemic adverse events reported 3 days after product administration, 4 of 17 subjects 
(25%) receiving VRC07-523LS IV reported mild or moderate systemic reactogenicity symptoms. 
The reported symptoms were malaise (n=2 mild, n=1 moderate), myalgia (n=2 mild, n=1 moderate), 
mild headache (n=2), and moderate chills (n=2). Five (5) of 8 subjects (62.5%) receiving VRC07-
523LS SC reported mild systemic reactogenicity symptoms: malaise (n=3), myalgia (n=2), 
headache (n=3), chills (n=1), nausea (n=1), and joint pain (n=2). 
Refer to the IB for more details on the VRC07-523LS safety data. 
1.3.4 Antiviral Effect of VRC01 
Analysis of the VRC 601 viral load data obtained from 8 viremic adults showed that VRC01 has a 
statistically significant in vivo virological effect on HIV viral load when administered as a single 40 
mg/kg IV dose. None of these adults were taking ARV when enrolled into the study and had not 
started ARV during the time period when the viral load data were collected. Six (6) of the 8 adult 
subjects had ≥1 log10 copies/mL decrease in viral load and 2 subjects had a viral load drop of 0.26 
and 0.18 log10 copies/mL, respectively [15]. 

PRODUCT: VRC01LS/VRC07-523LS 
PROTOCOL: VRC 607/A5378, VERSION 4.0  
DATE:  MAY 29, 2018 
 
 
Page 17 of 73 
These data indicated the following for a single dose of VRC01 at 40 mg/kg IV: 
• 
A statistically significant change from baseline viral load post-infusion days 5 to 16;  
• 
The median time to reach ≥0.5 log10 decrease in viral load was 5 days; and, 
• 
The median time to greatest decrease in viral load was 7 days. 
A 0.5 log10 copies/mL or greater decrease in viral load is considered to be a positive response to 
ARV [18]. To have clinical benefit, such a change would need to be sustained. In VRC 601, 
subjects were administered only one dose of VRC01 at 40 mg/kg and, thus, a sustained effect on 
viral load was not expected.   
 PHARMACOKINETIC PARAMETERS 
Based on animal studies, VRC01LS has a 2.5- to 3-fold increase in half-life in macaques as 
compared to VRC01 [5]. The PK parameters of VRC01LS is currently under evaluation in VRC 
606 in healthy individuals. In our interim, preliminary evaluation of the pharmacokinetics in VRC 
606, VRC01LS appears to persist longer and at a higher serum concentration than VRC01 following 
infusion at comparable doses. Formal statistical and PK analysis is ongoing. 
Based on the Gaudinski, et al. study of VRC01LS, the clearance for the 5-40 mg/kg dose range 
(n=16) was 36 ± 8 mL/d with an elimination half-life of 71 ± 18 days [16].  
This trial will study VRC01LS and VRC07-523LS pharmacokinetics in HIV-1 infected adults.  
 STUDY PRODUCTS 
The study products, VRC-HIVMAB080-00-AB (VRC01LS) and VRC-HIVMAB075-00-AB 
(VRC07-523LS), were produced under current Good Manufacturing Practice (cGMP) by 
VRC/NIAID/NIH at the VRC Vaccine Pilot Plant operated under contract by the Vaccine Clinical 
Materials Program (VCMP), Leidos Biomedical Research, Inc. (formerly SAIC-Frederick, Inc.), 
Frederick, MD. Specific manufacturing information is included on the study product vial labels and 
Certificates of Analysis, and can be found in the IBs. Quality Assurance (QA) lot release testing by 
the manufacturer and ongoing stability programs verify conformance to product specifications prior 
to use in clinical trials. 
 VRC-HIVMAB080-00-AB 
VRC-HIVMAB080-00-AB (VRC01LS) is a broadly neutralizing human MAb targeted against the 
HIV-1 CD4+ binding site. It was developed by VRC/NIAID/NIH.  
VRC01 was modified by site-directed mutagenesis to increase its binding affinity for the neonatal 
Fc receptor (FcRn). The resulting antibody is designated VRC01LS. The LS designation specifies 
methionine to leucine (L) and asparagine to serine (S) (M428L/N434S, referred to as LS) changes 
within the C-terminus of the heavy chain constant region far outside of the antigen-combining site 
[7]. The VRC01LS is an IgG1, and the glycosylation pattern is derived from its production in a 
Chinese Hamster Ovary (CHO) mammalian cell line.    

PRODUCT: VRC01LS/VRC07-523LS 
PROTOCOL: VRC 607/A5378, VERSION 4.0  
DATE:  MAY 29, 2018 
 
 
Page 18 of 73 
The bulk lot of the drug substance was manufactured under cGMP using a stably transfected CHO 
cell line, purified, and the drug product vials were filled and labeled. Each product vial contains 
6.25 mL volume at a concentration of 100 mg/mL VRC01LS in formulation buffer containing 25 
mM sodium citrate, 50 mM sodium chloride, and 150 mM L-arginine hydrochloride at pH 5.8.   
More details on the VRC-HIVMAB080-00-AB composition and manufacturing can be found in the 
IB.  
 VRC-HIVMAB075-00-AB 
Like VRC01LS, VRC-HIVMAB075-00-AB (VRC07-523LS) is a broadly neutralizing human MAb 
targeted against the HIV-1 CD4+ binding site. VRC07-523LS was developed by VRC/NIAID/NIH.  
Generation and testing of VRC07-523LS is briefly described. The VRC07 (wild-type) heavy chain 
was identified by 454 deep sequencing based on its similarity to the VRC01 MAb and paired with 
the VRC01 (wild-type) light chain. The mutations that together define the 523 designations are a 
glycine to histidine mutation at residue 54 of the heavy chain, a deletion of the first 2 amino acids, 
glutamate and isoleucine, from the light chain, and a valine to serine mutation at the third amino 
acid residue of the light chain. The LS designation specifies methionine to leucine (L) and 
asparagine to serine (S) (M428L/N434S, referred to as LS) changes within the C-terminus of the 
heavy chain constant region. The LS mutation was introduced by site-directed mutagenesis to 
increase the binding affinity for the neonatal Fc-receptor (FcRn), resulting in increased recirculation 
of functional IgG, thus increasing plasma half-life. 
The bulk lot of the drug substance was manufactured under cGMP using a stably transfected CHO 
DG44 cell line and purified. The drug product was filled into glass vials and labeled at the VRC 
Pilot Plant. Each 10 mL glass vial contains 6.25 ± 0.10 mL at a concentration of 100 mg/mL ± 10 
mg/mL of VRC07-523LS in formulation buffer consisting of 50 mM Histidine, 50 mM Sodium 
Chloride, 5% Sucrose, and 2.5% Sorbitol at pH 6.8.   
More details on VRC-HIVMAB075-00-AB composition and manufacturing are found in the IB.  
 PRECLINICAL SAFETY STUDIES 
The in vitro preclinical safety studies performed to assess potential off target binding by VRC01LS 
and VRC07-523LS are summarized in Table 2.3-1. There was no unexpected off target binding.   

PRODUCT: VRC01LS/VRC07-523LS 
PROTOCOL: VRC 607/A5378, VERSION 4.0  
DATE:  MAY 29, 2018 
 
 
Page 19 of 73 
Table 2.3-1: In Vitro Preclinical Safety Studies with VRC01LS and VRC07-523LS 
Study Purpose 
Study Outcome 
Assessment of anti-phospholipid reactivity 
VRC01LS does not react to phospholipids.  
VRC07-523LS has slight reactivity to phospholipids.  
Assessment of anti-nuclear antigen reactivity 
VRC01LS does not react with nuclear antigens.  
VRC07-523LS does react with a small subset of 
nuclear antigens.  
Assessment of binding to a human epithelial cell 
line (HEp-2) by Immunohistochemistry 
VRC01LS does not bind to HEp-2 cells.  
VRC07-523LS has minimal reactivity with Hep-2 
cells.  
Assessment of potential “off target” binding in a 
human Tissue Cross-Reactivity study with 
VRC01LS and VRC07-523LS 
VRC01LS variably stained cytoplasm and 
cytoplasmic granules in epithelial and/or decidual 
cells in several human tissues. The findings were 
judged of no toxicologic relevance for MAb [19, 20]. 
VRC07-523LS staining that was observed in both 
human and Sprague-Dawley rat tissues included 
cytoplasm, cytoplasmic granules, perinuclear, and/or 
apical cytoplasm of endothelium, epithelial cells, 
spindle cells, mononuclear cells, granulosa lutein 
cells, and neural cell processes. VRC07-523LS 
staining that was observed in human tissues only 
included cytoplasmic elements of hematopoietic cells, 
cells/processes associated with peripheral nerve, glial 
cell processes, reticular cells, mesothelial cells, 
interstitial cells, and adipocytes, and extracellular 
proteinaceous material in connective tissue of the 
sclera.   
More information on these and other preclinical studies with VRC01LS and VRC07-523LS can be 
found in the IB.  
 NONHUMAN PRIMATE (NHP) STUDIES  
Several non-GLP studies of VRC01LS and VRC07-523LS have been completed in NHP to assess 
for preclinical evidence of potential efficacy for prevention of HIV infection. Table 2.4-1 is a brief 
summary of the studies performed and supports the plan to evaluate up to 40 mg/kg dose 
administered IV as a dose range of potential interest for a preventive or therapeutic indication. More 
information on these studies can be found in the IB for both study products. 

PRODUCT: VRC01LS/VRC07-523LS 
PROTOCOL: VRC 607/A5378, VERSION 4.0  
DATE:  MAY 29, 2018 
 
 
Page 20 of 73 
Table 2.4-1: Pre-clinical Proof-of-concept Studies Performed with VRC01LS and VRC07-523LS in NHP 
Study Outcome 
Study Purpose 
Determine if VRC07-523LS could protect male 
Rhesus Macaques against SHIV infection compared 
to VRC01LS after IV administration of low sub-
optimal protective dose (0.3 mg/kg) of MAb 
7/12 animals were protected after receiving 
VRC01LS at 0.3 mg/kg IV, 3/4 animals were 
protected after receiving VRC07-523LS at 0.2 
mg/kg IV and 0/4 were protected after receiving 
VRC07-523LS at 0.05 mg/kg IV. VRC07-523LS 
showed >5-fold increase in potency compared to 
VRC01LS, consistent with its ability to better 
neutralize viruses in vitro 
Determine serum and rectal tissue concentrations in 
female rhesus macaques administered 10 mg/kg of 
VRC01 (WT) or VRC01LS IV 
Introduction of the LS mutation increased the half-
life of VRC01LS 2.5-fold and reduced clearance 3-
fold compared to VRC01 (WT). VRC01LS 
remained detectable in rectal tissue for more than 70 
days and persisted at significantly higher levels, 
while the VRC01 (WT) could not be measured after 
28 days [5].    
Determine serum and mucosal sample 
concentrations in male and female cynomolgus 
macaques administered 10 mg/kg of VRC07-523LS 
IV or 10 mg/mL of VRC01LS IV 
When administered IV at a single dose of 10 mg/mL 
in cynomolgus macaques, the half-life of VRC01LS 
was about 30 days, a 3-fold increase compared to 
VRC01 (WT). Increased levels of VRC01LS were 
noted in rectal tissue, rectal secretions, and vaginal 
tissue at 28 days post antibody infusion compared to 
VRC01 [5]. When administered IV at a single dose 
of 10 mg/kg in cynomolgus macaques, the half-life 
of VRC07-523LS was about 12 days. In all 4 
animals, plasma concentrations of VRC07-523LS 
exceeded 10 µg/mL at day 14 and were greater than 
3 µg/mL at day 28. Detectable concentrations of 
VRC07-523LS were found in rectal and vaginal 
secretions and tissues for at least 28 days (last 
collection point). 
Determine serum and mucosal secretion 
concentrations in male and female rhesus macaques 
administered 10 mg/kg of VRC07-523LS SC or 
VRC01LS SC 
When administered SC at a single dose of 10 mg/kg 
to rhesus macaques, the half-life of VRC01LS was 
about 28 days and VRC01LS was found in rectal, 
vaginal, and nasal secretions up to day 49 post 
administration (last day of testing). When 
administered SC at a single dose of 10 mg/kg in 
rhesus macaques, the half-life of VRC07-523LS was 
about 14 days. In all 6 animals, detectable 
concentrations of VRC07-523LS were found in 
rectal, vaginal and nasal secretions for at least 49 
days (last collection point). 

PRODUCT: VRC01LS/VRC07-523LS 
PROTOCOL: VRC 607/A5378, VERSION 4.0  
DATE:  MAY 29, 2018 
 
 
Page 21 of 73 
 
STUDY OBJECTIVES 
 PRIMARY OBJECTIVES 
• To evaluate the safety and tolerability of VRC01LS or VRC07-523LS administered at 40 
mg/kg IV to HIV-1 infected viremic adults. 
 SECONDARY OBJECTIVES 
• To evaluate the pharmacokinetics of VRC01LS or VRC07-523LS at 40 mg/kg IV through 
the first 48 weeks post administration. 
• To evaluate the effect on CD4+ count and viral load through study week 48. 
• To determine whether anti-drug antibody (ADA) to VRC01LS or VRC07-523LS can be 
detected post-administration.  
 EXPLORATORY OBJECTIVES 
• To evaluate HIV-1 isolates throughout the study for a variety of genotypic and phenotypic 
parameters including sensitivity to VRC01LS or VRC07-523LS neutralization. 
 STUDY DESIGN 
This is an open-label, single dose study to examine the safety, tolerability, pharmacokinetics, and 
virologic effect of the MAbs, VRC01LS or VRC07-523LS, in HIV-1 infected viremic adults 
conducted at the VRC and sites within the ACTG network. The hypothesis is that both VRC01LS 
and VRC07-523LS will be safe for administration to HIV-1 infected adults by the IV route. The 
secondary hypothesis is that VRC01LS and VRC07-523LS will be detectable in human sera with a 
definable half-life.  
The study schema is shown in Table 4-1. 
Table 4-1. VRC 607/A5378 Study Schema 
Parts 
Participants 
Product 
Administration Schedule 
Day 0 
Part A 
(Enrollment Complete) 
7 
VRC01LS 
40 mg/kg IV 
Part B 
7 
VRC07-523LS 
40 mg/kg IV  
Total* 
14 
 
*The expected enrollment is 14 participants (i.e., a minimum of 7 participants in each part). However, up to 20 
participants (i.e., 10 participants in each part) may be enrolled in the event that there are participants who do not 
complete the sampling schedule, if additional PK evaluations are needed, or if additional participants are needed for 
safety evaluations. 

PRODUCT: VRC01LS/VRC07-523LS 
PROTOCOL: VRC 607/A5378, VERSION 4.0  
DATE:  MAY 29, 2018 
 
 
Page 22 of 73 
Enrollment into Part A (VRC01LS) is complete. Participants will be enrolled into Part B (VRC07-
523LS). Blood and urine samples for safety laboratory, and PK evaluations will be collected from 
all participants at specified time points per the Schedule of Evaluations (Appendix III). Participants 
will keep a daily diary of solicited systemic symptoms for 3 days after product administration. 
Participants will be strongly encouraged to initiate 3-drug antiretroviral therapy (ART), that is 
prescribed by their primary HIV clinician and not study-provided, any time after completing day 14 
study evaluations. PK-enhancing agents will not be counted as part of the 3-drug ART regimen. 
 STUDY POPULATION 
All inclusion and exclusion criteria must be met for eligibility. 
4.1.1 Inclusion Criteria 
A participant must meet all of the following criteria: 
1. Able and willing to complete the informed consent process. 
2. 18-70 years old  
3. Available for clinic visits for 48 weeks after study product administration.  
4. HIV-1 infected and clinically stable. 
[Note: Documented HIV-1 infection by HIV enzyme immunoassay (EIA) performed by a 
CLIA certified outside lab within 28 days of enrollment is acceptable.]  
5. At least one plasma viral load ≥500 copies/mL within 28 days of enrollment. A plasma viral 
load within 28 days and closest to the day of enrollment, that is detectable but not greater 
than 100,000 copies/mL.  
[Note: outside laboratory results will be acceptable]. 
6. A CD4+ count ≥350 cells/mcL on 2 of 3 consecutive testing occasions (or on 2 of 2 
sequential tests) within 28 days prior to enrollment.  
[Note: outside laboratory results will be acceptable]. 
7. In general good health as assessed by a study clinician and under the care of a primary 
health care provider for medical management of HIV infection while participating in the 
study. Willing to give consent to contact and send laboratory results to the participant’s 
primary health provider.  
8. Willing to have blood samples collected, stored indefinitely, and used for various research 
purposes.  
9. Able to provide proof of identity to the satisfaction of the study clinician completing the 
enrollment process. 
10. Screening laboratory values within 28 days prior to enrollment must meet the following 
criteria: 
• Absolute neutrophil count ≥800/mcL 

PRODUCT: VRC01LS/VRC07-523LS 
PROTOCOL: VRC 607/A5378, VERSION 4.0  
DATE:  MAY 29, 2018 
 
 
Page 23 of 73 
• Platelets ≥100,000/mcL 
• Hemoglobin ≥10.0 g/dL 
• Creatinine ≤1.31 mg/dL 
• ALT ≤2.5 x ULN 
• Negative Hepatitis B Surface Antigen (HBsAg) 
• Undetectable Hepatitis C Viral Load (HCV RNA) 
[Note: Documented negative HBsAg and HCV RNA performed by an outside CLIA 
certified lab within 28 days of enrollment are acceptable.] 
Female-Specific Criteria: 
11. If a woman is sexually active with a male partner and has no history of hysterectomy, tubal 
ligation, or menopause, she must agree to use either a prescription birth control method or a 
barrier birth control method from the time of study enrollment until the last study visit, or 
have a monogamous partner who has had a vasectomy. 
12. Negative β-HCG (human chorionic gonadotropin) pregnancy test (urine or serum) on day of 
enrollment for women presumed to be of reproductive potential. 
4.1.2 Exclusion Criteria 
A participant will be excluded if one or more of the following conditions apply: 
1. Previous receipt of humanized or human monoclonal antibody whether licensed or 
investigational. 
2. Prior use of antiretroviral therapy. 
3. Ongoing AIDS-related opportunistic infection (including oral thrush). 
4. Active drug or alcohol use or dependence in the opinion of the site investigator that would 
interfere with adherence to study requirements. 
5. Any history of a severe allergic reaction, including generalized urticaria, angioedema or 
anaphylaxis prior to enrollment, that has a reasonable risk of recurrence during the study. 
6. Physical finding on examination considered clinically significant. 
7. Hypertension that is not well controlled. 
8. Weight >115 kg (253 pounds). 
9. Breast-feeding. 
10. Receipt of any investigational study product within 28 days prior to enrollment. 
11. Any other chronic or clinically significant medical condition that in the opinion of the 
investigator would jeopardize the safety or rights of the volunteer.   

