A Multicenter, Randomized, Partially Blinded Phase 1 Clinical Trial to Evaluate the Safety and Serum Concentrations of a Human Monoclonal Antibody, VRC-HIVMAB075-00-AB (VRC07-523LS), Administered in Multiple Doses and Routes to Healthy, HIV-uninfected Adults
Phase: PHASE1
Conditions: HIV Infections
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

  
 
PROTOCOL 
HVTN 127/HPTN 087 
A multicenter, randomized, partially blinded phase 1 
clinical trial to evaluate the safety and serum 
concentrations of a human monoclonal antibody, VRC-
HIVMAB075-00-AB (VRC07-523LS), administered in 
multiple doses and routes to healthy, HIV-uninfected 
adults 
DAIDS DOCUMENT ID 38458 
IND 137719 HELD BY DAIDS 
CLINICAL TRIAL SPONSORED BY 
Division of AIDS (DAIDS) 
National Institute of Allergy and Infectious Diseases (NIAID) 
National Institutes of Health (NIH) 
Department of Health and Human Services (DHHS) 
Bethesda, Maryland, USA 
STUDY PRODUCT PROVIDED BY 
Dale and Betty Bumpers Vaccine Research Center (VRC), NIAID, NIH, DHHS 
Bethesda, Maryland, USA 
March 8, 2018 
HVTN 127/HPTN 087 
Version 2.0 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 2 of 142 
Contents 
1 
Ethical considerations ..............................................................................................5 
2 
IRB/EC review considerations .................................................................................7 
2.1 
Minimized risks to participants ......................................................................7 
2.2 
Reasonable risk/benefit balance .....................................................................8 
2.3 
Equitable participant selection .......................................................................8 
2.4 
Appropriate informed consent ........................................................................8 
2.5 
Adequate safety monitoring ...........................................................................9 
2.6 
Protect privacy/confidentiality .......................................................................9 
3 
Overview ................................................................................................................10 
3.1 
Protocol Team ..............................................................................................13 
4 
Background ............................................................................................................15 
4.1 
Rationale for trial concept ............................................................................15 
4.2 
VRC01 ..........................................................................................................15 
4.3 
VRC01LS .....................................................................................................17 
4.4 
VRC07-523LS ..............................................................................................18 
4.5 
Trial design rationale ....................................................................................20 
4.6 
Plans for future product development and testing ........................................22 
4.7 
Preclinical safety studies of VRC07-523LS .................................................22 
4.8 
Preclinical PK and challenge studies of VRC07-523LS ..............................24 
4.9 
Clinical studies .............................................................................................25 
4.10 Potential risks of study products and administration ...................................37 
5 
Objectives and endpoints .......................................................................................41 
5.1 
Primary objectives and endpoints ................................................................41 
5.2 
Secondary objectives and endpoints ............................................................41 
5.3 
Exploratory objectives ..................................................................................42 
6 
Statistical considerations ........................................................................................43 
6.1 
Accrual and sample size calculations ...........................................................43 
6.2 
Randomization .............................................................................................48 
6.3 
Blinding ........................................................................................................49 
6.4 
Statistical analyses ........................................................................................49 
7 
Selection and withdrawal of participants ...............................................................55 
7.1 
Inclusion criteria ...........................................................................................55 
7.2 
Exclusion criteria ..........................................................................................57 
7.3 
Participant departure from study product administration schedule or 
withdrawal ....................................................................................................60 
8 
Study product preparation and administration .......................................................64 
8.1 
Study product regimen .................................................................................64 
8.2 
Study product formulation ...........................................................................65 
8.3 
Preparation of study products .......................................................................65 
8.4 
Administration ..............................................................................................70 
8.5 
Acquisition of study products ......................................................................72 
8.6 
Pharmacy records .........................................................................................72 
8.7 
Final disposition of study products ..............................................................72 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 3 of 142 
9 
Clinical procedures ................................................................................................73 
9.1 
Informed consent ..........................................................................................73 
9.2 
Pre-enrollment procedures ...........................................................................75 
9.3 
Enrollment and study product administration visits .....................................76 
9.4 
Follow-up visits ............................................................................................78 
9.5 
HIV counseling and testing ..........................................................................79 
9.6 
Contraception status .....................................................................................80 
9.7 
Urinalysis .....................................................................................................80 
