VRC 609: A Phase I, Open-Label, Dose-Escalation Study of the Safety and Pharmacokinetics of a Human Monoclonal Antibody, VRC-HIVMAB091-00-AB (N6LS), Administered Intravenously or Subcutaneously With or Without Recombinant Human Hyaluronidase PH20 (rHuPH20) to Healthy Adults
Phase: PHASE1
Conditions: HIV Antibodies
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Protocol Title: VRC 609: A Phase I, Open-Label, Dose-Escalation Study of the Safety 
and Pharmacokinetics of a Human Monoclonal Antibody, VRC-HIVMAB091-00-AB 
(N6LS), Administered Intravenously or Subcutaneously with or without recombinant 
human hyaluronidase PH20 (rHuPH20) to Healthy Adults 
 
NCT: 03538626 
 
Documents: 
· IRB-approved Protocol (v9.0 07OCT2022) - Statistical Analysis Considerations located 
in Section 6 of the Protocol  
· IRB-approved Main Informed Consent (v9.0 07OCT2022) - IRB approval date: 
31OCT2022 
· IRB-approved Supplementary Informed Consent (v8.0 07OCT2022) - IRB approval date: 
31OCT2022 
 
 
 
 

 
Page 1 of 73 
VACCINE RESEARCH CENTER 
 
Protocol VRC 609 
(18-I-0105) 
 
A PHASE I, OPEN-LABEL, DOSE-ESCALATION STUDY OF THE SAFETY AND 
PHARMACOKINETICS OF A HUMAN MONOCLONAL ANTIBODY,  
VRC-HIVMAB091-00-AB (N6LS), ADMINISTERED INTRAVENOUSLY OR 
SUBCUTANEOUSLY WITH OR WITHOUT RECOMBINANT HUMAN HYALURONIDASE 
PH20 (RHUPH20) TO HEALTHY ADULTS  
Study Product Provided by: 
National Institute of Allergy and Infectious Diseases  (NIAID),Vaccine Research Center (VRC) 
National Institutes of Health (NIH) 
Bethesda, Maryland 
Clinical Trial Sponsored by: 
NIAID, VRC 
Bethesda, Maryland 
IND Sponsored by: 
NIAID, VRC  
Bethesda, Maryland 
IND 134081 - held by VRC 
NIH Principal Investigator: Richard Wu M.D. 
VRC 
NIAID 
Version 9.0 
October 07, 2022 

Product: VRC-HIVMAB091-00-AB (N6LS)  
Protocol VRC 609, Version 9.0  
 
October 07, 2022  
 
Page 2 of 73 
 
 
TABLE OF CONTENTS 
ABBREVIATIONS .........................................................................................................................7 
PRINCIPAL INVESTIGATOR PROTOCOL SIGNATURE PAGE ...........................................10 
PRÉCIS 
 ....................................................................................................................................11 
STATEMENT OF COMPLIANCE ...............................................................................................13 
1. 
INTRODUCTION ......................................................................................................14 
1.1. 
N6LS Background ......................................................................................................14 
1.2. 
Recombinant Human Hyaluronidase PH20 (rHuPH20) .............................................15 
1.3. 
Nonclinical Experience ...............................................................................................15 
1.3.1. 
N6LS ...........................................................................................................................15 
1.3.2. 
rHuPH20 .....................................................................................................................16 
1.4. 
Clinical Experience .....................................................................................................16 
1.4.1. 
N6LS ...........................................................................................................................16 
1.4.2. 
rHuPH20 .....................................................................................................................18 
1.5. 
Rationale for the Study Design ...................................................................................18 
1.6. 
Research-specific Laboratory Assessments ................................................................19 
1.6.1. 
Pharmacokinetic (PK) Analysis ..................................................................................19 
1.6.2. 
Anti-drug Antibody (ADA) Analysis .........................................................................19 
1.6.3. 
HIV Pseudovirus Neutralization .................................................................................20 
1.6.4. 
Allotype-specific Effects ............................................................................................20 
2. 
INVESTIGATIONAL PRODUCTS ..........................................................................21 
2.1. 
N6LS (VRC-HIVMAB091-00-AB) ...........................................................................21 
2.1.1. 
Overview .....................................................................................................................21 
2.1.2. 
Manufacturing and Drug Product Production .............................................................21 
2.2. 
ENHANZETM Drug Product (EDP) ............................................................................21 
3. 
STUDY OBJECTIVES ..............................................................................................23 
3.1. 
Primary Objectives .....................................................................................................23 
3.2. 
Secondary Objectives .................................................................................................23 
3.3. 
Exploratory Objectives ...............................................................................................23 
4. 
STUDY DESIGN AND CLINICAL PROCEDURES ...............................................24 
4.1. 
Study Population .........................................................................................................25 

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4.1.1. 
Inclusion Criteria ........................................................................................................25 
4.1.2. 
Exclusion Criteria .......................................................................................................26 
4.2. 
Inclusion of Vulnerable Subjects ................................................................................26 
4.2.1. 
Participation of Children .............................................................................................26 
4.2.2. 
Participation of NIH Employees .................................................................................26 
4.2.3. 
Adult Subjects who Lack the Capacity to Consent ....................................................27 
4.3. 
Clinical Procedures and Laboratory Assays ...............................................................27 
4.3.1. 
Recruitment and Retention Strategies ........................................................................27 
4.3.2. 
Screening ....................................................................................................................27 
4.3.3. 
Enrollment, Study Days and Visit Numbers ...............................................................28 
4.3.4. 
Administration of N6LS .............................................................................................28 
4.3.5. 
Solicited Adverse Events and Clinical Follow-up ......................................................29 
4.3.6. 
Pharmacokinetics ........................................................................................................30 
4.3.7. 
Schedule of Evaluations .............................................................................................30 
4.3.8. 
Concomitant Medications ...........................................................................................30 
4.4. 
Criteria for Dose-Escalation and Repeat-Dosing .......................................................31 
4.5. 
Criteria for Subject Discontinuation from Protocol Participation ..............................32 
4.6. 
Criteria for Discontinuation of N6LS or N6LS+ rHuPH20 Administration ..............32 
4.7. 
Criteria for Pausing and Resuming the Study .............................................................32 
5. 
SAFETY AND ADVERSE EVENTS ........................................................................34 
5.1. 
Adverse Events ...........................................................................................................34 
5.2. 
Serious Adverse Events ..............................................................................................34 
5.3. 
Adverse Event Reporting to the IND Sponsor ...........................................................35 
5.4. 
IND Sponsor Reporting to the FDA ...........................................................................35 
5.5. 
Reporting to the Institutional Review Board ..............................................................35 
5.5.1. 
Unanticipated Problem (UP) Definition .....................................................................36 
5.5.2. 
Non-Compliance Definition .......................................................................................36 
5.5.3. 
Protocol Deviation Definition .....................................................................................37 
5.5.4. 
Death ...........................................................................................................................37 
5.5.5. 
New Information .........................................................................................................37 
5.5.6. 
Suspension or Termination of Research Activities ....................................................38 
5.5.7. 
Expedited Reporting to the IRB .................................................................................38 

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5.5.8. 
Annual Reporting to the IRB ......................................................................................38 
6. 
STATISTICAL CONSIDERATIONS .......................................................................39 
6.1. 
Overview .....................................................................................................................39 
6.1.1. 
Treatment Assignments ..............................................................................................39 
6.2. 
Sample Size Considerations .......................................................................................39 
6.3. 
Statistical Analysis ......................................................................................................40 
6.3.1. 
Analysis Variables ......................................................................................................40 
6.3.2. 
Baseline Characteristics ..............................................................................................40 
6.3.3. 
Safety Analysis ...........................................................................................................40 
6.3.4. 
Tolerability Evaluation ...............................................................................................41 
6.3.5. 
Pharmacokinetics Analysis .........................................................................................41 
6.3.6. 
Interim Analyses .........................................................................................................42 
7. 
PHARMACY PROCEDURES ...................................................................................43 
7.1. 
Study Product and Administration Regimen ..............................................................43 
7.2. 
N6LS (VRC-HIVMAB091-00-AB) Vialed Product ..................................................43 
7.3. 
EDP Vialed Product ....................................................................................................43 
7.4. 
Temperature Excursions .............................................................................................44 
7.5. 
Preparation of Study Product(s) (N6LS ± rHuPH20) for Administration ..................44 
7.5.1. 
N6LS: Preparation for IV Administration ..................................................................45 
7.5.2. 
N6LS: Preparation for SC Administration .................................................................45 
7.5.3. 
N6LS with rHuPH20: Preparation for SC Administration via Infusion Pump ..........46 
7.5.4. 
Handling of Prepared Product for IV or SC Administration: N6LS and 
N6LS+rHuPH20 .........................................................................................................46 
7.6. 
Labeling of Study Product ..........................................................................................47 
7.7. 
Study Product Accountability .....................................................................................47 
7.8. 
Study Product Disposition ..........................................................................................47 
8. 
HUMAN SUBJECT PROTECTIONS AND ETHICAL OBLIGATIONS................48 
8.1. 
Informed Consent .......................................................................................................48 
8.2. 
Risk/Benefit Assessment ............................................................................................48 
8.2.1. 
Potential Risks ............................................................................................................48 
8.2.2. 
Benefits .......................................................................................................................49 
8.3. 
Institutional Review Board .........................................................................................49 
8.4. 
Subject Confidentiality ...............................................................................................50 

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8.5. 
Plan for Use and Storage of Biological Samples ........................................................50 
8.5.1. 
Use of Samples, Specimens and Data .........................................................................50 
8.5.2. 
Storage and Tracking of Blood Samples and Other Specimens .................................51 
8.5.3. 
Disposition of Samples, Specimens and Data at Completion of the Protocol ............51 
8.5.4. 
Loss or Destruction of Samples, Specimens or Data ..................................................51 
8.6. 
Subject Identification and Enrollment of Study Subjects ...........................................51 
8.7. 
Costs ...........................................................................................................................51 
8.8. 
Compensation .............................................................................................................51 
8.9. 
Safety Monitoring .......................................................................................................52 
9. 
ADMINISTRATIVE AND LEGAL OBLIGATIONS ..............................................53 
9.1. 
Protocol Amendments and Study Termination ...........................................................53 
9.2. 
Study Documentation and Storage .............................................................................53 
9.3. 
Clinical Monitoring, Data Collection and Data Sharing ............................................53 
9.3.1. 
Clinical Monitoring Plan ............................................................................................53 
9.3.2. 
Data Collection ...........................................................................................................54 
9.3.3. 
Source Documents ......................................................................................................54 
9.3.4. 
Data Sharing ...............................................................................................................54 
9.4. 
Language .....................................................................................................................54 
9.5. 
Policy Regarding Research-Related Injuries ..............................................................54 
10. 
REFERENCES ...........................................................................................................55 
APPENDIX I: SCHEDULE OF EVALUATIONS .......................................................................57 
APPENDIX II:  ASSESSMENT OF RELATIONSHIP TO STUDY PRODUCT AND 
TABLE FOR GRADING SEVERITY OF ADVERSE EVENTS .............................72 
 
 
 

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LIST OF TABLES 
Table 1: 
VRC 609 Study Schema .............................................................................................24 
Table 2: 
Schema for Dose-escalation and Repeat-Dosing PSRT Data Reviews ......................31 
Table 3: 
Event Probabilities for Different Scenarios ................................................................39 
Table 4: 
95% Confidence Intervals of the True Rate for All Possible Number of 
Observed Events within a Dose Group .......................................................................40 
 
 
 
 
 
 

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ABBREVIATIONS 
Abbreviation 
Term 
ADA 
anti-drug antibody 
ADL 
activities of daily living 
AE 
adverse event 
AIDS 
Acquired Immunodeficiency Syndrome 
ALT 
alanine aminotransferase 
AoU 
Assessment of Understanding 
ART
antiretroviral therapy 
AST 
aspartate aminotransferase 
AUC 
area under the curve 
bNAb 
broadly-neutralizing human monoclonal antibody 
CFR  
Code of Federal Regulations 
cGMP 
current Good Manufacturing Practice 
CL 
clearance 
Cmax 
maximum concentration 
CRS 
cytokine release syndrome  
DP 
drug product 
DS 
drug substance 
ECL 
electrochemiluminescence 
EDP 
ENHANZE® Drug Product 
ELISA 
enzyme-linked immunosorbent assay 
EOI 
end of infusion; end of injection 
F 
bioavailability 
FBS
Fetal Bovine Serum 
FDA
Food and Drug Administration 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practice 
HA  
hyaluronan 
HCL
hydrochloric acid 
HIV
human immunodeficiency virus 
HLA 
human leukocyte antigen 
HRPP 
Human Research Protections Program 
IB 
Investigator’s Brochure 
ICF
informed consent form 
ICH 
International Conference on Harmonisation 

Product: VRC-HIVMAB091-00-AB (N6LS)  
Protocol VRC 609, Version 9.0  
 
October 07, 2022  
 
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Abbreviation 
Term 
IgG1 
Immunoglobulin G1 
IND
investigational new drug application 
IRB 
Institutional Review Board 
IV 
intravenous 
kg 
kilogram 
LIMS 
Laboratory Information Management System 
MAb 
monoclonal antibody 
MedDRA 
Medical Dictionary for Regulatory Activities 
mcg 
microgram 
mg 
milligram 
mL 
milliliter 
mM, mmol 
millimole 
MO 
medical officer 
MSD 
Meso Scale Discovery 
N6LS 
Antibody directed against the CD4-binding site of the HIV-1 envelope 
trimer 
NHP
Non-human primate 
NIAID 
National Institute of Allergy and Infectious Diseases 
NIH
National Institutes of Health 
NIH CC 
National Institutes of Health Clinical Center 
OHRP 
Office for Human Research Protections 
PBS
phosphate buffered saline 
PCR 
polymerase chain reaction 
PI 
Principal Investigator 
PK 
pharmacokinetic 
PSRT 
Protocol Safety Review Team 
PT 
preferred term 
Q
Inter-compartmental clearance 
QA 
quality assurance 
PH20 
posterior head protein 20 
rHuPH20  
recombinant human hyaluronidase PH20 
SAE 
serious adverse event 
SC 
subcutaneous 
SHIV 
simian-human immunodeficiency virus 
SOC 
system organ class 
SOE 
Schedule of Evaluation 

Product: VRC-HIVMAB091-00-AB (N6LS)  
Protocol VRC 609, Version 9.0  
 
October 07, 2022  
 
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Abbreviation 
Term 
SUSAR 
serious and unexpected suspected adverse reaction 
T½ 
half-life 
TCR 
tissue cross reactivity 
Tmax 
time of maximal concentration (Cmax) 
TMB 
3,3’,5,5’-Tetramethylbenzidine 
ULN 
upper limit of normal 
UNAIDS 
Joint United Nations Programme on HIV/AIDS 
UP 
unanticipated problem 
USP 
United States Pharmacopeia 
Vd 
volume of distribution 
VIP 
Vaccine Immunology Program 
VRC 
Vaccine Research Center 
WBC 
white blood cell 
β-HCG 
human chorionic gonadotropin 
λz
terminal slope of concentration vs time profile 
 
 
 

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PRINCIPAL INVESTIGATOR PROTOCOL SIGNATURE PAGE 
 
VRC 609: A Phase I, Open-Label, Dose-Escalation Study of the Safety and 
Pharmacokinetics of a Human Monoclonal Antibody, VRC-HIVMAB091-00-AB (N6LS), 
Administered Intravenously or Subcutaneously with or without recombinant human 
hyaluronidase PH20 (rHuPH20) to Healthy Adults  
 
I, the Principal Investigator for the study site indicated above, agree to conduct the study in full 
accordance with the provisions of this protocol and all applicable protocol-related documents.  I 
agree to conduct the study in compliance with United States (US) Health and Human Services 
(HHS) regulations (45CFR 46); applicable US Food and Drug Administration (FDA) 
regulations; standards of the International Conference on Harmonization Guidelines for Good 
Clinical Practice (E6); Institutional Review Board/Ethics Committee (IRB/EC) determinations; 
all applicable in-country, state, and local laws and regulations; and other applicable requirements 
(e.g., US National Institutes of Health) and institutional policies. I will comply with all 
requirements regarding the obligations of investigators as outlined in the Statement of 
Investigator (Form FDA 1572), which I have also signed. 
I agree to maintain all study documentation pertaining to the conduct of this study, including but 
not limited to, case report forms, source documents, laboratory test results, and medication 
inventory records, for at least 2 years following submission of a marketing application to FDA 
(21 CFR 312.62).  If no marketing application is filed, or if the application is not approved, the 
records will be retained for two years after the investigation is discontinued and the FDA is 
notified.  The HHS protection of human subjects’ regulations require that institutions retain 
records of IRB/EC activities and documentation of informed consent of subjects for at least 3 
years after study completion (45 CFR 46).  No study records will be destroyed without prior 
authorization from VRC/NIAID.  Publication of the results of this study will be governed by the 
VRC/NIAID policies. Any presentation, abstract, or manuscript will be made available by the 
investigators to VRC Leadership for review prior to submission. 
I have read and understand the information in this protocol and will ensure that all associates, 
colleagues, and employees assisting in the conduct of the study are informed about the 
obligations incurred by their contribution to the study. 
 
 
Richard Wu, MD_______________    NIH-Clinical Center Vaccine Evaluation Clinic 
Name/Title of Principal Investigator       Study Site Name 
 
 
___________________________________   __________________________________ 
Signature of Principal Investigator                  Date 
 
 
 

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PRÉCIS 
 
 
VRC 609: 
A Phase I, Open-Label, Dose-Escalation Study of the Safety and Pharmacokinetics 
of a Human 
Monoclonal Antibody, VRC-HIVMAB091-00-AB (N6LS), 
Administered Intravenously or Subcutaneously with or without Recombinant 
Human Hyaluronidase PH20 (rHuPH20) to Healthy Adults 
Study 
Design:   
This is the first study in healthy adults of the N6LS monoclonal antibody (MAb). 
It is a dose-escalation study to examine safety, tolerability, dose, and 
pharmacokinetics (PK) of N6LS administered intravenously (IV) and 
subcutaneously (SC) to healthy adults. For SC administration, N6LS will be 
administered alone or coadministered with the permeation enhancer rHuPH20 
enzyme. Primary hypotheses are that N6LS administration to healthy adults will 
be safe by the IV and SC routes, alone and with rHuPH20 coadministration.  A 
secondary hypothesis is that all N6LS administrations will be detectable in human 
sera with a definable half-life. 
Product 
Description:
N6LS (VRC-HIVMAB091-00-AB ) is a human MAb targeted to the HIV-1 CD4 
binding site. It was developed by the VRC/NIAID/NIH and manufactured under 
current Good Manufacturing Practice (cGMP) regulations at the VRC Vaccine 
Pilot Plant operated under contract by the Vaccine Clinical Materials Program 
(VCMP), Leidos Biomedical Research, Inc., Frederick, MD. The product is 
provided as a sterile aqueous buffered solution in 10 mL glass vials at a 
concentration of 100 mg/mL and volume of 6.25 mL.  
Each vial of ENHANZETM Drug Product (EDP) contains 0.5 mL of rHuPH20 
formulated at a concentration of 1 mg/mL (~110,000 U/mL rHuPH20). rHuPH20 
is a tissue permeability modifier that depolymerizes hyaluronan (HA), increasing 
the dispersion of a substance into the subcutaneous space, which enables SC 
deliveryofco‐administeredantibody(-ies) at higher dose volumes  (e.g., >10 mL) 
that cannot be administered quickly without rHuPH20. EDP is manufactured by 
Ajinomoto Althea, Inc, (San Diego, CA) for Halozyme Therapeutics, Inc. (San 
Diego, CA) and is supplied in 2 mL glass vials as a sterile, single-dose, injectable 
liquid.  
Subjects: 
Healthy adults, 18-50 years of age. 
Study 
Plan: 
This open-label study includes 8 dose groups to assess N6LS alone given as a 
single IV infusion at the 5, 20, or 40 mg/kg dose level (Groups 1, 3,4); a single SC 
injection at the 5 mg/kg dose level (Group 2); or in 3 administrations, spaced 12 
weeks apart by SC injection at the 5 mg/kg dose level (Group 5), or by IV infusion 
at the 20 mg/kg dose level (Group 6). Two additional groups will assess N6LS 
given as a single SC injection mixed with rHuPH20 (2000 U/mL) at 5 mg/kg 
(Group 7) or 20 mg/kg (Group 8) doses. Enrollment opened with Groups 1, 2 and 
5; and was followed by the sequential activation of Groups 3, 4, and 6. With 
implementation of the two SC N6LS+ rHuPH20  arms as a protocol amendment, 
Group 7 will open first to accrual, followed by Group 8.  

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VRC 609 Study Schema 
Group Subjects 
Study Products 
Dosing Schedule 
N6LS Dose 
& Route 
rHuPH20 
Dose 
Day 0 
Week 12 Week 24 
1 
3 
5 mg/kg IV 
- 
X 
 
 
2 
3 
5 mg/kg SC 
- 
X 
 
 
3 
3 
20 mg/kg IV 
- 
X 
 
 
4 
3 
40 mg/kg IV 
- 
X 
 
 
5 
5 
5 mg/kg SC 
- 
X 
X 
X 
6 
5 
20 mg/kg IV 
- 
X 
X 
X 
7 
5 
5 mg/kg SC 
2000 U/mL 
X 
 
 
8 
5 
20 mg/kg SC 2000 U/mL 
X 
 
 
Total 
32* 
* The expected enrollment is  32 subjects.  Enrollment up to a total of 40 
subjects is permitted if additional subjects are necessary for safety or PK 
evaluations. 
IV = Intravenous; SC = subcutaneous 
Note: rHuPH20 and N6LS are mixed and administered by SC infusion. The dose of rHuPH20 is
2000 Units per mL relative to the N6LS dose volume. 
Study 
Duration:   
Study participation will be approximately 24 weeks for subjects in Groups 1 to 4, 
7 and 8; and 48 weeks for subjects in Groups 5 and 6.  
 
 

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STATEMENT OF COMPLIANCE 
 
The trial will be carried out in accordance with International Council on Harmonisation Good 
Clinical Practice (ICH GCP) and the following:  
• United States (US) Code of Federal Regulations (CFR) applicable to clinical studies (45 
CFR Part 46, 21 CFR Part 50, 21 CFR Part 56, 21 CFR Part 312, and/or 21 CFR Part 812)  
National Institutes of Health (NIH)-funded investigators and clinical trial site staff who are 
responsible for the conduct, management, or oversight of NIH-funded clinical trials have 
completed Human Subjects Protection and ICH GCP Training. 
The protocol, informed consent form(s), recruitment materials, and all participant materials will 
be submitted to the Institutional Review Board (IRB) for review and approval.  Approval of both 
the protocol and the consent form must be obtained before any participant is enrolled.  Any 
amendment to the protocol will require review and approval by the IRB before the changes are 
implemented to the study.  In addition, all changes to the consent form will be IRB-approved; a 
determination will be made regarding whether a new consent needs to be obtained from 
participants who provided consent, using a previously approved consent form. 
 