PRODUCT: VRC01LS/VRC07-523LS 
PROTOCOL: VRC 607/A5378, VERSION 4.0  
DATE:  MAY 29, 2018 
 
 
Page 24 of 73 
 CLINICAL PROCEDURES AND LABORATORY ASSAYS 
Evaluation of safety for this study will include laboratory studies, medical history, and physical 
assessment by clinicians. The study schedule is provided in Appendix III. Total blood volume 
drawn from each participant will comply with the NIH Clinical Center Guidelines, which is 
available on the NIH intranet at: http://cc-internal.cc.nih.gov/policies/PDF/M95-9.pdf.  
All participants will be counseled to continue follow up with their primary HIV care provider 
throughout the duration of the study and to follow the DHHS guidelines to initiate ARVs for all 
HIV-infected individuals, regardless of CD4+ count. The study team will ensure that all participants 
have a primary health provider for medical management of HIV infection while participating in the 
study. Participants will be informed about the risks of not starting on ARV. 
• In Part A, participants will be encouraged to start ARVs in the following situations specifically 
(with documentation): prior to enrollment into the study; at the time of any increase in viral 
load; when the CD4+ count drops by 30%; when the CD4+ cell count drops below 200 
cells/mm3; and should a female participant become pregnant during the study. 
• In Part B, initiation of 3-drug ART (prescribed by primary HIV clinician; not study-provided) 
will be strongly encouraged after participants complete day 14 study evaluations. PK-enhancing 
agents will not be counted as part of the 3-drug ART regimen. 
Participants who are viremic on ARVs will be encouraged to talk to their primary care provider 
about their ARV regimen, per DHHS guidelines [21].  
Participants who receive the study product will continue to be followed for safety purposes 
according to the study schedule of evaluations. Participants will not be discontinued or replaced in 
the study for initiating or changing ARVs. They will continue to be followed for safety purposes 
according to the study schedule of evaluations. ARV regimen changes will be documented in the 
participant’s record. Additionally, PK assay for ARVs will be performed in Part B, if needed, to 
evaluate for the presence of ART and the period before and during viral rebound in participants who 
initiate ART. Data will be analyzed according to the Statistical Analysis plan in Section 6.4.  
In Part B, a participant who does not complete all of the required visit through day 14 will be 
replaced (up to a total of 10 participants enrolled). 
4.2.1 Screening 
Screening for Part A: (This part of the study has completed enrollment.) 
The screening protocol, VRC 500 (NIH 11-I-0164), will be used at the sites to screen for potential 
participants. Participants will be recruited through Institutional Review Board (IRB)-approved 
advertising. The evaluations and sample collection that will be included in screening are a medical 
history, physical exam, any laboratory tests needed to confirm eligibility, and pregnancy test (for 
females of reproductive potential). Additional assessments of health will be conducted at screening 
based on clinical judgment. Samples of PBMCs, plasma and serum will also be collected. Informed 
consent documents will be reviewed. Counseling related to pregnancy prevention (including 

PRODUCT: VRC01LS/VRC07-523LS 
PROTOCOL: VRC 607/A5378, VERSION 4.0  
DATE:  MAY 29, 2018 
 
 
Page 25 of 73 
potential risk of study product) will be performed at screening and subsequently as noted in the 
Schedule of Evaluations in Appendix III. Screening records will be kept documenting the reason 
why an individual was screened but not enrolled into the clinical trial. 
Screening for Part B: 
Screening evaluations to determine eligibility must be completed within 28 days prior to study 
enrollment unless otherwise specified. Screening evaluations, as noted in the Schedule of 
Evaluations in Appendix III, must occur prior to the participant starting any study products, 
treatments, or interventions. 
4.2.2 Enrollment, Study Days and Visit Numbers  
In this study, enrollment is defined as the day of assignment of a study identification number in the 
clinical database. A clinician will discuss the timing of the study product administration and blood 
sample collection before completing an enrollment to help ensure that the participant can comply 
with the projected schedule. Positive prevention counseling will be performed at enrollment and 
subsequently as noted in the Schedule of Evaluations. An Assessment of Understanding (AoU) will 
be completed in association with screening into VRC 607/A5378. The schedule will not require 
administration in an inpatient unit or an overnight stay but inpatient administration is an option to 
facilitate collection of timed research samples.  
Day 0 is defined as the day of study product administration. Day 0 may occur on the same day as 
enrollment, or up to 4 weeks (28 days) after enrollment in Part A or up to 10 days after enrollment 
in Part B. This period may be increased with approval from the protocol team (contact the protocol 
team at actg.teama5378@fstrf.org).  
For calculating elapsed days, each subsequent calendar date is labeled by the next sequential “Study 
Day” as shown in the Schedule of Evaluations in Appendix III. Because there may be more than 1 
research sampling timepoint of interest per study day, each sample collection timepoint has its own 
“Visit Number.” For this reason, there may be more than one visit number recorded on the same 
calendar date. 
Medical history and Day 0 evaluations prior to the study product administration are the baseline for 
subsequent safety assessments.  
4.2.3 Administration of Study Product 
All study product administrations will be completed according to the study schema. For women of 
childbearing potential, study product administration may not proceed unless a negative pregnancy 
test has been obtained on the day of enrollment and on the day of study product administration (Day 
0). Prior to administration, temperature, blood pressure, heart rate (pulse), and weight will be 
collected and a targeted physical examination (based on signs, reported symptoms, or interim 
medical history) may be conducted.   
The IV access will be placed in an arm in an aseptic manner. A different site will be used for 
collection of PK blood samples; however, the same site may be used after flushing the line if 

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another site is not available. Study product will be administered with approximately 100 mL normal 
saline IV with a target of about 30 minutes. Infusions lasting longer than 30 minutes are allowed. If 
there is evidence of intolerance by the participant, the infusion rate will be slowed or stopped. 
All participants will be observed for at least 30 minutes following product administration. 
4.2.4 Solicited Adverse Events and Clinical Follow-up   
Participants will be given a “Diary Card” to use as a memory aid for solicited adverse events and on 
which to record temperature and systemic symptoms daily for 3 days after study product 
administration. Participants will be trained to use a secure electronic database but may complete the 
paper “diary”, if preferred. When the 3-day diary card parameters are recorded directly by the 
participant through a password-protected secure database, the participant’s electronic record will be 
available to clinicians in real time, and will be the source for these data. If concerns arise based on 
the electronic diary card data, or if a participant uses a paper diary card, clinicians may follow up 
with additional phone calls during the reactogenicity period, as needed. The written (paper) diary 
may be used as a source document. When neither a written nor electronic diary card is available 
from the participant, the study clinician will note the source of reactogenicity information recorded 
in the study database.  
After receipt of study product solicited systemic parameters occurring within 3 days include: fever, 
unusually tired/feeling unwell, muscle aches, headache, chills, nausea, and joint pain. Participants 
will record highest measured temperature daily. Reactogenicity data will be reviewed for accuracy 
and completeness at follow-up visits and recorded without an attribution assessment. Clinicians will 
follow up with participants and collect resolution information for any reactogenicity symptoms that 
are not resolved within 3 days. 
Local reactogenicity parameters will include pain/tenderness, swelling, redness, bruising, and 
pruritus (itchiness) at the product administration site. Clinician assessment of the IV administration 
site will be conducted on day of study product administration and during the scheduled follow-up 
timepoints after product administration. 
Events that may require a clinic visit include rash, urticaria, fever of 38.6°C (Grade 2) or higher 
lasting greater than 24 hours, or significant impairment in the activities of daily living (such as those 
consistent with Grade 2 or higher impairment). Other clinical concerns may prompt a study visit 
based on the judgment of a study clinician. Clinical laboratory assays and clinical evaluations will 
assess safety and tolerability at specified intervals after each administration.  
4.2.5 Pharmacokinetics Procedures  
PK samples will be collected as close as reasonably possible to the target timepoint. However, 
actual time of collection is critical for PK analysis and will be recorded for all samples. The PK 
timepoints are shown in Appendix III.    

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4.2.6 Schedule of Evaluations  
Refer to the table in Appendix III for details on the Schedule of Evaluations and the windows 
permitted for completion of each visit. After enrollment, deviations from the visit windows are 
discouraged and will be recorded as protocol deviations, but will be permitted at the discretion of 
the PI (or designee).  
Additional visits and diagnostic tests may be scheduled during the study if needed to assess 
participant safety or for sample collection for immunological testing. 
Any evaluation for an adverse event or possible exacerbation of a pre-existing condition may be 
evaluated at study team discretion as a “protocol related” evaluation (contact the protocol team at 
actg.teama5378@fstrf.org). 
In the event that Grade 2 or higher proteinuria is detected, a nephrology consultation will be 
arranged, as well as any other clinically necessary investigations. 
4.2.7 Monitoring HIV Infection Status 
HIV infection status will be monitored at specified intervals by CD4+/CD8+ T cell count and HIV-1 
RNA PCR for viral load. CD4+ counts are known to have diurnal variation; therefore, participants 
will be encouraged to return for appointments that include CD4+ count at approximately the same 
time (e.g., morning or afternoon), whenever possible. 
If the CD4+ count decreases to less than 200 cells/mcl, the participant will be promptly informed 
and strongly urged to seek evaluation and advice from their primary HIV care provider. 
Documentation of ARV counseling session performed by study staff to review current DHHS 
guidelines for ARV therapy will be included in the research record. 
4.2.8 Concomitant Medications 
Only routine prescription medications will be entered in the database at the time of enrollment. 
Subsequently, concomitant medications associated with an adverse event that requires expedited 
reporting or the development of a new chronic condition requiring ongoing medical management 
will be recorded in the database. Otherwise, concomitant medications taken throughout the study 
will be recorded in the participant’s chart as needed for general medical records, but will not be 
recorded in the study database. In Part B, participants will be strongly encouraged to initiate 3-drug 
ART (prescribed by their primary HIV clinician; not study-provided) any time after completing day 
14 study evaluations. PK-enhancing agents will not be counted as part of the 3-drug ART regimen. 
The ART therapy will be documented as concomitant medications and any changes in the ARV 
regimen will be recorded in the database.  
 DISCONTINUATION OF STUDY PARTICIPATION FOLLOWING PRODUCT ADMINISTRATION 
Under certain circumstances, a participant may be terminated from participating in the study or may 
choose to withdraw participation. A participant may be terminated from participating in the study 
for any of the following reasons: 

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• Repeatedly non-compliant (missing visits or not following study procedures) 
• Develops a serious illness requiring ongoing medical care 
• Enrolls in another research study while on this study 
• Pregnancy 
• Study is stopped or canceled 
Participants who received study product will be asked to continue follow-up visits for safety 
monitoring purposes according to the protocol (Schedule of Evaluations, Appendix III), but 
collection of samples that are for research purposes only will be discontinued. Women who become 
pregnant will be asked to continue follow-up for safety monitoring (in which case we do not 
continue research blood draws) and to report the outcome of the pregnancy to the study team. The 
study team will notify the Antiretroviral Pregnancy Registry (http://www.apregistry.com; 
Telephone: 800-258-4263; Fax: 800-800-1052) of any pregnancies that occur after receiving study 
product for any participant still on the study.  
 PROTOCOL CRITERIA FOR PAUSING THE STUDY AND RESUMING THE STUDY 
Administration of the study products and new enrollments will be paused by the protocol team 
according to the criteria noted below. In the event of a pause, the IND Sponsor Medical Officer 
(MO) and Independent Safety Monitor (ISM) will be promptly notified. Refer to Section 5.3.2, for 
definitions of “related” and “not related” to study product when using these study pause criteria. 
Pause criteria are as follows:  
One (or more) participant experiences a Serious Adverse Event (SAE) that is assessed as related to 
study product, or 
Two (or more) participants experience the same Grade 3 or higher adverse events (AE) assessed as 
related to study product (other than self-limited Grade 3 solicited reactogenicity AEs).  
 PLAN FOR REVIEW OF PAUSES AND RESUMING RULES   
Administration of the study product and enrollments would resume only if review of the adverse 
events that caused the pause resulted in a recommendation to permit further study product 
administrations and study enrollments. The reviews to make this decision will occur as follows: 
Pauses for related SAEs: The IND Sponsor MO, with participation by the protocol team, will 
conduct the review and consult with the FDA to make the decision to resume, amend, or close the 
study, and notify the IRB accordingly. 
Pauses for related Grade 3 Events: The IND Sponsor MO, in consultation with the protocol team, 
will conduct the review and make the decision to resume, amend, or close the study for the Grade 3 
that meet the criteria for pausing the study. As part of the pause review, the reviewers will also 
advise on whether the study needs to be paused again for any subsequent events of the same type. 
The FDA and the IRB will be notified of grade 3 pause reviews and the IND sponsor decisions.   

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 SAFETY AND ADVERSE EVENT REPORTING 
 ADVERSE EVENTS 
An adverse event (AE) is any untoward or unfavorable medical occurrence in a human participant, 
including any abnormal sign (e.g., abnormal physical exam or laboratory finding), symptom, or 
disease temporally associated with the use of study treatment, whether or not considered related to 
the study treatment. In the event of proteinuria Grade 2 or higher, a nephrology consultation will be 
arranged, as well as other clinically necessary investigations.  
Severity of AEs will be assessed using the Version 2.0 of the DAIDS Table for Grading the Severity 
of Adult and Pediatric Adverse Events [November 2014]. The table is available from:  
http://rsc.tech-res.com/docs/default-source/safety/daids_ae_grading_table_v2_nov2014.pdf?sfvrsn=8 
Additional information can be found in Appendix IV.   
Reporting of all AEs will occur during the period from first study product administration through 56 
days (or 8 weeks) after study product administration.   
 SERIOUS ADVERSE EVENTS (SAE) 
The term “Serious Adverse Event” (SAE) is defined in 21 CFR 312.32 as follows: “An adverse 
event or suspected adverse reaction is considered serious if, in the view of either the investigator or 
the sponsor, it results in any of the following outcomes: Death, a life-threatening adverse event, 
inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant 
incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital 
anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or 
require hospitalization may be considered serious when, based upon appropriate medical judgment, 
they may jeopardize the patient or subject and may require medical or surgical intervention to 
prevent one of the outcomes listed in this definition. Examples of such medical events include 
allergic bronchospasm requiring intensive treatment in an emergency room or at home, blood 
dyscrasias or convulsions that do not result in inpatient hospitalization, or the development of drug 
dependency or drug abuse.” 
“Life-threatening” refers to an adverse event that at occurrence represents an immediate risk of 
death to the participant. An event that may cause death if it occurs in a more severe form is not 
considered life-threatening. Similarly, a hospital admission for an elective procedure is not 
considered an SAE. In Section 5.3 the term “Expedited Adverse Event” (EAE) encompasses the 
events that would be considered an SAE by the 21 CFR 312.32 definition. 
 ADVERSE EVENT REPORTING TO THE IND SPONSOR 
5.3.1 Expedited Adverse Event (EAE) Reporting Criteria 
Requirements, definitions and methods for expedited reporting of AEs are outlined in Version 2.0 
(January 2010) of the Manual for Expedited Reporting of Adverse Events to DAIDS (DAIDS EAE 

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Manual), which is available on the Regulatory Support Center (RSC) website at http://rsc.tech-
res.com/clinical-research-sites/safety-reporting. The SAE Reporting Category will be used for this 
study. 
The internet-based DAIDS Adverse Experience Reporting System (DAERS) will be used for 
expedited AE reporting to DAIDS. In the event of system outages or technical difficulties, 
expedited AE reports may be submitted via the DAIDS EAE Form. This form is available on the 
DAIDS RSC website at http://rsc.tech-res.com/clinical-research-sites/safety-
reporting/daids/paper-eae-reporting. For questions about DAERS, please contact NIAID CRMS 
Support at CRMSSupport@niaid.nih.gov or from within the DAERS application itself. For 
questions about expedited reporting, please contact the DAIDS RSC Safety Office at 
(DAIDSRSCSafetyOffice@tech-res.com). 
The study products for which expedited reporting is required is as follows: 
• VRC-HIVMAB080-00-AB (VRC01LS MAb) 
• VRC-HIVMAB075-00-AB (VRC07-523LS MAb) 
The NIAID/DAIDS will report all unexpected SAEs related to the study products observed in this 
clinical trial to the FDA in accordance with 21 CFR 312.32 (IND Safety Reports). 
While the participant is in the study reporting period, as defined in Section 5.1, the SAE 
Reporting Category will be used. 
The EAE Manual should be consulted for further details. Also, ensure that any protocol-specific 
reporting requirements are met. 
An EAE report form will be completed and reported to DAIDS within 3 days of investigator 
awareness, regardless of relationship to study product. 
The SAE criteria are as follows: 
• Results in death 
• Is life-threatening1 
• Requires (unplanned) inpatient hospitalization or prolongation of hospitalization2 
• Results in persistent or significant disabilities/incapacity. 
• Is a congenital anomaly/birth defect3 
• Is an important medical event (may jeopardize the patient or may require intervention to 
prevent one of the outcomes above 
Footnotes: 
1 “Life-threatening” refers to an event in which the patient was at immediate risk of death at the time of the event. It 
does NOT refer to an event that hypothetically might have caused death if it were more severe. 
2 Per ICH SAE definition, hospitalization is NOT an adverse event (AE), but is an outcome of the event. DO NOT 
REPORT: Any admission unrelated to an AE (e.g., for labor/delivery, cosmetic surgery, administrative or social 
admission for temporary placement for lack of a place to sleep); protocol-specified admission (e.g., for a procedure 
required by protocol); admission for diagnosis or therapy of a condition that existed before receipt of study product(s) 
and has not increased in severity or frequency as judged by the clinical investigator. (NOTE: A new AIDS-defining 

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event in a subject already known to be HIV-infected would be considered an increase in severity of a pre-existing 
condition [HIV infection] and would be reportable.) 
3 Clinically insignificant physical findings at births including those regarded as normal variants do NOT meet reporting 
criteria. If a clinically significant anomaly is reported, all findings (including those of no individual significance) 
should be included in the same report. For example, do NOT report an isolated finding of polydactyly (extra fingers 
or toes) or Mongolian spot in an infant. But if either finding occurred with a major cardiac defect, report all findings 
in the SAE Report. 
5.3.2 Attribution Categories 
Attribution categories used (i.e., terms used for assessment of relationship of AE to study product) 
for this study are consistent with those described in the DAIDS EAE Manual, Version 2.0 (January 
2010), as follows: 
• Related – There is a reasonable possibility that the AE may be related to the study 
product(s). 
• Not Related – There is not a reasonable possibility that the AE is related to the study 
product(s). 
If circumstances arise where other attribution categories are used in describing an adverse event, the 
attribution terms “Definitely”, “Probably” and “Possibly” related will be mapped to the “Related” 
category while the terms “Unlikely”, “Probably Not Related” and “Not Related” will be mapped to 
the “Not Related” category under EAE Manual, Version 2.0. 
 REPORTING TO THE INSTITUTIONAL REVIEW BOARD 
5.4.1 Unanticipated Problem (UP) Definition 
A serious “Unanticipated Problem (UP)” is defined as any incident, experience, or outcome that 
meets all three of the following criteria: 
• Unexpected in nature, severity, or frequency in relation to the research risks that are 
described in the protocol, informed consent, IB, other study documents, or in consideration 
of the characteristics of the participant population being studied; and 
• Related to participation in the research; and 
• Suggests that the research places participants or others at a greater risk of harm (including 
physical, psychological, economic, or social harm) than was previously known or 
recognized. 
Non-serious UP: An UP that is not an Adverse Event (UPnonAE) is an unanticipated problem that 
does not fit the definition of an adverse event, but which may, in the opinion of the investigator, 
involve risk to the participant, affect others in the research study, or significantly impact the 
integrity of research data. Such events would be considered a non-serious UP. For example, we will 
report occurrences of breaches of confidentiality, accidental destruction of study records or samples, 
or unaccounted-for study drug. 