9.8 
Assessments of Solicited AEs ......................................................................81 
9.9 
Visit windows and missed visits ..................................................................82 
9.10 Early termination visit ..................................................................................83 
9.11 Pregnancy .....................................................................................................83 
10 
Laboratory ..............................................................................................................84 
10.1 CRS laboratory procedures ..........................................................................84 
10.2 Total blood volume ......................................................................................84 
10.3 VRC07-523LS concentrations .....................................................................84 
10.4 Endpoint assays: humoral .............................................................................85 
10.5 Exploratory studies .......................................................................................85 
10.6 Specimen storage and other use of specimens .............................................85 
10.7 Biohazard containment .................................................................................86 
11 
Safety monitoring and safety review .....................................................................87 
11.1 Safety monitoring and oversight ..................................................................87 
11.2 Safety reporting ............................................................................................88 
11.3 Safety pause and prompt PSRT AE review..................................................91 
11.4 Review of cumulative safety data ................................................................93 
11.5 Study termination .........................................................................................93 
12 
Protocol conduct ....................................................................................................94 
12.1 Social impacts ..............................................................................................95 
12.2 Emergency communication with study participants ....................................95 
13 
Version history .......................................................................................................96 
14 
Document references (other than literature citations) ............................................98 
15 
Acronyms and abbreviations................................................................................100 
16 
Literature cited .....................................................................................................103 
Appendix A Sample informed consent form ..................................................................110 
Appendix B Approved birth control methods (for sample informed consent form) ......127 
Appendix C Sample consent form for use of samples and information in other studies 129 
Appendix D Table of procedures (for sample informed consent form) ..........................133 
Appendix E Schema graphic (for sample informed consent form) ................................134 
Appendix F Laboratory procedures ................................................................................135 
Appendix G Procedures at CRS ......................................................................................137 
Appendix H Adverse events of special interest (AESI) ..................................................139 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 4 of 142 
Appendix I Low risk guidelines for the US and Switzerland ........................................140 
Appendix J Protocol Signature Page .............................................................................142 
 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 5 of 142 
1 
Ethical considerations 
It is critical that universally accepted ethical guidelines are followed at all sites 
involved in the conduct of clinical trials. The HVTN and HPTN (hereafter, 
referred to as the “Networks”) have addressed ethical concerns in the following 
ways: 
 Network trials are designed and conducted to enhance the knowledge base 
necessary to find new methods for preventing HIV infection, using methods 
that are scientifically rigorous and valid, and in accordance with International 
Council for Harmonisation of Technical Requirements for Pharmaceuticals for 
Human Use (ICH) Good Clinical Practice (GCP) guidelines. 
 Network scientists and operational staff incorporate the philosophies 
underlying major codes (1-3), declarations, and other guidance documents 
relevant to human subjects research into the design and conduct of HIV 
vaccine clinical trials. 
 Network scientists and operational staff are committed to substantive 
community input—into the planning, conduct, and follow-up of its research—
to help ensure that locally appropriate cultural and linguistic needs of study 
populations are met. Community Advisory Boards (CAB) are required by 
DAIDS and supported at all Network research sites to ensure community 
input.  
 Network clinical trial staff counsel study participants routinely on how to 
reduce HIV risk. Participants who become HIV-infected during the trial are 
provided counseling on notifying their partners and about HIV infection 
according to local guidelines. Staff members will also counsel them about 
reducing their risk of transmitting HIV to others. 
 The Networks require that all international Network sites lacking national 
plans for providing ART develop plans for the care and treatment of 
participants who acquire HIV infection during a trial. Each plan is developed 
in consultation with representatives of host countries, communities from 
which potential trial participants will be drawn, sponsors, and the Networks. 
Participants who become HIV-infected during the trial will be referred to 
programs for ART provision when the appropriate criteria for starting ART 
are met. If a program for antiretroviral therapy (ART) provision is not 
available at a site and ART is needed, a privately established fund will be used 
to pay for access to treatment to the fullest extent possible. 
 The Networks provide training so that all participating sites similarly ensure 
fair participant selection, protect the privacy of research participants, and 
obtain meaningful informed consent. During the study, participants will have 
their wellbeing monitored, and to the fullest extent possible, their privacy 
protected. Participants may withdraw from the study at any time. 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 6 of 142 
 Prior to implementation, Network trials are rigorously reviewed by scientists 
who are not involved in the conduct of the trials under consideration.  