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1. 
INTRODUCTION  
1.1. 
N6LS Background 
The human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) has 
remained a major global public health problem since the discovery of the virus in 1983. Reports 
by the Joint United Nations Programme on HIV/AIDS (UNAIDS) estimate that 76.1 million 
people have been infected with HIV since the start of the epidemic, contributing to 35 million 
deaths from AIDS-related illnesses [1]. Despite these statistics, global incidences of new HIV 
infections have actually declined from peak rates in the mid-1990s; a reduction attributed in part 
to increased availability of antiretroviral therapy (ART) and the effective execution of 
prevention/treatment programs such as those that target mother-to-child transmission.   
Unfortunately HIV infection is extremely complex and none of the current therapeutic or 
prophylactic regimens can completely prevent or cure an infection or induce a full recovery of 
the host immune system. Thus, novel prevention and cure strategies are being investigated. 
The VRC/NIAID is investigating clinical applications of broadly-neutralizing human 
monoclonal antibodies (bNAbs) that bind the HIV-1 envelope protein [2-5]. Such antibodies 
block infection of target cells in vitro, and have been shown to prevent infection of non-human 
primates (NHP) in in vivo models for HIV [6-8].Through advances in B-cell immunology 
utilizing single-cell cloning methods, next-generation sequencing, high throughput 
computational analysis techniques, and increased cell culture survivability procedures, an 
extensive group of HIV-1 bNAbs have been isolated. These include antibodies with specificities 
to the CD4 binding site (VRC01 [9], VRC07-523LS [5], 3BNC117 [10]); the high-mannose 
patch (10-1074 [11], PGT121 [12]); the V2 apex (PG9 [13, 14], PGDM1400 [12],  CAP256.25 
[15]); and the membrane-proximal external region (10E8 [3, 16]).  Another HIV-1 specific 
bNAb identified as N6 was recently isolated from a patient with a 21-year known history of 
HIV-1 infection that was controlled in the absence of ART [2].  
N6 was characterized for IgG germline identity, recombination, and somatic hypermutation 
changes, and compared extensively to other HIV-1 bNAbs for epitope/paratope mapping and 
neutralization breadth and potency [2].  Analyses showed N6 belongs to the VRC01 class of 
CD4 binding site-directed bNAbs, which block HIV infection by occluding the binding site for 
the cellular receptor CD4. VRC01 and many members of the VRC01 class are broadly cross-
reactive, however N6 is the best in class to date [2]. N6 employs two novel mechanisms to 
achieve unprecedented breadth and potency.  First, the angle at which N6 binds to the CD4 
molecule is tilted relative to other MAbs in this class,  enabling it to retain robust binding 
regardless of changes in the adjacent HIV envelop V5 loop (a region known to cause steric 
clashes, decreased binding capacity, and reduced neutralization breadth and potency).  Secondly, 
mutations in the variable gp120 V5 loop that may diminish N6 contact are offset by increased 
contacts to the conserved D loop mediated by the addition of novel amino acid sequences within 
the antibody.  Moreover, comparison ribbon structures of N6 and VRC01 show  how mutations 
and insertions in HIV-1 gp120 that likely render VRC01 ineffective by inducing steric 
hindrances against certain HIV isolates are resolved by the positional changes exerted by N6 [2].   
In order to improve the pharmacokinetics of N6, two amino acid substitutions (methionine to 
leucine and an asparagine to serine M428L/N434S, that collectively yielded N6LS) were 

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introduced within the C-terminus of the heavy chain constant region of N6 via site-directed 
mutagenesis to increase its binding affinity for the neonatal Fc-receptor (FcRn). Incorporation of 
the LS mutations did not affect the neutralization breadth or potency of N6LS compared to N6 
[2]. Based on preclinical and clinical studies of passively administered VRC01LS and VRC07-
523LS [8, 17, 18], the LS modification is expected to result in enhanced recirculation and longer 
plasma half-life of N6LS relative to the wild-type Ab. 
N6LS is being developed for the prevention of HIV-1 infection in uninfected adults and for 
treatment of HIV-1 infection in infected adults. VRC 609 is the first-in-human study to evaluate 
the safety, tolerability, and pharmacokinetics of this antibody.  
1.2. 
Recombinant Human Hyaluronidase PH20 (rHuPH20)  
Recombinant human hyaluronidase PH20 (rHuPH20) enzyme optimizes theSCdeliveryofco‐
administered therapeutics by depolymerizing hyaluronan (HA) in the extracellular matrix of the 
SC space that normally serves to restrict bulk fluid flow. ENHANZETM Drug Product (EDP) is 
an investigational ready to use injectable drug product that contains 1 mg/mL (110,000 U/mL) 
recombinant human hyaluronidase PH20 (rHuPH20). rHuPH20 is the active ingredient of the 
commercial product Hylenex® recombinant (hyaluronidase human injection), hereafter referred 
to as HYLENEX (150 U/mL of rHuPH20), which has been FDA-approved since 2005 for 
subcutaneous fluid administration for achieving hydration, to increase the dispersion and 
absorption of other injected drugs, and in subcutaneous urography for improving resorption of 
radiopaque agents. Product administration once limited to IV infusion because of volume limits, 
can now use rHuPH20 to facilitate SC injections with advantages such as reduced administration 
time, decreased number of individual injections at administration, and delivery of higher product 
dosages/dose volumes.  
Published reports have shown additional beneficial effects of rHuPH20 when co-administered 
with a therapeutic agent (antibody, protein), such as improved absorption, increased 
bioavailability, and reduced pharmacokinetics (PK) variability of certain agents [19, 20].  
Importantly, the local permeability barrier tissue changes induced by rHuPH20 are reversible 
within 24-48 hoursafteradministration,withoutanyinflammatoryorhistologicalchanges [21].  
This Phase 1 study will be the first to evaluate the safety, tolerability, and pharmacokinetics of 
N6LS coadministered with rHuPH20 by SC infusion in healthy adults.   
1.3. 
Nonclinical Experience  
1.3.1. 
N6LS 
The N6/N6LS antibodies have been evaluated in pseudovirus neutralization assays to assess for 
breadth and potency against Clades A, B, C, and AG viruses; lipid and tissue cross-reactivity 
studies to assess for binding to antigenic determinants in a full panel of normal human and 
Sprague-Dawley rat tissues and selected tissues from neonatal human donors; and proof-of-
concept immunotherapy studies of SHIV-infected rhesus macaques. Results showed N6 
demonstrated superior neutralization and breath when assessed in parallel comparisons with a 
panel of HIV-specific bNAbs. Specifically, N6 was able to neutralize 98% of viruses within a 
181-pseudovirus panel at an IC50 threshold of 50 mcg/mL and 96% at an IC50 threshold of 1 

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mcg/mL. N6 neutralized 16 of 20 VRC01-resistant pseudoviruses, further demonstrating its 
extraordinary neutralization breadth and potency [2]. Additionally, N6 neutralized 98% of 
pseudoviruses in an extended panel of 173 clade C pseudoviruses at an IC50 <50 mcg/mL and a 
median IC50 of 0.066 mcg/mL.   
Lipid or tissue cross reactivity (TCR) studies have not shown any strong evidence of 
toxicologically relevant self-reactivity. Minimal binding of N6LS to cardiolipin and mild 
reactivity with Hep-2 cells were observed in vitro. Moreover, in an activated partial 
thromboplastin time assay, which is a surrogate assay used to detect phospholipid binding, 
N6LS-spiked sera did not have a prolonged activated thromboplastin time when compared to 
positive and negative controls. A single Good Laboratory Practice (GLP) TCR study using a full 
panel of normal human and Sprague-Dawley rat tissues and selected tissues from neonatal 
human donors showed only limited staining with N6LS: extracellular staining in vascular smooth 
muscle of the walls of hyalinized vessels in the human uterus and cytoplasmic staining in the 
root sheath of hair follicles in rat skin. No membrane specific binding was observed suggesting 
that there is no cross-reactivity of toxicologic concern. Overall, the cumulative N6LS binding 
profile to the antigenic determinants examined closely resembles that elicited by the VRC01 
class of HIV-1 bNAbs.   
Passive immunization of chronically simian-human immunodeficiency virus (SHIV)-infected 
rhesus macaques with N6LS resulted in transient viremia control, the extent and duration of 
which appeared to correlate with N6LS plasma levels and baseline plasma viremia levels before 
N6LS treatment. 
A repeat dose single GLP toxicology study in male and female Sprague-Dawley rats was 
conducted to assess the safety of three repeat-dose administrations, 10 days apart of N6LS at 
three dose-levels (4, 40, or 400 mg/kg) intravenously or at two dose-levels (5 or 50 mg/kg), 
subcutaneously and to evaluate the toxicity and reversibility of adverse effects after a 35-day 
recovery period. The study also included a PK analysis through 56 days-post first product 
exposure to measure N6LS levels after passive immunization with low and high IV and SC 
antibody dosages. Please refer to the Investigator’s Brochure (IB) for additional information. 
1.3.2. 
rHuPH20 
The specific nonclinical pharmacology, pharmacokinetic, and toxicity studies evaluating 
rHuPH20 are summarized in the rHuPH20 IB, Section 4.  
1.4. 
Clinical Experience  
1.4.1. 
N6LS 
As of August 4, 2021, 27 subjects have enrolled into Groups 1-8. A total of 22 out of 23 subjects 
enrolled in Groups 1-6 received N6LS study product administrations and completed the protocol. 
One subject in Group 2 terminated the study after enrolling but prior to product administration. 
The N6LS product has been administered to 14 subjects by IV infusion and 12 subjects by SC 
injection. Unsolicited AEs were reported by 16/26 (62%) subjects that received N6LS, with the 
most frequent events of upper respiratory tract infection (URTI) reported by 6 subjects (23%) 
and diarrhea reported by 4 subjects (15%). All unsolicited events were mild or moderate in 

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severity except for one grade 3 diarrhea that began 4 days after administration, spontaneously 
resolved 2 days later, and was determined to be possibly related to N6LS.  
Solicited systemic symptoms were reported in 4/14 (29%) subjects following IV administration 
and 3/12 (25%) subjects following SC administration. Symptoms reported after IV 
administration included 4 events of mild headache, 1 mild event each of malaise, chills, and 
nausea.  Symptoms reported after SC administration included 1 mild event each of malaise, 
myalgia, headache, and nausea. No fevers occurred after IV or SC administration. 
Solicited local symptoms reported included moderate bruising (1/14 subjects, 7%) following IV 
administration. Solicited local symptoms after SC administration included mild pain/tenderness 
(9/12 subjects, 75%), mild to moderate swelling (4/12 subjects, 33%), mild to severe redness 
6/12 subjects, 50%), and mild pruritus (3/12 subjects, 25%).  
A study pause occurred on 7/23/2021 after criteria for a pause was met due to two Grade 3 
injection site erythema events not resolving during the solicited diary card reporting period. A 
Group 7 (5 mg/kg SC N6LS + 2000 U rHuPH20/mL) subject developed injection site erythema 
to a maximum diameter of 13 cm which resolved after 30 days. A Group 8 (20 mg/kg SC N6LS 
+ 2000 U rHuPH20/mL) subject developed injection site erythema to a maximum of 20 cm 
which resolved after 7 days. Since the episodes of Grade 3 erythema observed in both individuals 
were well tolerated, not accompanied by any other symptoms or lab abnormalities that would 
indicate potential systemic toxicity, and resolved without clinical sequelae, the erythema was 
judged to not represent an increased safety risk for study participants. Therefore, the study pause 
was lifted on 7/28/2021. In addition, the PSRT determined that the protocol would not need to be 
paused for future events of the same type and severity.   
Data cleaning and analysis are currently ongoing for Groups 7 and 8 in preparation for the 
database lock.  
Additional clinical experience is derived from other bNAbs such as VRC01, VRC01LS, and 
VRC07-523LS, with reactivity to the CD4-binding site of the HIV envelop protein and 
administered at the same doses, dose-schedules, and routes proposed in this study in healthy 
adults [9, 18, 22, 23]. Overall, Phase 1 and 2 trials with VRC MAbs have shown they are 
generally well-tolerated, with no deaths or serious adverse events assessed as related by the 
Sponsor reported. Local reactogenicity observed with IV administration of CD4-binding site 
mAbs to adults has included pain/tenderness, bruising, swelling, and localized erythema at the 
site of infusion that resolved within a few minutes to a few hours after the administration. Most 
participants reported no systemic reactogenicity symptoms with VRC01 IV administration; when 
observed, systemic solicited symptoms were of mild or moderate severity, started 1-3 days after 
administration of study product and lasted 1-2 days, with malaise/fatigue, myalgias, headaches 
and mild nausea being most common. There have been no severe solicited reactogenicity 
symptoms related to VRC01 IV injections.   
SC administration of CD4-binding site mAbs has been well tolerated in adults and infants.  Most 
study participants had either no local reactogenicity or  local symptoms limited to injection site 
pain and/or tenderness, redness, and mild localized pruritus (itchiness). Most local symptoms 
resolve within the first days after product administration. In some cases moderate to severe 
erythema at the injection site have lasted up to six weeks post product administration before 
resolving without clinical sequelae.  

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Preliminary N6LS PK data showed the maximum serum concentrations (Cmax) occurred within 
the first few hours after IV administration, and approximately 6 days following SC 
administration. The mean (±SD) Cmax values after a single administration of N6LS were 28±10 
µg/mL for the 5 mg/kg SC dose, 101+23 µg/mL for the 5 mg/kg IV dose, 589±236 µg/mL for 
the 20 mg/kg IV dose, and 1717±51 µg/mL for the 40 mg/kg IV dose.  
Preliminary mean (±SD) C28D serum concentrations after the first administration of N6LS were 
15±6.1 µg/mL, 32±2.3 µg/mL, 96±25.4 µg/mL, and 43±1.3 µg/mL for the 5 mg/kg SC, 5mg/kg 
IV, 20 mg/kg IV, and 40 mg/kg IV doses, respectively. 
1.4.2. 
rHuPH20 
As of December 2021, 1,592 subjects were exposed to HYLENEX and other rHuPH20 drug 
products in 30 clinical studies conducted under IND 66,888, or in post-marketing Phase 4 
studies. In partnered trials with co-administered therapeutics, more than 9000 subjects were 
exposed. Individual doses of rHuPH20 ranged from 15 to 96,000 U (See rHuPH20 IB, section 
5.1).  
Across all Halozyme-sponsored studies, SC injections of rHuPH20 have been well-tolerated in 
healthy subjects, dehydrated pediatric subjects, hospice and palliative care subjects, subjects with 
type 1 and 2 diabetes, and subjects with rheumatoid arthritis. SC injections of rHuPH20 alone or 
in combination with hydration fluids (Lactated Ringer’s, normal saline), co-injected small 
molecules (morphine, ceftriaxone, ondansetron), peptides (insulin, and insulin analogs), and  
proteins (IgG and adalimumab) have been well-tolerated in all clinical trials [21, 24]. Most AEs 
were mild, transient injection site reactions, including erythema, pain, bruising, pruritus, burning, 
tenderness, edema, induration, irritation, paresthesia, numbness, and rash. Moderate injection site 
reactions, which have occurred less frequently, include burning, erythema, pain, and numbness. 
Mild-to-moderate headache was also commonly reported. 
rHuPH20 is currently co-formulated with four approved anticancer therapies, trastuzumab 
(HERCEPTIN HYLECTATM/Herceptin® SC) PHESGOTM (pertuzumab/trastuzumab), Darzalez 
FASPROTM (daratumumab), and rituximab (i.e., RITUXAN HYCELA®/RITUXAN® 
SC/MabThera® SC) and dosed sequentially with human immunoglobin to treat primary 
immunodeficiency (HyQvia®/HYQVIA®). 
1.5. 
Rationale for the Study Design 
Animal and in vitro models of HIV infection have suggested bNAbs reactive to antigenically 
diversified Env proteins expressed by quasispecies of circulating virus may hold significant 
promise as immunoprophylactic and/or therapeutic agents to thwart the subversive effects of 
HIV on the immune system. N6LS can mediate extraordinary breadth and potency against 
various HIV isolates, including strains traditionally resistant to other antibodies in this class. 
Moreover, its potency may indicate less antibody is required to mediate an effect, offering the 
possibility of subcutaneous administration as a more feasible approach to immunoprophylaxis. 
The introduction of the LS site-directed mutation to increase FcRn binding affinity is postulated 
to result in increased antibody half-life and persistence at biologically higher concentrations in 
the plasma, as was shown for VRC01LS and VRC07-523LS [8, 17, 18].   

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This study is the first-in-human trial to evaluate the safety of a single- or three, repeat-dose 
regimen of N6LS administered intravenously or subcutaneously. The study will also evaluate the 
feasibility of larger SC dose volumes (>2.5 mL) of N6LS administration facilitated by rHuPH20. 
The dosages selected for evaluation of N6LS are based on prior experience with another CD4-
binding site antibody VRC01, which was shown in two clinical trials (VRC 601 and VRC 602 
[22, 23]) to be safe and well-tolerated at 5-40 mg/kg dosages given intravenously and at a 5 
mg/kg dosage given subcutaneously in both HIV-infected and -uninfected adult populations.  
While Groups 1 through 4 will receive a single dose of N6LS by SC injection or IV infusion, 
Groups 5 and 6 will be administered three-repeat doses of N6LS at 12-week intervals (i.e., on 
Weeks 0, 12, and 24). A 12-week interval for repeat-dosing has been used in clinical trials with 
VRC01LS [18] and VRC07-523LS [25]. Groups 7 and 8 will receive a single 5 or 20 mg/kg dose 
of N6LS co-mixed with rHuPH20 by SC infusion (Refer to the pharmacy manual for study 
product preparation and administration instructions).  Aligning the antibody dose levels and 
administration interval with that used in the current and prior studies with other HIV-1 bNAbs 
will allow for a direct comparison of the serum concentration of each bNAb at identical time-
points. This in turn will support pharmacokinetic (PK) profile comparisons and characterization 
of the bNAbs currently in development by the VRC. The PK of N6LS administered using 
different regimens, dosages, and routes is also being evaluated in healthy adults aged 18 to 50 
years.      
1.6. 
Research-specific Laboratory Assessments 
The research assays described in this section are designed to characterize the investigational 
product rather than assess the health of the subjects. Laboratory assessments in this Phase 1 study 
will include PK analysis, evaluation for anti-drug antibody (ADA) development following 
product exposure, and ex vivo analysis to assess the neutralization activity of N6LS post-
injection/infusion.  
The VRC’s Vaccine Immunology Program (VIP), Gaithersburg, MD, will process blood and 
store coded samples, and will either perform sample testing or ship coded samples to designated 
research laboratories at the VRC or other approved collaborators.  Some immunogenicity assays 
may be performed by VRC laboratories in Bethesda, MD, or by approved contract laboratories or 
research collaborators.  See Appendix I for schedules, volumes and tube types to be used for 
research sample collection.  Tube types for clinical laboratory evaluations and research 
collections are selected according to institutional requirements and are shown in the Schedule of 
Evaluations to estimate blood volumes.  Different tubes may be used to meet site requirements. 
Samples will be transported according to approved site procedures. 
1.6.1. 
Pharmacokinetic (PK) Analysis  
The N6LS concentration for the PK analysis will be measured by a Meso Scale Discovery 
(MSD) or similar assay [22]. 
1.6.2. 
Anti-drug Antibody (ADA) Analysis  
A three-level algorithm will be used to screen, confirm, and functionally characterize ADA to 
N6LS and rHuPH20 in clinical serum and plasma samples collected at baseline (day 0), Week 4 
(Day 28), and Week 8 (Day 56) for groups 1-4, and Groups 7-8.  For groups 5-6, ADA is 

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analyzed at baseline (Day 0), Week 4 (Day 28), Week 28 (Day 196),  and Week 32 (Day 224).  
Analysis will be conducted according to the Food and Drug Administration (FDA) guidance 
[26]. Screening and confirmation will involve a Meso Scale Discovery (MSD) 
electrochemiluminescence (ECL) bridging or similar assay [22].   
Tier 1 and 2 N6LS ADA assays are qualified and method development to functionally 
characterize ADA activity in clinical serum samples that also contain N6LS (tier 3 assay) is 
ongoing and not presently available. However, the stored clinical serum samples will be tested 
once the assay is qualified.  
1.6.3. 
HIV Pseudovirus Neutralization   
For all study groups, subject sera collected (but not limited to) at baseline (Day 0), 48 hours post-
administration, and at Day 84 may be evaluated to assess the functional capacity of passively 
administered N6LS to neutralize pseudotyped HIV viruses using an in vitro cell-based virus 
neutralization assay such as previously described for VRC01, VRC01LS, and VRC07-523LS  [2, 
22, 23, 25, 27].  
1.6.4. 
Allotype-specific Effects 
Exploratory evaluation  to detect for theoretical immunoglobulin G1 (IgG1) allotype-specific 
effects may be performed in cases when PK measures suggest a reduced N6LS antibody half-life 
or an ADA response [28-30]. Coded stored samples will be used for evaluation of the genetic 
sequence of the immunoglobulin heavy chain constant region allotype.  
 
 

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2. 
INVESTIGATIONAL PRODUCTS 
This protocol will evaluate the use of two investigational products: the antibody N6LS and 
rHuPH20, the active pharmaceutical ingredient in EDP. A summary of the manufacturing 
process for N6LS is provided in this section. Please refer to the rHuPH20 IB, Section 3 for 
additional information on rHuPH20 and EDP. Refer to the pharmacy manual for product 
preparation and administration guidance.  
2.1. 
N6LS (VRC-HIVMAB091-00-AB)  
2.1.1. 
Overview 
The N6LS antibody binds to the CD4-binding site of HIV-1 gp120 protein and contains a 
methionine to leucine (L) and asparagine to serine (S) (M428L/N434S, referred to as (LS) 
change within the C-terminus of the heavy chain constant region to increase its binding affinity 
for the neonatal Fc receptor (FcRn) [31]. The antibody is expressed as a recombinant IgG1 
antibody in a Chinese Hamster Ovary (CHO) mammalian cell line, CHO-DG44, and is 
manufactured under current Good Manufacturing Practices (cGMP) by VRC/NIAID/NIH at the 
VRC Pilot Plant operated under contract by the Vaccine Clinical Materials Program, Leidos 
Biomedical Research, Inc., Frederick, MD.  Specific manufacturing information is included in 
the IB. Quality Assurance (QA) lot release testing by the manufacturer and ongoing stability 
programs verify the continued conformance to product specifications and justification of use 
prior to, and during conduct of the clinical trial.  
2.1.2. 
Manufacturing and Drug Product Production  
Drug substance (DS) is manufactured under cGMP using a stable transfected CHO-DG44 cell 
line. Purification steps include an initial harvest by membrane-based clarification and 
diafiltration into chromatography buffer, followed by protein-A affinity chromatography, low pH 
treatment of the eluate, and anion exchange membrane chromatography. The eluate is then 
subjected to a 20 nm virus reduction filtration step, followed by concentration and diafiltration 
into the final formulation buffer, prior to filtering with a 0.22μm-filter. The DS concentration is 
determined and filled into containers for storage at≤-65°C until further formulation is required.   
The N6LS DS is diluted to a concentration of 100 mg/mL in formulation buffer composed of 10 
mM Sodium Citrate, 50 mM Sodium Chloride, 150 mM Arginine-HCl, and 0.002% Polysorbate-
80 (PS-80) at pH 6.5 to generate the drug product (DP). The product is filled into 10 mL single-
use glass vials at a concentration of 100 ± 10 mg/mL and volume of 6.25 ± 0.10 mL. The drug 
product (DP) should be stored at -35°C to -15°C.   
More details on the N6LS composition and manufacturing can be found in the IB. 
2.2. 
ENHANZETM Drug Product (EDP) 
Recombinant human hyaluronidase PH20 (rHuPH20) is the active ingredient of the 
investigational ENHANZE™ Drug Product (EDP). rHuPH20 is produced by genetically 
engineered Chinese hamster ovary (CHO) cells containing a deoxyribonucleic plasmid encoding 
a soluble fragment of human hyaluronidase PH20. The purified hyaluronidase glycoprotein 
contains 444-447 amino acids with an approximate molecular weight of 61,000 Daltons.  

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EDP, manufactured by Ajinomoto Althea, Inc. (San Diego, CA) for Halozyme, Inc. (San Diego, 
CA), is a purified preparation of rHuPH20 supplied in glass vials as a sterile, clear, colorless, 
non-preserved, ready-for-use solution. Each mL contains ~110 kU of rHuPH20. The solution has 
a pH of approximately 6.5 and contains 130 mM sodium chloride, 10 mM L-histidine 
hydrochloride as a buffer, and 10 mM L-methionine, 0.02% w/w PS80. The solution is filled to 
0.5 mL in a 2 mL glass vial and should be stored as labeled, either at -20°C ± 5°C or 5°C ± 3°C 
and protected from light. 
More details on rHuPH20 and EDP are provided in the rHuPH20 IB (Edition 10.0, February 04, 
2022). 
 
 

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3. 
STUDY OBJECTIVES  
3.1. 
Primary Objectives 
• To evaluate the safety and tolerability of N6LS administered as a single dose at 5 
mg/kg IV, 20 mg/kg IV, 40 mg/kg IV, or 5 mg/kg SC to healthy adults. 
• To evaluate the safety and tolerability of N6LS administered at 5 mg/kg SC or 20 
mg/kg IV by repeat dosing every 12 weeks for a total of 3 injections/infusions in 
healthy adults. 
• To evaluate the safety and tolerability of a single 5 or 20 mg/kg SC dose of N6LS 
coadministered with rHuPH20 in healthy adults. 
3.2. 
Secondary Objectives 
• To evaluate the pharmacokinetics of N6LS at each dose level through 24 weeks after 
the last dose. 
• To determine whether anti-drug antibody (ADA) to N6LS can be detected in sera of 
N6LS recipients at specific timepoints throughout the study. 
3.3. 
Exploratory Objectives 
• To evaluate for evidence of functional activity of N6LS in samples collected during 
the study at specific timepoints. 
• To assess for IgG1 allotypes by polymerase chain reaction (PCR) and evaluate for 
allotype-specific effects on N6LS pharmacokinetics. 
 