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5.4.2 Protocol Deviation Definition 
A Protocol Deviation is defined as any change, divergence, or departure from the IRB-approved 
study procedures in a research protocol. Protocol deviations are designated as serious or non-serious 
and further characterized as: 
• Those that occur because a member of the research team deviates from the protocol. 
• Those that are identified before they occur but cannot be prevented. 
• Those that are discovered after they occur. 
Serious Protocol Deviation: A deviation that meets the definition of an SAE or compromises the 
safety, integrity of the data, welfare, or rights of participants or others. 
5.4.3  Non-Compliance Definition 
Non-compliance is the failure to comply with applicable NIH Human Research Protections Program 
(HRPP) policies, IRB requirements, or regulatory requirements for the protection of human 
participants. Non-compliance is further characterized as serious, continuing, or minor. 
“Serious non-compliance” is defined as non-compliance that: 
• Increases risks, or causes harm, to participants 
• Decreases potential benefits to participants 
• Compromises the integrity of the NIH-HRPP 
• Invalidates the study data 
“Continuing non-compliance” is non-compliance that is recurring. 
“Minor non-compliance” is non-compliance that is neither serious nor continuing. 
5.4.4 Expedited Reporting to the IRB 
Sites under the oversight of the NIAID IRB will report the following to the IRB within 7 calendar 
days of investigator awareness: 
• Serious and non-serious UP 
• Deaths 
• Serious protocol deviations 
• Serious or continuing non-compliance  
• SAEs that are possibly, probably, or definitely related to the research regardless of 
expectedness 
The following waiver applies to reporting anticipated protocol deviations and expected UPnonAEs:  
Anticipated deviations in the conduct of the protocol will not be reported to the IRB unless they 
occur at a rate greater than anticipated by the study team. Expected adverse events will not be 
reported to the IRB unless they occur at a rate greater than that known to occur in healthy adults. If 

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the rate of these events exceeds the rate expected by the study team, the events will be classified and 
reported as though they are unanticipated problems. 
For Part B, ACTG sites under the oversight of a local IRB will follow their local IRB guidelines for 
expedited reporting.  
5.4.5 Annual Reporting to the IRB 
Sites under the oversight of the NIAID IRB will report the following to the IRB in a summary at the 
time of Continuing Review: 
• Serious and non-serious UP  
• Expected SAEs that are possibly, probably, or definitely related to the research 
• SAEs that are not related to the research 
• All AEs, except expected AEs granted a waiver of reporting  
• Serious and non-serious protocol deviations  
• Serious, continuing, and minor non-compliance  
• Any trends or events which in the opinion of the investigator should be reported 
For Part B, ACTG sites under the oversight of a local IRB will follow their local IRB guidelines for 
annual reporting. 
 STATISTICAL CONSIDERATIONS 
 OVERVIEW 
A phase 1, single dose study of the safety and virologic effect of HIV-1 specific broadly 
neutralizing human monoclonal antibodies, VRC-HIVMAB080-00-AB (VRC01LS) or VRC-
HIVMAB075-00-AB (VRC07-523LS), administered intravenously to HIV-infected adults. In Part 
B, as participants will be strongly encouraged and some may initiate 3-drug ART (prescribed by 
their primary HIV clinician; not study-provided; PK-enhancing agents not counted in the ART 
regimen) after completing day 14 study evaluations, all analysis will be done separating the two 
periods of time (off concomitant ART and on concomitant ART). 
Results from Part A and Part B may be analyzed, published, and presented separately since they 
involve two different MAbs. 
 OBJECTIVES 
The primary objective is to evaluate the safety and tolerability of either VRC01LS or VRC07-
523LS administered at 40 mg/kg IV to HIV-1 infected viremic adults. Secondary objectives include 
evaluation of the pharmacokinetics and the effects on CD4+ and viral load through the first 48 
weeks post administration of the study products, as well as the presence of anti-drug antibody 
response. Exploratory objectives include evaluating HIV-1 isolates throughout the study for a 
variety of genotypic and phenotypic parameters including sensitivity to VRC01LS or VRC07-
523LS neutralization. 

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 SIZE AND ACCRUAL 
Recruitment will target about 14 HIV-1 infected viremic adults of age 18-70, 7 participants enrolled 
in each part (Part A and Part B). The permitted accrual is 20 participants (or up to 10 participants in 
each part) to allow for additional enrollments in the event that some participants do not complete 
the sampling schedule, if additional PK evaluations are needed, or if additional participants are 
needed for safety evaluations.  
A participant in Part B who does not complete all of the required visits through day 14 will be 
replaced up to a maximum of 10 participants enrolled. 
6.3.1 Sample Size Considerations 
This study is primarily descriptive. For safety analysis, the goal is to identify safety concerns 
associated with the products.   
The ability of the study to identify SAEs will be expressed in terms of the probability of observing a 
certain number of serious adverse events. Useful values are the minimum true rate such that the 
probability of observing at least one event is at least 90%, and the maximum true rate such that the 
probability of not observing any event is at least 90%. With n=7 participants in an arm, there is over 
90% chance to observe at least one SAE if the true rate is at least 0.281 and over 90% chance to 
observe no SAE if the true rate is no more than 0.014. 
Probabilities of observing zero or more than 1 serious adverse event are presented in Table 6.3-1 for 
a range of possible true event rates. These calculations provide a more complete picture of the 
sensitivity of this study design to identify potential safety problems with the product.  
Table 6.3-1:  Probability of Event for Different Scenarios (n=7) 
True event rate 
Pr (observing zero 
events) 
Pr (observing more 
than one event) 
0.005 
0.966 
0.001 
0.010 
0.932 
0.002 
0.020 
0.868 
0.008 
0.035 
0.779 
0.023 
0.050 
0.698 
0.044 
0.100 
0.478 
0.15 
0.150 
0.321 
0.283 
0.200 
0.21 
0.423 
0.300 
0.082 
0.671 

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Table 6.3-2 gives the upper and lower bounds for 95% exact binomial confidence intervals of the 
true SAE rate at all possible numbers of events. If none of the 7 participants experience serious 
adverse events, the 95% exact 2-sided upper confidence bound for the SAE rate is 0.41.  
Table 6.3-2: 95% Confidence Intervals for the True Rate at Possible Observed Number of Events 
(n=7) 
# of observed events 
95% Confidence Interval 
Lower Bound 
Upper Bound 
0 
0 
0.410 
1 
0.004 
0.579 
2 
0.037 
0.710 
3 
0.099 
0.816 
4 
0.184 
0.901 
5 
0.290 
0.963 
Tables 6.3-1 and 6.3-2 apply to the secondary binary endpoints as well. 
 STATISTICAL ANALYSIS 
6.4.1 Analysis Variables 
The analysis variables consist of baseline variables, pharmacokinetics, and safety variables for 
primary and secondary objective analyses. 
6.4.2 Baseline Demographics 
Baseline characteristics including demographics and laboratory measurements will be summarized. 
6.4.3 Safety Analysis 
Summaries of the number and percentage of participants experiencing any AE or reactogenicity will 
be tallied by subgroup and presented along with exact 95% confidence intervals for the proportion. 
Solicited Adverse Events: 
Solicited AE data will be collected after each study product administration. The number and 
percentage of participants experiencing each type of solicited sign or symptom will be tabulated by 
severity. For a given sign or symptom, each participant’s solicited AEs will be counted once under 
the maximum severity for all assessments. 
Unsolicited Adverse Events: 
Unsolicited AEs are coded into MedDRA preferred terms. The number and percentages of 
participants experiencing each specific AE will be tabulated by severity and relationship to 

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treatment. For the calculations in these tables, each participant’s adverse experience will be counted 
once under the maximum severity or strongest recorded causal relationship to treatment. 
A complete listing of adverse experiences for each participant will provide details including 
severity, relationship to treatment type, onset, duration, and outcome. 
Local Laboratory Values: 
Boxplots of local laboratory values will be generated for baseline values and for values measured 
during the course of the study. Each boxplot will show the 1st quartile, the median, and the 3rd 
quartile. Outliers, or values outside the boxplot, will also be plotted. If appropriate, horizontal lines 
representing boundaries for abnormal values will be plotted. 
6.4.4 Tolerability Evaluation 
The tolerability of the medical product represents the degree to which overt adverse effects can be 
tolerated by the participant [17]. VRC 607/A5378 is the first trial of VRC01LS or VRC07-523LS in 
HIV-1 viremic adults. The tolerability evaluation will be mostly descriptive by nature and consist of 
solicited AEs that occur during the 3 days following study product administration and reasons for 
any withdrawal or discontinuation based upon participant discomfort. This early assessment of 
tolerability of VRC01LS or VRC07-523LS will inform which parameters should be solicited or 
routinely assessed to further characterize the tolerability profile in a larger number of participants. 
6.4.5 Analysis of effect on CD4+ and HIV Viral load 
The positive response rate and the magnitude of CD4+ response will be evaluated through 48 weeks 
post product administration. The profile of HIV viral load will be evaluated both numerically and 
graphically.  
In Part B, as participants will be strongly encouraged and some may initiate 3-drug ART 
(prescribed by their primary HIV clinician; not study-provided; PK-enhancing agents not counted in 
the ART regimen) after completing day 14 study evaluations, all analysis will be done separating 
the two periods of time (off concomitant ART and on concomitant ART). 
6.4.6 Pharmacokinetics Analysis 
Blood samples for PK evaluations will be collected at time points defined in the Schedule of 
Evaluations (Appendix III).  
Individual Participant Pharmacokinetic Analysis: A non-compartmental PK analysis will be 
performed using Phoenix (Centara) or a similar program on the VRC01LS or VRC07-523LS 
concentration data generated from each participant. Calculated PK parameters will include: area-
under-the-curve (AUC), maximum concentration (Cmax), clearance (CL), volume of distribution 
(Vdz), terminal elimination rate constant (z), and the terminal half-life (T1/2). Cmax will be taken 
directly from the observed concentration-time data. The terminal slope, z, will be determined from 
the log-linear portion of the curve and the terminal T1/2 calculated as 0.693/z. AUC0-Clast will be 
determined using the linear trapezoidal method, where Clast is the concentration at 336 days or the 

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earlier if earlier samples are below the quantitative limit or the participant does not complete the 
final PK sample collections. If the final sample, Clast, has measurable VRC01LS or VRC07-523LS 
concentrations, the remaining AUC after the final concentration (AUCClast-inf) will be estimated as 
Clast/z. Additional compartmental analysis will be performed as warranted by the data. 
Population Pharmacokinetic Analyses: Population PK analyses will be performed on the VRC01LS 
and the VRC07523LS PK data following IV administration to determine compartmental PK 
parameters with the program NONMEM. One, two, and three compartment PK models will be 
assessed. Based on prior PK studies of antibodies, including VRC01, it is anticipated that a two-
compartment model will adequately characterize the data. The population analysis will generate 
estimates for initial and final volumes of distribution (Vd1 and Vd2), inter-compartmental clearance 
(Q), and CL. Given the small participant numbers, the population PK analysis will not include an 
exploratory covariate analysis to assess clinical factors as fixed effects associated with VRC01LS 
and VRC07-523LS PK parameters. The terminal half-life, t1/2β, will be determined from CL, Vd1, 
Vd2, and Q. Final model selection will be based on changes in the objective function and 
graphically by goodness of fit plots. The final population model will be assessed using bootstrap 
analysis and visual posterior predictive check. VRC01LS and VRC07-523LS dosing strategies and 
their ability to achieve and maintain target study product concentrations will be performed using the 
final population PK model and Monte Carlo simulations with at least 5000 replicates. 
In Part B, as participants will be strongly encouraged and some may initiate 3-drug ART 
(prescribed by their primary HIV clinician; not study-provided; PK-enhancing agents not counted in 
the ART regimen) after completing day 14 study evaluations, all PK analysis will be done 
separating the two periods of time (off concomitant ART and on concomitant ART). Additionally, 
PK analysis for ARVs will be performed in Part B, if needed, to evaluate for the presence of ART 
and the period before and during viral rebound in participants who initiate ART.  
6.4.7 Interim Analyses 
Preliminary analyses of pharmacokinetics may be done once participants complete Visit 21 (week 
24). This preliminary information will be used for subsequent studies that may begin while VRC 
607/A5378 is still in progress.  
 PHARMACY PROCEDURES 
Refer to the IB for further information about the investigational study products.   
 STUDY PRODUCTS AND ADMINISTRATION REGIMEN 
VRCHIVMAB080-00-AB (VRC01LS) and VRC-HIVMAB075-00-AB (VRC07-523LS) are 
supplied at a concentration of 100 (± 10) mg/mL an isotonic and sterile solution; two fill volumes 
are available, 2.25 ± 0.1 mL in a 3mL glass vial and 6.25 ± 0.1 mL in a 10 mL glass vial Vials 
contain a clear, colorless to yellow liquid, essentially free of visible particles; some opaque or 
translucent particles may be present. The formulation buffer for VRC01LS is composed of 25 mM 
sodium citrate, 50 mM sodium chloride, and 150 mM L-arginine hydrochloride at pH 5.8. The 

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formulation buffer for VRC07-523LS is composed of 50 mM histidine, 50 mM sodium chloride, 
5% sucrose, and 2.5% sorbitol at pH 6.8. Vials are intended for single use only and thus do not 
contain a preservative.  
VRC01LS and VRC07-523LS are highly concentrated protein solutions and may develop white, 
opaque to translucent particles after thawing. When particles are observed, they may disappear after 
a few hours at room temperature or storage at 2°C to 8°C.  
For Part A, VRC01LS will be administered as 40 mg/kg IV once on D0.  
For Part B, VRC07-523LS will be administered as 40 mg/kg IV once on D0. 
In calculating the dose to administer and number of vials to thaw, it should be assumed that the 
concentration is 100 mg/mL and that a volume of at least 2 mL or 6 mL can be withdrawn from a 
vial. In this trial, dose is limited or established based on participant weight.  
Preparation of VRC01LS or VRC07-523LS will require a 100 mL bag of 0.9% sodium chloride for 
injection, USP (normal saline). Note that the normal saline bags referred to as “100 mL bags” in the 
IV administration instructions will typically have 103 mL volume before any VRC01LS or VRC07-
523LS is added and this is acceptable in the context of the instructions below.  
 VIALED STUDY PRODUCT STORAGE 
The study product label designates long-term storage temperature as -35°C to -15°C. Clinical site 
storage in a qualified, continuously monitored, temperature-controlled freezer with temperature 
excursions between -45°C to -10°C is acceptable.  
Following thaw, vials of VRC01LS may be stored for up to 24 hours at controlled room temperature 
(maximum 27°C) and/or up to 4 weeks at 2°C to 8°C. Following thaw, vials of VRC07-523LS may 
be stored for up to 24 hours at controlled room temperature (maximum 27°C) and or up to 2 weeks 
at 2°C to 8°C. Products may not be stored in direct sunlight. If stored at 2°C to 8°C, vials must be 
equilibrated to controlled room temperature (maximum 27°C) for a minimum of 30 minutes and 
may be held at room temperature for up to 8 hours prior to product preparation.  
7.2.1 Temperature Excursions 
The site pharmacist must promptly report any storage temperature excursions outside of the normal 
allowance to the IND sponsor (see Appendix II). The affected product must be quarantined in a 
separate area. The IND Sponsor will notify the site pharmacist if continued clinical use of the 
product is acceptable. 
 PREPARATION OF STUDY PRODUCTS FOR ADMINISTRATION  
This section describes how the site pharmacist will prepare the study products for administration 
and how the clinician will administer the products. Clinician instructions on how to select an 
administration site are in Section 4.2.3.   