 Network trials are reviewed by local and national regulatory bodies and are 
conducted in compliance with all applicable national and local regulations. 
 The Networks design their research to minimize risk and maximize benefit to 
both study participants and their local communities. For example, Network 
protocols provide enhancement of participants’ knowledge of HIV and HIV 
prevention, as well as counseling, guidance, and assistance with any social 
impacts that may result from research participation. Network protocols also 
include careful medical review of each research participant’s health conditions 
and reactions to study products while in the study.  
 Network research aims to benefit local communities by directly addressing the 
health and HIV prevention needs of those communities and by strengthening 
the capacity of the communities through training, support, shared knowledge, 
and equipment. Researchers involved in Network trials are able to conduct 
other critical research in their local research settings. 
 The Networks recognize the importance of institutional review and value the 
role of in country Institutional Review Boards (IRBs), Ethics Committees 
(ECs), and other Regulatory Entities (REs) as custodians responsible for 
ensuring the ethical conduct of research in each setting. 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 7 of 142 
2 
IRB/EC review considerations 
US Food and Drug Administration (FDA) and other US federal regulations 
require IRBs/ECs/REs to ensure that certain requirements are satisfied on initial 
and continuing review of research (Title 45, Code of Federal Regulations (CFR), 
Part 46.111(a) 1-7; 21 CFR 56.111(a) 1-7). The following section highlights how 
this protocol addresses each of these research requirements. Each Network 
Investigator welcomes IRB/EC/RE questions or concerns regarding these research 
requirements. 
This trial is being conducted in the US and Switzerland with funding from the US 
NIH. Due to this, the trial is subject to both US and local regulations and 
guidelines on the protection of human research subjects and ethical research 
conduct. Where there is a conflict in regulations or guidelines, the regulation or 
guideline providing the maximum protection of human research subjects will be 
followed. 
In compliance with international and local (as appropriate) GCP guidelines, each 
research location has a locally based Principal Investigator (PI) who is qualified to 
conduct (and supervise the conduct of) the research; and the research addresses an 
important local health need for an HIV prevention method. In addition, the 
investigators take responsibility for the conduct of the study and the control of the 
study products, including obtaining all appropriate regulatory and ethical reviews 
of the research. Each participating clinical research site (CRS) has a standard 
operating procedure for ensuring that participants receive and understand the 
necessary information to make a decision whether or not to consent to the 
research.  
The sections below address each of the review concerns by IRBs/ECs and any 
applicable REs regarding how the research will be conducted. 
2.1 
Minimized risks to participants 
45 CFR 46.111 (a) 1 and 21 CFR 56.111 (a) 1: Risks to subjects are 
minimized. 
This protocol minimizes risks to participants by (a) correctly and promptly 
informing participants about risks so that they can join in partnership with the 
researcher in recognizing and reporting harms; (b) respecting local/national blood 
draw limits; (c) performing direct observation of participants post-product 
administration and collecting information regarding side effects for several days 
post-product administration; (d) having staff properly trained in administering 
study procedures that may cause physical harm or psychological distress, such as 
blood draws, infusions, injections, HIV testing and counseling and HIV risk 
reduction counseling; (e) providing HIV risk reduction counseling and checking 
on contraception use (for persons assigned female at birth); and (f) providing 
safety monitoring. 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 8 of 142 
2.2 
Reasonable risk/benefit balance 
45 CFR 46.111(a) 2 and 21 CFR 56.111(a) 2: Risks to subjects are 
reasonable in relation to anticipated benefits, if any, to subjects, and 
the importance of the knowledge that may reasonably be expected to 
result. 
In all public health research, the risk-benefit ratio may be difficult to assess 
because the benefits to a healthy participant are not as apparent as they would be 
in treatment protocols, where a study participant may be ill and may have 
exhausted all conventional treatment options. However, this protocol is designed 
to minimize the risks to participants while maximizing the potential value of the 
knowledge it is designed to generate.  