 

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4. 
STUDY DESIGN AND CLINICAL PROCEDURES 
This is an open-label, dose-escalation study to examine the safety, tolerability, dose, and PK of  
N6LS in healthy adults. As shown in the study schema in Table 1, subjects in Groups 1 to 4 will 
receive a single dose of N6LS at the 5, 20, or 40 mg/kg dose level; subjects in Groups 5 and 6 
will receive repeat dosing of N6LS every 12 weeks for a total of 3 injections at the 5 mg/kg dose 
level or 3 infusions at the 20 mg/kg dose level, respectively; subjects in Groups 7 and 8 will 
receive a single dose of N6LS at the 5 mg/kg and 20 mg/kg dose level (respectively) co-
administered with rHuPH20 (2000 U/mL) via SC infusion.  
If enrolled into Groups 1, 4, 7 and 8 subjects will be expected to be available for follow-up visits 
through 24 weeks of study participation. Subjects enrolled into Groups 5 and 6 will be expected 
to be available for follow-up visits through 48 weeks of study participation. 
Table 1:
VRC 609 Study Schema 
Group 
Subjects 
Study Products 
Dosing  Schedule 
N6LS Dose 
and Route 
 rHuPH20 
Dose 
Day 0 
Week 12 
Week 24 
1 
3 
5 mg/kg IV 
- 
X 
 
 
2 
3 
5 mg/kg SC 
- 
X 
 
 
3 
3 
20 mg/kg IV 
- 
X 
 
 
4 
3 
40 mg/kg IV 
- 
X 
 
 
5 
5 
5 mg/kg SC 
- 
X 
X 
X 
6 
5 
20 mg/kg IV 
- 
X 
X 
X 
7 
5 
5 mg/kg SC 
2000 U/mL 
X 
 
 
8 
5 
20 mg/kg SC 2000 U/mL 
X 
 
 
Total 
32* 
* A total of  32 subjects are planned for enrollment. However, up to 40 subjects may 
be enrolled to replace subjects who fail to complete the assigned dosing regimen and to 
meet requests for additional pharmacokinetic (PK) and/or new safety evaluations. 
IV = Intravenous; SC = subcutaneous 
Note: rHuPH20 and N6LS are mixed and administered by SC infusion. The dose of rHuPH20 is 2000 Units per mL 
relative to the N6LS dose volume. Refer to the pharmacy manual for study product preparation and 
administration instructions.   
Enrollment began with the 5 mg/kg dose groups (Groups 1, 2,  and 5) when the protocol opened 
to accrual. Enrollments into the subsequent dose groups (Groups 3, 4, and 6) proceeded after 
dose-escalation reviews as described in Section 4.3. With implementation of the two N6LS+ 
rHuPH20 groups as a protocol amendment, Group 7 will open first to accrual, followed by 
Group 8 pending a dose-escalation review.  For each dose level and administration route with or 
without rHuPH20, the study team will wait at least 3 days following the first product 
administration before the same dose and administration route of N6LS is administered to 
additional subjects.  Safety review decisions and the status of the enrollment process will be 
transparent to the Protocol Safety Review Team (PSRT) throughout the trial and discussed 

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during the weekly and/or monthly safety review. The composition of the PSRT is discussed in 
Section 8.8. 
Safety laboratory samples will be collected throughout the study as per the Schedule of 
Evaluations (SOE) shown in Appendix I.  Subjects will keep a daily diary of solicited systemic 
symptoms for 3 days after each product administration.  PK samples will be collected at specified 
intervals through 24 weeks after the subject’s last product administration.  
The study will be conducted at the Vaccine Evaluation Clinic located at the NIH Clinical Center 
(NIH CC). 
4.1. 
Study Population 
All inclusion and exclusion criteria must be met for eligibility. 
4.1.1. 
Inclusion Criteria 
A subject must meet all of the following criteria: 
1. Willing and able to complete the informed consent process. 
2. 18 to 50 years of age.  
3. Based on history and examination, must be in good general health and without history of any 
of the conditions listed in the exclusion criteria. 
4. Willing to have blood samples collected, stored indefinitely, and used for research purposes. 
5. Able to provide proof of identity to the satisfaction of the study clinician completing the 
enrollment process. 
6. Screening laboratory criteria within 84 days prior to enrollment must meet the following 
criteria: 
• White blood cell count (WBC): 2,500-12,000/mm3. 
• WBC differential: Within institutional normal range or accompanied by the Principal 
Investigator (PI) or designee approval. 
• Platelets: 125,000 – 400,000/mm3. 
• Hemoglobin: Within institutional normal range or accompanied by PI or designee 
approval. 
• Creatinine:≤1.1xUpperLimitofNormal(ULN). 
• ALT:≤1.25xULN. 
• AST:≤1.25xULN.  
• Negative for HIV infection by an FDA approved method of detection. 
Female-Specific Criteria: 
7. If a woman is of reproductive potential and sexually active with a male partner, then she agrees 
to use an effective means of birth control from the time of study enrollment until the last study 
visit, or to be monogamous with a partner who has had a vasectomy. 

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8. 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 subject will be excluded if one or more of the following conditions apply: 
1. Prior receipt of licensed or investigational monoclonal antibody. 
2. Weight > 115 kg. 
3. Any history of a severe allergic reaction with generalized urticaria, angioedema or anaphylaxis 
within the 2 years prior to enrollment that has a reasonable risk of recurrence during the study. 
4. Hypertension that is not well controlled. 
5. Woman who is breast-feeding, or planning to become pregnant during the study participation.  
6. Receipt of any investigational study agent within 28 days prior to enrollment. 
7. Any other chronic or clinically significant medical condition that in the opinion of investigator 
would jeopardize the safety or rights of the subject including (but not limited to): diabetes 
mellitus type I, chronic hepatitis; OR clinically significant forms of drug or alcohol abuse, 
asthma, autoimmune disease, infectious disease, psychiatric disorders, heart disease, or cancer. 
8. Known hypersensitivity to hyaluronidase or any of the excipients in EDP. 
4.2. 
Inclusion of Vulnerable Subjects 
4.2.1. 
Participation of Children 
Children are not eligible to participate in this clinical trial because the study agent 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. 
4.2.2. 
Participation of NIH Employees 
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 FAQs for NIH Staff Who are Considering Participation in 
NIH Research ” published by Office of Human Research Subjects Protections on Research 
Involving NIH Staff as Subjects, Policy 404.  
For NIH employee subjects, consent will be obtained by an individual who is independent of the 
employee’s team.  If an NIH staff member seeks to enroll in research taking place within their 
own work unit or conducted by any of their supervisors, the employee will be: 
• Informed that neither participation nor refusal to participate as a research subject will 
have an effect, either beneficial or adverse, on the subject’s employment, training or 
position at the NIH, 
• When possible, consent should be obtained by an individual in a non-supervisory 
relationship with the subject, and 

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• When consent is conducted, a third party (e.g. a consent monitor) will be included 
through the Bioethics Consultation Service or another party independent of the research 
team or, if a consent monitor is not available, the consent process will be observed by 
another qualified investigator on the study who is independent of the NIH staff member’s 
work unit and not a supervisor to the NIH staff member.  If no such person exists, 
consent observation may be performed by any qualified investigator on the study.  
Protocol study staff will be trained on obtaining potentially sensitive and private 
information from co-workers or subordinates.  
4.2.3. 
Adult Subjects who Lack the Capacity to Consent 
Adults who are unable to provide initial informed consent are not eligible to enroll. Also, adults 
who permanently lose the capacity to provide on-going consent after initial consent and during 
the study will be discontinued from protocol participation as it is described in Section 4.5 
4.3. 
Clinical Procedures and Laboratory Assays 
Evaluation of study product safety for this study will include laboratory studies, medical history, 
and physical assessment by clinicians, and subject self-assessment on a diary card for 3 days 
after product administration.  The study schedule is provided in the Schedule of Evaluations, 
Appendix I.  Total blood volume drawn from each subject will comply with the NIH CC 
Guidelines, which is available on the NIH intranet at the following link: http://cc-
internal.cc.nih.gov/policies/PDF/M95-9.pdf. 
4.3.1. 
Recruitment and Retention Strategies  
Study enrollments will be conducted at the NIH Clinical Center. Study subjects will be recruited 
through the VRC’s screening protocol, VRC 500 (NCT 01375530). The on-site and off-site 
Institutional Review Board (IRB)-approved advertising will be implemented. Per a recruitment 
plan described in the VRC 500 protocol, efforts will be made to include women and minorities in 
proportions similar to that of the community from which they are recruited. 
4.3.2. 
Screening  
All screening procedures for this study are described and will be completed through the Vaccine 
Research Center’s screening protocol, VRC 500 (NIH 11-I-0164) used for all VRC IND studies 
conducted at the NIH Clinical Center.  The Recruitment Plan per NIH Policy 302 for all VRC 
studies can be found in the NIH IRB approved VRC 500 protocol. Subjects will be recruited 
through Institutional Review Board (IRB)-approved advertising.  Screening evaluations 
performed to determine eligibility for study participation will include medical history review, 
physical exam, and the clinical laboratory tests as detailed in the Schedule of Evaluations, 
Appendix I). No screening procedures will be done under protocol VRC 609.  
Additional assessments of health may be conducted at screening based on clinical judgment.  
Screening evaluations for specific eligibility criteria must be completed within the time interval 
specified prior to enrollment for the given parameter and may be repeated, as needed, to confirm 
eligibility.  
Blood samples for research can be drawn at any time during the screening period and are not 
required to be repeated if outside the screening period. Informed consent documents will be 

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reviewed.  Counseling related to potential risks of the study product, pregnancy prevention and 
HIV risk-reduction will be performed.  An Assessment of Understanding (AoU) will be 
completed in association with enrollment into VRC 609.  Screening records will be kept to 
document the reason why an individual was screened but not enrolled.  
4.3.3. 
Enrollment, Study Days and Visit Numbers 
In this study, enrollment is defined as the assignment of a study identification number and study 
group schedule in the clinical database.  A clinician will discuss the target dates and timing of the 
study product administration(s) and sample collections before completing an enrollment to help 
ensure that the subject can comply with the projected schedule.  
Day 0 is defined as the day of first N6LS administration.  Day 0 may occur on the same day as 
enrollment or up to 6 weeks after enrollment.  This period may be increased with PI approval.  If 
Day 0 does not coincide with enrollment, then the enrollment day may be referred to by a 
negative number of days (i.e., Day -1 to Day -42).  For calculating elapsed days following Day 0, 
each subsequent calendar date is labeled by the next sequential “Study Day” as shown in the 
Schedule of Evaluations (Appendix I).  Since there may be more than one 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 first study product administration are the 
baseline for subsequent safety assessments. 
4.3.4. 
Administration of N6LS 
All study product administrations will be completed according to the assigned group. For women 
of childbearing potential, a negative pregnancy test must be obtained prior to product 
administration that day. Refer to the pharmacy manual for study product preparation and 
administration instructions.  
Prior to each product administration, temperature, blood pressure, heart rate (pulse) and weight 
will be recorded and a targeted physical examination will be conducted.  All subjects will be 
observed for 4 hours after the first product administration.  Subjects in the multi-dose groups will 
be observed for at least 2 hours after the second and third product administrations.  
IV Administration 
If a subject is assigned to an IV administration group, the IV access will be placed in an arm vein 
in an aseptic manner.  A different site may be used for collection of PK blood samples; however, 
the same site may be used after flushing the line if another site is not available.  N6LS will be 
administered with approximately 100 mL of normal saline IV (as described in the IB) over about 
15-30 minutes, with a target of 30 minutes for the initial infusion for each subject. Infusions 
lasting longer than 30 minutes are allowed. If the subject experiences side effects during the 
infusion, the rate of infusion may be slowed or stopped to alleviate the symptoms.   
SC Administration without rHuPH20 
If a subject is assigned to a SC administration group, the SC administration site(s) to be used 
must be assessed as acceptable by the clinician and the subject.  The preferred SC administration 

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site is the abdomen, but the upper arm or thigh may be used.  Given the weight criterion in this 
study, the maximum volume needed to administer a 5 mg/kg SC dose is not expected to exceed 
5.75 mL.  The SC dose will be administered by standard needle in a maximum volume of about 
2.5 mL per injection site.  Up to 4 SC injection sites may be used if deemed necessary by the 
clinician.  SC administration sites should be at least 2 inches apart. 
SC Administration with rHuPH20 
If a subject is assigned to a SC administration group, the SC administration site(s) to be used 
must be assessed as acceptable by the clinician and the subject.  The preferred SC administration 
site is the abdomen. N6LS will be mixed with rHuPH20 in the pharmacy and then administered 
via standard Medfusion 3500 syringe pump (or equivalent) in one infusion site at a rate of no 
more than 3 mL/minute. Given the weight criterion in this study, the maximum volume needed 
to administer a 20 mg/kg SC dose is not expected to exceed 23.42 mL. If the subject experiences 
side effects during the infusion, the rate of infusion may be slowed or stopped to alleviate the 
symptoms. Procedures for all N6LS preparations and administrations are described in Section 7.  
4.3.5. 
Solicited Adverse Events and Clinical Follow-up 
Subjects will be given a 3-day diary (paper or electronic-based), a thermometer, and a measuring 
tool. The subjects will use the diary daily as a memory aid to record their highest temperature, 
local and systemic symptoms, and concomitant medications taken for 3 days after any product 
administration. Subjects will be provided training on diary completion, proper thermometer 
usage, and the use of the measuring tool to measure injection site bruising, swelling and redness. 
Completion of diary card training will be noted in the source documents. Note that while the 
electronic diary is preferred, subjects will have the option to use a paper diary instead. The paper 
diary if used, will be transcribed into the study database and stored in the subject file for 
monitoring purposes. 
The signs and symptoms solicited by diary will include systemic events of unusually 
tired/feeling unwell, muscles aches (outside the injection site), headache, chills, nausea and joint 
pain; and local (at the product administration site) events of pain/tenderness, swelling, redness, 
bruising, and pruritus. Subjects will record their highest measured temperature daily for 
assessment of fever and largest measured diameter of redness, swelling, and bruising at the 
injection site.  Subject diaries will be reviewed by a clinician for accuracy and completeness at 
follow-up visits. No attribution assessment will be performed for solicited events reported in the 
diary. Clinicians will follow and collect resolution information for any reactogenicity symptoms 
that are not resolved within 3 days. 
Diary card data will be available in real-time for subjects who use the electronic diary. The 
clinician may contact the subject by phone if any moderate or severe side effect is reported. 
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 (ADL) 
(such as those consistent with Grade 2 or higher impairment). Additionally, arthralgia or 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.  Throughout the study, clinicians will also assess subjects for 

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any changes in symptoms.  Any new or concerning symptoms will be fully assessed to include 
specialty consultation at the NIH Clinical Center as indicated clinically.  
4.3.6. 
Pharmacokinetics   
PK samples will be collected as close as reasonably possible to the target timepoints.  However, 
actual time of collection is critical for PK analysis and will be recorded for all samples.  The PK 
timepoints are shown in the Schedule of Evaluations (Appendix I). 
4.3.7. 
Schedule of Evaluations 
The Schedule of Evaluations (Appendix I) provides details on the study schedule and the 
permitted visit windows.  Schedule 1 is for the IV dose escalation groups receiving one infusion 
(Groups 1, 3, and 4). Schedule 2 is for the SC dose group receiving one injection (Group 2).  
Schedule 3 and Schedule 4 are for the groups receiving repeat dosing: Group 5 (5 mg/kg SC) and 
Group 6 (20 mg/kg IV), respectively.  Schedule 6 is for the N6LS+ rHuPH20 SC dose groups 
receiving one infusion at N6LS dose levels of 5 mg/kg (Group 7) or 20 mg/kg (Group 8). After 
enrollment, deviations from the visit windows are discouraged but will be permitted at the 
discretion of the PI or designee; and will be recorded as protocol deviations.  
If product administration is discontinued for a Group 5 or 6 subject assigned to receive repeat 
product administrations, then the study schedule may be modified and the subject will be 
followed for 24 weeks after the last product administration received. Schedule 5 of the SOE 
outlines this altered schedule. Briefly, subjects will be followed according to the assigned group 
visit schedule until the 12th week after their last product administration where they will complete 
the protocol according to Schedule 5 starting at Visit 11 for those who received only one product 
administration or Visit 17 for those who received two product administrations.  
Additional visits and blood draws may be scheduled during the study if needed to assess subject 
safety or for sample collection for immunological testing.  After study completion, subjects may 
be invited to participate in one of the VRC sample collection protocols (VRC 200 or VRC 900) 
for follow-up sample collection. 
Any evaluation for an AE or possible exacerbation of a pre-existing condition may be evaluated 
at study team discretion as a “protocol related” evaluation. 
4.3.8. 
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 (AE) that requires 
expedited reporting or the development of a new chronic condition requiring ongoing medical 
management will be recorded in the database.  Receipt of a FDA-approved vaccine at any time 
during the study will be recorded in the database (clinicians should work with subjects regarding 
the timing of licensed vaccines relative to study product administration).  Otherwise, 
concomitant medications taken throughout the study will be recorded in the subject’s chart as 
needed for general medical documentation but will not be recorded in the database.  

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4.4. 
Criteria for Dose-Escalation and Repeat-Dosing 
Dose groups will be enrolled sequentially in a staged manner, depending on the outcome of 
planned PSRT Data Reviews. These reviews will determine if dose-escalation to the next higher 
N6LS dose level may occur, and if 2nd and 3rd doses (repeat-dosing) may be administered to 
applicable dose groups (Table 2). Whenever possible and as data are available, PSRT Data 
Reviews for dose-escalation and repeat-dosing will be held concurrently as follows:    
Table 2: 
Schema for Dose-escalation and Repeat-Dosing PSRT Data Reviews 
Data Review  
Objective
Minimum Evaluable  
Safety Data* 
Favorable  
Review Outcome 
Review #1
• Dose-escalation 
from 5 to 20 mg/kg IV 
 
• Repeat-dosing at 5 
mg/kg SC 
• All post-administration safety data from Day 0 
through at least the “Day 14” visit in at least 3 
subjects in Group 1.   
• All post-administration safety data from Day 0 
through at least the “Day 14” visit in at least 3 
subjects in Group 2 or 5.   
• Proceed with enrollments 
into Groups 3 and 6. 
 
• Proceed with second and 
third doses in Group 5. 
Review #2
• Dose-escalation from 
20 to 40 mg/kg IV 
 
• Repeat-dosing at 20 
mg/kg IV 
• All post-administration safety data from Day 0 
through at least the “Day 14” visit in at least 3 
subjects in Group 3 or 6.   
 
• Proceed with enrollments 
into Group 4. 
 
• Proceed with second and 
third doses in Group 6 
Review #3 
• Dose-escalation 
from 5 to 20 mg/kg 
N6LS with rHuPH20 
by SC infusion 
• All post-administration safety data from Day 0 
through at least the “Day 14” visit in at least 3 
subjects in Group 7 
• Proceed with enrollments 
into Group 8. 
If the first product administration is not completed or there are discontinuations from the study 
before there are sufficient data to conduct the dose escalation review, then extra subjects may be 
enrolled in order to have the requisite data on at least 3 subjects at the dose level and route being 
evaluated. Additionally, AEs assessed as related to the study product at the time of a dose-
escalation review may be judged by the PSRT to warrant adding additional subjects at a given 
dose group. 
The IRB will be provided with documentation of the safety review process and notification of 
the dose-escalation.  Consultation with the IRB and notification of the FDA, if needed, as per 
study pause criteria (Section 4.6) will occur if indicated by the review.  One outcome of a dose-
escalation review may be to recommend evaluation of additional subjects at the current dose and 
reassess for safety before proceeding to a higher dose. 

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4.5. 
Criteria for Subject Discontinuation from Protocol Participation 
A subject may be discontinued from protocol participation for the following reasons: 
• Subject voluntarily withdraws; 
• The IND Sponsor or regulatory authorities stop the study;  
• The PI assesses that it is not in the best interest of the subject to continue participation 
in the study; or 
• Severe non-compliance as determined by the PI. 
4.6. 
Criteria for Discontinuation of N6LS or N6LS+ rHuPH20 
Administration 
Under certain circumstances, a subject may be prohibited from receiving further study product 
administrations. These include: 
• Pregnancy (female subjects only); 
• Grade 3 adverse event assessed as related to N6LS or N6LS+rHUPH20 (with the 
exception that self-limited Grade 3 solicited reactogenicity will not require 
discontinuation of product administration); 
• Grade 4 adverse event assessed as related to N6LS or N6LS+rHUPH20;  
• Immediate hypersensitivity reaction associated with N6LS or N6LS+rHUPH20; 
• Intercurrent illness that is not expected to resolve prior to the next scheduled study 
product administration AND for which PI (or designee) believes is in the best interest 
of the subject to restrict further exposure;  
• Repeated failure to comply with protocol requirements;  
• Co-enrollment into a study to receive another investigational research product prior to 
completion of the requisite study follow-up following the last N6LS product 
administration; 
• The IND sponsor or the study PI decide to terminate the study; 
• The IRB, Office for Human Research Protections (OHRP) or the FDA halt the study. 
Subjects who have received at least one dose of N6LS but have been discontinued from further 
study product administrations, will continue with follow-up as shown in the Schedule 5 of the 
SOE with the exception that research sample collections will be discontinued for pregnant 
women or others in which it is contraindicated.     
4.7. 
Criteria for Pausing and Resuming the Study  
Administration of either study product (N6LS or N6LS+ rHuPH20) and new enrollments will be 
paused by the PI if any of the following criteria is met:  
• One (or more) subject experiences a serious adverse event (SAE) that is assessed as 
related (possible, probably, or definitely) to the study product, or 

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• Two (or more) subjects experience the same Grade 3 or higher AE that is assessed 
as related (possible, probably, or definitely) to study agent (other than self-limited 
Grade 3 AEs that resolve during the solicited reactogenicity period). 
In the event of a pause, the IND Sponsor Medical Officer (MO) and the PSRT will be promptly 
notified.  
Plan for Review of Pauses and Resuming Rules:   
Study product administration and enrollments would resume only if review of the AEs that 
caused the pause results 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 Medical Officer (MO), with 
participation by the PI, will conduct the review and make the decision to resume, 
amend or close the study. The IRB and FDA will be notified accordingly. 
• Pauses for Grade 3 or higher related AEs: The IND Sponsor MO, in consultation 
with the PI, will conduct the review and make the decision to resume, amend or close 
the study for the Grade 3 or higher AEs that meet 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 or higher pause reviews and of the IND Sponsor’s 
decisions. 
 
 

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5. 
SAFETY AND ADVERSE EVENTS 
5.1. 
Adverse Events 
An adverse event (AE) is any untoward or unfavorable medical occurrence in a human subject, 
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.   
Severity of AEs will be assessed using the DAIDS Table for Grading the Severity of Adult and 
Pediatric Adverse Events, Corrected Version 2.1 [July 2017]. Available from: https://rsc.tech-
res.com/docs/default-source/safety/division-of-aids-(daids)-table-for-grading-the-severity-of-
adult-and-pediatric-adverse-events-corrected-v-2-1.pdf. Additional information can be found in 
Appendix II. This grading scale has been used in all prior studies with other HIV-1 bNAbs and 
will allow for a direct comparison of safety across all available HIV-1 bNAbs. 
Reporting of all AEs will occur during the period from first study product administration through 
56 days after each study product administration. After this through completion of study 
participation only serious adverse events (SAEs) and new chronic medical conditions that require 
ongoing medical management will be recorded as AEs in the study database. 
When a subject who receives N6LS coadministered with rHuPH20 experiences an AE assessed 
by the investigator as related to study product, this attribution reflects relatedness to N6LS and 
not rHuPH20. Any differences in safety and tolerability between the 5 mg/kg SC N6LS dose 
without rHuPH20 and 20 mg/kg N6LS SC dose with rHuPH20 will be interpreted as a dose-
response difference of N6LS delivered subcutaneously. The extant experience with rHuPH20 
indicates that rHuPH20 itself does not confer a unique set of AEs and this protocol will not 
specifically evaluate rHuPH20 itself for safety and tolerability.  
5.2. 
Serious Adverse Events 
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 AE that at occurrence represents an immediate risk of death to a 
subject. It does not include an adverse event or suspected adverse reaction that, had it occurred in 
a more severe form, might have caused death. Similarly, a hospital admission for an elective 
procedure is not considered a SAE.  