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The following instructions apply to thawing VRC01LS and VRC07-523LS: 
1. Thaw vials for a minimum of 1 hour at controlled room temperature (maximum 27°C) after 
removing from freezer.  
2. Keep the material at controlled room temperature (maximum 27°C) during the preparation 
period, up to the maximum storage times described in Section 7.2.  
3. Prior to preparation for administration, vials should be swirled for 30 seconds with sufficient 
force to resuspend any visible particles yet avoiding foaming. DO NOT SHAKE THE 
VIALS. If particles are observed, return the vials to 2°C to 8°C storage. If particles 
redissolve within the maximum storage times described in Section 7.2, the vials may be used 
for product preparation. If particles continue to be observed, do not use the vialed product 
for IV administration. Refrigerated product must be equilibrated at controlled room 
temperature (maximum 27°C) for a minimum of 30 minutes before preparation and must be 
used within 8 hours of any subsequent return to room temperature. 
4. If the thawed material is not administered within 24 hours of thaw, follow the storage 
information provided in Section 7.2.  
Preparation is to be done using aseptic technique in a laminar flow biosafety cabinet. Assure that 
only the required vials are present in the preparation unit during dilution, and medication labels are 
strictly segregated to avoid mix-ups. 
More information on product preparation can be found in the IB. 
7.3.1 VRC-HIVMAB080-00-AB or VRC-HIVMAB075-00-AB: Preparation for IV 
Administration  
For each IV infusion order, the participant’s weight, dosage, and group will be included in the 
pharmacy order. The weight measured within 10 days prior to the scheduled study product 
administration (Day 0) can be used. To prepare an IV infusion, the pharmacist will calculate the 
total milligrams needed, retrieve the minimum number of thawed, particle free vials needed to 
prepare the full dose and add the calculated total milligrams needed to a 100 mL bag of normal 
saline using good pharmacy practices to maintain sterility. Prior to preparation for administration, 
the vials should be gently swirled for 30 seconds to avoid foaming. DO NOT SHAKE THE VIAL. 
Typically, 50 to 100 mL of additional volume may be added to 100 mL bag of normal saline. Each 
pharmacist should test the capacity of the brand of saline bags that will be used at the site to confirm 
the capacity for additional volume. Refer to the Manual of Procedures for Part B for alternative 
preparation instructions if 100 mL bags of normal saline are not available. 
After preparation in IV bags, the prepared product may be stored at 2°C to 8°C up to 24 hours or at 
room temperature (maximum 30°C) for a maximum of 8 hours total including the infusion time, out 
of direct sunlight. If stored at 2°C to 8°C, prepared product must be equilibrated to room  

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temperature (maximum 30°C) for a minimum of 30 minutes prior to product administration. Prior to 
IV administration, the nurse responsible for administration and another clinician will each check the 
bag label and confirm that the identifier is correct and that the correct total mg to be administered is 
shown based on the participant’s current weight. 
An in-line filter infusion set must be used for IV administration. In-line filters must comply with the 
following specifications: 1.2 micron PES (polyether sulfone) filter membrane, DEHP-free, latex-
free (equivalent to Braun # 473994 filter extension set). When the in-line filter is added to the 
tubing, the administration set must then be primed. The administration set must be flushed with 
about 30 mL or appropriate volume of normal saline at the end of product administration. 
The study product solution will be administered IV over about 30 minutes using a volumetric pump. 
The total time needed to administer the dose may be longer based on factors such as participant 
tolerance. The mL/hr infusion rate may vary based on the total volume needed to administer the full 
dose.   
 LABELING OF STUDY PRODUCTS 
Study product vials will be individually labeled with the name of the material, volume, lot number, 
concentration, storage instructions, Investigational Use Statement (“Limited by Federal Law to 
Investigational Use”), and manufacturer information. 
The prepared IV product label shall contain:  
• Participant identifier  
• Participant weight (kg) 
• Dose of VRC01LS or VRC07-523LS (40 mg/kg) and total amount (mg) added to the NS 
bag 
• Final volume of the IV product 
• For IV administration 
• Lot number 
• Do not infuse after date and time: 
o 24 hours, if stored at 2°C to 8°C 
o 8 hours, if stored at controlled room temperature (not to exceed 27°C) 
 STUDY PRODUCT DISTRIBUTION/ACCOUNTABILITY 
The VRC will follow the NIH CC pharmacy SOP for distribution and accountability of the study 
product.   
For the ACTG sites, VRC07-523LS will be available through the NIAID Clinical Research 
Products Management Center (CRPMC). The site pharmacist should obtain the study product for 
this protocol by following the instructions in the Pharmacy Guidelines and Instructions for DAIDS 
Clinical Trials Networks manual. 
Due to the small sample size, study product will be shipped to each site as participants are enrolled. 
The site staff should coordinate with their respective site pharmacy to inform the pharmacist when a 

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participant is being enrolled so an order for study product can be placed with the CRPMC. Study 
product should be available on site one day prior to the scheduled infusion (D0). Refer to the MOP 
for detailed study product ordering instructions.  
The site pharmacist is required to maintain complete records of all study products received from the 
NIAID CRPMC and subsequently dispensed. 
 STUDY PRODUCT DISPOSITION 
At VRC, the empty vials and unused portions of a vial will be discarded as per NIH CC pharmacy 
SOP.  
At ACTG sites, all unused study products at US Clinical Research Sites must be returned to the 
NIAID CRPMC (or as otherwise directed by the sponsor) after the study is completed or 
terminated. The procedures to be followed are in the Pharmacy Guidelines and Instructions for 
DAIDS Clinical Trials Networks manual. 
 HUMAN SUBJECT PROTECTIONS AND ETHICAL OBLIGATIONS 
This research study will be conducted in compliance with the protocol, Good Clinical Practices 
(GCP), and all applicable regulatory requirements. 
 INFORMED CONSENT 
The study informed consent form (ICF) is provided in Appendix I. It describes the investigational 
product to be used and all aspects involved in protocol participation. 
Before an individual’s participation in the study, it is the investigator’s responsibility to obtain 
written ICF from the participant, after adequate explanation of the aims, methods, anticipated 
benefits, and potential hazards of the study and before any protocol-specific procedures are 
conducted or study product is administered. The Assessment of Understanding quiz will be 
completed before the study consent is signed. 
The acquisition of ICF will be documented in the participant’s medical records, as required by 21 
CFR 312.62. The ICF will be signed and personally dated by the participant and the person who 
conducted the ICF discussion. The original signed ICF will be retained in the medical chart and a 
copy will be provided to the participant.   
 RISKS AND BENEFITS  
8.2.1 Risks 
VRC-HIVMAB080-00-AB or VRC-HIVMAB075-00-AB: The first human clinical trials of 
predecessor VRC01 MAb determined that VRC01 is safe for further evaluation in HIV-1 infected 
and healthy adults. The solicited local and systemic signs and symptoms following administration 
of VRC01 were generally none to mild. Some mild transient changes included elevated creatinine, 
elevated transaminases, neutropenia, and proteinuria. The SC administrations were sometimes 

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associated with mild transient local reactions (Section 1.3.1). In the ongoing clinical trial VRC 606, 
VRC01LS is administered to healthy adults who reported mostly mild solicited adverse events 
(Section 1.3.2). VRC07-523LS is currently being evaluated in healthy adults in a Phase I dose 
escalation study, VRC 605. There have been no SAEs and no study safety pauses for AEs. VRC 
607/A5378 is the first study to evaluate IV administrations of VRC-HIVMAB080-00-AB 
(VRC01LS) and VRC-HIVMAB075-00-AB (VRC07-523LS) in HIV-1 infected adults. 
Administration of some MAbs may cause immune reactions such as acute anaphylaxis, serum 
sickness, and the generation of antibodies. However, these reactions are rare and more often 
associated with MAb targeted to human proteins or with the use of murine MAbs which would have 
a risk of human anti-mouse antibodies [22]. In this regard, as VRC01LS and VRC07-523LS are 
targeted to a viral antigen and are human MAbs, they are expected to have a low risk of such side 
effects.  
Typically, the side effects of MAbs are mild but may include reactions at injection site (pain, 
redness, bruising, swelling), fever, chills, rigors, nausea, vomiting, pain, headache, dizziness, 
shortness of breath, bronchospasm, hypotension, hypertension, pruritus, rash, urticaria, angioedema, 
diarrhea, tachycardia, or chest pain. Clinical use of MAbs that are targeted to cytokines or antigens 
associated with human cells may be associated with an increased risk of infections [22]; however, 
this is not expected to be a risk for MAbs like VRC01LS and VRC07-523LS targeted to a viral 
antigen. 
It is known from published experience with human MAbs directed against the cell surface targets on 
lymphocytes, that infusion of a MAb may be associated with cytokine release, causing a reaction 
known as “cytokine release syndrome” (CRS) [23]. Most infusion-related events occur within the 
first 24 hours after beginning administration. Severe reactions, such as anaphylaxis, angioedema, 
bronchospasm, hypotension, and hypoxia, are infrequent and more often associated with MAbs 
targeted to human proteins or when non-human MAbs, such as a murine MAb, is used [22]. 
Specifically, with regard to CRS reactions, these most commonly occur within the first few hours of 
beginning the infusion and are more common with the first MAb infusion received. This is because 
the cytokine release is associated with lysis of the cells targeted by the MAb and the burden of 
target cells is greatest at the time of the first MAb treatment. With licensed therapeutic MAbs, CRS 
is managed by temporarily stopping the infusion, administering histamine blockers, and restarting 
the infusion at a slower rate [24]. 
Delayed allergic reactions to other MAbs may include a serum sickness type of reaction, which may 
include rash, fever, lymph node enlargement, and joint pains. These symptoms may not appear until 
several days after the exposure to the MAb and is noted to be more common with chimeric types of 
MAbs rather than with human MAbs such as VRC01LS and VRC07-523LS [22]. 
There are several FDA-licensed MAbs for which reactions related to the rate of IV infusion have 
been described. Some symptoms may be treated by slowing or stopping the infusion. Supportive 
treatment may also be indicated for some signs and symptoms.   
Participation in this study may limit a participant’s eligibility for other future MAb studies. 

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Risks of Blood Drawing: Blood drawing may cause pain and bruising and may, infrequently, cause 
a feeling of lightheadedness or fainting. Rarely, it may cause infection at the site where the blood is 
taken. In this study, an IV line that can be used for the collection of blood may be placed and left in 
place for several hours on the days when there are frequent PK blood draws. Problems from use of 
an IV for blood drawing are generally mild and may include pain, bruising, minor swelling or 
bleeding at the IV site and rarely, infection, vein irritation (called phlebitis), or blood clot.  
8.2.2 Benefits 
There are no direct benefits to study participants from study participation. Others may benefit from 
knowledge gained in this study that may aid in the development of HIV prevention or therapeutic 
methods. 
 INSTITUTIONAL REVIEW BOARD 
A copy of the protocol, ICF, other written participant information, and any advertising material will 
be submitted to the IRB for written approval. 
The investigator must submit and, where necessary, obtain approval from the IRB for all subsequent 
protocol amendments and changes to the ICF. The investigator will notify the IRB of unanticipated 
problems, non-compliance, deviations from the protocol, and serious SAEs as described in Section 
5.4. 
The investigator will be responsible for obtaining IRB approval of the annual Continuing Review 
throughout the duration of the study. 
 PROTOCOL REGISTRATION 
Prior to implementation of this protocol, and any subsequent full version amendments, each site 
must have the protocol and the protocol ICF(s) approved, by the appropriate IRB/ethics committee 
(EC) and any other applicable regulatory entity (RE). Upon receiving final approval, sites will 
submit all required protocol registration documents to the DAIDS Protocol Registration Office 
(DAIDS PRO) at the Regulatory Support Center (RSC). The DAIDS PRO will review the submitted 
protocol registration packet to ensure that all of the required documents have been received.   
Site-specific ICF(s) WILL be reviewed and approved by the DAIDS PRO and sites will receive an 
Initial Registration Notification from the DAIDS PRO that indicates successful completion of the 
protocol registration process. A copy of the Initial Registration Notification should be retained in 
the site's regulatory files. 
Upon receiving final IRB/EC and any other applicable RE approval(s) for an amendment, sites 
should implement the amendment immediately. Sites are required to submit an amendment 
registration packet to the DAIDS PRO at the RSC. The DAIDS PRO will review the submitted 
protocol registration packet to ensure that all the required documents have been received. Site-
specific ICF(s) WILL NOT be reviewed and approved by the DAIDS PRO and sites will receive an 
Amendment Registration Notification when the DAIDS PRO receives a complete registration 

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packet. A copy of the Amendment Registration Notification should be retained in the site's 
regulatory files. 
For additional information on the protocol registration process and specific documents required for 
initial and amendment registrations, refer to the current version of the DAIDS Protocol Registration 
Manual. 
 PARTICIPANT CONFIDENTIALITY 
The investigator must ensure that no information identifying the participant will be released to any 
unauthorized party. Individual identifying information will not be included in any reports. 
Participants will be identified only by coded numbers. All records will be kept confidential to the 
extent provided by federal, state, and local law. Medical records are made available for review 
when required by the FDA or other authorized users, such as the study product manufacturer, only 
under the guidelines set by the Federal Privacy Act. Direct access includes examining, analyzing, 
verifying, and reproducing any records and reports that are important to the evaluation of the study. 
The investigator is obligated to inform the participants that the above-named representatives will 
review their study-related records without violating the confidentiality of the participants.  
8.5.1 Loss or Destruction of Samples, Specimens or Data 
The NIH Intramural Protocol Deviation definition related to loss of or destruction of samples or 
data will be followed. Any loss or unanticipated destruction of samples (for example, due to freezer 
malfunction) or data (for example, misplacing a printout of data with identifiers) that compromises 
the scientific integrity of the study will be reported to the IRB in accordance with institutional 
policies. The PI will also notify the IRB if the decision is made to destroy the remaining samples. 
 PLAN FOR USE AND STORAGE OF BIOLOGICAL SAMPLES 
The plan for use and storage of biological samples from this protocol is as outlined in the following 
sections. 
8.6.1 Use of Samples, Specimens and Data 
Samples, specimens, and data collected under this protocol may be used to conduct protocol-related 
safety and immune response evaluations, exploratory laboratory evaluations related to the type of 
infection the study product was designed to prevent, exploratory laboratory evaluations related to 
vaccine or infectious disease research in general, and for research assay validation. Genetic testing 
may be performed in accordance with the genetic testing information that was included in the study 
ICF. 
8.6.2 Storage and Tracking of Blood Samples and Other Specimens 
All of the stored study research samples will be labeled by a code (such as a number) that only the 
study site can link to the participant. Samples will be stored in secure facilities with controlled 
access at the sites. The NIAID Vaccine Immune T-Cell and Antibody Laboratory (NVITAL) in 

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Gaithersburg, MD, under the direction of the VRC, NIAID, NIH (Bethesda, MD) will serve as a 
central repository for stored samples. Samples collected for research may be transferred for testing 
to the VRC/NIAID/NIH, other approved collaborators, or contract laboratories. Data will be kept 
secure. Only approved investigators or their designees will have access to samples and data.   
In the future, other investigators (both at NIH and outside) may wish to study these samples and/or 
data. Regulatory approval through the proper human participants’ protection agency will be sought 
prior to any sharing of samples that constitutes human participant research. The research use of 
stored, unlinked, or unidentified samples may be exempt from the need for IRB review and 
approval. When appropriate, exemption may be obtained through the proper regulatory procedures. 
 PARTICIPANT IDENTIFICATION AND ENROLLMENT OF STUDY PARTICIPANTS 
All study activities will be carried out at the study site. In Part A, study participants will be recruited 
through on-site and off-site advertising done for the screening protocol, VRC 500 (NCT 01375530) 
(https://clinicaltrials.gov/ct2/show/NCT01375530?term=VRC+500&rank=1). In Part B, study 
participants will be recruited and screened following the screening evaluations in this protocol. 
Effort will be made to include women and minorities in proportions similar to that of the 
community from which they are recruited and will be limited to persons at least 18 years of age and 
no older than 70 years of age at enrollment. 
8.7.1 Participation of Children 
Children are not eligible to participate in this clinical trial because the study product has not been 
previously evaluated in adults. If the product is assessed as safe for further study other protocols 
specifically designed for children may be conducted. 
8.7.2 Participation of Site Employees 
Clinic sites will follow institutional policy regarding participation of site employees in VRC 
607/A5378. Site-specific policies related to employee involvement in research protocols have been 
provided to the NIAID IRB. 
NIH- Specific Employee Participation  
NIH employees and members of their immediate families may participate in this protocol. We will 
follow the Guidelines for the Inclusion of Employees in NIH Research Studies and will give each 
employee a copy of the “NIH Information Sheet on Employee Research Participation” and a copy 
of the “Leave Policy for NIH Employees Participating in NIH Medical Research studies.” Neither 
participation nor refusal to participate will have an effect, either beneficial or adverse, on the 
participant’s employment or work situation. The NIH information sheet regarding NIH employee 
research participation will be distributed to all potential participants who are NIH employees. The 
employee participant’s privacy and confidentiality will be preserved in accordance with NIH 
Clinical Center and NIAID policies. For NIH employee participants, consent will be obtained by an 
individual who is independent of the employee’s team. If the individual obtaining consent is a co-
worker to the participant, independent monitoring of the consent process will be included through 

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the Bioethics Consultation Service. Protocol study staff will be trained on obtaining potentially 
sensitive and private information from co-workers or subordinates.  
 COMPENSATION 
Compensation for time and inconvenience of study participation will be provided to participants in 
accordance with the local site-specific guidelines as outlined in the IRB approved site-specific 
Informed Consent. The total compensation for the participant is based on the number of study clinic 
visits, injections completed, and other protocol-related activities.  
 SAFETY MONITORING 
Close cooperation between the designated members of the Protocol Team will occur to evaluate and 
respond to individual AEs in a timely manner. The VRC designated Safety Officer for the day 
conducts a daily safety review of clinical data per VRC Standard Operating Procedures. The 
Protocol Safety Review Team (PSRT), comprised of the Study Chair, PI(s), Associate Investigators, 
Study Coordinator, Protocol Specialists, other Study Clinicians, DAIDS MO, and an ISM, will 
review the summary study safety data reports on a weekly basis through 4 weeks after the last 
participant receives the last product administration, in order to be certain that the study product has 
an acceptable safety profile, and will continue to monitor the study safety data reports on a monthly 
basis through completion of the last study visit.   
 ADMINISTRATIVE AND LEGAL OBLIGATIONS 
 PROTOCOL AMENDMENTS AND STUDY TERMINATION 
Protocol Amendments must be made only with the prior approval of the DAIDS/NIAID, VRC, and 
ACTG. Agreement from the protocol team and DAIDS Medical Officer (MO) must be obtained for 
all protocol amendments and amendments to the ICF. All study amendments will be submitted to 
the IRB for approval. 
The DAIDS, VRC, ACTG, the NIAID or local IRB (as applicable), the Office of Human Research 
Protections, the study PI, and FDA reserve the right to terminate the study. The PI will notify the 
IRB in writing of the study’s completion or early termination. 
 STUDY DOCUMENTATION AND STORAGE 
The PI will maintain a list of appropriately qualified persons to whom trial duties have been 
delegated. 
Source documents are original documents, data, and records from which the participant’s data are 
obtained. These include but are not limited to hospital records, clinical and office charts, laboratory 
and pharmacy records, microfiches, radiographs, and correspondence.  
The PI and staff are responsible for maintaining a comprehensive and centralized filing system of 
all study-related (essential) documentation, suitable for inspection at any time by representatives 

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from the DAIDS/NIAID, VRC, ACTG, IRB, FDA, and/or other local, US, and international 
regulatory entities. Elements include: 
• Participant files containing completed ICF, and supporting copies of source documentation 
(if kept). 
• Study files containing the protocol with all amendments, IBs, and copies of all 
correspondence with the IRB, the NIAID’s Division of AIDS and Vaccine Research Center, 
and ACTG. 
In addition, all original source documentation must be maintained and be readily available. 
All essential documentation should be retained by the institution for the same period of time 
required for medical records retention. The FDA requires study records to be retained for up to 2 
years after marketing approval or refusal (21 CFR 312.62). No study document should be destroyed 
without prior written agreement between the NIAID’s Division of AIDS, VRC, ACTG, and the 
investigator. Should the investigator wish to assign the study records to another party or move them 
to another location, they must notify the DAIDS/NIAID, VRC, and ACTG in writing of the new 
responsible person and/or the new location. 
 STUDY MONITORING, DATA COLLECTION AND DATA SHARING 
9.3.1 Study Monitoring 
The DAIDS/NIAID and VRC/NIAID monitors and regulatory authorities inspectors (if applicable) 
or their authorized representatives are responsible for contacting and visiting the investigator for the 
purpose of inspecting the facilities and, upon request, inspecting the various records of the trial, 
provided that participant confidentiality is respected. 
Site visits by study monitors will be made in accordance with the IND Sponsor (DAIDS) policy to 
monitor the following: study operations, the quality of data collected in the research records, the 
accuracy and timeliness of data entered in the database, and to determine that all process and 
regulatory requirements are met. 
Site investigators will allow the study monitors, the NIAID or local IRB (as applicable), FDA, and 
other local, US or international regulatory entities to inspect study documents (e.g., consent forms, 
drug distribution forms, case report forms) and pertinent hospital or clinic records for confirmation 
of the study data. 
9.3.2 Data Collection 
Clinical research data will be collected in a secure electronic data management system through a 
contract research organization, EMMES (Rockville, MD). Extracted data without patient identifiers 
will be sent to the PSRT for safety review and to Protocol Statistician for statistical analysis. 