2.3 
Equitable participant selection  
45 CFR 46.111 (a) 3 and 21 CFR 56.111 (a) 3: Subject selection is 
equitable 
This protocol has specific inclusion and exclusion criteria for investigators to 
follow in admitting participants into the protocol. Participants are selected 
because of these criteria and not because of positions of vulnerability or privilege. 
Investigators are required to maintain screening and enrollment logs to document 
volunteers who screened into and out of the protocol and for what reasons. 
2.4 
Appropriate informed consent 
45 CFR 46.111 (a) 4 and 5 and 21 CFR 56.111 (a) 4 and 5: Informed 
consent is sought from each prospective subject or the subject’s 
legally authorized representative as required by 45 CFR 46.116 and 
21 CFR Part 50; informed consent is appropriately documented as 
required by 45 CFR 46.117 and 21 CFR 50.27 
The protocol specifies that informed consent must be obtained before any study 
procedures are initiated and assessed throughout the trial (see Section 9.1). Each 
site is provided training in informed consent by the Networks as part of its 
entering the Network. The Networks require a signed consent document for 
documentation, in addition to chart notes or a consent checklist. 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 9 of 142 
2.5 
Adequate safety monitoring 
45 CFR 46.111 (a) 6 and 21 CFR 56.111 (a) 6: There is adequate 
provision for monitoring the data collected to ensure the safety of 
subjects. 
This protocol has extensive safety monitoring in place (see Section 11). Safety is 
monitored daily by the HVTN Clinical Safety Specialist (CSS) or HVTN Core 
designee and routinely by the HVTN 127/HPTN 087 Protocol Safety Review 
Team (PSRT). In addition, the HVTN Safety Monitoring Board (SMB) 
periodically reviews study data. 
2.6 
Protect privacy/confidentiality 
45 CFR 46.111 (a) 7 and 21 CFR 56.111 (a) 7: There are adequate 
provisions to protect the privacy of subjects and maintain the 
confidentiality of data. 
Privacy refers to an individual’s right to be free from unauthorized or 
unreasonable intrusion into his/her private life and the right to control access to 
individually identifiable information about him/her. The term “privacy” concerns 
research participants or potential research participants as individuals whereas the 
term “confidentiality” is used to refer to the treatment of information about those 
individuals. This protocol respects the privacy of participants by informing them 
about who will have access to their personal information and study data (see 
Appendix A). The privacy of participants is protected by assigning unique 
identifiers in place of the participant’s name on study data and specimens. In the 
United States, research participants in Network protocols are protected by a 
Certificate of Confidentiality from the US NIH, which can prevent disclosure of 
study participation even when that information is requested by subpoena. 
Participants are told of the use and limits of the certificate in the study consent 
form. In addition, each staff member at each study site in this protocol signs an 
Agreement on Confidentiality and Use of Data and Specimens with the Networks 
and each study site participating in the protocol is required to have a standard 
operating procedure on how the staff members will protect the confidentiality of 
study participants. 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 10 of 142 
3 
Overview 
Title  
A multicenter, randomized, partially blinded phase 1 clinical trial to evaluate the 
safety and serum concentrations of a human monoclonal antibody, VRC-
HIVMAB075-00-AB (VRC07-523LS), administered in multiple doses and routes 
to healthy, HIV-uninfected adults 
Primary objective(s) 
Primary objective 1:  
To evaluate the safety and tolerability of different doses of VRC07-523LS 
administered IV, SC, and IM by repeat dosing every 16 weeks for a total of 5 
administrations to healthy adults 
Primary objective 2:  
To evaluate the serum concentrations of VRC07-523LS administered IV, SC, and 
IM over a total of 6 regimens  
Study products and routes of administration 
 VRC07-523LS: VRC-HIVMAB075-00-AB (VRC07-523LS) is a human 
monoclonal antibody (mAb) targeted to the HIV-1 CD4 binding site. It was 
developed by the VRC/NIAID/NIH and manufactured under current Good 
Manufacturing Practice regulations at the VRC Pilot Plant operated under 
contract by the Vaccine Clinical Materials Program, Leidos Biomedical 
Research, Inc., Frederick, MD. Product is provided at 100 ± 10 mg/mL as 10 
mL glass vials with a 6.25 ± 0.1 mL fill volume and 3 mL glass vials with a 
2.25 mL ± 0.1 mL fill volume.  