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5.3. 
Adverse Event Reporting to the IND Sponsor 
AEs that meet SAE criteria must be reported and submitted by the clinical site on an expedited 
basis to the IND Sponsor, VRC/NIAID/NIH, according to Sponsor guidelines as follows:  
• Results in death 
• Is life threatening 
• Results in persistent or significant disability/incapacity 
• Requires unplanned inpatient hospitalization or prolongation of existing 
hospitalization 
• Is a congenital anomaly/birth defect in the offspring of a study subject 
• Is an important medical event that may jeopardize the subject or may require 
intervention to prevent one of the other outcomes listed above.  
In addition, any event, regardless of severity, which in the judgment of an investigator represents 
a SAE, may be reported on an expedited basis. 
An investigator will communicate an initial SAE report within 24 hours of site awareness of 
occurrence to the IND sponsor by email to the VRC Protocol Operations Office.  
A written report by the investigator should be submitted to the IND Sponsor within 3 working 
days.  In order for the IND Sponsor to comply with regulations mandating sponsor notification of 
specified SAEs to the FDA within 7 and/or 15 calendar days, the investigator must submit 
additional information as soon as it is available. 
5.4. 
IND Sponsor Reporting to the FDA 
The IND Sponsor is responsible for making the determination of which SAEs are “serious and 
unexpected suspected adverse reactions” (SUSARs) as defined in 21 CFR 312.32. 
• Suspected adverse reaction means any adverse event for which there is a reasonable 
possibility that the drug caused the adverse event. 
• Unexpected Adverse Event means an AE that is not listed in the IB or is not listed at 
the specificity or severity that has been observed.   
All SUSARs (as determined by the IND Sponsor) will be reported to the FDA as IND Safety 
Reports; IND Safety Reports will also be provided to the IRB. 
The IND Sponsor will also submit an IND Annual Report of the progress of the investigation to 
the FDA as defined in 21 CFR 312.32. 
5.5. 
Reporting to the Institutional Review Board 
The following information is consistent with NIH IRB Policy 801: Reporting Research Events, 
Version 1, effective July 1, 2019.  
Reportable Event - An event that occurs during the course of human subject research that 
requires notification to the IRB. 
For the purposes of this policy, reportable events include the following: 

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• Unanticipated Problems (UPs) involving risks to subjects or others, 
• Non-compliance (including major protocol deviations and noncompliance that is not 
related to a protocol deviation), 
• Deaths related or possibly related to research activities, and 
• New information that might affect the willingness of subjects to enroll or continue 
participation in the study. 
5.5.1. 
Unanticipated Problem (UP) Definition 
An unanticipated problem (UP) is defined as any incident, experience, or outcome that meets all 
of the following criteria: 
• Unexpected (in terms of nature, severity, or frequency) given (a) the research 
procedures that are described in the protocol-related documents, such as the IRB- 
approved research protocol and informed consent document; and (b) the 
characteristics of the subject population being studied; and 
• Related or possibly related to participation in the research (possibly related means 
there is a reasonable possibility that the incident, experience, or outcome may have 
been caused by the procedures involved in the research); and 
• Suggests that the research places subjects or others (which may include research staff, 
family members or other individuals not directly participating in the research) at a 
greater risk of harm (including physical, psychological, economic, or social harm) 
related to the research than was previously known or expected. 
A UP must be reported within 7 calendar days of an investigator becoming aware of the actual or 
suspected UP. 
5.5.2. 
Non-Compliance Definition 
Non-compliance is the failure of investigator(s) to follow the applicable laws, regulations, or 
institutional policies governing the protection of human subjects in research, or the requirements 
or determinations of the IRB, whether intentional or not.   
Non-compliance may be unintentional (e.g. due to lack of understanding, knowledge, or 
commitment), or intentional (e.g. due to deliberate choice to ignore or compromise the 
requirements of any applicable regulation, organizational policy, or determination of the IRB). 
Non-compliance is further characterized as serious or continuing as follows:  
• Serious non-compliance - Non-compliance, whether intentional or not, that results in harm 
or otherwise materially compromises the rights, welfare and/or safety of the subject. Non-
compliance that materially affects the scientific integrity or validity of the research may be 
considered serious non-compliance, even if it does not result in direct harm to research 
subjects.  
•  Continuing non-compliance– A pattern of recurring non-compliance that either has 
resulted, or, if continued, may result in harm to subjects or otherwise materially 
compromise the rights, welfare and/or safety of subjects, affect the scientific integrity of 

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the study or validity of the results.  The pattern may comprise repetition of the same non-
compliant action(s), or different noncompliant events.   
Any actual or suspected non-compliance by any investigator or entity associated with the 
protocol must be reported to the IRB by the PI/designee within 7 calendar days of any 
investigator or individual associated with the protocol first becoming aware. 
5.5.3. 
Protocol Deviation Definition 
A protocol deviation is defined as any change, divergence, or departure from the IRB-approved 
research protocol and is further characterized as major and minor as follows: 
• Major Deviations – Deviations from the IRB approved protocol that have, or may 
have the potential to, negatively impact, the rights, welfare or safety of the subject, or 
to substantially negatively impact the scientific integrity or validity of the study.  
• Minor Deviations – Deviations that do not have the potential to negatively impact the 
rights, safety, or welfare of subjects or others, or the scientific integrity or validity of 
the study.   
For the reporting purposes, failure of subjects to comply with the research protocol does not 
represent non-compliance unless that failure is due to an action or omission of a member of the 
research team, for example, the failure to give adequate instruction to the subject. 
A major deviation must be reported within 7 calendar days of an investigator becoming aware of 
an actual or suspected deviation.  Although PDs are also non-compliance, these should only be 
reported once as deviations.  Major deviations resulting in death must be reported within 24 
hours of the occurrence of the event or of any member of the study team becoming aware of the 
death.   
Researchers are responsible for monitoring their studies throughout the year for adherence to the 
IRB-approved protocol.  The purpose of this monitoring is to identify major deviations and to 
look for trends in minor deviations that may indicate a systemic issue in how the study is being 
conducted that could potentially negatively impact the rights, safety, or welfare of participants or 
the study’s ability to produce scientifically valid results.  A series of minor deviations pointing 
toward a more global issue that could affect the rights, safety or welfare of the participant or 
affect the validity of the study should be reported as a major deviation.  In all other instances, a 
summary of minor deviations should be provided to the IRB at the time of continuing review. 
5.5.4. 
Death 
Any death of a research subject that is possibly, probably or definitely related to the research 
must be reported within 24 hours of an investigator becoming aware of the death. 
5.5.5. 
New Information  
New information that might affect the willingness of a subject to enroll or remain in the study 
should be reported within 7 calendar days of an investigator first becoming aware.  

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5.5.6. 
Suspension or Termination of Research Activities 
Any suspension or termination of research activities, including holds on new enrollment, placed 
upon the research by the study sponsor, NIH or IC leadership, or any regulatory agency must be 
reported within 7 calendar days of an investigator becoming aware. 
5.5.7. 
Expedited Reporting to the IRB 
Death related to research must be reported within 24 hours. 
The following will be reported within 7 calendar days of investigator awareness:  
• Actual or suspected UPs; 
• Actual or suspected non-compliance; 
• Actual or suspected Major PDs; 
• SAEs that are actual or suspected UPs; 
• New information that might affect the willingness of a subject to enroll or remain in 
the study; 
Suspension or termination of research activities, including holds on new enrollment, placed upon 
the research by the study sponsor, NIH or IC leadership, or any regulatory agency.  
5.5.8. 
Annual Reporting to the IRB 
 
The following will be reported to the IRB in summary at the time of Continuing Review: 
• Summary of UPs and non-compliance; 
• AEs, including SAEs, that are not UPs, as a narrative summary statement indicating 
whether these events were within the expected range; 
• Minor PDs (aggregate summary); 
Any trends or events which in the opinion of the investigator should be reported 
 

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6. 
STATISTICAL CONSIDERATIONS 
6.1. 
Overview 
This is a phase I dose-escalation study in healthy adults to assess the safety and 
pharmacokinetics of N6LS (VRC-HIVMAB091-00-AB), a human monoclonal antibody with 
broad HIV-1 neutralizing activity, with or without rHuPH20. Recruitment will target about  32 
healthy adults, 18 to 50 years of age, as shown in Table 1. The permitted accrual is 40 subjects in 
total to allow for additional enrollments in the event that an enrolled subject does not complete 
the minimum evaluations needed to meet the protocol criteria for the group dose safety or dose-
escalation evaluation. Dose escalation rules are described in Section 4.3.  
6.1.1. 
Treatment Assignments 
The Advantage eClinical system (Emmes Corp, Rockville, MD) will be used to assign subjects 
to a dose group in active accrual at the time of enrollment. If an enrolled subject is discontinued 
from the study before he/she has received any study product,  a new eligible subject may be 
enrolled into the same group.  If a replacement is needed in the case of a subject withdrawal, the 
replacement subject will be assigned to the same treatment as the dropout subject in order to 
complete the safety dataset as planned.  
6.2. 
Sample Size Considerations 
Although the study is primarily descriptive, the primary goal is to identify safety concerns 
associated with different N6LS dosages in group sizes ranging from 3 to 5 subjects. For a group 
size of 3 subjects, there is a 90% chance of observing at least 1 SAE if the true event rate is ≥ 
0.536 and a 90% chance of observing no SAE if the true event rate is ≤ 0.034. For a group size of 
5 subjects, there is a 90% chance of observing at least SAE if the true rate is ≥0.37 and a 90% 
chance of observing no event if the true rate is ≤0.02. The probabilities of observing 0 and 1 or 
more event are presented in Table 3 for a range of possible true event rates. These calculations 
provide a complete picture of the sensitivity of this study design to identify potential safety 
problems with the study agent. For example, within the group of size n=3, if the true event rate is 
0.01, then there is a probability of 0.97 to observe no event and a probability of 0.03 to observe 
at least 1 event; while, within the group of size n=5, if the true event rate is 0.01, then there is a 
probability of 0.951 to observe no event and a probability of 0.05 to observe more than 1 event.  
Table 3: 
Event Probabilities for Different Scenarios 
True Event Rate
Group Size, N=3 
Group Size, N=5 
Probability, 
No Events Observed 
Probability,  
≥1EventObserved 
Probability, 
No Events Observed 
Probability,  
≥1EventObserved 
0.01 
0.97 
0.03 
0.95 
0.05 
0.03 
0.91 
0.09 
0.86 
0.14 
0.05 
0.86 
0.14 
0.77 
0.23 
0.1
0.73 
0.27 
0.59 
0.41 
0.2
0.51 
0.49 
0.33 
0.67 
0.3
0.34 
0.66 
0.17 
0.83 
0.4
0.22 
0.78 
0.08 
0.92 

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Table 4 displays the upper and lower 95% exact binomial confidence bounds for all possible 
number of observed events in a group. For a group size of 3 subjects, the upper 95% exact 
confidence bound on the true rate is 0.708 if no events are observed; the lower bound will be 
0.292 if all subjects experience the event. Likewise, for a group size of 5 subjects, the upper 95% 
exact confidence bound of the true rate is 0.522 if no events are observed; the rate of the lower 
bound is 0.478 if all subjects experience the event.  
Table 4: 
95% Confidence Intervals of the True Rate for All Possible Number of 
Observed Events within a Dose Group 
Group Size, N=3 
95% Confidence Interval 
Group Size, N=5 
95% Confidence Interval 
Observed Rate 
Lower Bound
Upper Bound 
Observed Rate 
Lower Bound 
Upper Bound
0/3
0 
0.708 
0/5 
0 
0.522 
1/3
0.008
0.906 
1/5 
0.005 
0.716 
2/3
0.094
0.992 
2/5 
0.053 
0.853 
3/3
0.292
1 
3/5 
0.147 
0.947 
 
4/5 
0.284 
0.995 
5/5 
0.478 
1 
 
Table 3 and Table 4 also apply to the secondary and exploratory objectives. 
6.3. 
Statistical Analysis  
6.3.1. 
Analysis Variables 
The analysis variables will consist of baseline, pharmacokinetics, and safety variables to support 
analyses of the primary and secondary objectives. 
6.3.2. 
Baseline Characteristics  
Descriptive statistics will be used to summarize baseline characteristics, inclusive of  
demographics and safety laboratory measurements. 
6.3.3. 
Safety Analysis 
The number and percentage of subjects with one or more AEs and associated exact 95% 
confidence intervals will be summarized by dose group. Summaries will also include the number 
and percentage of subjects with any solicited or unsolicited AE, overall and by dose for each 
event.  
Solicited Adverse Events: 
Solicited AE data will be collected after each product administration.  The number and 
percentage of subjects experiencing each type of solicited sign or symptom will be tabulated by 
severity and by dose group, select pooled groups (i.e., all IV dose groups, all 5 mg/kg SC dose 
groups (no rHuPH20), and all rHuPH20 dose groups), and overall (all dose groups). Subjects 
with multiple occurrences of the same event will be counted once using the event of highest 
severity.   

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Adverse Events: 
All unsolicited AEs reported through 56-days post each product administration will be recorded 
and coded by Medical Dictionary for Regulatory Activities (MedDRA) system organ class 
(SOC) and preferred term (PT). The number and percentages of subjects with each unsolicited 
AE will be tabulated by severity and relationship to the study product, by dose group, select 
pooled groups (i.e., all IV dose groups, all 5 mg/kg SC dose groups (no rHuPH20), and all 
rHuPH20 dose groups), and overall (all dose groups). Subjects with multiple occurrences of the 
same event will be counted once using the event highest severity or strongest relationship to the 
study treatment. 
A by-subject listing of all unsolicited AEs will provide details including severity, relationship to 
treatment type, seriousness, new medical condition status, onset and end date, 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. 
6.3.4. 
Tolerability Evaluation  
The tolerability of an investigational medicinal product represents the degree to which overt 
adverse effects can be tolerated by the subject [32]. Since VRC 609 will be the first trial of N6LS 
in healthy adults, the tolerability evaluation will include mostly descriptive summaries of the 
frequency of solicited AE reports with an onset in the 3 days following each N6LS 
administration and subject withdrawals or discontinuations based upon subject discomfort or 
AEs.  This early assessment of tolerability to N6LS will inform the parameters to solicit or 
routinely assess in future studies to further characterize the tolerability profile in a larger subject 
cohort.   
6.3.5. 
Pharmacokinetics Analysis 
Blood samples for PK evaluations will be collected at time-points defined in the Schedule of 
Evaluations (Appendix I).  
Individual Subject Pharmacokinetic Analysis: A non-compartmental PK analysis will be 
performed using Phoenix 7.0 (CertaraR) or a similar program on the N6LS concentration data 
generated from each subject.  Calculated PK parameters for IV Groups 1, 3, 4, and 6 will 
include: area-under-the-curve (AUC), maximum concentration (Cmax), time to Cmax (Tmax), 
clearance (CL), volume of distribution (Vdz),terminaleliminationrateconstant(λz) and the 
terminal half-life (T1/2).  For Groups 2, 5, 7 and 8, the PK parameters will include AUC, Cmax, 
Tmax, apparent clearance (CL/F), apparent volume of distribution (Vdz/F),λz and T1/2.  Cmax and 
Tmax will be taken directly from the observed concentration-timedata.Theterminalslope,λz, 
will be determined from the log-linear portion of the curve and the T1/2 calculatedas0.693/λz.  
AUC will be determined using the linear trapezoidal method through the Week 24 PK sample for 
single dose groups (1-4, 7 and 8) and through Week 48 for multiple dose groups (5 and 6) or 
through the last PK sample with a concentration above the quantitative limit.  The AUC over the 

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first 12 weeks following the first dose (AUC0-WK12) will be determined for all dose groups.  If the 
final sample (Clast) has a measurable N6LS concentration, the remaining AUC after the final 
concentration (AUCClast-inf) will be estimated as Clast/λz.  Data will be summarized by dose group 
and overall for IV administration groups for CL, Vd and T1/2.  For Groups 5 and 6, potential 
accumulation will be assessed as the ratios of the AUC0-WK12 and Cmax for the first and the third 
doses.  The potential for non-linearity PKs among IV groups will be determined by comparing 
the dose-adjusted ratios for Cmax and AUC0-WK12 between IV groups.  Additional compartmental 
analysis will be performed as warranted by the data. 
Population Pharmacokinetic Analyses:  Population PK analyses will be performed on the 
N6LS PK data following IV and SC administration to determine compartmental PK parameters 
with the PK program NONMEM version 7.3 or later (ICONR).  Based on prior PK studies of 
bNAbs, a two compartment model will be used to analyze the N6LS PK data.  The population 
analysis will generate estimates for initial and final volumes of distribution (Vd1 and Vd2), inter-
compartmental clearance (Q), CL and bioavailability (F).  Individual subjects’ empiric Bayesian 
PK parameter estimates will be generated using the NONMEM posthoc subroutine.  Given the 
small subject numbers, the population PK analysis will include a limited exploratory covariate 
analysis to assess dosing and clinical factors as fixed effects associated with N6LS PK 
parameters. The three factors that will be evaluated are dose level  (5 vs 20 vs 40 mg/kg) on CL 
Vd1, Vd2 and F;  repeat dosing CL Vd1, Vd2, and F; and EPD co-administration on SC F and 
absorption rate.   
The longer compartmental half-life, T1/2beta will be determined from CL,  Vd1, Vd2 and Q using 
standard PK equations.  Final model selection will be based on changes in the objective function 
and graphically by goodness of fit plots.  The final population PK model will be assessed using 
bootstrap analysis. N6LS dosing strategies and their ability to achieve and maintain target N6LS 
concentrations will be performed using the final population PK model and Monte Carlo 
simulations with at least 5000 replicates. 
6.3.6. 
Interim Analyses 
Preliminary PK analyses may be done once per dose level as the data for each dose level is 
obtained.  This may be performed before a dose group’s PK data is complete and may only 
generate a subset of the final PK parameters.  The interim analyses will be used to inform 
decisions about the dose levels to be administered in future studies with N6LS.  
 

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7. 
PHARMACY PROCEDURES 
The dose groups and N6LS dosing schedule are shown in Table 1. Refer to the N6LS IB for 
further information about N6LS (VRC-HIVMAB091-00-AB) administered in the absence and 
presence of rHuPH20. 
7.1. 
Study Product and Administration Regimen  
N6LS (VRC-HIVMAB091-00-AB) is a clear, colorless to yellow liquid, sterile aqueous buffered 
solution that is essentially free of visible particles and is filled into 10 mL single-dose vials.  
Each vial contains a 6.25 ± 0.10 mL volume of N6LS at a concentration of 100 ± 10 mg/mL in 
formulation buffer composed of 10 mM Sodium Citrate, 50 mM Sodium Chloride, 150 mM 
Arginine-HCl, and 0.002% Polysorbate-80 (PS-80) at pH 6.5. Vials have a nominal fill volume 
of 6.25 mL to enable withdrawal up to 6.0 mL. 
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 6 mL can be withdrawn from a vial. In 
this trial, dose is limited or established based on subject weight. For example, for a subject 
weighing 115 kg (the upper limit per protocol eligibility) who receives the 40 mg/kg dose, the 
N6LS amount needed is calculated as follows: 115 kg x 40 mg/kg = 4600 mg of N6LS, which 
corresponds to 46 mL of the 100 mg/mL solution. Since each product vial contains at least 6 mL, 
8 vials will be needed for the dose preparation for this subject. 
Preparation of N6LS for IV administration will require a 100 mL bag of 0.9% sodium chloride, 
United States Pharmacopeia (USP) (normal saline) and a weight-based amount of N6LS, as 
described in the IB. Preparation of N6LS (with and without rHuPH20) for SC administration will 
not require any diluent. 
There are 6 different schedules in the study described in Appendix I. 
7.2. 
N6LS (VRC-HIVMAB091-00-AB) Vialed Product 
The N6LS product label designates the 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, N6LS vials may be stored for up to 24 hours at 15°C to 27°C and/or up to 4 
weeks at 2°C to 8°C.  Product may not be stored in direct sunlight. If stored at 2°C to 8°C, vials 
must be equilibrated to 15°C to 27°C for a minimum of 60 minutes and may be held at this 
temperature for up to 8 hours prior to product preparation. 
7.3. 
EDP Vialed Product  
EDP is supplied as a sterile solution at a concentration of 1 mg/mL in 2 mL single-use glass vial 
containing 0.5 mg rHuPH20 (~110,000 U/mL). EDP should be stored as labeled, either at -20°C 
± 5°C or 5°C ± 3°C and protected from light. Vials of EDP for injection can be removed from 
frozen storage and placed in the refrigerator at 2°C to 8°C for thawing (1 to 2 hours), or room 
temperature (20ºC to 25ºC) for 10 to 30 minutes. Once thawed, vials of EDP may be kept at 
room temperature (20ºC to 25ºC) for up to 24 hours before use and protected from bright light 
and direct sunlight.  

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7.4. 
Temperature Excursions 
The site pharmacist must promptly report any storage temperature excursions outside of the 
normal allowance for the investigational products to the IND Sponsor. In the case of storage or 
shipping/handling temperature excursions outside of the normal allowance for the storage device, 
the following procedure is to be followed: 
1. Quarantine the affected product in a separate area.  If the excursion results in thawed 
material, it must not be refrozen. Thawed vials must be quarantined at 5°C ± 3°C.  
2. Report the excursion to the IND sponsor’s authorized representative (SAR) or designee, 
any other parties required by site procedures, and via email to 
VRCProductinquiries@nih.gov.  Do not use until the IND SAR or designee informs the 
site pharmacist whether continued clinical use of the product is acceptable. 
3. Inquiries sent to VRCProductinquiries@nih.gov. will prompt an automatic email reply to 
the notifier that includes the Clinical Excursion Reporting Form (CERF) as an 
attachment.   
4. Fill out the CERF as completely as possible, either electronically or manually.   
5. Email the completed form and relevant attachments (e.g., temperature charts) to 
VRCProductinquiries@nih.gov, replying to the previous email.   
6. After receipt and evaluation of the reported information, the Sponsor or manufacturer’s 
designee will notify the site pharmacist whether continued clinical use of the product is 
acceptable. 
7.5. 
Preparation of Study Product(s) (N6LS ± rHuPH20) for 
Administration  
This section describes how the site pharmacist will prepare the study products for administration 
and how the clinician will administer each product.  Clinician instructions on how to select an 
administration site are in Section 4.2.3.   
N6LS is a highly concentrated protein solution and may develop white, opaque to translucent 
particles after thawing. When particles are observed, they may disappear after a few hours at 
15°C to 27°C or storage at 2oC to 8oC.  
The following instructions apply to thawing N6LS: 
1. Thaw vial(s) for a minimum of 90 minutes at 15°C to 27°C after removing from the freezer.  
(DO NOT move vials directly from the freezer to storage at 2°C to 8°C.) 
2. Keep the material at 15°C to 27°C during the entire preparation period until use, 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. 
a. Visually inspect the vials; if 10 or fewer visible particles are present, the vial may be used 
for product preparation.  

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b. If more than 10 particles are observed, return the vials to 2°C to 8°C storage. If the 
particles dissolve or if 10 or fewer visible particles are present within the maximum 
storage times described in Section 7.2, the vials may be used for product preparation.  
c. Refrigerated product must be equilibrated at 15°C to 27oC for a minimum of 60 minutes 
before preparation and must be used within 8 hours of any subsequent return to 15°C to 
27oC.   
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. 
7.5.1. 
N6LS: Preparation for IV Administration 
For each IV infusion order, the subject’s weight, dose level, and study group code will be 
included in the pharmacy order.  To prepare an IV infusion, the pharmacist will: 1) fill an empty 
sterile bag with 100 mL of normal saline or (if commercially available) obtain a pre-filled 100 
mL bag of normal saline, 2) calculate the total milligrams of N6LS needed, 3) retrieve the 
minimum number of thawed vials required to prepare the full dose, 4) withdraw the necessary 
amount of N6LS, 5) add this volume to the sterile bag using good pharmacy practices to 
maintain sterility, and 6) immediately remove all air remaining in the bag.  Prepared IV bags 
should contain 10 particles or fewer to proceed with the administration to subjects.     
An in-line filter infusion set must be used for IV product administrations and MUST comply 
with the following specifications: 1.2 micron PES (polyethersulfone) 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. At the end of product 
administration, the IV administration set must be flushed with about 30 mL (or appropriate 
volume) of normal saline.  
The study product solution will typically be administered IV over about 15-30 minutes using a 
volumetric pump.  The total time needed to administer the dose may be longer based on factors 
such as subject tolerance. The rate of infusion may range from 10-20 mg/kg/hr at the lowest dose 
level to 80-160 mg/kg/hr at the highest dose level.  The mL/hr infusion rate may vary based on 
the total volume needed to administer a full dose. An infusion time greater than 30 minutes is 
permitted. 
7.5.2. 
N6LS: Preparation for SC Administration  
For each SC administration order, the subject’s weight, dose level, and study group code will be 
included in the pharmacy order.  To prepare a SC administration dose, the pharmacist will 
calculate the total mg needed and retrieve the minimum number of thawed N6LS vials needed to 
prepare the full dose.  Prior to preparation for administration, vials should be gently swirled for 
30 seconds  avoiding foaming. DO NOT SHAKE THE VIALS. If particles are observed, follow 
instructions in Section 7.5.  