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9.3.3 Data Sharing 
Data generated in this study will be shared as de-identified data in the government-funded public 
repository, www.ClinicalTrials.gov. Data may be shared prior to publication at approved public 
presentations or for collaborative development and will be shared at the time of publication or 
within 1 year of the study completion date.  
 LANGUAGE 
All written information and other material to be used by participants and investigative staff must use 
vocabulary and language that are clearly understood.  
 POLICY REGARDING RESEARCH-RELATED INJURIES 
The study site will provide short-term medical care for any injury resulting from participation in this 
research. In general, the National Institutes of Health, the Clinical Center, or the U.S. Federal 
Government will provide no long-term medical care or financial compensation for research-related 
injuries. 
 MULTI-SITE MANAGEMENT 
For Part A, the Vaccine Research Center, NIAID, NIH is the coordinating center as well as a site for 
this protocol. 
For Part B, the ACTG Network Coordinating Center will function as the coordinating center. 
The protocol plan for previous versions of the protocol was to establish a Reliance Agreement with 
each collaborating study site such that the NIAID IRB is the IRB of Record for the conduct of the 
VRC 607/A5378 protocol (Part A). A reliance agreement was established for the University of 
Pennsylvania for the previous protocol versions and will continue to be effective for version 4 of the 
protocol. However for Part B, the participating ACTG sites are not expected to establish a reliance 
agreement and will use their local IRB as the IRB of Record for the conduct of VRC 607/A5378 
Version 4.0 at their site. 
 

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 REFERENCES 
1. UNAIDS. Fact sheet: 2014 statistics. 2014; Available from: 
http://www.unaids.org/sites/default/files/media_asset/20150714_FS_MDG6_Report_en.pdf. 
2. Wu, X., et al., Rational design of envelope identifies broadly neutralizing human monoclonal 
antibodies to HIV-1. Science, 2010. 329(5993): p. 856-61. 
3. Rudicell, R.S., et al., Enhanced Potency of a Broadly Neutralizing HIV-1 Antibody In Vitro 
Improves Protection against Lentiviral Infection In Vivo. J Virol, 2014. 88(21): p. 12669-82. 
4. Kwon, Y., et al., Structure-guided modification and optimization of antibody VRC07. 
Retrovirology, 2012. 9(Suppl 2): p. O34. 
5. Ko, S.Y., et al., Enhanced neonatal Fc receptor function improves protection against primate 
SHIV infection. Nature, 2014. 514(7524): p. 642-5. 
6. Wu, X., et al., Selection pressure on HIV-1 envelope by broadly neutralizing antibodies to the 
conserved CD4-binding site. J Virol, 2012. 86(10): p. 5844-56. 
7. Zalevsky, J., et al., Enhanced antibody half-life improves in vivo activity. Nat Biotechnol, 2010. 
28(2): p. 157-9. 
8. Montefeori, D.C., Measuring HIV Neutralization in a Luciferase Reporter Gene Assay, in HIV 
Protocols, Second Edition, Vol. 485, V.R. Prasad, and Kalpana, G.V., Editor. 2009, Humana 
Press: New York, NY. p. 395-405. 
9. Ozaki, D.A., et al., International technology transfer of a GCLP-compliant HIV-1 neutralizing 
antibody assay for human clinical trials. PLoS One, 2012. 7(1): p. e30963. 
10. Todd, C.A., et al., Development and implementation of an international proficiency testing 
program for a neutralizing antibody assay for HIV-1 in TZM-bl cells. J Immunol Methods, 
2012. 375(1-2): p. 57-67. 
11. Allen, J.C. and H.G. Kunkel, Antibodies to genetic types of gamma globulin after multiple 
transfusions. Science, 1963. 139(3553): p. 418-9. 
12. Jefferis, R. and M.P. Lefranc, Human immunoglobulin allotypes: possible implications for 
immunogenicity. MAbs, 2009. 1(4): p. 332-8. 
13. Kickler, T.S., et al., The expression of IgG allotypes on platelets and immunization to IgG 
allotypes in multitransfused thrombocytopenic patients. Blood, 1990. 76(4): p. 849-52. 
14. Ledgerwood, J.E., et al., Safety, pharmacokinetics and neutralization of the broadly 
neutralizing HIV-1 human monoclonal antibody VRC01 in healthy adults. Clin Exp Immunol, 
2015. 
15. Lynch, R.M., et al., Virologic effects of broadly neutralizing antibody VRC01 administration 
during chronic HIV-1 infection. Sci Transl Med, 2015. 7(319): p. 319ra206. 
16. Gaudinski, M.R., et al., Safety and pharmacokinetics of the Fc-modified HIV-1 human 
monoclonal antibody VRC01LS: A Phase 1 open-label clinical trial in healthy adults. PLoS 
Med, 2018. 15(1): p. e1002493. 

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17. Patel, S.V. and D.A. Khan, Adverse Reactions to Biologic Therapy. Immunol Allergy Clin 
North Am, 2017. 37(2): p. 397-412. 
18. DHHS. Panel On Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use 
of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and 
Human Services. Available at http://aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf. 
Assessed December 15, 2014. 
19. Hall, W.C., et al., Tissue Cross-Reactivity Studies for Monoclonal Antibodies: Predictive Value 
and Use for Selection of Relevant Animal Species for Toxicity Testing, in Preclinical Safety 
Evaluation of Biopharmaceuticals: A Science-Based Approach to Facilitating Clinical Trials 
(ed J. A. Cavagnaro). 2008, John Wiley & Sons, Inc.: Hoboken, NJ, USA. p. 208-40. 
20. Leach, M.W., et al., Use of tissue cross-reactivity studies in the development of antibody-based 
biopharmaceuticals: history, experience, methodology, and future directions. Toxicol Pathol, 
2010. 38(7): p. 1138-66. 
21. DHHS. Panel On Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use 
of antiretroviral agents in HIV-1-infected adults and adolescents. January 28, 2016; Available 
from: https://aidsinfo.nih.gov/contentfiles/lvguidelines/adultandadolescentgl.pdf. 
22. Hansel, T.T., et al., The safety and side effects of monoclonal antibodies. Nature reviews. Drug 
discovery, 2010. 9(4): p. 325-38. 
23. Bugelski, P.J., et al., Monoclonal antibody-induced cytokine-release syndrome. Expert review 
of clinical immunology, 2009. 5(5): p. 499-521. 
24. Vogel, W.H., Infusion reactions: diagnosis, assessment, and management. Clin J Oncol Nurs, 
2010. 14(2): p. E10-21. 
 
 

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APPENDIX I 
 
STUDY INFORMED CONSENT TEMPLATE 
 

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TITLE:  VRC 607/ACTG A5378: A Phase 1, Single Dose Study of the Safety and Virologic 
Effect of an HIV-1 Specific Broadly Neutralizing Human Monoclonal Antibody, VRC-
HIVMAB080-00-AB (VRC01LS) or VRC-HIVMAB075-00-AB (VRC07-523LS), Administered 
Intravenously to HIV-Infected Adults. 
INTRODUCTION 
We invite you to take part in a research study at the [insert institution’s name]. This study is a 
collaboration between the Vaccine Research Center (VRC), NIAID, NIH and the AIDS 
Clinical Trials Group (ACTG). 
First, we want you to know that: 
• Taking part in this study is entirely voluntary. 
• You may choose not to take part, or you may withdraw from the study at any time. In 
either case, you will not lose any benefits to which you are otherwise entitled. You will 
be treated the same no matter what.  
• If you are at the NIH and would like to receive care at the NIH, you must be taking part 
in a study or be under evaluation for study participation. 
• You may receive no benefit from taking part. The research may give us knowledge that 
may help people in the future. 
• We will tell you about new information from this study or other studies that may affect 
your health, welfare, or willingness to stay in this study. If you want the results of the 
study, let the study staff know. 
Second, some people have personal, religious or ethical beliefs that may limit the kinds of 
medical or research treatments they would want to receive (such as blood transfusions). If you 
have such beliefs, please discuss them with your NIH doctors or research team before you 
agree to the study. 
Now we will describe this research study. Before you decide to take part, please take as much 
time as you need to ask any questions and discuss this study with anyone at NIH, or with family, 
friends, or your personal physician or other health professional.

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PURPOSE AND PLAN OF THE STUDY 
In this study, we are testing two experimental products or drugs called “VRC01LS” and “VRC07-
523LS”. Experimental means that these products have not been approved by the U.S. Food and 
Drug Administration (FDA), but the FDA has allowed us to test them in research studies. VRC01LS 
and VRC07-523LS are antibodies directed against HIV virus. The main purpose of this study is to 
see if these antibodies are safe and how your body will respond to them. (An antibody is a type of 
protein that helps protect the body against foreign matter, such as bacteria and viruses; it can be 
either produced by your body or made in a laboratory.) 
There are two different parts in this study (Part A and Part B). In Part A, 7 people got VRC01LS. In 
Part B, 7 people (up to 10 people) will get VRC07-523LS. People were put in Part A first and now 
Part A of the study is done. People will now be put in Part B. If you agree to take part in this study 
(Part B), you will get VRC07-523LS only and we will measure the amount of the drug in your body 
and how much stays in your body over time. We will check to see if your immune system makes 
antibodies against the product you get. 
About 14 to 20 people (7 to 10 people in each part) will take part in this study at the NIH Clinical 
Center in Bethesda, Maryland and sites within the ACTG Network. The study will include a total of 
23 clinic visits per person over a period of about 11 months.  
You will be able to start 3-drug antiretroviral therapy (prescribed by your primary HIV clinician; 
not study-provided) after you have completed the day 14 study procedures. We strongly advise that 
you start antiretroviral therapy after you have completed this stage of the study.  
STUDY PRODUCTS 
VRC01LS and VRC07-523LS are study products that contain monoclonal antibodies. 
“Monoclonal” means that all antibodies in each product are exactly the same. These antibodies 
target the virus that causes HIV infection. As of May 10, 2018, approximately 60 people have 
received one of these antibodies and have not had any serious side effects or safety concerns.   
In other research studies, over 840 adults with or without HIV-infection got other monoclonal 
antibodies similar to VRC01LS and VRC07-523LS, without serious side effects.  
VRC01LS and VRC07-523LS are based on an antibody that was first found in an HIV-infected 
person. Both of these study products were developed by the Vaccine Research Center (VRC), NIH 
and made in a drug manufacturing laboratory. There are currently research studies of these products 
in adults without HIV infection. This is the first study to give VRC01LS or VRC07-523LS to 
people with HIV infection. 
There is currently no cure for HIV. We do not expect the products in this study to cure or control 
your HIV. 

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In laboratory and animal studies, VRC01LS and VRC07-523LS were shown to attach to and 
inactivate many types of HIV viruses. It is not known if the products will act the same way when 
given to humans. It will take many studies to learn if the products are useful for preventing or 
treating HIV. This study alone will not answer this question.  
SCREENING VISIT 
If you decide to join this study, you will be asked to sign this consent form. After you have signed 
the form, you will be asked some questions and will undergo some tests at the screening visit to see 
if it is safe for you to join the study. 
At the screening visit you will have a physical exam. You will be asked about your medical history, 
including your HIV history, any medicines you have taken in the past and are currently taking, and 
if you have ever received antibodies directed against the HIV virus or taken any anti-HIV 
medicines. We will draw about 6 tubes of blood from you for routine blood tests, tests for Hepatitis 
B virus or Hepatitis C virus infection, tests for HIV antibodies and viral load (the amount of HIV in 
your blood), and CD4+/CD8+ T cell count (cells in your blood that fight infection). You will be 
informed if any tests show a medical problem. You will be advised if results show that you should 
seek medical care.  Some medical conditions may make you not eligible for a clinical trial of an 
investigational product. 
If you are female and able to become pregnant, you will have a pregnancy test done to see if you are 
pregnant. You cannot participate in this study if you are pregnant. If you are not pregnant or you are 
having sex that could lead to pregnancy, you will be asked and must agree to use birth control 
before you are able to participate in this study. We will discuss effective birth control methods with 
you. 
ELIGIBILITY 
You are eligible to participate in this study if you have completed the screening process and are: 
• 18 to 70 years old 
• HIV infected, have never taken antiretroviral (ARV) medications, but otherwise in good general 
health  
• Under the care of a primary care provider for management of HIV  
• Willing to let the study team give your lab test results to your primary care provider while you 
are in this study. 
• Willing to receive VRC07-523LS 
• Willing to donate blood samples for future research 
• Willing to use birth control for the whole study, if you are able to become pregnant  
STUDY PROCEDURES 
Study product infusion: If you agree to enroll in this study, you will get one dose of VRC07-523LS. 
The exact dose you get will depend on how much you weigh.  

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Before you are given the study product, your temperature, blood pressure, heart rate, and weight 
will be taken. You may also have a brief physical exam. If you are female and able to become 
pregnant, you must use an effective form of birth control for the entire study. A pregnancy test will 
be done to see if you are pregnant. If you are pregnant, we will not give you the study product. 
VRC07-523LS will be given to you by intravenous (IV) infusion. This means we will place a thin 
tube or IV line into a vein in your arm. The IV line will be attached to a bag that contains the study 
product mixed with a liquid called “normal saline” or salt water. It will flow into your vein for 
about 30 minutes. If you have side effects during the infusion, it will be slowed or stopped as 
needed. You will be observed for at least 30 minutes immediately after receiving the study product. 
If possible, we will also place an IV line in your other arm to collect blood samples. We will draw 
your blood before and right after the infusion, then at least 5 more times over the next 4 hours from 
this IV line. There are other blood draws at 8, 12, and 36 hours after infusion, which are optional. 
At least one IV line will stay in your arm for several hours. You will not lose any benefits if you 
choose not to give the optional blood samples. If you choose to get these blood draws, you may be 
admitted to the hospital for an overnight stay. The hospital stay is for convenience only and not to 
give you care or treatment.  
We will give you a thermometer and ask you to check your temperature every day for 3 days after 
you get the study product. You will need to record your temperature and any symptoms you may 
have. Even if you do not feel sick, it is still very important that you record this information. You 
will get a password to a secure website to enter this information on an electronic form or “diary”. If 
you do not have a computer, you may use a paper diary instead.  
If you have any side effects after you get the study product, you should tell a study nurse or doctor 
as soon as possible. You can reach the clinic staff by phone 24 hours a day. If you have symptoms, 
you may be asked to come into the clinic for an examination before your next scheduled visit. It is 
very important that you follow the instructions you get from the clinic staff.  
Follow-up visits: After you get the study product, you will need to come back to the clinic 11 times 
over a 4-week period. During the next 9 months, you will have 10 more follow-up visits.  
At most visits, we will check you for any health changes or problems. Your temperature, blood 
pressure, and pulse will be taken and you will have a physical exam. We will ask you how you are 
feeling and if you have taken any medications. We will also provide pregnancy prevention 
counseling (counseling to prevent pregnancy) and positive prevention counseling (counseling to 
prevent illness and promote good health in people who know they are HIV-positive) while you are 
in the study. 
We will draw about 1 to 11 tubes of blood from you at each visit, depending on the type of visit. We 
will also ask you to provide a urine sample for a urine test at most visits. We will tell you right 
away if any of your test results show a health problem. You might need to have extra clinic visits 
and laboratory tests if you have health changes that need to be checked. The total amount of blood 
we draw from you will meet NIH guidelines.  

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We will use some blood samples to see how long the study product remains in your body and if 
your immune system makes antibodies against it. Results of these tests are not for checking on your 
health and we will not give you these results. We may also use some blood samples to check the 
level of ARV medications in your blood while you are in this study.   
Research studies follow a set schedule. This helps us answer the research questions. The visit 
schedule is a little flexible, but it is important that you work with the staff to follow the schedule as 
closely as possible. You should try not to miss any visits. You should contact the clinic staff as soon 
as possible if you need to change the date or time of any visit.  
For the entire duration that you are on study, which will be 48 weeks or about 11 months, a 
maximum of about 922 mL (or about 2 pints) of blood will be collected.  
HIV TESTING AND MANAGEMENT  
As you take part in this study, you will have frequent testing of your HIV viral load and CD4+ T cell 
count for research purposes. These test results will be given to you and sent to your primary care 
provider. You should discuss these results and any questions about management of your HIV 
infection with your primary care provider.  
This study does not include standard medical care or management of your HIV infection. The U.S. 
Department of Health and Human Services and the clinical research team recommend that all HIV-
infected individuals take (ARV) medication to reduce the chance of getting sick from HIV, increase 
life expectancy with HIV infection, and prevent the spread of HIV to others. 
We will not give you ARV medications as part of this research study. You must have a primary 
health care provider for HIV to take part in this study. If you do not have one and need help finding 
one or getting ARV medications, please tell a study doctor or nurse. We will help you find a 
qualified HIV doctor and ARV medications. You and your primary health care provider will make 
all decisions about starting, stopping, or changing ARV medications. However, we strongly advise 
that you start ARV medications after you have completed the day 14 study procedures. We expect 
you to tell us about changes in your ARV medications. We do not expect VRC07-523LS to control 
HIV by itself. You should not change or stop ARV treatment without talking about it with your 
primary care provider. Changes in ARV treatment will not affect your continued participation in the 
study. 
MONITORING OF THE STUDY 
A group of physicians and scientists at NIH will monitor this study. This group will review the 
information from the study and will pay close attention to possible harmful reactions. If serious side 
effects occur, study product infusions may be delayed or canceled. 

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GENETIC TESTING 
In the future, genetic research tests may be done on your stored samples to help understand how 
VRC07-523LS works and interacts with your body. In research studies, genetic tests are done to see 
if different types of immune response are related to genetic differences in people, this includes 
testing your antibody genes. Genetic tests done in a research lab from your stored samples will not 
be recorded in your medical record and will not have your name on the sample. The performance of 
these tests is not for health care purposes. 
HLA type is a genetic test. People with certain HLA types might be more likely to develop certain 
diseases. Simply having those HLA types does not mean they will develop those diseases. HLA 
typing can reveal family relationships. It is our policy not to discuss your HLA results unless they 
have direct medical or reproductive implications for you or your family. Genetic information about 
you will not be revealed to others, including your relatives, without your permission. We will not 
release any information about you or your family to any insurance company or employer unless you 
sign a document allowing release of information. 
VRC clinic only: HLA typing may be ordered through the NIH Clinical Center medical laboratory. 
If performed at the NIH Clinical Center, your HLA results will be in your medical record.  
STORED SAMPLES 
We will collect blood samples from you during the study. We will keep these samples for future 
research to learn more about monoclonal antibodies, vaccines, the immune system, and/or other 
medical conditions. Results from research done with your stored samples will not be in your 
medical record or reported to you. 
Some of your blood samples that are left over after all required study testing are done may be stored 
and used for VRC-approved and ACTG-approved HIV-related research.  
Labeling of Stored Samples: We will label your stored samples by a code (like a number). Only the 
study team can link this code to you. Any identifying information about you will be kept 
confidential as much as the law allows. Despite protections, there is a small chance that information 
identifying you will be given to someone who should not get it. 
Risks from Stored Samples: There is a risk of unplanned release of information from your medical 
records. The chance that this information will be given to an unauthorized person without your 
permission is very small. Possible problems with the unplanned release of information include 
discrimination when applying for insurance and employment. Similar problems may occur if you 
give information about yourself or agree to have your medical records released. 
Future studies: In the future, other investigators (at NIH or outside of NIH; in the ACTG or outside 
of the ACTG) may wish to study your stored samples. When your stored samples are shared, they 
will be marked with a code. Your samples will not have any identifying information on them. Some 
information about you, such as your gender, age, health history, or ethnicity may also be shared 
with other researchers. 