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The needed volume of N6LS must be withdrawn from the vial into 1 to 4 syringes (BD Luer-Lok 
3 mL syringe; REF # 309657) using a 5 micron filter needle (BD Blunt Fill Needle – Filter , 18G 
1 ½ inch; REF# 305211). A new filter needle must be used for each syringe. The filter needle 
must be discarded prior to dispensing and replaced with a needle suitable for SC injection at the 
time of administration. 
The product may be administered by direct SC injection with needle and syringe. The clinician 
will use proper SC technique to ensure administration into the SC fatty layer and a slow push to 
minimize discomfort or the excessive distention of overlying skin. 
7.5.3. 
N6LS with rHuPH20: Preparation for SC Administration via Infusion Pump 
For each SC administration order, the subject’s weight, dose level, and study group code will be 
included in the pharmacy order.  To prepare a SC administration dose, the pharmacist will 
calculate the total mg of N6LS and units of rHuPH20 needed to achieve a 2000 U/mL 
concentration of rHuPH20, and retrieve the minimum number of thawed vials of N6LS and 
rHuPH20 needed to prepare the full dose (inclusive of infusion tubing residual volume). Prior to 
preparation for administration, vials of N6LS should be gently swirled for 30 seconds. AVOID 
FOAMING and DO NOT SHAKE THE VIALS. If particles are observed, follow instructions in 
Section 7.5. The vial(s) of EDP should be placed at room temperature (20°C to 25°C) for a 
minimum of 10 to 30 minutes (but for not more than 24 hours at 20°C to 25°C), and then gently 
swirled and inverted 3-5 times to mix thoroughly.  
The required volume of N6LS must be withdrawn from the N6LS vial using a 5 micron filter 
needle (e.g., BD Blunt Fill Needle – Filter , 18G 1 ½ inch; REF# 305211) and gently injected 
into a new vial/recipient used for mixing. The required volume of EDP must be withdrawn from 
the EDP vial using a BD Luer-Lok 1 mL syringe and gently injected into the vial/recipient 
containing N6LS. The combined N6LS and EDP solution should then be mixed thoroughly by 
gentle swirling and inversion, 5 to 6 times (~10 seconds), while avoiding foaming. The mixed 
material can then be drawn into a sterile syringe with size dependent on total fill volume (Note: 
The prepared syringe should contain sufficient volume to accommodate the final dose volume, 
the priming volume, and the residual volume in the syringe after infusion.) The product may be 
administered in a single site using an infusion pump and syringe (i.e., Terumo Surflo® 23G 
winged infusion set with B/Braun extension set [product code ET06L or equivalent] and 
Medfusion syringe pump or equivalent) at a rate of 2-3 mL/min to ensure accurate and consistent 
administration. The clinician will use proper SC technique to ensure administration into SC fatty 
layer.  
7.5.4. 
Handling of Prepared Product for IV or SC Administration: N6LS and 
N6LS+rHuPH20 
After product preparation in an IV bag, the prepared N6LS may be stored at 15°C to 27°C for a 
maximum of 8 hours total, including the infusion time. Product may not be stored in direct 
sunlight.  
After preparation in syringes for SC administration, the prepared N6LS may be stored at 2°C to 
8°C for up to 24 hours, followed by storage at 15°C to 27°C for up to 4 hours, including 
administration time. The product may not be stored in direct sunlight.  

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Chemical and physical in-use stability data supports storage of N6LS mixed with EDP in 
syringes at 2°C to 8°C for up to 24 hours and at 15°C to 27°C for up to 4 hours, including 
administration time. 
7.6. 
Labeling of Study Product 
Vials of both study products 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. 
7.7. 
Study Product Accountability 
The study pharmacist will be responsible for maintaining an accurate record of the study group 
codes, inventory, and an accountability record of all study products.  Electronic documentation 
as well as paper copies may be used. 
7.8. 
Study Product Disposition 
Empty vials, including equipment used to prepare the N6LS and EDP mixture, and the unused 
portion of a vial will be discarded in a biohazard containment bag for incineration or 
decontamination by autoclave and disposed in accordance with the institutional or pharmacy 
policy.  Partially used vials will not be administered to other subjects or used for in vitro 
experimental studies. Any unopened vials that remain at the end of the study will be returned to 
the production facility or discarded at the discretion of the sponsor in accordance with policies 
that apply to investigational agents.   
 
 

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8. 
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. 
8.1. 
Informed Consent 
The study informed consent (ICF) is provided as a separate hard copy which describes the 
investigational product to be used and all aspects involved in protocol participation.  
The PI or designee is responsible for obtaining written informed consent from the subject after 
adequate explanation of the aims, methods, anticipated risks and benefits of the study before any 
protocol- specific procedures or study product is administered. The Assessment of 
Understanding (AoU) must be completed before the study ICF is signed. 
The acquisition of informed consent will be documented in the subject’s medical records, as 
required by 21 CFR 312.62, and the ICF will be signed and personally dated by the subject and 
the person who conducted the informed consent discussion. The signed ICF will be retained in 
the medical chart and a copy will be provided to the subject.  
8.2. 
Risk/Benefit Assessment  
8.2.1. 
Potential Risks 
Risks of N6LS and mAb Administration 
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. Up to Grade 3 injection site erythema has been 
observed after N6LS+ rHuPH20 injection, and some injection site reactions have lasted up to six 
weeks before completely resolving. Clinical use of MAbs that are targeted to cytokines or 
antigens associated with human cells may be associated with an increased risk of infections [33]; 
however, this is not expected to be a risk for a MAb targeted to a viral antigen. 
Administration of 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 monoclonal antibodies which 
would have a risk of human anti-mouse antibodies [33].  In this regard, as N6LS is expected to 
have a low risk of such side effects since it is directed against a viral antigen and is human in 
origin.  
Published experience with other human MAb directed against the cell surface targets on 
lymphocytes have shown that infusion of a MAb may be associated with cytokine release, 
causing a reaction known as “cytokine release syndrome” (CRS) [34]. 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 a non-human MAb, such as a 
murine MAb, is used [33].  Specifically, with regard to the rare CRS reactions, these generally  

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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, administration of histamine blockers and restarting the infusion at a slower rate [35]. 
Delayed allergic reactions to other MAbs may include a serum sickness type of reaction, which 
is characterized by urticaria, 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 [33]. 
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 subject’s eligibility for other future MAb studies. 
Risks of EDP Coadministration 
EDP coadministration may cause mild, transient injection site reactions, including erythema, 
pain, bruising, pruritus, burning, tenderness, edema, induration, irritation, paresthesia, numbness, 
and rash. Moderate injection site reactions have occurred less frequently and include burning, 
erythema, pain, and numbness. Mild-to-moderate headache is also commonly reported. Adverse 
events in clinical trials have otherwise reflected the adverse reaction profiles of the co-
administered drug or have been associated with the rapid introduction of a relatively large 
volume of fluid in the SC space. 
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 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 subjects from study participation. Others may benefit from 
knowledge gained in this study that may aid in the development of HIV risk-reduction or 
therapeutic methods. 
8.3. 
Institutional Review Board 
A copy of the protocol, informed consent form, other written subject 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 informed consent document. The 
investigator will notify the IRB of unanticipated problems, non-compliance, deviations from the 
protocol, and serious AEs per IRB policy. 

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The investigator will be responsible for obtaining IRB approval of the annual Continuing Review 
throughout the duration of the study. 
8.4. 
Subject Confidentiality 
The investigator must ensure that no information identifying the subject will be released to any 
unauthorized party. Individual identifying information will not be included in any reports. 
Subjects 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 agent 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 subjects that the above named 
representatives will review their study-related records without violating the confidentiality of the 
subjects. Other US, local, and international regulatory entities may also review study records. 
8.5. 
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. 
8.5.1. 
Use of Samples, Specimens and Data 
Samples, specimens and data collected under this protocol may be used to conduct protocol-
related safety and immunology evaluations, exploratory laboratory evaluations related to the 
biological target of the study product, 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 Informed Consent Form (ICF).  
Additional optional genetic testing, including transcriptome sequencing may be done on 
collected specimens in an effort to assess the expression of genes involved in the immune 
response to vaccination.  
Results of genetic testing may have psychological implications for patients such as revelations 
regarding future health risks, incurable conditions, and/or information contradictory to stated 
biological relationships. Genetics counseling and advice will be available from the NIH to help 
subjects at all study sites with the implications of findings, where appropriate.  
Following genetic testing, the data will be shared in a controlled-access public database for other 
investigators to benefit from it (e.g. the Database of Genotypes and Phenotypes dbGAP). 
However no personal, identifiable information will be shared in this process as the results will 
only be shared with a code. 
Other optional analysis, including proteome, lipidome, metabolome, and exosome may be done 
on collected specimens to evaluate some proteins, lipids, metabolites, and low molecular weight 
molecules involved in the immune response to vaccination. 

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8.5.2. 
Storage and Tracking of Blood Samples and Other Specimens 
All research samples use coded labels that only the VRC Clinic can link to the subject.  Samples 
are stored at the Vaccine Immunology Program laboratory (Gaithersburg, MD) or VRC 
Laboratories in Building 40, which are both secure facilities with limited access.  Data will be 
kept in password-protected computers.  Only investigators or their designees will have access to 
the samples and data.  Samples will be tracked in the Laboratory Information Management 
System (LIMS) database or using another software designed for this purpose (e.g., Freezerworks 
or GlobalTrace). 
8.5.3. 
Disposition of Samples, Specimens and Data at Completion of the Protocol  
In the future, other investigators (both at NIH and outside) may wish to study these samples 
and/or data.  IRB approval must be sought prior to any sharing of samples.  Any clinical 
information shared about those samples would similarly require prior IRB approval.  The 
research use of stored, unlinked or unidentified samples may be exempt from the need for 
prospective IRB review and approval.  Exemption requests will be submitted in writing to the 
NIH Office of Human Subjects Research, which is authorized to determine whether a research 
activity is exempt. 
At the time of protocol termination, samples will remain in the VIP facility or VRC laboratories 
or, after IRB approval, transferred to another repository.  Regulatory oversight of the stored 
samples and data may be transferred to a stored samples protocol as part of the IRB-approved 
termination plan.  Data will be archived by the VRC in compliance with requirements for 
retention of research records, or after IRB and study sponsor approval, it may be either destroyed 
or transferred to another repository. 
8.5.4. 
Loss or Destruction of Samples, Specimens or Data 
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. 
8.6. 
Subject Identification and Enrollment of Study Subjects 
All study activities will be carried out at the NIH CC. Study subjects will be recruited through 
on-site and off-site advertising done for the screening protocol, VRC 500 (NCT 01375530). 
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 50 years of age at enrollment. 
8.7. 
Costs 
There are no costs to subjects for their participation in this trial 
8.8. 
Compensation 
Subjects will be compensated for time and inconvenience in accordance with the standards for 
compensation of the Clinical Research Volunteer Program. Study product administration. 

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accompanied by the same day PK blood draws combined will be $430; product administration 
visits without PK blood draws will be $375.  The compensation will be $200 for scheduled visits 
that include blood drawing, $85 for clinic visits that do not include a blood draw or procedure, 
and $25 total for timely completion of all 3 days of the electronic diary.  
8.9. 
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 
PSRT, comprised of the PI, Associate Investigators, Study Coordinator, Protocol Specialists, 
other Study Clinicians, and MO will review the summary study safety data reports on a weekly 
basis through 4 weeks after the last subject receives the last product administration and will 
continue to monitor the safety data reports on a monthly basis through completion of the last 
study visit. A representative from Halozyme Therapeutics will also participate in any scheduled 
or ad hoc safety review meetings when Groups 7 and 8 are active.     
8.10. 
Conflict of Interest Policy 
The independence of this study from any actual or perceived influence, such as by the 
pharmaceutical industry, is critical.  Therefore, any actual conflict of interest of persons who 
have a role in the design, conduct, analysis, publication, or any aspect of this trial will be 
disclosed and managed. Furthermore, persons who have a perceived conflict of interest will be 
required to have such conflicts managed in a way that is appropriate to their participation in the 
design and conduct of this trial. NIAID has established policies and procedures for all study 
group members to disclose all conflicts of interest and will establish a mechanism for the 
management of all reported dualities of interest. 
 
 

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9. 
ADMINISTRATIVE AND LEGAL OBLIGATIONS 
9.1. 
Protocol Amendments and Study Termination 
Protocol amendments may be made only with the prior approval from the IND Sponsor.  
Agreement from the PI and MO must be obtained for all amendments to the protocol and the 
informed consent document. Approval from Halozyme Therapeutics, Inc. may also be required, 
in accordance with any cooperative research and development agreement (CRADA) or clinical 
trial agreement (CTA) established for the study.  All study amendments will be submitted to the 
IRB for approval. 
The IND Sponsor, NIH IRB, Office of Human Research Protections, 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. 
9.2. 
Study Documentation and Storage 
The PI will delegate the study responsibilities to the study team, and a list of appropriately 
qualified persons to whom trial duties have been delegated will be maintained. 
Source documents are original documents, data, and records from which the subject’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. Long-term 
storage of source documents may be in the form of electronic files.  
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 
from the VRC, IRB, FDA, and/or applicable regulatory authorities. Elements include: 
• Subject files containing completed informed consent forms, and supporting copies of 
source documentation (if kept). 
• Study files containing the protocol with all amendments, IBs, copies of all 
correspondence with the IRB and the VRC. 
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 
two years after marketing approval or refusal (21 CFR 312.62).  No study document should be 
destroyed without prior written agreement between the VRC 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 VRC in writing of the new responsible person and/or the new location. 
9.3. 
Clinical Monitoring, Data Collection and Data Sharing 
9.3.1. 
Clinical Monitoring Plan 
The IND Sponsor or their authorized representatives are responsible for ensuring integrity of 
study data and compliance with the protocol. The PI will allow the study monitors, the IRB and 
the FDA to inspect study documents (e.g., consent forms, drug distribution forms, and case 

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report forms) and pertinent hospital or clinic records for confirmation of the study data. Site 
visits by study monitors will be made to monitor the following: study operations, 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. Study monitoring visits will 
occur as defined by the IND Sponsor approved monitoring plan. 
9.3.2. 
Data Collection 
Clinical research data will be collected in a secure electronic web-based clinical data 
management system (CDMS) through a contract research organization, The Emmes Company 
LLC (Rockville, MD).  Extracted, anonymized data will be sent to the PSRT for safety review 
and to Protocol Statistician for statistical analysis. 
9.3.3. 
Source Documents 
The site will maintain appropriate medical and research records for this trial, in compliance with  
International Conference on Harmonisation (ICH) E6 GCP, regulatory and institutional 
requirements for the protection of confidentiality of subjects. Source data are all information, 
original records of clinical findings, observations, or other activities in a clinical trial necessary 
for the reconstruction and evaluation of the trial. Examples of these original documents and data 
records include, but are not limited to, medical records, laboratory reports, pharmacy records and 
other research records maintained for the clinical trial.  
9.3.4. 
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 primary completion date. 
9.4. 
Language 
All written information and other material to be used by subjects and investigative staff must use 
vocabulary and language that are clearly understood.  
9.5. 
Policy Regarding Research-Related Injuries 
The NIH CC will provide short-term medical care for any injury resulting from participation in 
this research. In general, the National Institutes of Health, the NIH CC, or the U.S. Federal 
Government will provide no long-term medical care or financial compensation for research-
related injuries. 
 
 

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10. 
REFERENCES 
1. 
UNAIDS. Fact sheet: 2017 statistics. 2017; Available from: 
www.unaids.org/sites/default/files/media_asset/UNAIDS_FactSheet_en.pdf. 
2. 
Huang, J., et al., Identification of a CD4-Binding-Site Antibody to HIV that Evolved 
Near-Pan Neutralization Breadth. Immunity, 2016. 45(5): p. 1108-1121. 
3. 
Huang, J., et al., Broad and potent neutralization of HIV-1 by a gp41-specific human 
antibody. Nature, 2012. 491(7424): p. 406-12. 
4. 
Wu, X., et al., Rational design of envelope identifies broadly neutralizing human 
monoclonal antibodies to HIV-1. Science, 2010. 329(5993): p. 856-61. 
5. 
Kwon, Y., et al., Structure-guided modification and optimization of antibody VRC07. 
Retrovirology, 2012. 9(Suppl 2): p. O34. 
6. 
Mascola, J.R., et al., Protection of macaques against vaginal transmission of a 
pathogenic HIV-1/SIV chimeric virus by passive infusion of neutralizing antibodies. Nat 
Med, 2000. 6(2): p. 207-10. 
7. 
Pegu, A., et al., Neutralizing antibodies to HIV-1 envelope protect more effectively in 
vivo than those to the CD4 receptor. Sci Transl Med, 2014. 6(243): p. 243ra88. 
8. 
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. 
9. 
Bar, K.J., et al., Effect of HIV Antibody VRC01 on Viral Rebound after Treatment 
Interruption. N Engl J Med, 2016. 375(21): p. 2037-2050. 
10. 
Scheid, J.F., et al., Sequence and structural convergence of broad and potent HIV 
antibodies that mimic CD4 binding. Science, 2011. 333(6049): p. 1633-7. 
11. 
Mouquet, H., et al., Complex-type N-glycan recognition by potent broadly neutralizing 
HIV antibodies. Proc Natl Acad Sci U S A, 2012. 109(47): p. E3268-77. 
12. 
Walker, L.M., et al., Broad neutralization coverage of HIV by multiple highly potent 
antibodies. Nature, 2011. 477(7365): p. 466-70. 
13. 
Walker, L.M., et al., Broad and potent neutralizing antibodies from an African donor 
reveal a new HIV-1 vaccine target. Science, 2009. 326(5950): p. 285-9. 
14. 
McLellan, J.S., et al., Structure of HIV-1 gp120 V1/V2 domain with broadly neutralizing 
antibody PG9. Nature, 2011. 480(7377): p. 336-43. 
15. 
Doria-Rose, N.A., et al., New Member of the V1V2-Directed CAP256-VRC26 Lineage 
That Shows Increased Breadth and Exceptional Potency. J Virol, 2015. 90(1): p. 76-91. 
16. 
Kwon, Y.D., et al., Optimization of the Solubility of HIV-1-Neutralizing Antibody 10E8 
through Somatic Variation and Structure-Based Design. J Virol, 2016. 
17. 
Ko, S.Y., et al., Enhanced neonatal Fc receptor function improves protection against 
primate SHIV infection. Nature, 2014. 514(7524): p. 642-5. 
18. 
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. 
19. 
Morrow, L., et al., Reduction in intrasubject variability in the pharmacokinetic response 
to insulin after subcutaneous co-administration with recombinant human hyaluronidase 
in healthy volunteers. Diabetes Technol Ther, 2011. 13(10): p. 1039-45. 

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20. 
Morcos, P.N., et al., Pharmacokinetics and pharmacodynamics of single subcutaneous 
doses of tocilizumab administered with or without rHuPH20. Int J Clin Pharmacol Ther, 
2013. 51(7): p. 537-48. 
21. 
Locke, K.W., D.C. Maneval, and M.J. LaBarre, ENHANZE((R)) drug delivery 
technology: a novel approach to subcutaneous administration using recombinant human 
hyaluronidase PH20. Drug Deliv, 2019. 26(1): p. 98-106. 
22. 
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. 
23. 
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. 
24. 
Shpilberg, O. and C. Jackisch, Subcutaneous administration of rituximab (MabThera) 
and trastuzumab (Herceptin) using hyaluronidase. Br J Cancer, 2013. 109(6): p. 1556-61. 
25. 
Gaudinski, M.R., et al., Safety and pharmacokinetics of broadly neutralising human 
monoclonal antibody VRC07-523LS in healthy adults: a phase 1 dose-escalation clinical 
trial. Lancet HIV, 2019. 
26. 
FDA. Immunogenicity Testing of Therapeutic Protein Products —Developing and 
Validating Assays for Anti-Drug Antibody Detection. 2019; Available from: 
https://www.fda.gov/regulatory-information/search-fda-guidance-
documents/immunogenicity-testing-therapeutic-protein-products-developing-and-
validating-assays-anti-drug. 
27. 
Li, M., et al., Human immunodeficiency virus type 1 env clones from acute and early 
subtype B infections for standardized assessments of vaccine-elicited neutralizing 
antibodies. J Virol, 2005. 79(16): p. 10108-25. 
28. 
Allen, J.C. and H.G. Kunkel, Antibodies to genetic types of gamma globulin after 
multiple transfusions. Science, 1963. 139(3553): p. 418-9. 
29. 
Jefferis, R. and M.P. Lefranc, Human immunoglobulin allotypes: possible implications 
for immunogenicity. MAbs, 2009. 1(4): p. 332-8. 
30. 
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. 
31. 
Zalevsky, J., et al., Enhanced antibody half-life improves in vivo activity. Nat Biotechnol, 
2010. 28(2): p. 157-9. 
32. 
FDA, Guidance for Industry: E9 Statistical Principles for Clinical Trials. 1998, U. S. 
DHHS, FDA, CDER, CBER. 
33. 
Hansel, T.T., et al., The safety and side effects of monoclonal antibodies. Nature reviews. 
Drug discovery, 2010. 9(4): p. 325-38. 
34. 
Bugelski, P.J., et al., Monoclonal antibody-induced cytokine-release syndrome. Expert 
review of clinical immunology, 2009. 5(5): p. 499-521. 
35. 
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: SCHEDULE OF EVALUATIONS

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Schedule 1: IV Group 1 (5 mg/kg), 3 (20 mg/kg), and 4 (40 mg/kg)   
Visit Number 
01R 
02 
02A 
02B 
02C 
02D 
03 
04 
06 
07 
08 
09 
10 
11 
15 
16 
17 
Time After Infusion 
 
Pre 
EOI 
1hr 
3h 
6h 
24hr 
48hr 
Wk1 Wk2 Wk3 Wk4 Wk8 Wk12 Wk16 Wk20 Wk24 
1Day of Study -42 to 0 
D0 
D0 
D0 
D0 
D0 
D1 
D2 
D7 
D14 
D21 
D28 
D56 
D84 D112 D140 D168 
Clinical 
Tube^ Screen Enroll 
Day of Administration 
 
 
 
 
 
 
 
 
 
 
 
VRC 500 Screening Consent 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
VRC 609 AoU; Consent 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2 Screen: Physical exam, ht, wt; Other: 
targeted exam, BP, pulse, temp; also wt at 
visit 02 
 
X 
X 
X 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Complete med history at screen; then 
interim med history 
 
X 
X 
X 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
3N6LS Administration 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Begin 3-day Diary Card 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CBC / differential 
EDTA 
3 
 
3 
 
 
 
 
3 
 
3 
3 
 
3 
 
3 
 
 
 
ALT, AST,  ALP, creatinine 
GLT 
4 
 
4 
 
 
 
 
4 
 
4 
4 
 
4 
 
4 
 
 
 
Total bili, BUN, albumin, protein, calcium, 
Na, K, Cl, CO2, glucose (CMP) 
GLT 
X 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
X 
 
 
 
4Pregnancy test: urine or serum 
 
X 
X 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
X 
 
X 
4Pregnancy prevention counseling/ 
Reproductive Information Form 
 
X 
X 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
X 
 
X 
HIV Ab/Ag combo test 
EDTA 
3 
 
 
 
 
 
 
 
 
3 
 
 
 
 
 
 
 
 
HIV risk-reduction counseling 
 
X 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
Research Samples 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Timed PK samples 
SST 
 
 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
PBMCs 
EDTA 
20 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum 
SST 
8 
8 
8 
 
 
 
 
 
8 
8 
8 
8 
8 
8 
8 
8 
8 
8 
Daily Volume (mL) 
 
38 
8 
19 
4 
4 
4 
4 
11 
12 
22 
19 
12 
19 
12 
19 
12 
12 
12 
Cumulative Volume (mL) 
 
38 
46 
65 
69 
73 
77 
81 
92 
104 
126 
145 
157 
176 
188 
207 
219 
231 
243 
Visit windows: Schedule visits 02A through 17 with respect to day 0. Visit 02A (+10 min); Visits 02B and 02C (±10 min); Visit 02D (-2 hrs); Visits 03, 04 
(± 6 hrs); Visits 06, 07, 08, 09 (±2 days), and Visits 10, 11, 15, 16 and 17 (±7 days).Visits 05, 12, 13 and 14 are not applicable to Schedule 1. 
1 Day 0=day of first product administration.  Day 0 is preferably scheduled within 14 days after enrollment, but may be scheduled up to 42 days after enrollment 
to allow for the possibility of study pauses or scheduling difficulty with the approval of the PI. Day 0 evaluations prior to product administration are the 
baseline for assessing subsequent AEs.   
2 Screening includes physical exam with vital signs, height (ht) and weight (wt).  At other visits, if medically indicated, a targeted exam is performed. 
Otherwise only blood pressure (BP), pulse, and temperature are required, except at Visit 02 when the current weight is also obtained to use for ordering the 
study product, dosed based on “mg/kg”. 

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3 The PK blood draw “visits,” defined by hours after an infusion, are relative to the exact time of the end of infusion (EOI).  The exact start and end times of 
product administration and the time of PK blood draw(s) are recorded to ensure accurate PK analysis.  All subjects will be observed for 4 hours after product 
administration.  
4 Pregnancy test results must be negative for women of reproductive potential before each product administration. Complete a Reproductive Information 
Form when pregnancy test is given.  
^ Tube types and blood volumes are shown to meet current institutional requirements and projected blood volumes. Different tubes for clinical evaluations 
may be used to meet site requirements. Slightly different volumes and tubes may be used for research blood samples when tubes as shown are not 
available, or as otherwise instructed by the IND Sponsor. Collected blood volumes will stay within the NIH CC blood draw limits for each subject. 
 
 
 

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Schedule 2: SC Group 2 (5 mg/kg) 
Visit Number 
01R 
02 
02A 
03 
04 
05 
06 
07 
08 
09 
10 
11 
15 
16 
17 
Time After Infusion 
 
Pre 
EOI 
24hr 
48hr 
72hr 
Wk1 
Wk2 
Wk3 
Wk4 
Wk8 Wk12 Wk16 Wk20 Wk24 
1Day of Study 
-42 to 0 
D0 
D0 
D1 
D2 
D3 
D7 
D14 
D21 
D28 
D56 
D84 
D112 D140 D168 
Clinical 
Tube^ Screen Enroll 
Day of Injection 
 
 
 
 
 
 
 
 
 
 
 
 
VRC 500 Screening Consent 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
VRC 609 AoU; Consent 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2Screen: Physical exam, ht, wt; Other: 
targeted exam, BP, pulse, temp; also wt 
at visit 02 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Complete med history at screen; then 
interim med history 
 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
3 N6LS Administration 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Begin 3-day Diary Card 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
CBC / differential 
EDTA 
3 
 
3 
 
3 
 
 
3 
3 
 
3 
 
3 
 
 
 
ALT, AST,  ALP, creatinine 
GLT 
4 
 
4 
 
4 
 
 
4 
4 
 
4 
 
4 
 
 
 
Total bili, BUN, albumin, protein, calcium, 
Na, K, Cl, CO2, glucose (CMP) 
GLT 
X 
 
X 
 
 
 
 
 
X 
 
 
 
X 
 
 
 
4Pregnancy test: urine or serum 
 
X 
X 
X 
 
 
 
 
 
X 
 
 
 
 
X 
 
X 
4Pregnancy prevention counseling/ 
Reproductive Information Form 
 
X 
X 
X 
 
 
 
 
 
X 
 
 
 
 
X 
 
X 
HIV Ab/Ag combo test 
EDTA 
3 
 
 
 
 
 
 
3 
 
 
 
 
 
 
 
 
HIV risk-reduction counseling 
 
X 
 
X 
 
 
 
 
X 
 
 
 
 
 
 
 
 
Research Samples 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Timed PK samples 
SST 
 
 
4 
 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
PBMCs 
EDTA 
20 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum 
SST 
8 
8 
8 
 
 
8 
8 
8 
8 
8 
8 
8 
8 
8 
8 
8 
Daily Volume (mL) 
 
38 
8 
19 
0 
11 
12 
12 
22 
19 
12 
19 
12 
19 
12 
12 
12 
Cumulative Volume (mL) 
 
38 
46 
65 
65 
76 
88 
100 
122 
141 
153 
171 
184 
203 
215 
227 
239 
Visit windows: Schedule visits 02A through 17 with respect to day 0. Visit 02A (+10 min); Visits 03, 04, 05 (± 6 hrs); Visits 06, 07, 08, 09 (±2 days); 
Visits 10, 11, 15, 16, 17 (±7 days). Visits 12-14 are not applicable to Schedule 2. 
1 Day 0=day of first product administration.  Day 0 is preferably scheduled within 14 days after enrollment, but may be scheduled up to 42 days after 
enrollment to allow for the possibility of study pauses or scheduling difficulty with the approval of the PI.  Day 0 evaluations prior to product 
administration are the baseline for assessing subsequent AEs.   
2 Screening includes physical exam with vital signs, height (ht) and weight (wt).  At other visits, if medically indicated, a targeted exam is performed. 
Otherwise only blood pressure (BP), pulse, and temperature are required, except at Visit 02 when the current weight is also obtained to use for ordering 
the study product, dosed based on “mg/kg”. 

Product: VRC-HIVMAB091-00-AB (N6LS)  
Protocol VRC 609, Version 9.0  
 
October 07, 2022  
 
Page 61 of 73 
 
3 The PK blood draw “visits,” defined by hours after an injection, are relative to the exact time of the end of injection (EOI).  The exact start and end times 
of product administration and the time of PK blood draw(s) are recorded to ensure accurate PK analysis.  All subjects will be observed for 4 hours after 
product administration.  
4 Pregnancy test results must be negative for women of reproductive potential before each product administration. Complete a Reproductive Information 
Form when pregnancy test is given.  
^ Tube types and blood volumes are shown to meet current institutional requirements and projected blood volumes. Different tubes for clinical evaluations 
may be used to meet site requirements. Slightly different volumes and tubes may be used for research blood samples when tubes as shown are not 
available, or as otherwise instructed by the IND Sponsor. Collected blood volumes will stay within the NIH CC blood draw limits for each subject. 
 
 
 

Product: VRC-HIVMAB091-00-AB (N6LS)  
Protocol VRC 609, Version 9.0  
 
October 07, 2022  
 
Page 62 of 73 
 
Schedule 3: SC Group 5 (5 mg/kg by repeat dosing) 
Visit Number 
01R 
02 
02A 03 
04 
05 06 07 
09 
10 
11 
11A 11E 12 
13 
14 
15 
16 
17 
17A 
17E 
Time After Infusion 
 
Pre 
D0 
EOI 
D0 24hr 48hr 72hr 1wk Wk2 Wk4 Wk8 
Pre 
Wk12 
EOI 
Wk12 24hr 72hr Wk13 Wk14 Wk16 Wk20 Pre 
Wk24 
EOI 
Wk24 24hr 
1Day of Study -42 to  
0 
D0 
D0 D1 D2 D3 D7 D14 D28 D56 D84 
D84 D85 D87 D91 D98 D112 D140 D168 D168 D169 
Clinical 
Tube^ Screen Enroll 
Day of 
injection 
 
 
 
 
 
 
 
Day of 
injection 
 
 
 
 
 
 
Day of 
injection 
 
VRC 500 Screening Consent 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
VRC 609 AoU; Consent 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2Screen: Physical exam, ht, wt; Other: 
targeted exam, BP, pulse, temp; wt at 
visits 02, 11, and 17 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
 
Complete med history at screen; then 
interim med hx 
 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
X 
X 
X 
X 
X 
X 
 
 
3 N6LS Administration 
 
 
 
X 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
Begin 3-day Diary Card 
 
 
 
X 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
Phone contact; clinic visit if indicated 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
CBC / diff 
EDTA 
3 
 
3 
 
3 
 
 
3 
3 
 
3 
3 
 
 
3 
3 
3 
 
3 
3 
 
 
ALT, AST,  ALP, creatinine 
GLT 
4 
 
4 
 
4 
 
 
4 
4 
 
4 
4 
 
 
4 
4 
4 
 
4 
4 
 
 
Total bili, BUN, albumin, protein, calcium
Na, K, Cl, CO2, glucose (CMP) 
GLT 
X 
 
X 
 
 
 
 
 
X 
 
 
X 
 
 
 
 
X 
 
 
X 
 
 
4Pregnancy test: urine or serum 
 
X 
X 
X 
 
 
 
 
 
X 
 
 
X 
 
 
 
 
X 
 
 
X 
 
 
4Pregnancy prevention counseling/ 
Reproductive Information Form 
 
X 
X 
X 
 
 
 
 
 
X 
 
 
X 
 
 
 
 
X 
 
 
X 
 
 
HIV Ab/Ag combo test 
EDTA 
3 
 
 
 
 
 
 
3 
 
 
 
 
 
 
 
3 
 
 
 
 
 
 
HIV risk-reduction counseling 
 
X 
 
X 
 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
Research Samples 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Timed PK samples 
SST 
 
 
4 
 
4 
4 
4 
4 
4 
4 
4 
4 
 
 
4 
4 
4 
4 
4 
4 
 
 
PBMCs 
EDTA 
20 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum 
SST 
8 
8 
8 
 
 
8 
8 
8 
8 
8 
8 
8 
 
 
 
8 
8 
8 
8 
8 
 
 
Daily Volume (mL) 
 
38 
8 
19 
0 
11 
12 
12 22 19 
12 
19 
19 
0 
0 
11 
22 
19 
12 
19 
19 
0 
0 
Cumulative Volume (mL) 
 
38 
46 
65 
65 
76 
89 100 122 141 153 172 
191 
191 
191 202 224 
243 255 
273 293 
293 
293 
Visit windows: Schedule visits 02A through 11 with respect to day 0. Schedule visits 11A through 17 with respect to visit 11. Visit A (+10 min); Visit E 
(+ 1 day); Visits 03, 04, 05, and 12 (± 6 hrs); Visits 06, 07, 13, and 14 (±2 days); Visits 09, 10, 11, 15, 16 and 17 (±7 days, with not less than 21 days 
between injections). Visits 08, 11B, 11C, 17B, and 17C are not applicable to Schedule 3. 
1 Day 0=day of first product administration.  Day 0 is preferably scheduled within 14 days after enrollment, but may be scheduled up to 42 days after 
enrollment to allow for the possibility of study pauses or scheduling difficulty with the approval of the PI.  Day 0 evaluations prior to product administration 
are the baseline for assessing subsequent AEs.   

Product: VRC-HIVMAB091-00-AB (N6LS)  
Protocol VRC 609, Version 9.0  
 
October 07, 2022  
 
Page 63 of 73 
 
2 Screening includes physical exam with vital signs, height (ht) and weight (wt).  At other visits, if medically indicated, a targeted exam is performed. 
Otherwise only blood pressure (BP) and temperature are required, except at Visits 02, 11, and 17 when weight is also obtained to use for ordering the study 
product, dosed based on “mg/kg”. 
3 The PK blood draw “visits,” defined by hours after an injection, are relative to the exact time of the end of injection (EOI).  The exact start and end times 
of product administration and the time of PK blood draw(s) are recorded to ensure accurate PK analysis.  Subjects will be observed for 4 hours after the first 
product administration, and at least 2 hours after the second and third product administrations. 
4 Pregnancy test results must be negative before each study product administration.  Complete a Reproductive Information Form when pregnancy test is 
given.  
*The study schedule for subjects who discontinue product administration will be modified as follows:  
• Subjects who have only received one product administration will follow Schedule 3 through Visit 10, and then move to Schedule 5.  
• Subjects who have received two product administrations will follow Schedule 3 through Visit 16 and then move to Schedule 5. 
^ Tube types and blood volumes are shown to meet current institutional requirements and projected blood volumes. Different tubes for clinical evaluations 
may be used to meet site requirements. Slightly different volumes and tubes may be used for research blood samples when tubes as shown are not 
available, or as otherwise instructed by the IND Sponsor. Collected blood volumes will stay within the NIH CC blood draw limits for each subject. 
 
 
 
 

Product: VRC-HIVMAB091-00-AB (N6LS)  
Protocol VRC 609, Version 9.0  
 
October 07, 2022  
 
Page 64 of 73 
 
Schedule 3 (continued): SC Group 5 (5 mg/kg by repeat dosing) 
Visit Number* 
18 
19 
20 
21 
22 
23 
24 
25 
26 
Time After Infusion 
72hr 
Wk25 Wk26 Wk28 Wk32 Wk36 Wk40 Wk44 Wk48 
Day of Study 
D171 
D175 
D182 
D196 
D224 
D252 
D280 
D308 
D336 
Clinical 
Tube^ 
 
 
 
 
 
 
 
 
 
 Targeted physical exam, BP, pulse, temp 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Complete med history at screen; then interim 
med hx 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
CBC / diff 
EDTA 
3 
3 
3 
 
3 
 
 
 
 
ALT, AST,  ALP, creatinine 
GLT 
4 
4 
4 
 
4 
 
 
 
 
Total bili, BUN, albumin, protein, calcium, Na, K, Cl, 
CO2, glucose (CMP) 
GLT 
 
 
X 
 
 
 
 
 
 
1Pregnancy test: urine or serum 
 
 
 
X 
 
 
X 
 
 
X 
1Pregnancy prevention counseling / Reproductive 
Information Form 
 
 
 
X 
 
 
X 
 
 
X 
HIV Ab/Ag combo test 
EDTA 
 
3 
 
 
 
 
 
 
 
HIV risk-reduction counseling 
 
 
X 
 
 
 
 
 
 
 
Research Samples 
 
 
 
 
 
 
 
 
 
 
Timed PK samples 
SST 
4 
4 
4 
4 
4 
4 
4 
4 
4 
Serum 
SST 
 
8 
8 
8 
8 
8 
8 
8 
8 
Daily Volume (mL) 
 
11 
22 
19 
12 
19 
12 
12 
12 
12 
Cumulative Volume (mL) 
 
307 
329 
348 
360 
379 
391 
403 
415 
427 
 
Visit windows: Schedule visits 17A through 26 with respect to visit 17. Visit 18 (± 6 hrs), Visits 19-22 (±2 days), and Visits 23-26 (±7 
days).  
1 Complete a Reproductive Information Form when pregnancy test is given. 
*The study schedule for subjects who discontinue product administration will be modified as follows:  
• Subjects who have only received one product administration will follow Schedule 3 through Visit 10, and then move to Schedule 5.  
• Subjects who have received two product administrations will follow Schedule 3 through Visit 16 and then move to Schedule 5. 
^ Tube types and blood volumes are shown to meet current institutional requirements and projected blood volumes. Different tubes for clinical 
evaluations may be used to meet site requirements. Slightly different volumes and tubes may be used for research blood samples when tubes as 
shown are not available, or as otherwise instructed by the IND Sponsor. Collected blood volumes will stay within the NIH CC blood draw limits 
for each subject. 
 
 

Product: VRC-HIVMAB091-00-AB (N6LS)  
Protocol VRC 609, Version 9.0  
 
October 07, 2022  
 
Page 65 of 73 
 
Schedule 4: IV Group 6 (20 mg/kg by repeat dosing) 
Visit Number 
01R 
02 02A 02B 02C 02D 03 
04 
06 
07 
09 
10 
11 11A 11B 11E 
12 
13 
14 
15 
16 
17 
17A 17B 
Time After Day 0 Infusion 
 
Pre 
D0 
EOI 
D0 1hr 3hr 6hr 24hr 48h Wk1 Wk2 Wk4 Wk8 
Pre 
Wk 
12 
EOI 
Wk 
12 
1hr 24hr 72hr Wk13 Wk14 Wk16 Wk20 Pre 
Wk24
EOI 
Wk24 1hr 
1Day of Study -42 to 
0 
D0 D0 D0 D0 D0 D1 D2 D7 D14 D28 D56 D84 D84 D84 D85 D87 D91 D98 D112 D140 D168 D168 D168 
Clinical 
Tube^ ScreenEnroll 
Day of 
infusion 
 
 
 
 
 
 
Day of 
infusion 
 
 
 
 
 
 
Day of 
infusion 
VRC 500 Screening Consent 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
VRC 609 AoU; Consent 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2Screen: Physical exam, ht, wt; 
Other: targeted exam, BP, pulse, 
temp; also wt at visits 02, 11, 17 
 
X 
X 
X 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
 
Complete med history at screen; 
then interim med hx 
 
X 
X 
X 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
X 
X 
X 
X 
X 
X 
 
 
3 N6LS Administration 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
X 
 
 
Begin 3-day Diary Card 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
X 
 
 
Phone contact; clinic visit if 
indicated 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
CBC / diff 
EDTA
3 
 
3 
 
 
 
 
3 
 
3 
3 
 
3 
3 
 
 
 
3 
3 
3 
 
3 
3 
 
 
ALT, AST,  ALP, creatinine 
GLT 
4 
 
4 
 
 
 
 
4 
 
4 
4 
 
4 
4 
 
 
 
4 
4 
4 
 
4 
4 
 
 
Total bili, BUN, albumin, protein, 
calcium, Na, K, Cl, CO2, glucose (CMP) GLT 
X 
 
X 
 
 
 
 
 
 
 
X 
 
 
X 
 
 
 
 
 
X 
 
 
X 
 
 
 4Pregnancy test: urine or serum 
 
X 
X 
X 
 
 
 
 
 
 
 
X 
 
 
X 
 
 
 
 
 
X 
 
 
X 
 
 
 4Pregnancy prevention counseling/   
Reproductive Information Form 
 
X 
X 
X 
 
 
 
 
 
 
 
X 
 
 
X 
 
 
 
 
 
X 
 
 
X 
 
 
HIV Ab/Ag combo test 
EDTA 
3 
 
 
 
 
 
 
 
 
3 
 
 
 
 
 
 
 
 
3 
 
 
 
 
 
 
HIV risk-reduction counseling 
 
X 
 
X 
 
 
 
 
 
 
X 
 
 
 
X 
 
 
 
 
X 
 
 
 
X 
 
 
Research Samples 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Timed PK samples 
SST 
 
 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
 
4 
4 
4 
4 
4 
4 
4 
4 
PBMCs 
EDTA 
20 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum 
SST 
8 
8 
8 
 
 
 
 
 
8 
8 
8 
8 
8 
8 
 
 
 
 
8 
8 
8 
8 
8 
 
 
Daily Volume (mL) 
 
38 
8 
19 
4 
4 
4 
4 
11 
12 
22 
19 
12 
19 
19 
4 
4 
0 
11 
22 
19 
12 
19 
19 
4 
4 
Cumulative Volume (mL) 
 
38 
46 
65 
69 73 77 81 92 104 126 145 157 176 195 199 203 203 214 236 255 267 286 305 309 313 
Visit windows: Schedule visits 02A through 11 with respect to Day 0. Schedule visits 11A through 17 with respect to Visit 11. Visits A (+10 min); Visits B 
and C (±10 min); Visit 02D (-2 hrs); Visit E (+1 day); Visits 03, and 04 (±6 hrs); Visits 06, 07, 13, and 14 (±2 days); Visit 12 (+2 days), Visits 09, 10, 11, 15, 
16 and 17 (±7 days, with not less than 21 days between infusions). Visits 05 and 08 are not applicable to Schedule 4. 

Product: VRC-HIVMAB091-00-AB (N6LS)  
Protocol VRC 609, Version 9.0  
 
October 07, 2022  
 
Page 66 of 73 
 
1 Day 0=day of first product administration.  Day 0 is preferably scheduled within 14 days after enrollment, but may be scheduled up to 42 days after enrollment 
to allow for the possibility of study pauses or scheduling difficulty with the approval of the PI. Day 0 evaluations prior to product administration are the baseline 
for assessing subsequent AEs.   
2 Screening includes physical exam with vital signs, height (ht) and weight (wt).  At other visits, if medically indicated, a targeted exam is performed. Otherwise 
only blood pressure (BP), pulse, and temperature are required, except at Visits 02, 11, and 17 when the current weight is also obtained to use for ordering the 
study product, dosed based on “mg/kg.” 
3 The PK blood draw “visits,” defined by hours after an infusion, are relative to the exact time of the end of infusion.  Exact start and end times of product 
administration and the time of PK blood draw(s) are recorded to ensure accurate PK analysis.  All subjects will be observed for 4 hours after the first product 
administration, and at least 2 hours after the second and third product administrations. 
4 Pregnancy test results must be negative for women of reproductive potential before each product administration. Complete a Reproductive 
Information Form when pregnancy test given.  
*The study schedule for subjects who discontinue product administration will be modified as follows:  
• Subjects who have only received one product administration will follow Schedule 4 through Visit 10, and then move to Schedule 5.  
• Subjects who have received two product administrations will follow Schedule 4 through Visit 16 and then move to Schedule 5. 
^ Tube types and blood volumes are shown to meet current institutional requirements and projected blood volumes. Different tubes for clinical evaluations 
may be used to meet site requirements. Slightly different volumes and tubes may be used for research blood samples when tubes as shown are not 
available, or as otherwise instructed by the IND Sponsor. Collected blood volumes will stay within the NIH CC blood draw limits for each subject. 
 
 

Product: VRC-HIVMAB091-00-AB (N6LS)  
Protocol VRC 609, Version 9.0  
 
October 07, 2022  
 
Page 67 of 73 
 
Schedule 4 (continued): IV Group 6 (20 mg/kg by repeat dosing) 
Visit Number* 
17E 
18 
19 
20 
21 
22 
23 
24 
25 
26 
Time After Infusion 
24hr 
72hr Wk25 Wk26 Wk28 Wk32 Wk36 Wk40 Wk44 
Wk48 
Day of Study D169 D171 D175 D182 D196 D224 D252 D280 D308 
D336 
Clinical 
Tube^ 
 
 
 
 
 
 
 
 
 
 
Targeted physical exam, BP, pulse, temp 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Complete med history at screen; then interim med hx 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Phone contact; clinic visit if indicated 
 
X 
 
 
 
 
 
 
 
 
 
CBC / diff 
EDTA 
 
3 
3 
3 
 
3 
 
 
 
 
ALT, AST,  ALP, creatinine 
GLT 
 
4 
4 
4 
 
4 
 
 
 
 
Total bili, BUN, albumin, protein, calcium, Na, K, Cl, CO2, glucose 
(CMP) 
GLT 
 
 
 
X 
 
 
 
 
 
 
1Pregnancy test: urine or serum 
 
 
 
 
X 
 
 
X 
 
 
X 
1Pregnancy prevention counseling / Reproductive 
Information Form 
 
 
 
 
X 
 
 
X 
 
 
X 
HIV Ab/Ag combo test 
EDTA 
 
 
3 
 
 
 
 
 
 
 
HIV risk-reduction counseling 
 
 
 
X 
 
 
 
 
 
 
 
Research Samples 
 
 
 
 
 
 
 
 
 
 
 
Timed PK samples 
SST 
 
4 
4 
4 
4 
4 
4 
4 
4 
4 
Serum 
SST 
 
 
8 
8 
8 
8 
8 
8 
8 
8 
Daily Volume (mL) 
 
0 
11 
18 
19 
12 
19 
12 
12 
12 
12 
Cumulative Volume (mL) 
 
316 
327 
345 
364 
376 
395 
407 
419 
431 
443 
 
Visit windows: Schedule visits 17A through 26 with respect to visit 17. Visit E (+1 day); Visit 18 (+2 days), Visits 19-22 (±2 days), and Visits 23-
26 (±7 days). 
1 Complete a Reproductive Information Form when pregnancy test is given.   
* The study schedule study schedule for subjects who discontinue product administration will be modified as follows:  
• Subjects who have only received one product administration will follow Schedule 4 through Visit 10, and then move to Schedule 5.  
• Subjects who have received two product administrations will follow Schedule 4 through Visit 16 and then move to Schedule 5. 
^ Tube types and blood volumes are shown to meet current institutional requirements and projected blood volumes. Different tubes for clinical 
evaluations may be used to meet site requirements. Slightly different volumes and tubes may be used for research blood samples when tubes as 
shown are not available, or as otherwise instructed by the IND Sponsor. Collected blood volumes will stay within the NIH CC blood draw limits 
for each subject. 