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Any future research studies using your samples will be conducted in a way that protects the rights 
and privacy of study participants. 
Your stored samples will be used only for research and will not be sold. The research done with 
your materials may be used to develop new products in the future but you will not receive payment 
for such products. 
Making your Choice: You can only take part in this study if you agree to let us collect, store, and 
use your blood samples in future unspecified research. If you decide not to take part in this study, 
you may still take part in other studies at the NIH or at the research site.     
POSSIBLE STUDY RISKS 
Risks of Blood Drawing and IV insertion: The risks of drawing blood from a vein and having an IV 
include pain, bruising, bleeding, lightheadedness and fainting. Rarely, infection or inflammation can 
occur in the skin or vein. Blood clots are possible risks when using an IV for blood draw. 
Risks of VRC07-523LS: This study is the first time that VRC07-523LS is being given to people 
with HIV infection. As of January 2018, the people who have received at least one dose of VRC07-
523LS had no concerning reactions to the product. VRC07-523LS may have other unknown risks or 
side effects. We do not know if getting VRC07-523LS will affect how you respond to any similar 
monoclonal antibody against HIV.  
General risks of monoclonal antibodies: Side effects to infusions of monoclonal antibodies may 
include fever, chills, shaking, nausea, vomiting, pain, headache, dizziness, trouble breathing, high or 
low blood pressure, itchiness, rash, hives, lip or face swelling, diarrhea, racing heart or chest pain. 
These reactions may be related to how fast the product is infused. If you have symptoms while you 
get VRC07-523LS, tell the nurse right away. Slowing or stopping the infusion may help improve 
these symptoms. Side effects may also include reactions at the injection site, such as redness, 
bruising, and swelling.  
Some antibody products have a risk of serious allergic reactions or cytokine release syndrome that 
can be life threatening.   
• Anaphylaxis is one type of allergic reaction that may happen soon after an antibody product 
is given. This reaction can include difficulty breathing, low blood pressure, hives or rash, 
swelling in the mouth and face.     
• Serum sickness is a delayed type of allergic reaction that may happen several days to three 
weeks after an antibody product is given. This reaction can include hives or rash, fever, 
enlarged lymph nodes, muscle pains, joint pains, chest discomfort, and shortness of breath. 
• Cytokine release syndrome can happen when an antibody targets a cell protein that triggers 
immune cells to release cytokine (proinflammatory molecules in your body).   
All of these reactions are very unlikely because VRC07-523LS is a fully human antibody that 
attacks the HIV virus, and not your cells. 

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In addition to the possible risks that are listed above, the study products may have other side effects 
that we do not know about yet. Taking part in this study may affect your eligibility for future studies 
of other experimental monoclonal antibodies, antibody mixtures or other similar products. 
We will give you any new information about risks or other information that becomes available that 
may affect your decision to continue in the study. 
Risks during Pregnancy: We do not know what effects the study products may have on a fetus or 
nursing infant. Women must agree not to get pregnant during the study. We will discuss effective 
birth control methods with you. If you are able to become pregnant, you and your partner must use 
reliable birth control from the time you start the study until you complete the last study visit. 
If you can become pregnant, you must have a pregnancy test before you enter this study. The test 
must show that you are not pregnant. You must tell the clinic staff right away if you become 
pregnant during this study or think that you might be pregnant. If you become pregnant after getting 
the study product, we will not collect any more blood for research. However, you will be asked to 
continue with study follow-up visits to check on your health and to report the outcome of the 
pregnancy to us, which will be reported to the Antiretroviral Pregnancy Registry 
(http://www.apregistry.com). This report will not use your name or other information that could be 
used to identify you. 
POSSIBLE BENEFITS 
This study will not provide you with any direct health benefit. You and others may benefit in the 
future from the information that we learn from the study. 
COSTS TO YOU FOR YOUR PARTICIPATION 
There are no costs to you for taking part in this study. You or your health insurance will have to pay 
for all medical costs for medical care that you get outside this study. It is possible that you may 
have some expenses that are not covered by the study compensation provided. 
COMPENSATION TO YOU FOR YOUR PARTICIPATION 
You will be compensated [insert site IRB-approved amount] for your study participation as follows: 
[insert site plan]. This will be based on the number and type of study visits that you complete.  
REASONS FOR REMOVING YOU FROM THE STUDY WITHOUT YOUR CONSENT 
You may be removed from the study for several different reasons, including: 
• 
You do not keep appointments or follow study procedures. 
• 
You get a serious illness that needs ongoing medical care. 
• 
You enroll in another research study at the same time you are in this study. 
• 
You become pregnant. 
• 
The study is stopped or canceled. 

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A study may be stopped or canceled by a study sponsor, a regulatory agency or by the study 
investigators. If this happens, you will be told the reason why. 
You may choose to stop taking part in the study at any time. 
If you received the study product before you discontinue the study early, you will be asked to 
continue to be part of the study and return for the rest of the study visits. At the visits you will have 
some tests performed for safety monitoring, however samples for research purposes will not be 
collected.  
ALTERNATIVES 
This study is not designed to treat or prevent HIV infection or any disease. You may choose to not 
take part in this study. You may be eligible for other studies. Instead of being in this study you have 
the choice of: 
• Treatment with prescription drug available to you 
• Treatment with experimental drugs, if you qualify 
• No treatment 
Please talk to your doctor about these and other choices that may be available to you. Your doctor 
will explain the risks and benefits of these choices.  
CONFLICT OF INTEREST 
The research staff are reviewed at least yearly for conflicts of interest. You may ask the research 
team for additional information. 
The National Institutes of Health, including some members of the Vaccine Research Center 
scientific staff, developed the experimental product in this research study. The results of this study 
could play a role in whether the FDA will approve the experimental product for sale at some time in 
the future. If approved, the future sale of the vaccine could lead to payments to NIH and some NIH 
scientists. By U.S. law, government scientists are required to receive such payments for their 
inventions.   
You will not get any money from the development or sale of the product. 
This protocol may have investigators who are not NIH employees. Non-NIH investigators are 
expected to follow the principles of the Protocol Review Guide but are not required to report their 
personal financial holdings to the NIH. 
CLINICALTRIALS.GOV 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov. This web 
site will not include information that can identify you. At most, the website will include a 
summary of the results. You can search this website at any time. 

PRODUCT: VRC01LS/VRC07-523LS 
PROTOCOL: VRC 607/A5378, VERSION 4.0  
DATE:  MAY 29, 2018 
 
 
Page 61 of 73 
OTHER PERTINENT INFORMATION 
1. Confidentiality.   
When results of an NIH research study are reported in medical journals or at scientific meetings, 
the people who take part are not named and identified. In most cases, the NIH will not release any 
information about your research involvement without your written permission. However, if you 
sign a release of information form, for example, for an insurance company, the NIH will give the 
insurance company information from your medical record. This information might affect (either 
favorably or unfavorably) the willingness of the insurance company to sell you insurance. 
The Federal Privacy Act protects the confidentiality of your NIH medical records. However, you 
should know that the Act allows release of some information from your medical record without 
your permission, for example, if it is required by the Food and Drug Administration, members of 
Congress, law enforcement officials, National Institute of Allergy and Infectious Diseases 
institutional review board, study monitors, or other authorized people. 
ACTG Clinical Research Sites: We will do everything we can to protect your privacy. In addition 
to the efforts of the study staff to help keep your personal information private, we have gotten a 
Certificate of Confidentiality from the U.S. Federal Government. This certificate means that 
researchers cannot be forced to tell people who are not connected with this study, such as the 
court system, about your participation. Also, any publication of this study will not use your name 
or identify you personally. 
Your records may be reviewed by the U.S. Food and Drug Administration (FDA), the ACTG, the 
U.S. Office for Human Research Protections (OHRP), or other local, US, and international 
regulatory entities as part of their duties (insert name of site) institutional review board (IRB) (a 
committee that protects the rights and safety of participants in research), National Institutes of 
Health (NIH), study staff, study monitors, and their designees. Having a Certificate of 
Confidentiality does not prevent you from releasing information about yourself and your 
participation in the study. 
Even with the Certificate of Confidentiality, if the study staff learns of possible child abuse and/or 
neglect or a risk of harm to yourself or others, we will be required to tell the proper authorities. 
2. Policy Regarding Research-Related Injuries.   
The [insert institution’s name] will provide short-term medical care for any injury resulting from 
your participation in research here. The cost of this treatment will be charged to you or your 
insurance company. In general, no long-term medical care or financial compensation for research-
related injuries will be provided by the [insert institution’s name], National Institutes of Health, or 
the Federal Government. However, you have the right to pursue legal remedy if you believe that 
your injury justifies such action. 
3. Payments. 
The amount of payment to research participants is guided by the National Institutes of Health policies 
or as approved by the Institutional Review Board (IRB) of the clinical research site.   

PRODUCT: VRC01LS/VRC07-523LS 
PROTOCOL: VRC 607/A5378, VERSION 4.0  
DATE:  MAY 29, 2018 
 
 
Page 62 of 73 
4. Problems or Questions. 
If you have any problems or questions about this study or about any research-related injury, contact 
the Principal Investigator, [insert site PI name], or the Study Coordinator, [study coordinator name] 
at [contact phone number]. 
If you have any questions about your rights as a research participant, you may contact: 
VRC Clinic only: The Clinical Center Patient Representative at 301-496-2626. 
ACTG Clinical Research Sites: 
• Name or title of person on the Institutional Review Board (IRB) or other organization 
appropriate for the site 
• Telephone number of above 
5. Consent Document.   
Please keep a copy of this document in case you want to read it again. 
COMPLETE APPROPRIATE ITEM(S) BELOW: 
Adult Study Participant’s Consent 
 
I have read the explanation about this study and have been given the opportunity to discuss it and to ask questions.  I 
hereby consent to take part in this study. 
 
 
                  
 
Signature of Adult Participant/Legal Representative                Date 
 
 
Print Name 
 
  
Time 
THIS CONSENT DOCUMENT HAS BEEN APPROVED FOR USE  
FROM XXXXXX THROUGH XXXXXX. 
 
 
 
 
 
 
 
Signature of Investigator/Person Obtaining Consent 
 
 
 
 
Date 
 
 
 
 
Print Name 
Signature of Witness 
 
 
 
 
Date 
 
 
 
 
Print Name 

PRODUCT: VRC01LS/VRC07-523LS 
PROTOCOL: VRC 607/A5378, VERSION 4.0  
DATE:  MAY 29, 2018 
 
 
Page 63 of 73 
APPENDIX II 
 
CONTACT INFORMATION 

PRODUCT: VRC01LS/VRC07-523LS 
PROTOCOL: VRC 607/A5378, VERSION 4.0  
DATE:  MAY 29, 2018 
 
Page 65 of 73 
APPENDIX III 
 
SCHEDULE OF EVALUATIONS

PRODUCT: VRC01LS/VRC07-523LS 
PROTOCOL: VRC 607/A5378, VERSION 4.0  
DATE:  MAY 29, 2018 
 
Page 66 of 73 
“Visits” 02G, 02H and 03A are optional 
Schedule of Evaluations Part A 
Visit Number 
01R 
02 
02A 
02B 
02C 
02D 
02E 
02F 
02G 
02H 
03 
03A 
04 
05 
06 
07 
Time After Day 0 Infusion 
 
Pre 
EOI 
30 
1hr 
2hr 
3h 
4hr 
8hr 
12hr 
24hr 
36hr 
48hr 
72hr 
Wk1 
Wk1 
Day of Study 
-28 to 0 
D0 
D0 
D0 
D0 
D0 
D0 
D0 
D0 
D0 
D1 
D1 
D2 
D3 
D5 
D7 
Study Procedures 
Tube 
Screen 
Enroll 
Outpatient (with optional inpatient admission) 
 
 
 
 
VRC 500 Screening Consent 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
VRC 607/A5378 Assessment of 
Understanding; Consent 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 Physical exam 
 
X 
X 
X 
X 
 
 
 
 
 
 
 
X 
 
X 
 
 
X 
2 Medical history 
 
X 
X 
X 
 
 
 
 
 
 
 
 
X 
 
X 
 
 
X 
3 Concomitant Medications 
 
X 
X 
X 
 
 
 
 
 
 
 
 
X 
 
X 
 
 
X 
4 ARV Medication Record 
 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study Product Administration 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
5 Diary “Card” Reactogenicity 
Review 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
Pregnancy prevention counseling 
 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Positive prevention counseling 
 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Clinical Labs 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CBC, platelets 
EDTA 
3 
 
3 
 
 
 
 
 
 
 
 
 
 
3 
 
 
3 
ALT, AST, ALP, creatinine 
GLT 
4 
 
4 
 
 
 
 
 
 
 
 
 
 
4 
 
 
4 
Hepatitis BsAg 
SST 
4 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hep C viral load 
SST 
4 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
6 Pregnancy test: urine or serum 
 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HIV EIA 
SST 
4 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HIV PCR 
EDTA 
6 
6 
6 
6 
6 
6 
6 
6 
6 
6 
6 
6 
6 
6 
6 
6 
6 
CD4+/CD8+ 
EDTA 
3 
 
3 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 
Research Samples 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Timed PK samples 
SST 
 
 
4 
4 
4 
4 
4 
4 
4 
 
 
4 
 
4 
 
 
4 
PBMC and plasma 
EDTA 
 
20 
 
 
 
 
 
 
 
 
 
 
 
10 
 
 
20 
Serum 
SST 
 
24 
 
 
 
 
 
 
 
 
 
 
 
8 
 
 
16 
Daily Volume (mL) 
 
28 
50 
20 
10 
10 
10 
10 
10 
10 
6 
6 
10 
6 
35 
6 
6 
56 
Cumulative Volume (mL) 
 
28 
78 
98 
108 
118 
128 
138 
148 
158 
164 
170 
180 
186 
221 
227 
233 
289 

PRODUCT: VRC01LS/VRC07-523LS 
PROTOCOL: VRC 607/A5378, VERSION 4.0  
DATE:  MAY 29, 2018 
 
Page 67 of 73 
SCHEDULE OF EVALUATIONS (continued): 
1 Physical exam: Screening includes complete physical exam with vital signs, height and weight. Day 0 
physical exam includes vital signs (blood pressure, temperature and pulse) and weight (used for ordering 
the study product which is based on a “mg/kg” dose). At other visits if medically indicated, a targeted 
exam is performed. Otherwise only blood pressure (BP), pulse and temperature are required. 
2 Medical history: Screening, 01R and Day 0 evaluations include a complete medical history to evaluate 
eligibility criteria as defined in Section 4.1. At other visits, an interim medical history will be done.  
3 Concomitant medications: Concomitant medications must be entered in the database at enrollment and 
updated as required in Section 4.2.8.  
4 ARV medication record: ARVs will be reviewed with the participant throughout the study, however 
the ARV medication record will be documented in the research chart and database as indicated and 
whenever changes are reported. 
5 Diary card reactogenicity review: Participants will begin to record 3-day reactogenicity as noted in 
Section 4.2.4. Clinicians will review with the participant at a minimum on Day 3 and prior to Day 3 as 
needed. If any reported reactogenicity is unresolved by Day 3, it will continue to be reviewed with the 
participant at each visit until resolved. Data from the data will be recorded in the database as noted in 
Section 4.2.4. 
6 Pregnancy test: Negative pregnancy test results must be confirmed for women of reproductive potential 
prior to study product administration. 
Visit Windows: 
Screening: evaluations for eligibility must be completed within 28 days of enrollment as noted in 
Section 4.1. 
Visit 01R and Day 0: Visit 01R may be done on the same day as Day 0. Day 0 = day of product 
administration. Day 0 is preferably scheduled within 14 days after enrollment at “Visit 01R”, but 
may be scheduled up to 28 days after enrollment. Day 0 evaluations prior to VRC01LS 
administration are the baseline for assessing subsequent AEs.   
EOI = End of Infusion Blood draw “visits,” defined by minutes or hours after an infusion are relative 
to the exact time of the end of infusion (EOI). The exact time of start (T0), EOI and each PK draw is 
recorded to ensure accurate PK analysis.   
Visit 02A: up to 10 minutes post EOI 
Visit 02B & 02C: ± 10 minutes 
Visits 02D – 02F: ± 15 minutes 
Visit 02G: ± 30 minutes Note: This visit is optional. 
Visit 02H, 03, 03A: ± 1 hour Note: Visits 02H and 03A are optional. 
Visit 04: ± 6 hours 
Visit 05: ± 12 hours 
Visits 06 – 07:  1 day

PRODUCT: VRC01LS/VRC07-523LS 
PROTOCOL: VRC 607/A5378, VERSION 4.0  
DATE:  MAY 29, 2018 
 
Page 68 of 73 
1 Physical exam: If medically indicated, a targeted exam is performed. Otherwise only blood pressure (BP), pulse and temperature are required. 
2 HLA type blood sample is collected once in the study at the VRC Clinic; however, if HLA type is already available in the medical record it does not 
need to be repeated. HLA type may also be obtained from a frozen sample. 
3 PK samples: PK samples will be optional at visits 22 and 23 if VRC01LS levels are undetectable at the PK draw at visit 21. 
Visit windows: Visits 08 – 11:  1 day; Visits 12 – 17:  2 days; Visits 18 – 20:  5 days; Visits 21 -23: ± 7 days  
Schedule of Evaluations Part A (continued) 
Visit Number 
08 
09 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19 
20 
21 
22 
23 
Week of Study 
Wk2 
Wk2 
Wk2 
Wk3 
Wk3 
Wk4 
Wk5 
Wk6 
Wk7 
Wk8 
Wk12 Wk16 Wk20 Wk24 Wk36 Wk48 
Day of Study 
D9 
D12 
D14 
D16 
D21 
D28 
D35 
D42 
D49 
D56 
D84 
D112 
D140 
D168 
252 
336 
Study Procedures 
Tube 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 Physical exam 
 
 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Interim medical history 
 
 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant medications 
 
 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ARV medication record 
 
 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pregnancy prevention counseling 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
Positive prevention counseling 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
X 
X 
Clinical Labs 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CBC, platelets 
EDTA 
 
 
3 
 
3 
3 
3 
3 
3 
3 
3 
3 
3 
3 
3 
3 
ALT, AST, ALP, creatinine 
GLT 
 
 
4 
 
 
4 
 
 
 
 
4 
 
 
4 
4 
4 
Pregnancy test: urine or serum 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
X 
HIV PCR 
EDTA 
6 
6 
6 
6 
6 
6 
6 
6 
6 
6 
6 
6 
6 
6 
6 
6 
CD4+/CD8+ 
EDTA 
 