Product: VRC-HIVMAB091-00-AB (N6LS)  
Protocol VRC 609, Version 9.0  
 
October 07, 2022  
 
Page 68 of 73 
 
 
 

Product: VRC-HIVMAB091-00-AB (N6LS)  
Protocol VRC 609, Version 9.0  
 
October 07, 2022  
 
Page 69 of 73 
 
Schedule 5: For Subjects in Groups 5 and 6 Discontinued from Further Product Administration(s) 
Visit Number 
11 
15 
16 
17 
21 
22 
23 
Time After Infusion 
Wk12 
Wk16 
Wk20 
Wk24 
Wk28 
Wk32 
Wk36 
Day of Study 
D84 
D112 
D140 
D168 
D196 
D224 
D252 
Clinical 
Tube^ 
 
 
 
 
 
 
 
Targeted exam, BP, pulse, temp 
 
X 
X 
X 
X 
X 
X 
X 
Interim med history 
 
X 
X 
X 
X 
X 
X 
X 
Pregnancy test: urine or serum 
 
 
X 
 
X 
 
 
X 
Pregnancy prevention counseling/ Reproductive Information Form 
 
 
X 
 
X 
 
 
X 
Research Samples 
 
 
 
 
 
 
 
 
PK samples 
SST 
4 
4 
4 
4 
4 
4 
4 
Serum 
SST 
8 
8 
8 
8 
8 
8 
8 
Daily Volume (mL) 
 
12 
12 
12 
12 
12 
12 
12 
If starting at Visit 11 
Cumulative Volume (mL), Group 5 
 
184 
196 
208 
220 
 
 
 
Cumulative Volume (mL), Group 6 
 
188 
200 
212 
224 
 
 
 
If starting at Visit 17 
Cumulative Volume (mL), Group 5 
 
 
 
 
285 
297 
309 
321 
Cumulative Volume (mL), Group 6 
 
 
 
 
298 
310 
322 
334 
Visit windows: ±7 days for all visits shown.  
 
Group 5 or 6 subjects who do not receive the 2nd or 3rd study product will continue study participation under this modified schedule:   
• If only one product administration was received, subjects will follow their originally assigned study schedule through Visit 10 and then move to 
Schedule 5 for Visits 11-17. The final study visit will be Visit 17 for these subjects. 
• If two product administration were received, subjects will follow their originally assigned study schedule through Visit 16 and then move to 
Schedule 5 for Visits 17-23. The final study visit will be Visit 23 for these subjects. 
^ Tube types and blood volumes are shown to meet current institutional requirements and projected blood volumes. Different tubes for clinical 
evaluations may be used to meet site requirements. Slightly different volumes and tubes may be used for research blood samples when tubes as 
shown are not available, or as otherwise instructed by the IND Sponsor.  Collected blood volumes will stay within the NIH CC blood draw limits for 
each subject. 
 
 
 

Product: VRC-HIVMAB091-00-AB (N6LS)  
Protocol VRC 609, Version 9.0  
 
October 07, 2022  
 
Page 70 of 73 
 
Schedule 6: N6LS + rHuPH20 SC Infusion Groups 7 (5 mg/kg) and 8 (20 mg/kg) 
Visit Number 
01R 
02 
02A 
02B 
03 
04 
05 
06 
07 
08 
09 
10 
11 
15 
16 
17 
Time After Infusion 
 
Pre 
EOI 
4hr 
24hr 
48hr 
72hr 
Wk1 
Wk2 
Wk3 
Wk4 
Wk8 Wk12 Wk16 Wk20 Wk24 
1Day of Study -42 to 0 
D0 
D0 
D0 
D1 
D2 
D3 
D7 
D14 
D21 
D28 
D56 
D84 D112 D140 D168 
Clinical 
Tube^ Screen Enroll Day of Administration 
 
 
 
 
 
 
 
 
 
 
 
 
VRC 500 Screening Consent 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
VRC 609 AoU; Consent 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2Screen: Physical exam, ht, wt; Other: 
targeted exam, BP, pulse, temp; also wt 
at visit 02 
 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Complete med history at screen; then 
interim med history 
 
X 
X 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
3 N6LS Administration 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Begin 3-day Diary Card 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CBC / differential 
EDTA 
3 
 
3 
 
 
3 
 
 
3 
3 
 
3 
 
3 
 
 
 
ALT, AST,  ALP, creatinine 
GLT 
4 
 
4 
 
 
4 
 
 
4 
4 
 
4 
 
4 
 
 
 
Total bili, BUN, albumin, protein, calcium, 
Na, K, Cl, CO2, glucose (CMP) 
GLT 
X 
 
X 
 
 
 
 
 
 
X 
 
 
 
X 
 
 
 
4Pregnancy test: urine or serum 
 
X 
X 
X 
 
 
 
 
 
 
X 
 
 
 
 
X 
 
X 
4Pregnancy prevention counseling/ 
Reproductive Information Form 
 
X 
X 
X 
 
 
 
 
 
 
X 
 
 
 
 
X 
 
X 
HIV Ab/Ag combo test 
EDTA 
3 
 
 
 
 
 
 
 
3 
 
 
 
 
 
 
 
 
HIV risk-reduction counseling 
 
X 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
Research Samples 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Timed PK samples 
SST 
 
 
4 
 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
Serum 
SST 
8 
8 
8 
 
 
 
8 
8 
8 
8 
8 
8 
8 
8 
8 
8 
8 
PBMC and Plasma 
EDTA 
20 
 
10 
 
 
 
 
 
 
 
 
10 
10 
 
 
 
 
Daily Volume (mL) 
 
38 
8 
29 
0 
4 
11 
12 
12 
22 
19 
12 
29 
22 
19 
12 
12 
12 
Cumulative Volume (mL) 
 
38 
46 
75 
75 
79 
90 
102 
114 
136 
155 
167 
196 
218 
237 
249 
261 
273 
Visit windows: Schedule visits 02A through 17 with respect to day 0. Visit 02A (+10 min); Visit 02B (± 10 min); Visits 03, 04, 05 (± 6 hrs); Visits 06, 
07, 08, 09 (±2 days); Visits 10, 11, 15, 16, 17 (±7 days). Visits 12-14 are not applicable to Schedule 6. 
1 Day 0=day of first product administration.  Day 0 is preferably scheduled within 14 days after enrollment, but may be scheduled up to 42 days after 
enrollment to allow for the possibility of study pauses or scheduling difficulty with the approval of the PI.  Day 0 evaluations prior to product 
administration are the baseline for assessing subsequent AEs.   
2 Screening includes physical exam with vital signs, height (ht) and weight (wt).  At other visits, if medically indicated, a targeted exam is performed. 
Otherwise only blood pressure (BP), pulse, and temperature are required, except at Visit 02 when the current weight is also obtained to use for ordering 
the study product, dosed based on “mg/kg.” 

Product: VRC-HIVMAB091-00-AB (N6LS)  
Protocol VRC 609, Version 9.0  
 
October 07, 2022  
 
Page 71 of 73 
 
3 The PK blood draw “visits,” defined by hours after an infusion, are relative to the exact time of the end of infusion (EOI).  The exact start and end times 
of product administration and the time of PK blood draw(s) are recorded to ensure accurate PK analysis.  All subjects will be observed for 4 hours after 
product administration.   
4 Pregnancy test results must be negative for women of reproductive potential before each product administration. Complete a Reproductive Information 
Form when pregnancy test is given.  
^ Tube types and blood volumes are shown to meet current institutional requirements and projected blood volumes. Different tubes for clinical 
evaluations may be used to meet site requirements. Slightly different volumes and tubes may be used for research blood samples when tubes as shown 
are not available, or as otherwise instructed by the IND Sponsor. Collected blood volumes will stay within the NIH CC blood draw limits for each 
subject. 
  
 
 
 
 

Product: VRC-HIVMAB091-00-AB (N6LS)  
Protocol VRC 609, Version 9.0  
 
October 07, 2022  
 
Page 72 of 73 
 
APPENDIX II: ASSESSMENT OF RELATIONSHIP TO STUDY PRODUCT AND TABLE 
FOR GRADING SEVERITY OF ADVERSE EVENTS

Product: VRC-HIVMAB091-00-AB (N6LS)  
Protocol VRC 609, Version 7.0  
 
October 6, 2021 
Page 73 of 73 
 
Assessment of Causality Relationship of an Adverse Event to Study Product:  
The relationship between an adverse event (AE) and the product will be assessed by the 
investigator on the basis of his or her clinical judgment and the definitions below.  
• Definitely Related. The AE and administration of study product are related in time, and a 
direct association can be demonstrated.  
• Probably Related. The AE and administration of study product are reasonably related in 
time, and the AE is more likely explained by study product than other causes.  
• Possibly Related. The AE and administration of study product are reasonably related in 
time, but the AE can be explained equally well by causes other than study product.  
• Not Related. There is not a reasonable possibility that the AE is related to the study 
product.  
For purposes of preparing data reports in which AE attributions are limited to “Related” or “Not 
Related”, in this protocol, the “Definitely, Probably and Possibly” attributions will be mapped to 
the “Related” category. The definitions that apply when these two categories alone are used are 
as follows:  
• Related – There is a reasonable possibility that the AE may be related to the study 
product.  
• Not Related – There is not a reasonable possibility that the AE is related to the study 
product. 
Table for Grading Severity of Adverse Events: 
For consistency with other studies of VRC MAb products, 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, Corrected Version 2.1. [July 2017]. Available from: 
https://rsc.tech-res.com/docs/default-source/safety/division-of-aids-(daids)-table-for-grading-the-
severity-of-adult-and-pediatric-adverse-events-corrected-v-2-1.pdf. 
The Table will be used as posted at the link above with the following exemptions: 
• Weight loss will be recorded as an adverse event only if it is considered deleterious to 
the participant’s health. 
• For severity grading of the solicited bruising parameter at the product administration 
site, the definitions based on size of the largest diameter and listed for the “Injection 
Site Erythema or Redness” will be used. The severity grade definition for “Bruising” 
provided under the Dermatologic Clinical Conditions will be used only for 
unsolicited adverse events involving bruising at other body locations.  
• Creatinine changes will be graded on the basis of the upper limit of normal provided 
by the grading table and not change from baseline. 
• Creatinine clearance changes will be graded according to mL/min provided by the 
grading table  and not change from baseline. 
Subclinical CMP results for sodium, potassium, chloride, bicarbonate, BUN, and 
glucose will not be considered an AE unless grade 2 or greater. 

PATIENT IDENTIFICATION
Consent to Participate in a Clinical Research Study
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CONSENT TO PARTICIPATE IN AN NIH CLINICAL RESEARCH STUDY
PRINCIPAL INVESTIGATOR:  Richard Wu, MD
STUDY TITLE: VRC 609 (18I0105): A Phase I, Open-Label, Dose-Escalation Study of the 
Safety and Pharmacokinetics of a Human Monoclonal Antibody, VRC-HIVMAB091-00-AB 
(N6LS), Administered Intravenously or Subcutaneously with or without Recombinant Human 
Hyaluronidase PH20 (rHuPH20) to Healthy Adults
STUDY SITE: NIH Clinical Center
Cohort: Healthy Volunteer
Consent Version:  October 07, 2022, Version 9.0
WHO DO YOU CONTACT ABOUT THIS STUDY? 
Principal Investigator: Richard Wu, MD.,
Study Coordinator:
KEY INFORMATION ABOUT THIS RESEARCH 
This consent form describes a research study and is designed to help you decide if you would 
like to be a part of the research study.  
You are being asked to take part in a research study at the National Institutes of Health (NIH). 
This section provides the information we believe is most helpful and important to you in making 
your decision about participating in this study. Additional information that may help you decide 
can be found in other sections of the document. Taking part in research at the NIH is your choice.
This is a study of an experimental drug called N6LS. N6LS is a monoclonal antibody (mAb) 
that targets HIV. The main purpose of this study is to evaluate if N6LS is safe and how your 
body responds to it. Since this is the first time N6LS will be given to people, we do not know 
how your body will respond. We also want to check if your body will recognize N6LS and make 
an immune response to it. You cannot get HIV from N6LS. 
About 32 to 40 people will take part in this study at the NIH Clinical Center in Bethesda, MD. 
Study groups 1-6 have completed the study. If you decide to take part, you will be enrolled in 
Groups 7 or 8 and you will be in the study for about 24 weeks (6 months) and get N6LS one 
time on Day 0 as an injection in the fat under your skin, subcutaneously (SC). N6LS will be 
mixed with rHuPH20. rHuPH20 helps to increase the distribution of injected drugs. 
If you have side effects from N6LS, we expect them to like the side effects that occur with 
similar mAbs. These side effects usually occur within the first 24 hours or few days after the 
mAb is given and include local symptoms such as pain, redness, swelling, and itching, but 
injection site redness may take up to 6 weeks to fully resolve. Also, fever, tiredness, body 
aches, headache, chills, nausea, and joint pain may occur. The following side effects, although 
rare, may occur including trouble breathing, itchiness, rash, hives, swelling, or chest pain. 
Some mAbs have a risk of serious allergic reactions that can be life threatening.
During the study, we will collect blood samples from you. Some of your blood will be stored
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for future research. You will be compensated for your time and inconvenience for taking part
in this study. You will not benefit from this study.
To be in this study, you must be willing to use an effective birth control method and not 
become pregnant from at least 21 days prior to enrollment through the end of the study, if you 
are a woman who is able to get pregnant.
The remaining document will now describe the research study in more detail.  This information 
should be considered before you make your choice. Members of the study team will talk with you 
about the information in this document. Some people have personal, religious, or ethical beliefs 
that may limit the kinds of medical or research interventions in which they would want to 
participate. Take the time you need to ask any questions and discuss this study with NIH staff, and 
with your family, friends, and personal health care providers.
IT IS YOUR CHOICE TO TAKE PART IN THE STUDY
You may choose not to take part in this study for any reason. If you join this study, you may change 
your mind and stop participating in the study at any time and for any reason. In either case, you 
will not lose any benefits to which you are otherwise entitled. However, to be seen at the NIH, you 
must be taking part in a study or are being considered for a study. If you do choose to leave the 
study, please inform your study team to ensure a safe withdrawal from the research.  
WHY IS THIS STUDY BEING DONE?
HIV infection is a serious disease with no cure or vaccine to prevent it. Researchers have been 
working hard to figure out new ways to treat or prevent HIV infection. Using antibodies is one 
way to prevent HIV infection that seems promising. Antibodies are naturally made by the body 
to fight germs so that people remain healthy.  This study will test an antibody called N6LS. 
N6LS has been used in the lab to block an HIV-like virus from causing infection in animals. The 
U.S. Food and Drug Administration (FDA) only allows it to be used for research because it is an 
experimental product.  The study will also test N6LS mixed with an enzyme, rHuPH20 
(recombinant human hyaluronidase PH20). rHuPH20 increases the spread of fluids injected 
underneath your skin (subcutaneously, SC) and allows for the rapid delivery of large volume 
injections that can be given with a single needle. 
This study is the first time N6LS is tested in humans. N6LS is given into a vein in your arm 
(intravenously, IV) or as an injection underneath your skin subcutaneously. This study will be 
the first to test N6LS mixed with rHuPH20 in Groups 7 and 8. This study uses the same strength 
of enzyme that is given to patients receiving FDA approved products like trastuzumab and 
rituximab, used to treat cancer; and HyQvia®, used to treat immune problems in people with low 
antibody levels.
The goals of this study are:  

To see if N6LS alone and N6LS mixed with rHuPH20 is safe and well-tolerated.  

To measure the amount of N6LS that can be found in your body after you get it and how 
the levels of N6LS change over time.

To check if your body will recognize N6LS and make a response to it. 
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You will need to complete about 13 to 26 clinic visits over 24 to 48 weeks depending on your 
study group.
STUDY PRODUCT(S)
The N6LS antibody is a monoclonal antibody (MAb) that targets HIV. Monoclonal means that all 
the N6LS antibodies are exactly the same and have been made artificially in the lab. The part of 
N6LS that binds to HIV was first discovered in a person who had HIV and controlled the infection 
for more than 15 years without taking any HIV medicine. Scientists at the NIH studied many 
antibodies this person made, and then figured out how to make them in the lab. They then made 
changes to the antibodies so that they can stay in the body longer than usual. N6LS was made in 
the same high standards that are required for medications normally prescribed to people.  
We do not know if N6LS can be used to prevent or treat HIV in humans. This study will not be 
able to answer this question. Different studies will have to be done to do that. 
You cannot get HIV from N6LS. 
N6LS will be given together with rHuPH20 in study Groups 7 and 8. Your body naturally builds 
up and breaks down a substance called hyaluronan, which is a chain of natural sugars that are part 
of the normal tissue under your skin. rHuPH20 works by breaking down the hyaluronan. This way 
there is more space underneath your skin for larger amounts of N6LS to enter more easily. Once 
rHuPH20 is gone, your body builds the hyaluronan back up. The changes caused by rHuPH20 are 
gone within 24-48 hours after it is given. 
WHAT WILL HAPPEN DURING THE STUDY?
The study will have 8 groups as shown in the Study Design table.  Each group will have about 3 
to 5 people in it.  Different groups will get different doses of N6LS. Some groups will get more 
than one dose. Most people will get N6LS into a vein (IV).  Some people will get N6LS with or 
without rHuPH20 into the belly fat under the skin (SC). You will be in the clinic for about 8 hours 
on the day(s) N6LS is given.  Other clinic visits will take about 2 hours.  
The study will last about 24 weeks for people in Groups 1-4, 7, and 8 because they will only get 
N6LS once.  This will allow us to see if the doses of the antibody are safe and how long it lasts in 
the body. 
The study will last for about 48 weeks for people in Groups 5 and 6 because they will get N6LS 
three times. This will allow us to see how much of the antibody stays in the body through three 
doses.  
We also want to see the differences between getting N6LS by the IV or SC routes and the effect 
of N6LS mixed with rHuPH20 given in one SC injection. This information will be helpful for 
future uses of N6LS and rHuPH20. 
Enrollment in Groups 1-6 is complete. If you agree to take part in this study, you will be enrolled 
in Group 7 or Group 8 and get 1 dose of N6LS + rHuPH20.  You will be weighed on the day N6LS 
is to be given. Your body weight is used to calculate the amount of N6LS you will get.  
The dose groups are shown in the Study Design table. 
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The study opened with the lowest dose of N6LS. The dose groups were spaced out to allow the 
study team to look over the safety data in each group.  If there were no safety concerns in the 
lowest doses, then the next higher dose groups were enrolled. This pattern continued until all dose 
groups were enrolled.  
A pregnancy test will be given to all woman who are able to become pregnant before N6LS is to 
be given. The result of the test must be negative in order to get N6LS. 

IV Dosing Groups (1, 3, 4, and 6): 
If you are assigned to Groups 1, 3, 4, or 6, a thin tube will be placed in your arm vein on 
the day you are to get the study product.  We will place a second IV line in a vein on your 
other arm for blood sample collection. The N6LS will be given directly into your vein using 
a pump to control how fast it goes in.  The goal is to give the N6LS in about 30 minutes, 
but may take longer. If you have side effects, the rate may be slowed down or stopped.  
When the infusion is done, we will monitor you in the clinic for 4 hours when you get 
N6LS the 1st time. We will collect blood samples at 1 and 3 hours after the infusion. You 
may be allowed to leave the clinic after 4 hours if there are no safety concerns, but must 
return for a blood draw at 6 hours after the infusion. You will also be asked to come back 
to the clinic 1 to 3 times during that first week after the infusion for sample collection. 
If you are in Group 6, you will get N6LS two more times during the study. We will monitor 
you in the clinic for at least 2 hours after you get the 2nd and 3rd infusions of N6LS. We 
will collect blood samples from you before and after each infusion. You will also be asked 
to come back to the clinic 4-5 times between and after these doses.
Study Design
Study Products
Dosing Schedule
Dose
Groups
Participants
N6LS Dose
rHuPH20
Dosing Site
Day 0
Week 12
Week 24
Total Number 
of Study Visits
1
3
5 mg/kg  
-
IV
X
13
2
3
5 mg/kg  
-
SC
X
14
3
3
20 mg/kg  
-
IV
X
13
4
3
40 mg/kg  
-
IV
X
13
5
5
5 mg/kg  
-
SC
X
X
X
25
6
5
20 mg/kg  
-
IV
X
X
X
24
7
5
5 mg/kg  
+
SC
X
14
8
5
20 mg/kg  
+
SC
X
14
Total
32
IV= using an arm vein; SC = under skin
Note: The dose of rHuPH20 is 2000 units per mL relative to the N6LS dose
volume.
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
SC Dosing Groups (2 and 5):
If you are assigned to Groups 2 or 5, we will use a small needle to inject N6LS into the 
fatty tissue of your belly.  We may use your arm or thigh area instead. You will get 1 to 4 
of these injections for each dose. We will monitor you for 4 hours after you get N6LS the 
1st time. If there are no safety concerns, you will be allowed to leave the clinic after the 4 
hour safety check. If you are in Group 5, you will get N6LS two more times during the 
study. We will monitor you in the clinic for at least 2 hours after you get the 2nd and 3rd 
doses of N6LS. We will collect blood samples from you before the injection and then at 
every scheduled follow-up visit.  

SC Dosing Groups with rHuPH20 (7 and 8):
If you are assigned to Groups 7 or 8, we will use a small needle attached to a pump to 
infuse the mix of N6LS and rHuPH20 into the fatty tissue of your belly. We will monitor 
you for 4 hours after you get N6LS. If there are no safety concerns, you will be allowed to 
leave the clinic after the 4-hour safety check. We will collect 6 tubes of blood from you 
before the infusion, 1 tube 4 hours after the infusion, and then 2-5 tubes of blood at each 
follow-up visit.   
We will give you a measuring tool and thermometer and ask you to check your temperature every 
day for 3 days after you get the study product(s).  You will need to record your highest temperature 
and any symptoms you have. You will use the measuring tool to measure any redness, swelling, 
or bruising you may have at the injection site. You will get a password to a secure website to record 
this information. If you do not have a computer, you may use a paper diary instead.  
You should tell a VRC nurse or doctor as soon as possible if you have any side effects after you 
get the study product(s).  You can reach the staff by phone 24 hours a day, seven days a week.  If 
you have symptoms, you may need to come into the clinic for a physical exam before your next 
scheduled visit.  It is very important that you follow the instructions from the clinic staff. 
Follow-up visits:  We will check you for any health changes or problems at each visit.  We will 
ask you how you are feeling and if you have taken any medications.  We will draw about 1 to 5 
tubes of blood at scheduled study visits. We will tell you right away if any of your test results show 
a health problem.  
We will use some blood samples to study if your body develops an immune response to N6LS.  
These tests are for research purposes only and are not for checking on your health.  We will not 
give you these results.  After completing this study, we may invite you to take part in another study 
for follow-up sample collection.
Clinical studies follow a set schedule.  This helps us to 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 to not miss any visits.
HIV TESTING AND COUNSELING
HIV risk-reduction counseling and testing will be provided to you if you take part in this study. 
We will test you for HIV. We will tell you how to remain HIV-uninfected and give you prevention 
resources. If you are infected with HIV, you will not be able to receive N6LS. We will tell you 
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what the results mean, how to find care, how to avoid infecting others, how we report HIV 
infection, and the importance of informing your partners that may be at risk because of your HIV 
infection.
If you have questions about HIV testing, you should discuss them with the study nurse or doctor. 
You may also call an NIH Clinical Center HIV counselor at 301-496-2381.
MONITORING OF THE STUDY
A group of physicians and scientists at NIH will monitor safety in 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, further dosing with the study product(s) may be delayed or canceled.
GENETIC TESTING
Some of the blood drawn from you as part of this study will be used for genetic tests. Some genetic 
tests are done in research studies to see if genetic differences in people cause different types of 
immune responses.  Your blood sample used in these genetic tests will not have your name on it 
and the results will not be in your medical record.  These tests are not used to check your health 
and we will not tell you the results. 
The genetic testing performed in this study is for research purposes only. Any genetic information 
collected or learned about you will be kept confidential.
HOW MANY PEOPLE WILL PARTICIPATE IN THIS STUDY?
Thirty-two (32) to 40 people will take part in this study at the NIH Clinical Center in Bethesda, 
Maryland.
WHAT ARE THE RISKS AND DISCOMFORTS OF BEING IN THE STUDY?
Risks of N6LS: This study is the first time N6LS is given to people. As of August 4, 2021, N6LS 
has been given to 14 people by IV and 12 people by SC injection. 
The safety data described below is taken from studies with other antibodies that are like N6LS and 
may work the same and from observations seen in the study so far. Most side effects tend to happen 
within the first 24 hours to a few days after product administration. 
Side effects to N6LS-like antibodies given by IV dosing 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 symptoms usually go away 
within a few minutes to hours after the product is given. We are giving N6LS at a controlled rate.  
If you develop symptoms while N6LS is being given, then tell the nurse right away.  Slowing or 
stopping the flow rate may help improve the symptoms.   
Side effects to N6LS-like antibodies given by SC dosing may include pain/tenderness, itchiness, 
redness and/or swelling at the site of injection. Two people in the trial who received N6LS 
+rHuPH20 SC developed larger injection site redness. The redness was almost 8 inches at its 
largest and took up to 30 days to go away. They did not have other signs or symptoms such as 
fever, scarring, or any other skin related issues. The team determined it was safe to continue 
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because both individuals tolerated the redness well and did not have abnormal laboratory tests. 
Therefore the redness was judged not to represent an increased safety risk for study participants. 
Tiredness, muscle pain outside the injection site, and headache have also been reported. These 
symptoms usually cleared within 1 to 2 days.
Some antibody products have a risk of serious allergic reactions 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, rash, or swelling 
in the mouth and face. 
Serum sickness is a type of reaction that may happen several days or weeks after an antibody is 
given.  This reaction may include hives, rash, fever, enlarged lymph nodes, muscle pains, or joint 
pains.  
Some antibodies of the type that change how the immune system works can increase the risk of 
serious infections.  N6LS is not expected to increase the risk of serious infections because it attacks 
a virus and does not target the human immune system.
Unknown risks: N6LS may have other side effects that are not yet known. Participation in this 
study may affect your eligibility for future monoclonal antibody studies. We will give you any 
new information about risks or other information that may affect your decision to continue in the 
study as it becomes available.
You may not donate blood while taking part in this study and you may not donate blood for one 
year after the date of your last dose of N6LS. 
Risks of rHuPH20: This study is the first time that a combination of N6LS and rHuPH20 will be 
given to people. The active ingredient in rHuPH20 (hyaluronidase) has been given to roughly 
1,592 people alone and in combination with other products in controlled clinical studies by its 
manufacturer as of November 15, 2020. Also, SC injections of hyaluronidase when given with 
other antibodies and proteins, including 5 FDA-approved products, have been well-tolerated in 
over 600,000 people. Some people have experienced mild, short-term redness, pain, bruising, 
itching, swelling, tingling, numbness, and rash at the injection site. A few people have 
experienced more severe burning, redness, pain, and numbness, but this is less common. Several 
people have experienced mild to moderate headache. 
Risks of IV or SC dosing:  General risks of methods that use a needle include stinging, discomfort, 
pain, soreness, redness, bruising, swelling or a tiny cut at the needle insertion site.
Risks of Blood Drawing: Blood drawing may cause pain, bruising, and may cause a feeling of 
lightheadedness or fainting.  Rarely, it may cause infection at the site where the blood is taken. An 
IV line may be placed in your vein for a few hours on a day N6LS is given by IV.  Problems at the 
IV site are usually mild and may include pain, bruising, minor swelling, or bleeding.  Rarely, there 
may be an infection, vein irritation, nerve problem, or blood clot.  
What are the risks related to pregnancy? 
If you are able to become pregnant, we will ask you to have a pregnancy test before starting this 
study. You must use effective birth control methods and try not to become pregnant while 
participating in this study. If you become pregnant, there may be unknown risks to the fetus or 
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unborn child, or risks that we did not anticipate. There may be long-term effects of the treatment 
being studied that could increase the risk of harm to a fetus. You must tell the study doctor if your 
birth control method fails while you are in the study. If you think or know you have become 
pregnant while participating in this research study, please contact the study team as soon as 
possible.  If you get pregnant, you will not receive any further doses of N6LS, and 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. If you plan to become 
pregnant in the future, please discuss with the study team how long you need to wait before 
becoming pregnant after completing the study.
WHAT ARE THE BENEFITS OF BEING IN THE STUDY?
You will not benefit from being in this study.
Are there any potential benefits to others that might result from the study?
Others may benefit in the future from the information that will be learned from the study
WHAT OTHER OPTIONS ARE THERE FOR YOU?
Instead of being in this study, you could choose not to take part. You may be eligible 
for other VRC studies. 
DISCUSSION OF FINDINGS
New information about the study
If we find out any new information that may affect your choice to participate in this study, we 
will get in touch with you to explain what we have learned. This may be information we have 
learned while doing this study here at the NIH or information we have learned from other 
scientists doing similar research in other places.
Return of research results
At each visit you will be checked for any health changes or problems. Blood will be drawn at 
almost every study visit to check on your health. You will be told right away, either by phone call 
or text if any of your test results show a health problem.
The results of this study may be reported in medical journals, on the internet or at scientific 
meetings. We will give you information about how to find the study results once they are available.
EARLY WITHDRAWAL FROM THE STUDY 
You may be removed from the research study by the researcher for any of the following reasons:

You don't keep appointments or follow study procedures;

You get a serious illness that needs ongoing medical care;

You become pregnant;

You need to get treatment with a medication that affects your immune system 
(such as a steroid like prednisone);
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PATIENT IDENTIFICATION
Consent to Participate in a Clinical Research Study
NIH-2977 (4-17)
File in Section 4: Protocol Consent (1)
Version Date: 10/07/2022 V9.0
Page 9 of 14
CC ICF template v9 04.13.2021
MEDICAL RECORD
CONSENT TO PARTICIPATE IN AN NIH CLINICAL RESEARCH STUDY

If the researcher believes that it is in your best interest to remove you from the study;

The study is stopped by regulatory agencies, the study sponsor or study 
investigators. If  this happens, we will tell you why.
If you agree to take part in this study, it is important for you to keep all of your appointments. Your  
participation in this study is completely voluntary. You can choose to stop taking part in the study 
at any time. There is no penalty or loss of benefits if you choose to leave the study.
STORAGE, SHARING AND FUTURE RESEARCH USING YOUR SPECIMENS AND 
DATA
Will your specimens or data be saved for use in other research studies? As part of this study, we 
are obtaining specimens and data from you. We will remove all the identifiers, such as your 
name, date of birth, address, or medical record number and label your specimens and data with 
a code so that you cannot easily be identified. However, the code will be linked through a key to 
information that can identify you. We plan to store and use these specimens and data for studies 
other than the ones described in this consent form that are going on right now, as well as studies 
that may be conducted in the future. These studies may provide additional information that will 
be helpful in understanding other diseases or conditions. This could include studies to develop 
other research tests, treatments, drugs, or devices, that may lead to the development of a 
commercial product by the NIH and/or its research or commercial partners. There are no plans 
to provide financial compensation to you if this happens. Also, it is unlikely that we will learn 
anything from these studies that may directly benefit you.
By agreeing to take part in this study, you give permission for your coded specimens and data to 
be stored and used for future research as described above.
Will your specimens or data be shared for use in other research studies?
We may share your coded specimens and data with other researchers.  If we do, while we will 
maintain the code key, we will not share it, so the other researchers will not be able to identify 
you.  They may be doing research in areas that are similar to this study or in other unrelated 
areas. These researchers may be at NIH, other research centers and institutions, or commercial 
entities.
By agreeing to take part in this study, you give permission for your coded specimens and data to 
be shared with other researchers and used by these researchers for future research as described 
above. 
If you change your mind and do not want us to use your specimens and data for future research, 
you should contact the research team member identified at the top of this document. We will do 
our best to comply with your request but cannot guarantee it. For example, if research with your 
specimens and/or data has already been completed, the information from that research may still 
be used. Also, for example, if the specimens and data have been shared already with other 
researchers, it might not be possible to withdraw them. 
In addition to the planned use and sharing described above, we might remove all identifiers and 
codes from your specimens and data and use or share them with other researchers for future 
research at the NIH or other places.  When we or the other researchers access your anonymized 
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Consent to Participate in a Clinical Research Study
NIH-2977 (4-17)
File in Section 4: Protocol Consent (1)
Version Date: 10/07/2022 V9.0
Page 10 of 14
CC ICF template v9 04.13.2021
MEDICAL RECORD
CONSENT TO PARTICIPATE IN AN NIH CLINICAL RESEARCH STUDY
data, there will be no way to link the specimens or data back to you.  We will not contact you to 
ask your permission or otherwise inform you before we do this.  If we do this, we would not be 
able to remove your specimens or data to prevent their use in future research studies, even if you 
asked, because we will not be able to tell which are your specimens or data.
NIH policies require that your clinical and other study data be placed in an internal NIH database 
that is accessible to other NIH researchers for future research. Usually, these researchers will not 
have access to any of your identifiers, such as your name, date of birth, address, or medical 
record number; and your data will be labeled with only a code. We cannot offer you a choice of 
whether your data to be placed in this database or not.  If you do not wish to have your data 
placed in this database, you should not enroll in this study.  
How long will your specimens and data be stored by the NIH?
Your specimens and data may be stored by the NIH indefinitely. 
Risks of storage and sharing of specimens and data
When we store your specimens and data, we take precautions to protect your information from 
others that should not have access to it. When we share your specimens and data, we will do 
everything we can to protect your identity, for example, when appropriate, we remove information 
that can identify you. Even with the safeguards we put in place, we cannot guarantee that your 
identity will never become known or someone may gain unauthorized access to your information. 
New methods may be created in the future that could make it possible to re-identify your specimens 
and data.
PAYMENT
Will you receive any type of payment for taking part in this study?
You will be compensated for your time and inconvenience. Total compensation for completion of 
the study will be between $2500 to $4900 and is based on the number and type of study visits you 
complete. You will get: 

$200 for scheduled visits with a blood draw.

$85 for clinic visits that do not include a blood draw.

$430 for IV product administration visit(s) with blood draws on the same day. 

$430 for SC product administration visit(s) with blood draws on the same day.  

$375 for SC product administration visit(s) with no blood draw.  

$25 total for timely completion of all 3 days of an electronic diary.    
You will get your compensation about 2 weeks after each completed visit by direct deposit into a 
bank account that you specify to the Volunteer Payment Office.  If you are unable to finish the 
study, you will receive compensation for the parts you completed.  Your compensation may need 
to be reported to the internal revenue service (IRS) as taxable income.  IRS “Form 1099-Other 
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Consent to Participate in a Clinical Research Study
NIH-2977 (4-17)
File in Section 4: Protocol Consent (1)
Version Date: 10/07/2022 V9.0
Page 11 of 14
CC ICF template v9 04.13.2021
MEDICAL RECORD
CONSENT TO PARTICIPATE IN AN NIH CLINICAL RESEARCH STUDY
Income” will be sent to you if your total payments for research participation are $600 or more in 
a calendar year. 
We will need your social security number to process your payment. You can still take part in the 
study if you don’t give us your social security number, but you might not be able to get your 
payment. If you have unpaid debt to the federal government, some or all of your compensation 
may be automatically reduced to repay your debt.
REIMBURSEMENT
Will you receive reimbursement or direct payment by NIH as part of your participation?
This study does not offer reimbursement for, or payment of, travel, lodging or meals.
COSTS
Will taking part in this research study cost you anything?
NIH does not bill health insurance companies or participants for any research or related clinical 
care that you receive at the NIH Clinical Center. 
CONFLICT OF INTEREST (COI) 
The NIH reviews NIH staff researchers at least yearly for conflicts of interest.  This process is 
detailed in a COI Guide.  You may ask your research team for a copy of the COI Guide or for more 
information.  Members of the research team who do not work for NIH are expected to follow these 
guidelines or the guidelines of their home institution, but they do not need to report their personal 
The NIH and the research team for this study have developed N6LS being used in this study. 
This means it is possible that the results of this study could lead to payments to NIH. By law, the 
government is required to share such payments with the employee inventors. You will not 
receive any money from the development of N6LS. 
CLINICAL TRIAL REGISTRATION AND RESULTS REPORTING 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required 
by U.S. Law. This Web site will not include information that can identify you. At most, the Web 
site will include a summary of the results. You can search this Web site at any time.
CONFIDENTIALITY PROTECTIONS PROVIDED IN THIS STUDY  
Will your medical information be kept private? 
We will do our best to make sure that the personal information in your medical record will be kept 
private.  However, we cannot guarantee total privacy.  Organizations that may look at and/or copy 
your medical records for research, quality assurance, and data analysis include:

The NIH and other government agencies, like the Food and Drug Administration (FDA), 
which are involved in keeping research safe for people.

National Institutes of Health Intramural Institutional Review Board
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PATIENT IDENTIFICATION
Consent to Participate in a Clinical Research Study
NIH-2977 (4-17)
File in Section 4: Protocol Consent (1)
Version Date: 10/07/2022 V9.0
Page 12 of 14
CC ICF template v9 04.13.2021
MEDICAL RECORD
CONSENT TO PARTICIPATE IN AN NIH CLINICAL RESEARCH STUDY

The study Sponsor, Vaccine Research Center, NIAID or their agent(s) 

Qualified representatives from Halozyme Therapeutics, the pharmaceutical company who 
produces rHuPH20.
The researchers conducting this study and the NIH follow applicable laws and policies to keep 
your identifying information private to the extent possible.  However, there is always a chance 
that, despite our best efforts, your identity and/or information about your participation in this 
research may be inadvertently released or improperly accessed by unauthorized persons.
In most cases, the NIH will not release any identifiable information collected about you without 
your written permission.  However, your information may be shared as described in the section of 
this document on sharing of specimens and data, and as further outlined in the following sections.  
Further, the information collected for this study is protected by NIH under a Certificate of 
Confidentiality and the Privacy Act. 
Certificate of Confidentiality
To help us protect your privacy, the NIH Intramural Program has received a Certificate of 
Confidentiality (Certificate). With this certificate, researchers may not release or use data or 
information about you except in certain circumstances.  
NIH researchers must not share information that may identify you in any federal, state, or local 
civil, criminal, administrative, legislative, or other proceedings, for example, if requested by a 
court.  
The Certificate does not protect your information when it:  
1. is disclosed to people connected with the research, for example, information may be used 
for auditing or program evaluation internally by the NIH; or 
2. is required to be disclosed by Federal, State, or local laws, for example, when information 
must be disclosed to meet the legal requirements of the federal Food and Drug 
Administration (FDA); 
3. is for other research;
4. is disclosed with your consent. 
The Certificate does not prevent you from voluntarily releasing information about yourself or your 
involvement in this research. 
The Certificate will not be used to prevent disclosure to state or local authorities of harm to self or 
others including, for example, child abuse and neglect, and by signing below you consent to those 
disclosures. Other permissions for release may be made by signing NIH forms, such as the Notice 
and Acknowledgement of Information Practices consent.
Privacy Act
The Federal Privacy Act generally protects the confidentiality of your NIH medical information 
that we collect under the authority of the Public Health Service Act.  In some cases, the Privacy 
Act protections differ from the Certificate of Confidentiality.  For example, sometimes the Privacy 
Act allows release of information from your record without your permission, for example, if it is 
requested by Congress. Information may also be released for certain research purposes with due 
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PATIENT IDENTIFICATION
Consent to Participate in a Clinical Research Study
NIH-2977 (4-17)
File in Section 4: Protocol Consent (1)
Version Date: 10/07/2022 V9.0
Page 13 of 14
CC ICF template v9 04.13.2021
MEDICAL RECORD
CONSENT TO PARTICIPATE IN AN NIH CLINICAL RESEARCH STUDY
consideration and protection, to those engaged by the agency for research purposes, to certain 
federal and state agencies, for HIV partner notification, for infectious disease or abuse or neglect 
reporting, to tumor registries, for quality assessment and medical audits, or when the NIH is 
involved in a lawsuit.  However, NIH will only release information from your medical record if it 
is permitted by both the Certificate of Confidentiality and the Privacy Act.
POLICY REGARDING RESEARCH-RELATED INJURIES  
The NIH 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 NIH, the NIH Clinical Center, or the Federal 
Government. However, you have the right to pursue legal remedy if you believe that your injury 
justifies such action.
PROBLEMS OR QUESTIONS
If you have any problems or questions about this study, or about your rights as a research 
participant, or about any research-related injury, contact the Principal Investigator, Richard Wu, 
nother researcher you may call is: 
 You may also call the NIH Clinical Center Patient Representative at
 
or the NIH Office of IRB Operations, at 
 if you have a research-related complaint 
or concern.
CONSENT DOCUMENT 
Please keep a copy of this document in case you want to read it again.
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PATIENT IDENTIFICATION
Consent to Participate in a Clinical Research Study
NIH-2977 (4-17)
File in Section 4: Protocol Consent (1)
Version Date: 10/07/2022 V9.0
Page 14 of 14
CC ICF template v9 04.13.2021
MEDICAL RECORD
CONSENT TO PARTICIPATE IN AN NIH CLINICAL RESEARCH STUDY
Adult Research Participant: I have read the explanation about this study and have been given the opportunity 
to discuss it and to ask questions. I consent to participate in this study.
Signature of Research Participant
Print Name of Research Participant
Date
Investigator:
Signature of Investigator
Print Name of Investigator
Date
Witness should sign below if either:
1. A short form consent process has been used to enroll a non-English speaking subject or
2. An oral presentation of the full consent has been used to enroll a blind or illiterate subject
Signature of Witness
Print Name of Witness
Date
NIH ADMINISTRATIVE SECTION TO BE COMPLETED REGARDING THE USE OF AN 
INTERPRETER:
An interpreter, or other individual, who speaks English and the participant’s preferred language facilitated
the administration of informed consent and served as a witness. The investigator obtaining consent may not 
also serve as the witness.
An interpreter, or other individual, who speaks English and the participant’s preferred language facilitated
the administration of informed consent but did not serve as a witness. The name or ID code of the person 
providing interpretive support is:
.
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PATIENT IDENTIFICATION
Consent to Participate in a Clinical Research Study
NIH-2977 (4-17)
File in Section 4: Protocol Consent (2)
Version Date: 10/07/2022, V8.0
Page 1 of 4
CC ICF template v. 09.27.19
MEDICAL RECORD
CONSENT TO PARTICIPATE IN AN NIH CLINICAL RESEARCH STUDY
PRINCIPAL INVESTIGATOR:  Richard Wu; VRC, NIAID
STUDY TITLE:  VRC 609: A Phase I, Open-Label, Dose-Escalation Study of the Safety and 
Pharmacokinetics of a Human Monoclonal Antibody, VRC-HIVMAB091-00-AB (N6LS), 
Administered Intravenously or Subcutaneously with or Without Recombinant Human 
Hyaluronidase PH20 (rHUPH20) to Healthy Adults
STUDY SITE:  NIH Clinical Center
Cohort: Healthy volunteer supplemental
Supplementary Consent Version:  October 07, 2022, Version 8.0
WHO DO YOU CONTACT ABOUT THIS STUDY? 
Principal Investigator: Richard Wu, M.D.,
Study Coordinator:
Supplementary consent for extended genetic testing (optional)
You agreed to participate in VRC 609 study for testing of and an investigational human 
monoclonal antibody to the HIV-1 envelope. This additional consent covers optional extended 
genetic testing that you may agree to. You do not need to provide an additional sample if you 
agreed to extended genetic testing. If you do not agree to this additional testing, you still can 
participate in the VRC 609 study. 
There is a new type of genetic test that lets us look at the expressions of genes, called transcriptome 
sequencing. This test lets us look at the genes that are actively expressed at any given moment. 
However, it does not measure the amount of protein produced. Also, this new genetic test is still 
in development and researchers are working on understanding the data and how that data can be 
utilized in various clinical applications, such as in medicine to help prevent disease. 
Genetic Data Sharing 
Following genetic testing for transcriptome sequencing, your sequence data may be shared in a 
controlled access public database, for other investigators to benefit from it. However, no personal, 
identifiable information will be shared in this process, as the shared results will be coded with no 
link back to you.
Certificate of Confidentiality
To help us protect your privacy, the NIH Intramural Program has received a Certificate of 
Confidentiality (Certificate). With this certificate, researchers may not release or use data or 
information about you except in certain circumstances.  
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PATIENT IDENTIFICATION
Consent to Participate in a Clinical Research Study
NIH-2977 (4-17)
File in Section 4: Protocol Consent (2)
Version Date: 10/07/2022, V8.0
Page 2 of 4
CC ICF template v. 09.27.19
MEDICAL RECORD
CONSENT TO PARTICIPATE IN AN NIH CLINICAL RESEARCH STUDY
NIH researchers must not share information that may identify you in any federal, state, or local 
civil, criminal, administrative, legislative, or other proceedings, for example, if requested by a 
court.  
The Certificate does not protect your information when it:  
1. is disclosed to people connected with the research, for example, information may be used 
for auditing or program evaluation internally by the NIH; or 
2. is required to be disclosed by Federal, State, or local laws, for example, when information 
must be disclosed to meet the legal requirements of the federal Food and Drug 
Administration (FDA); 
3. is for other research;
4. is disclosed with your consent. 
The Certificate does not prevent you from voluntarily releasing information about yourself or your 
involvement in this research. 
The Certificate will not be used to prevent disclosure to state or local authorities of harm to self or 
others including, for example, child abuse and neglect, and by signing below you consent to those 
disclosures. Other permissions for release may be made by signing NIH forms, such as the Notice 
and Acknowledgement of Information Practices consent.
Privacy Act
The Federal Privacy Act generally protects the confidentiality of your NIH medical information 
that we collect under the authority of the Public Health Service Act.  In some cases, the Privacy 
Act protections differ from the Certificate of Confidentiality.  For example, sometimes the Privacy 
Act allows release of information from your record without your permission, for example, if it is 
requested by Congress. Information may also be released for certain research purposes with due 
consideration and protection, to those engaged by the agency for research purposes, to certain 
federal and state agencies, for HIV partner notification, for infectious disease or abuse or neglect 
reporting,  to tumor registries, for quality assessment and medical audits, or when the NIH is 
involved in a lawsuit.  However, NIH will only release information from your medical record if it 
is permitted by both the Certificate of Confidentiality and the Privacy Act.
POLICY REGARDING RESEARCH-RELATED INJURIES  
The NIH 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 NIH, the NIH Clinical Center, or the Federal 
Government. However, you have the right to pursue legal remedy if you believe that your injury 
justifies such action.
PROBLEMS OR QUESTIONS
If you have any problems or questions about this study, or about your rights as a research 
participant, or about any research-related injury, contact the Principal Investigator, Richard Wu, 
M.D.
 Another researcher you may call is
  You may also call the NIH Clinical Center Patient Representative at 
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PATIENT IDENTIFICATION
Consent to Participate in a Clinical Research Study
NIH-2977 (4-17)
File in Section 4: Protocol Consent (2)
Version Date: 10/07/2022, V8.0
Page 3 of 4
CC ICF template v. 09.27.19
MEDICAL RECORD
CONSENT TO PARTICIPATE IN AN NIH CLINICAL RESEARCH STUDY
 or the NIH Office of IRB Operations at 
 if you have a research-related 
complaint or concern.
CONSENT DOCUMENT 
Please keep a copy of this document in case you want to read it again.
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PATIENT IDENTIFICATION
Consent to Participate in a Clinical Research Study
NIH-2977 (4-17)
File in Section 4: Protocol Consent (2)
Version Date: 10/07/2022, V8.0
Page 4 of 4
CC ICF template v. 09.27.19
MEDICAL RECORD
CONSENT TO PARTICIPATE IN AN NIH CLINICAL RESEARCH STUDY
Adult Research Participant: I have read the explanation about this study and have been given the opportunity 
to discuss it and to ask questions. I consent to participate in this study.
Signature of Research Participant
Print Name of Research Participant
Date
Investigator:
Signature of Investigator
Print Name of Investigator
Date
Witness to the oral short-form consent process only: This section is only required if you are doing the oral 
short-consent process with a non-English speaking subject and this English consent form has been approved 
by the IRB for use as the basis of translation.
Witness:
Signature of Witness*
Print Name of Witness
Date
*NIH ADMINISTRATIVE SECTION TO BE COMPLETED REGARDING THE USE OF AN 
INTERPRETER:
An interpreter, or other individual, who speaks English and the participant’s preferred language facilitated
the administration of informed consent and served as a witness. The investigator obtaining consent may not 
also serve as the witness.
An interpreter, or other individual, who speaks English and the participant’s preferred language facilitated
the administration of informed consent but did not serve as a witness. The name or ID code of the person 
providing interpretive support is:
.
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