 
3 
 
3 
3 
3 
3 
3 
3 
3 
3 
3 
3 
3 
3 
2 HLA typing (VRC Clinic only) 
EDTA 
 
 
 
 
 
 
 
 
 
 
 
 
20 
 
 
 
Research Samples 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 PK samples 
SST 
 
 
4 
 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
PBMC and plasma 
EDTA 
 
 
 
 
 
20 
20 
 
 
20 
20 
 
 
20 
20 
20 
Serum 
SST 
 
 
 
 
 
24 
16 
 
 
24 
24 
24 
24 
24 
24 
24 
Daily Volume (mL) 
 
6 
6 
20 
6 
16 
64 
52 
16 
16 
60 
64 
40 
60 
64 
64 
64 
Cumulative Volume (mL) 
 
295 
301 
321 
327 
343 
407 
459 
475 
491 
551 
615 
655 
715 
779 
843 
907 

PRODUCT: VRC01LS/VRC07-523LS 
PROTOCOL: VRC 607/A5378, VERSION 4.0  
DATE:  MAY 29, 2018 
 
Page 69 of 73 
“Visits” 02G, 02H, and 03A are optional 
Schedule of Evaluations Part B 
Visit Number 
01R 
02 
02A 
02B 
02C 
02D 
02E 
02F 
02G 
02H 
03 
03A 
04 
05 
06 
07 
Time After Day 0 Infusion 
 
Pre 
EOI 
30 
1hr 
2hr 
3h 
4hr 
8hr 
12hr 
24hr 
36h 
48h 
72hr 
Wk1 
Wk1 
Day of Study -10 to 0 
D0 
D0 
D0 
D0 
D0 
D0 
D0 
D0 
D0 
D1 
D1 
D2 
D3 
D5 
D7 
Study Procedures 
Tube 
Screen Enroll 
Outpatient (with optional inpatient admission) 
 
 
 
 
VRC 607/A5378 Assessment of 
Understanding; Consent 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 Physical exam 
 
X 
X 
X 
X 
 
 
 
 
 
 
 
X 
 
X 
 
 
X 
2 Medical history 
 
X 
X 
X 
 
 
 
 
 
 
 
 
X 
 
X 
 
 
X 
3 Concomitant Medications 
 
X 
X 
X 
 
 
 
 
 
 
 
 
X 
 
X 
 
 
X 
4 ARV Medication Record 
 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
5 Study Product Administration 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
6 Diary “Card” Reactogenicity Review 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
Pregnancy prevention counseling 
 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Positive prevention counseling 
 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Clinical Labs 
 
(numbers indicate volume of blood and urine sample to be collected) 
CBC, platelets 
EDTA 
3 
 
3 
 
 
 
 
 
 
 
 
 
 
3 
 
 
3 
ALT, AST, ALP, creatinine 
GLT 
4 
 
4 
 
 
 
 
 
 
 
 
 
 
4 
 
 
4 
Hepatitis BsAg 
SST 
4 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hep C viral load 
SST 
4 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
7 Pregnancy test: urine or serum 
URN 
5 
5 
5 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SST 
3 
3 
3 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HIV EIA 
SST 
4 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HIV PCR 
EDTA 
6 
6 
6 
6 
6 
6 
6 
6 
6 
6 
6 
6 
6 
6 
6 
6 
6 
CD4+/CD8+ 
EDTA 
3 
 
3 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 
Urinalysis 
 
 
5 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Research Samples 
 
(numbers indicate volume of blood sample to be collected) 
Timed PK samples 
SST 
 
 
4 
4 
4 
4 
4 
4 
4 
 
 
4 
 
4 
 
 
4 
PBMC and plasma 
EDTA 
 
20 
 
 
 
 
 
 
 
 
 
 
 
10 
 
 
20 
Serum 
SST 
 
24 
 
 
 
 
 
 
 
 
 
 
 
8 
 
 
16 
Daily Blood Volume (mL) 
 
28-31 
50-53 
20-23 
10 
10 
10 
10 
10 
10 
6 
6 
10 
6 
35 
6 
6 
56 
Maximum Cumulative Blood Volume 
(mL) 
 
31 
84 
107 
117 
127 
137 
147 
157 
167 
173 
179 
189 
195 
230 
236 
242 
298 

PRODUCT: VRC01LS/VRC07-523LS 
PROTOCOL: VRC 607/A5378, VERSION 4.0  
DATE:  MAY 29, 2018 
 
Page 70 of 73 
SCHEDULE OF EVALUATIONS (continued): 
1 Physical exam: Screening includes complete physical exam with vital signs, height and weight. Day 0 physical 
exam includes vital signs (blood pressure, temperature and pulse) and weight. At other visits if medically 
indicated, a targeted exam is performed. Weight must be measured at enrollment (Visit 01R), which will be 
used for ordering the study product based on a “mg/kg” dose. Otherwise only blood pressure (BP), pulse and 
temperature are required. 
2 Medical history: Screening, 01R and Day 0 evaluations include a complete medical history to evaluate 
eligibility criteria as defined in Section 4.1. At other visits, an interim medical history will be done.  
3 Concomitant medications: Concomitant medications must be entered in the database at enrollment and 
updated as required in Section 4.2.8. Participants will be strongly encouraged to initiate 3-drug ART (prescribed 
by their primary HIV clinician; not study-provided) after completing day 14 study evaluations. Document them 
as concomitant medications. 
4 ARV medication record: ARVs will be reviewed with the participant throughout the study, however the ARV 
medication record will be documented in the research chart and database as indicated and whenever changes are 
reported. 
5 Study Product Administration: Administration should occur within 10 days after enrollment per Section 4.2.2 
and Day 0 visit window details below. Study product should be available on site one day prior to the scheduled 
infusion (D0). Refer to the MOP for detailed study product ordering instructions. 
6 Diary card reactogenicity review: Participants will begin to record 3-day reactogenicity as noted in Section 
4.2.4. Clinicians will review with the participant at a minimum on Day 3 and prior to Day 3 as needed. If any 
reported reactogenicity is unresolved by Day 3, it will continue to be reviewed with the participant at each visit 
until resolved. Data from the data will be recorded in the database as noted in Section 4.2.4. 
7 Pregnancy test: Negative pregnancy test results must be confirmed for women of reproductive potential prior 
to study product administration. 
Visit Windows: 
Screening: evaluations for eligibility must be completed within 28 days of enrollment as noted in Section 
4.1. 
Visit 01R and Day 0: Visit 01R may be done on the same day as Day 0. Day 0 = day of product 
administration. Day 0 should be scheduled within 10 days after enrollment at “Visit 01R”. Day 0 
evaluations prior to VRC07-523LS administration are the baseline for assessing subsequent AEs.   
EOI = End of Infusion Blood draw “visits,” defined by minutes or hours after an infusion are relative to the 
exact time of the end of infusion (EOI). The exact time of start (T0), EOI and each PK draw is recorded to 
ensure accurate PK analysis.   
Visit 02A: up to 10 minutes post EOI 
Visit 02B & 02C: ± 10 minutes 
Visits 02D – 02F: ± 15 minutes 
Visit 02G: ± 30 minutes Note: This visit is optional. 
Visit 02H, 03, and 03A: ± 1 hour Note: Visits 02H and 03A are optional. 
Visit 04: ± 6 hours 
Visit 05: ± 12 hours 
Visits 06 – 07:  1 day Note: These visits cannot occur on the same day. Visit 07 cannot occur on the same 
day as Visit 08.

PRODUCT: VRC01LS/VRC07-523LS 
PROTOCOL: VRC 607/A5378, VERSION 4.0  
DATE:  MAY 29, 2018 
 
Page 71 of 73 
1 Physical exam: If medically indicated, a targeted exam is performed. Otherwise only blood pressure (BP), pulse and temperature are required. 
2 HLA type blood sample is collected once in the study at the VRC Clinic; however, if HLA type is already available in the medical record it does not 
need to be repeated.  HLA type may also be obtained from a frozen sample. 
3 PK samples: PK samples will be optional at visits 22 and 23 if VRC07-523LS levels are undetectable at the PK draw at visit 21. If needed, PK assay 
for ARVs will be performed; however, no additional blood draw is required. 
Visit windows: Visits 08 – 11:  1 day (Note: Visit 08 cannot occur on the same day as Visit 07. Visits 09, 10, and 11 cannot occur on the same 
day.); Visits 12 – 17:  2 days; Visits 18 – 20:  5 days; Visits 21 -23: ± 7 days   
Schedule of Evaluations Part B (continued) 
Visit Number 
08 
09 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19 
20 
21 
22 
23 
Week of Study Wk2 
Wk2 
Wk2 
Wk3 
Wk3 
Wk4 
Wk5 
Wk6 
Wk7 
Wk8 
Wk12 Wk16 Wk20 Wk24 Wk36 Wk48 
Day of Study 
D9 
D12 
D14 
D16 
D21 
D28 
D35 
D42 
D49 
D56 
D84 
D112 
D140 
D168 
D252 
D336 
Study Procedures 
Tube 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 Physical exam 
 
 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Interim medical history 
 
 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant medications 
 
 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ARV medication record 
 
 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pregnancy prevention counseling 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
Positive prevention counseling 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
X 
X 
Clinical Labs 
 
(numbers indicate volume of blood and urine sample to be collected) 
CBC, platelets 
EDTA 
 
 
3 
 
3 
3 
3 
3 
3 
3 
3 
3 
3 
3 
3 
3 
ALT, AST, ALP, creatinine 
GLT 
 
 
4 
 
 
4 
 
 
 
 
4 
 
 
4 
4 
4 
Pregnancy test: urine or serum 
URN 
 
 
 
 
 
 
 
 
 
 
 
 
 
5 
 
5 
SST 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 
 
3 
HIV PCR 
EDTA 
6 
6 
6 
6 
6 
6 
6 
6 
6 
6 
6 
6 
6 
6 
6 
6 
CD4+/CD8+ 
EDTA 
 
 
3 
 
3 
3 
3 
3 
3 
3 
3 
3 
3 
3 
3 
3 
2 HLA typing (VRC Clinic only) 
EDTA 
 
 
 
 
 
 
 
 
 
 
 
 
20 
 
 
 
Urinalysis 
 
 
 
5 
 
 
5 
 
 
 
5 
5 
5 
5 
5 
5 
5 
Research Samples 
 
(numbers indicate volume of blood sample to be collected) 
3 PK samples 
SST 
 
 
4 
 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
PBMC and plasma 
EDTA 
 
 
 
 
 
20 
20 
 
 
20 
20 
 
 
20 
20 
20 
Serum 
SST 
 
 
 
 
 
24 
16 
 
 
24 
24 
24 
24 
24 
24 
24 
Daily Blood Volume (mL) 
 
6 
6 
20 
6 
16 
64 
52 
16 
16 
60 
64 
40 
60 
64-67 
64 
64-67 
Maximum Cumulative Blood Volume (mL) 
 
304 
310 
330 
336 
352 
416 
468 
484 
500 
560 
624 
664 
724 
791 
855 
922 

PRODUCT: VRC01LS/VRC07-523LS 
PROTOCOL: VRC 607/A5378, VERSION 4.0  
DATE:  MAY 29, 2018 
 
Page 72 of 73 
APPENDIX IV  
 
TABLE FOR GRADING SEVERITY OF ADVERSE EVENTS 
 

PRODUCT: VRC01LS/VRC07-523LS 
PROTOCOL: VRC 607/A5378, VERSION 4.0  
DATE:  MAY 29, 2018 
 
Page 73 of 73 
 
The U.S. Department of Health and Human Services, National Institutes of Health, National 
Institute of Allergy and Infectious Diseases, Division of AIDS. Division of AIDS (DAIDS) 
Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0. [November 
2014] will be used in this study. The table is available at the following link: http://rsc.tech-
res.com/docs/default-source/safety/daids_ae_grading_table_v2_nov2014.pdf?sfvrsn=8 
 
The grading table, the Manual for Expedited Reporting of Adverse Events to DAIDS, and 
supplementary tutorial and tools can be found on the Division of AIDS Regulatory Support 
Center (RSC) website:  
 
http://rsc.tech-res.com/clinical-research-sites/safety-reporting 
 
The Table will be used as posted at the link above with the following exemption: 
• Weight loss will be recorded as an adverse event only if it is considered deleterious to the 
participant’s health. 
 

CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY
MEDICAL RECORD
•  Adult Patient or     •  Parent, for Minor Patient
INSTITUTE:
National Institute of Allergy and Infectious Diseases
STUDY NUMBER:
16-I-0147
PRINCIPAL INVESTIGATOR:  
STUDY TITLE:
VRC 607/ACTG A5378: A Phase 1, Single Dose Study of the Safety and Virologic Effect of an HIV 
Specific Broadly Neutralizing Human Monoclonal Antibody, VRC-HIVMAB080-00-AB (VRC01LS) or 
VRC-HIVMAB075-00-AB (VRC07-523LS) Administered Intravenously to HIV-Infected Adults.
Continuing Review Approved by the IRB on 05/07/18
Amendment Approved by the IRB on 07/09/18 (D)
Date Posted to Web: 08/22/18
Study Consent [Version 4.0]
PATIENT IDENTIFICATION
CONSENT TO PARTICIPATE IN A CLINICAL
RESEARCH STUDY
•   Adult Patient or    •   Parent, for Minor Patient
NIH-2514-1 (07-09)
P.A.: 09-25-0099
File in Section 4:  Protocol Consent (1)
INTRODUCTION
We invite you to take part in a research study at the National Institutes of Health (NIH). This study is a collaboration 
between the Vaccine Research Center (VRC), NIAID, NIH and the AIDS Clinical Trials Group (ACTG).
First, we want you to know that:

Taking part in this study is entirely voluntary.

You may choose not to take part, or you may withdraw from the study at any time.  In either case, you 
will not lose any benefits to which you are otherwise entitled. You will be treated the same no matter 
what.

If you are at the NIH and would like to receive care at the NIH, you must be taking part in a study or be 
under evaluation for study participation. 

You may receive no benefit from taking part. The research may give us knowledge that may help people 
in the future.

We will tell you about new information from this study or other studies that may affect your health, 
welfare, or willingness to stay in this study. If you want the results of the study, let the study staff know. 
Second, some people have personal, religious or ethical beliefs that may limit the kinds of medical or research treatments 
they would want to receive (such as blood transfusions).  If you have such beliefs, please discuss them with your NIH 
doctors or research team before you agree to the study.
Now we will describe this research study.  Before you decide to take part, please take as much time as you need to ask 
any questions and discuss this study with anyone at NIH, or with family, friends or your personal physician or other 
health professional.

CONTINUATION SHEET for either:
MEDICAL RECORD
NIH 2514-1, Consent to Participate in A Clinical Research Study
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study
STUDY NUMBER:
16-I-0147
CONTINUATION:  page 2  of 10 pages
PATIENT IDENTIFICATION
CONTINUATION SHEET for either:
NIH-2514-1 (10-84)
NIH-2514-2 (10-84)
P.A.: 09-25-0099
PURPOSE AND PLAN OF THE STUDY
In this study, we are testing two experimental products or drugs called “VRC01LS” and “VRC07-523LS”.  Experimental 
means that these products have not been approved by the U.S. Food and Drug Administration (FDA), but the FDA has
allowed us to test them in research studies.  VRC01LS and VRC07-523LS are antibodies directed against HIV virus. The 
main purpose of this study is to see if these antibodies are safe and how your body will respond to them. (An antibody is 
a type of protein that helps protect the body against foreign matter such as bacteria and viruses; it can be either 
produced by your body or made in a laboratory.)
There are two different parts in this study (Part A and Part B). In Part A, 7 people got VRC01LS. In Part B, 7 people (up 
to 10 people) will get VRC07-523LS. People were put in Part A first and now Part A of the study is done. People will now 
be put in Part B. If you agree to take part in this study (Part B), you will get VRC07-523LS only and we will measure the 
amount of the drug in your body and how much stays in your body over time. We will check to see if your immune 
system makes antibodies against the product you get. 
About 14 to 20 people (7 to 10 people in each part) will take part in this study at the NIH Clinical Center in Bethesda, 
Maryland and sites within in the ACTG Network. The study will include a total of 23 clinic visits per person over a period 
of about 11 months. 
After you complete the day 14 study procedures, we strongly advise that you start the antiviral therapy prescribed by 
your primary HIV physician (not study-provided).
STUDY PRODUCTS
VRC01LS and VRC07-523LS are study products that contain monoclonal antibodies. “Monoclonal” means that all the 
antibodies in each product are the same. These antibodies target the virus that causes HIV infection. As of May 10, 2018, 
approximately 60 people have received one of these antibodies and have not had any serious side effects or safety 
concerns. 
VRC01LS and VRC07-523LS are based on an antibody that was first found in an HIV infected person. Both of these study 
products were developed by the Vaccine Research Center (VRC), NIH and made in a drug manufacturing laboratory.  
There are currently research studies of these products in adults without HIV infection. This is the first study to give 
VRC01LS or VRC07-523LS people with HIV infection.
There is currently no cure for HIV. We do not expect the products in this study to cure or control your HIV. 
In laboratory and animal studies, VRC01LS and VRC07-523LS were shown to attach to and inactivate many types of HIV 
viruses. It is not known if the products will act the same way when given to humans.  It will take many studies to learn if 
the products are useful for preventing or treating HIV.  This study alone will not answer this question.

CONTINUATION SHEET for either:
MEDICAL RECORD
NIH 2514-1, Consent to Participate in A Clinical Research Study
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study
STUDY NUMBER:
16-I-0147
CONTINUATION:  page 3  of 10 pages
PATIENT IDENTIFICATION
CONTINUATION SHEET for either:
NIH-2514-1 (10-84)
NIH-2514-2 (10-84)
P.A.: 09-25-0099
SCREENING VISIT 
If you decide to join this study, you will be asked to sign this consent form. After you have signed the form, you will be 
asked some questions and will undergo some tests at the screening visit to see if it is safe for you to join the study.
At the screening visit you will have a physical exam. You will be asked about your medical history, including your HIV 
history, any medicines you have taken in the past and are currently taking, and if you have ever received antibodies 
directed against the HIV virus or taken any anti-HIV medicines. We will draw about 6 tubes of blood from you for routine 
blood tests, tests for Hepatitis B virus or Hepatitis C virus infection, tests for HIV antibodies and viral load (the amount of 
HIV in your blood), and CD4+/CD8+ T cell count (cells in your blood that fight infection). You will be informed if any tests 
show a medical problem. You will be advised if results show that you should seek medical care.  Some medical conditions 
may make you not eligible for a clinical trial of an investigational product.
If you are female and able to become pregnant, you will have a pregnancy test done to see if you are pregnant. You 
cannot participate in this study if you are pregnant. If you are not pregnant or you are having sex that could lead to 
pregnancy, you will be asked and must agree to use birth control before you are able to participate in this study. We will 
discuss effective birth control methods with you.
ELIGIBILITY
You are eligible to participate in this study because you have completed the screening process and are:

18 to 70 years old

HIV infected, have never taken antiretroviral (ARV) medications, but otherwise in good general health

Under the care of a primary care provider for management of HIV 

Willing to let the study team give your lab test results to your primary care provider while you are in this study.

Willing to receive VRC07-523LS

Willing to donate blood samples for future research

Willing to use birth control for the whole study, if you are able to become pregnant 
STUDY PROCEDURES
Study product infusion: If you agree to enroll in this study, you will get one dose of VRC07-523LS. The exact dose you 
get will depend on much you weigh. 
Before you are given the study product, your temperature, blood pressure, heart rate, and weight will be taken. You may 
also have a brief physical exam. If you are female and able to become pregnant, you must use an effective form of birth 
control for the entire study. A pregnancy test will be done to see if you are pregnant. If you are pregnant, we will not 
give you the study product. 

CONTINUATION SHEET for either:
MEDICAL RECORD
NIH 2514-1, Consent to Participate in A Clinical Research Study
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study
STUDY NUMBER:
16-I-0147
CONTINUATION:  page 4  of 10 pages
PATIENT IDENTIFICATION
CONTINUATION SHEET for either:
NIH-2514-1 (10-84)
NIH-2514-2 (10-84)
P.A.: 09-25-0099
VRC07-523LS will be given to you by intravenous (IV) infusion. This means we will place a thin tube or IV line into a vein
in your arm. The IV line will be attached to a bag that contains the study product mixed with a liquid called “normal 
saline” or salt water. It will flow into your vein for about 30 minutes.  If you have side effects during the infusion, it will 
be slowed or stopped as needed. You will be observed for at least 30 minutes immediately after receiving the study 
product.   
If possible, we will also place an IV line in your other arm to collect blood samples. We will draw your blood before and 
right after the infusion, then at least 5 more times over the next 4 hours from this IV line. There are other blood draws at 
8, 12 and 36 hours after infusion, which are optional. At least one IV line will stay in your arm for several hours. You will 
not lose any benefits if you choose not to give the optional blood samples. If you choose to get these blood draws, you 
may be admitted to the hospital for an overnight stay. The hospital stay is for convenience only and not to give you care 
or treatment. 
We will give you a thermometer and ask you to check your temperature every day for 3 days after you get the study 
product. You will need to record your temperature and any symptoms you may have. Even if you do not feel sick, it is 
still very important that you record this information. You will get a password to a secure website to enter this information 
on an electronic form or “diary”. If you do not have a computer, you may use a paper diary instead. 
If you have any side effects after you get the study product, you should tell a study nurse or doctor as soon as possible. 
You can reach the clinic staff by phone 24 hours a day. If you have symptoms, you may be asked to come into the clinic 
for an examination before your next scheduled visit. It is very important that you follow the instructions you get from the 
clinic staff. 
Follow-up visits: After you get the study product, you will need to come back to the clinic 11 times over a 4-week period. 
During the next 9 months, you will have 10 more follow-up visits. 
At most visits, we will check you for any health changes or problems. Your temperature, blood pressure, and pulse will be 
taken and you will have a physical exam. We will ask you how you are feeling and if you have taken any medications. 
While you are in the study, we will also provide counseling about preventing pregnancy as well as positive-prevention 
counseling to help prevent illness and promote good health.
We will draw about 1 to 11 tubes of blood from you at each visit, depending on the type of visit. We will also ask you to 
provide a urine sample for a urine test at most visits. We will tell you right away if any of your test results show a health
problem. You might need to have extra clinic visits and laboratory tests if you have health changes that need to be 
checked. The total amount of blood we draw from you will meet NIH guidelines.
We will use some blood samples to see how long the study product remains in your body and if your immune system 
makes antibodies against it. Results of these tests are not for checking on your health and we will not give you these 
results. We may also use some blood samples to check the level of ARV medications in your blood while you are in this 
study.  
Research studies follow a set schedule. This helps us answer the research questions. The visit schedule is a little flexible, 
but it is important that you work with the staff to follow the schedule as closely as possible. You should try not to miss any
visits. You should contact the clinic staff as soon as possible if you need to change the date or time of any visit. 
For the entire duration that you are on study, which will be 48 weeks or about 11 months, a maximum of about 922 mL 
(or about 2 pints) of blood will be collected. 

CONTINUATION SHEET for either:
MEDICAL RECORD
NIH 2514-1, Consent to Participate in A Clinical Research Study
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study
STUDY NUMBER:
16-I-0147
CONTINUATION:  page 5  of 10 pages
PATIENT IDENTIFICATION
CONTINUATION SHEET for either:
NIH-2514-1 (10-84)
NIH-2514-2 (10-84)
P.A.: 09-25-0099
HIV TESTING AND MANAGEMENT 
As you take part in this study, you will have frequent testing of your HIV viral load and CD4+ T cell count for research 
purposes.  These tests will be given to you and sent to your primary care provider. You should discuss these results and
any questions about management of your HIV infection with your primary care provider.  
This study does not include standard medical care or the management of your HIV infection. The U.S. Department of 
Human Services and the clinical research team recommend that all HIV-infected individuals take (ARV) medication to 
reduce the chance of getting sick from HIV, increase life expectancy with HIV infection and prevent the spread of HIV to 
others. 
We will not give you ARV medications as part of this research study.  You must have a primary health care provider for 
HIV to take part in this study.  If you do not have one and need help finding one or getting ARV medications, please tell 
a study doctor or nurse. We will help you find a qualified HIV doctor and ARV medications. You and your primary health 
care provider will make all decisions about starting, stopping or changing ARV medications. However, we strongly advise 
that you start ARV medications after you have completed the day 14 study procedures. We expect you to tell us about 
changes in your ARV medications. We do not expect VRC07-523LS to control HIV by itself. You should not change or stop 
ARV treatment without talking about it with your primary care provider. Changes in ARV treatment will not affect your 
continued participation in the study.
MONITORING OF THE STUDY
A group of physicians and scientists at NIH will monitor this study.  This group will review the information from the study 
and will pay close attention to possible harmful reactions. If serious side effects occur, study product infusions may be 
delayed or canceled.
GENETIC TESTING
In the future, genetic research tests may be done on your stored samples to help understand how VRC07-523LS works 
and interacts with your body. In research studies, genetic tests are done to see if different types of immune response are 
related to genetic differences in people; this includes testing your antibody genes. Genetic tests done in a research lab 
from your stored samples will not be recorded in your medical record and will not have your name on the sample. The 
performance of these tests is not for health care purposes.
HLA type is a genetic test. People with certain HLA types might be more likely to develop certain diseases.  Simply having 
those HLA types does not mean they will develop those diseases. HLA typing can reveal family relationships. It is our 
policy not to discuss your HLA results unless they have direct medical or reproductive implications for you or your family.  
Genetic information about you will not be revealed to others, including your relatives, without your permission.  We will 
not release any information about you or your family to any insurance company or employer unless you sign a document 
allowing release of information.
HLA typing may be ordered through the NIH Clinical Center medical laboratory.  If performed at the NIH Clinical Center, 
your HLA type results will be in your medical record.

CONTINUATION SHEET for either:
MEDICAL RECORD
NIH 2514-1, Consent to Participate in A Clinical Research Study
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study
STUDY NUMBER:
16-I-0147
CONTINUATION:  page 6  of 10 pages
PATIENT IDENTIFICATION
CONTINUATION SHEET for either:
NIH-2514-1 (10-84)
NIH-2514-2 (10-84)
P.A.: 09-25-0099
HLA typing may be ordered through the NIH Clinical Center medical laboratory. If performed at the NIH Clinical Center, 
your HLA results will be in your medical record. 
STORED SAMPLES
We will collect blood samples from you during the study.  We will keep these samples for future research to learn more 
about monoclonal antibodies, vaccines, the immune system, and/or other medical conditions.  Results from research 
done with your stored samples will not be in your medical record or reported to you.
Some of your blood samples that are left over after all required study testing are done may be stored and used for VRC-
approved and ACTG-approved HIV-related research.
Labeling of Stored Samples: We will label your stored samples by a code (like a number).  Only the study team can 
link this code to you.  Any identifying information about you will be kept confidential as much as the law allows.  Despite 
protections, there is a small chance that information identifying you will be given to someone who should not get it.
Risks from Stored Samples: There is a risk of unplanned release of information from your medical records. The 
chance that this information will be given to an unauthorized person without your permission is very small. Possible 
problems with the unplanned release of information include discrimination when applying for insurance and employment. 
Similar problems may occur if you give information about yourself or agree to have your medical records released.
Future studies: In the future, other investigators (at NIH or outside of NIH; in the ACTG or outside of the ACTG) may 
wish to study your stored samples. When your stored samples are shared, they will be marked with a code.  Your 
samples will not have any identifying information on them.  Some information about you, such as your gender, age, 
health history, or ethnicity may also be shared with other researchers.
Any future research studies using your samples will be conducted in a way that protects the rights and privacy of study 
participants.
Your stored samples will be used only for research and will not be sold.  The research done with your materials may be 
used to develop new products in the future but you will not receive payment for such products.
Making your Choice: You can only take part in this study if you agree to let us collect, store, and use your blood 
samples in future unspecified research.  If you decide not to take part in this study, you may still take part in other 
studies at NIH.    
POSSIBLE STUDY RISKS
Risks of Blood Drawing and IV insertion: The risks of drawing from a vein and having an IV include pain, bruising, 
bleeding, lightheadedness and fainting. Rarely, infection or inflammation can occur in the skin or vein. Blood clots are 
possible risks when using an IV for blood draw.
Risks of VRC07-523LS:  This study is the first time that VRC07-523LS is being given to people with HIV infection. As of 
January 2018, the people who have received at least one dose of VRC07-523LS had no concerning reactions to the 

CONTINUATION SHEET for either:
MEDICAL RECORD
NIH 2514-1, Consent to Participate in A Clinical Research Study
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study
STUDY NUMBER:
16-I-0147
CONTINUATION:  page 7  of 10 pages
PATIENT IDENTIFICATION
CONTINUATION SHEET for either:
NIH-2514-1 (10-84)
NIH-2514-2 (10-84)
P.A.: 09-25-0099
product. VRC07-523LS may have other unknown risks or side effects We do not know if getting VRC07-523LS will affect 
how you respond to any similar monoclonal antibody against HIV. 
General risks of monoclonal antibodies: Side effects to infusions of monoclonal antibodies may include fever, chills, 
shaking, nausea, vomiting, pain, headache, dizziness, trouble breathing, high or low blood pressure, itchiness, rash, 
hives, lip or face swelling, diarrhea, racing heart or chest pain. These reactions may be related to how fast the product is 
infused. If you have symptoms while you get VRC07-523LS, tell the nurse right away. Slowing or stopping the infusion 
may help improve these symptoms. Side effects may also include reactions at the injection site, such as redness, 
bruising, and swelling. 
Some antibody products have a risk of serious allergic reactions or cytokine release syndrome that can be life-
threatening.  

Anaphylaxis is one type of allergic reaction that may happen soon after an antibody product is given.  This 
reaction can include difficulty breathing, low blood pressure, hives or rash, swelling in the mouth and face.   

Serum sickness is a delayed type of allergic reaction that may happen several days to three weeks after an 
antibody product is given.  This reaction can include hives or rash, fever, enlarged lymph nodes, muscle pains, 
joint pains, chest discomfort and shortness of breath. 

Cytokine release syndrome can happen when an antibody targets a cell protein that triggers immune cells to 
release cytokine (proinflammatory molecules in your body).
All of these reactions are very unlikely because VRC07-523LS is a fully human antibody that attacks the HIV virus, and 
not your cells. 
In addition to the possible risks that are listed above, the study products may have other side effects that we do not 
know about yet.  Taking part in this study may affect your eligibility for future studies of other investigational monoclonal 
antibodies, antibody mixtures and other similar products.
We will give you any new information about risks or other information that becomes available that may affect your 
decision to continue in the study.
Risks during Pregnancy: We do not know what effects the study products may have on a fetus or nursing infant.  
Women must agree not to get pregnant during the study. We will discuss effective birth control methods with you. If 
you are able to become pregnant, you and your partner must use reliable birth control from the time you start the 
study until you complete the last study visit. 
If you can become pregnant, you must have a pregnancy test before you enter this study. The test must show that you 
are not pregnant. You must tell the clinic staff right away if you become pregnant during this study or think that you 
might be pregnant. If you become pregnant after getting the study product, we will not collect any more blood for 
research.  However, you will be asked to continue with study follow-up visits to check on your health and to report the 
outcome of the pregnancy to us, which will be reported to the Antiretroviral Pregnancy Registry 
(http://www.apregistry.com). This report will not use your name or other information that could be used to identify 
you. 

CONTINUATION SHEET for either:
MEDICAL RECORD
NIH 2514-1, Consent to Participate in A Clinical Research Study
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study
STUDY NUMBER:
16-I-0147
CONTINUATION:  page 8  of 10 pages
PATIENT IDENTIFICATION
CONTINUATION SHEET for either:
NIH-2514-1 (10-84)
NIH-2514-2 (10-84)
P.A.: 09-25-0099
POSSIBLE BENEFITS
This study will not provide you with any direct health benefit. You and others may benefit in the future from the 
information that we learn from the study.
COSTS TO YOU FOR YOUR PARTICIPATION
There are no costs to you for taking part in this study.  You or your health insurance will have to pay for all medical costs 
for medical care that you get outside this study.  It is possible that you may have some expenses that are not covered by 
the study compensation provided.
COMPENSATION TO YOU FOR YOUR PARTICIPATION
You will be compensated for your study participation as follows:  
The compensation is $175 for outpatient scheduled visits including blood drawing. Compensation for IV product 
administration visit and follow-up blood sample collections within the first 24 hours after administration will be 
compensated at a combined amount of $600.  Compensation for timely completion of all 3 days of an electronic diary will 
be $25 total. Compensation for visits that do not include blood drawing is $75.
Total compensation for completion of the study is estimated to range from $4275 to $4300.  Actual compensation is 
based on the number and type of study visits you complete.  Your compensation will be reported to the Internal Revenue 
Service as taxable income.
REASONS FOR REMOVING YOU FROM THE STUDY WITHOUT YOUR CONSENT
You may be removed from the study for several different reasons, including:

You don't keep appointments or follow study procedures.

You get a serious illness that needs ongoing medical care.

You enroll in another research study at the same time you are in this study.

You become pregnant.

The study is stopped or canceled.
A study may be stopped or canceled by a study sponsor, a regulatory agency or by the study investigators. If this 
happens you will be told the reason why.
You may choose to stop taking part in the study at any time.  
If you received the study product before you discontinue the study early, you will be asked to continue to be part of the 
study and return for the rest of the study visits At the visits you will have some tests performed for safety monitoring, 
however samples for research purposes will not be collected.

CONTINUATION SHEET for either:
MEDICAL RECORD
NIH 2514-1, Consent to Participate in A Clinical Research Study
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study
STUDY NUMBER:
16-I-0147
CONTINUATION:  page 9  of 10 pages
PATIENT IDENTIFICATION
CONTINUATION SHEET for either:
NIH-2514-1 (10-84)
NIH-2514-2 (10-84)
P.A.: 09-25-0099
ALTERNATIVES
This study is not designed to treat or prevent HIV infection or any disease.  You may choose to not take part in this 
study. You may be eligible for other studies. Instead of being in this study you have the choice of:

Treatment with prescription drug available to you

Treatment with experimental drugs, if you qualify

No Treatment
CONFLICT OF INTEREST
The research staff are reviewed at least yearly for conflicts of interest.  You may ask the research team for additional 
information.
The National Institutes of Health, including some members of the Vaccine Research Center scientific staff, developed the 
experimental product in this research study. The results of this study could play a role in whether the FDA will approve 
the experimental product for sale at some time in the future.  If approved, the future sale of the vaccine could lead to 
payments to NIH and some NIH scientists. By U.S. law, government scientists are required to receive such payments for 
their inventions.
You will not get any money from the development or sale of the product.
This protocol may have investigators who are not NIH employees.  Non-NIH investigators are expected to follow the 
principles of the Protocol Review Guide but are not required to report their personal financial holdings to the NIH.
CLINICALTRIALS.GOV
A description of this clinical trial will be available on http://www.ClinicalTrials.gov. This web site will not include 
information that can identify you. At most, the website will include a summary of the results. You can search this 
website at any time  

CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY
MEDICAL RECORD
• Adult Patient or    • Parent, for Minor Patient
STUDY NUMBER:
16-I-0147
CONTINUATION:  page 10   of  10 pages
PATIENT IDENTIFICATION
CONSENT TO PARTICIPATE IN A CLINICAL
RESEARCH STUDY (Continuation Sheet)
•  Adult Patient or   •  Parent, for Minor Patient
NIH-2514-1 (07-09)
P.A.: 09-25-0099
File in Section 4:  Protocol Consent
OTHER PERTINENT INFORMATION
1.
Confidentiality.  When results of an NIH research study are reported in medical journals or at scientific meetings, 
the people who take part are not named and identified.  In most cases, the NIH will not release any information about 
your research involvement without your written permission.  However, if you sign a release of information form, for 
example, for an insurance company, the NIH will give the insurance company information from your medical record.  This 
information might affect (either favorably or unfavorably) the willingness of the insurance company to sell you insurance.
The Federal Privacy Act protects the confidentiality of your NIH medical records.  However, you should know that the Act 
allows release of some information from your medical record without your permission, for example, if it is required by the 
Food and Drug Administration (FDA), members of Congress, law enforcement officials, National Institute of Allergy and 
Infectious Diseases institutional review board, study monitors or other authorized people.
2.
Policy Regarding Research-Related Injuries.  The Clinical Center will provide short-term medical care for any 
injury resulting from your participation in research here.  In general, no long-term medical care or financial compensation 
for research-related injuries will be provided by the National Institutes of Health, the Clinical Center, or the Federal 
Government.  However, you have the right to pursue legal remedy if you believe that your injury justifies such action.
3.
Payments.  The amount of payment to research volunteers is guided by the National Institutes of Health policies.  
4.  Problems or Questions.  If you have any problems or questions about this study or about any research-related 
injury, contact the Principal Investigator, 
, or the Study Coordinator, 
 at 301-
451-8715.
If you have any questions about your rights as a research subject, you may call the Clinical Center Patient Representative 
at 
.
5.
Consent Document.  Please keep a copy of this document in case you want to read it again.
COMPLETE APPROPRIATE ITEM(S) BELOW:
A.
Adult Patient’s Consent
B.
Parent’s Permission for Minor Patient.
I have read the explanation about this study and have been given the 
opportunity to discuss it and to ask questions.  I hereby consent to take 
part in this study.
I have read the explanation about this study and have been given the 
opportunity to discuss it and to ask questions.  I hereby give permission 
for my child to take part in this study.  
(Attach NIH 2514-2, Minor’s Assent, if applicable.)
Signature of Adult Patient/Legal Representative
Date
Print Name
Signature of Parent(s)/Guardian
Date
Print Name
THIS CONSENT DOCUMENT HAS BEEN APPROVED FOR USE 
FROM MAY 07, 2018 THROUGH MAY 06, 2019.
Signature of Investigator
Date
Print Name
Signature of Witness
Date
Print Name