 Placebo: Sodium Chloride Injection, USP 0.9% 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 11 of 142 
Table 3-1 Schema 
Group 
N 
Route 
Dose 
Product administration schedule 
W0 
W16 
W32 
W48 
W64 
1 
20 
IV 
2.5 mg/kg 
X 
X 
X 
X 
X 
2 
20 
IV 
5 mg/kg 
X 
X 
X 
X 
X 
3 
20 
IV 
20 mg/kg 
X 
X 
X 
X 
X 
4 
20 
SC 
2.5 mg/kg 
X 
X 
X 
X 
X 
5 
20 
SC 
5 mg/kg 
X 
X 
X 
X 
X 
6 
20 
IM 
2.5 mg/kg 
X 
X 
X 
X 
X 
4 
Placebo 
X 
X 
X 
X 
X 
Total 
124 
IV = intravenous infusion 
SC = subcutaneous injection 
IM = intramuscular injection 
All groups to enroll simultaneously. 
Participants 
124 healthy, HIV-1–uninfected volunteers aged 18 to 50 years 
Design 
Multicenter, randomized clinical trial 
Duration per participant 
26 months of scheduled clinic visits  
Estimated total study duration 
32 months (includes enrollment and follow-up) 
Investigational New Drug (IND) sponsor 
DAIDS, NIAID, NIH, DHHS (Bethesda, Maryland, USA) 
Study product providers 
 VRC07-523LS: Dale and Betty Bumpers Vaccine Research Center (VRC), 
NIAID, NIH, DHHS (Bethesda, Maryland, USA) 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 12 of 142 
Core operations 
HVTN Vaccine Leadership Group/Core Operations Center, Fred Hutchinson 
Cancer Research Center (Fred Hutch) (Seattle, Washington, USA) 
HPTN Leadership Operations Center, FHI360 (Durham, North Carolina, USA) 
Statistical and data management center (SDMC) 
Statistical Center for HIV/AIDS Research and Prevention (SCHARP), Fred Hutch 
(Seattle, Washington, USA) 
HIV diagnostic laboratory 
University of Washington Virology Specialty Laboratory (UW-VSL) (Seattle, 
Washington, USA) 
Endpoint assay laboratories 
 Duke University Medical Center (Durham, North Carolina, USA) 
 Fred Hutch/University of Washington (Seattle, Washington, USA) 
 Vaccine Research Center – Immunology Testing Laboratory (Gaithersburg, 
MD) 
Study sites 
HVTN and HPTN CRSs to be specified in the Site Announcement Memo 
Safety monitoring 
HVTN 127/HPTN 087 PSRT; HVTN Safety Monitoring Board (SMB) 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 13 of 142 
3.1 
Protocol Team 
Protocol leadership 
HVTN Chair Stephen Walsh 
Brigham & Women’s 
Hospital 
617-525-8418 
swalsh@bwh.harvard.edu 
Statisticians Ollivier Hyrien 
SCHARP, Fred Hutch 
206-667-5780 
ohyrien@fhcrc.org 
HPTN Chair Cynthia Gay 
University of North 
Carolina, Chapel Hill 
919-843-2726 
cynthia_gay@med.unc.edu 
 Timothy Skalland 
SCHARP, Fred Hutch 
206-667-1186 
tskallan@fredhutch.org 
Protocol 
Team leader 
Shelly Karuna 
HVTN Core, Fred Hutch 
206-667-4355 
skaruna@fredhutch.org 
Laboratory leads David Montefiori 
HVTN Laboratory 
Program, Duke Univ. 
919-684-5278 
monte@duke.edu 
Medical 
officers 
Jane Baumblatt 
DAIDS, NIAID 
301-761-7754 
jane.baumblatt@nih.gov 
 Estelle Piwowar-
Manning 
HPTN Laboratory 
Program, JHU 
410-614-6736 
epiwowa@jhmi.edu 
 Wairimu Chege 
DAIDS, NIAID 
240-292-4786 
wairimu.chege@nih.gov 
  
Other contributors to the original protocol 
Core medical 
monitor 
Shelly Karuna 
HVTN Core, Fred Hutch 
DAIDS 
protocol 
pharmacist 
Oladapo Alli 
DAIDS, NIAID 
240-627-3593 
HPTN 
Pharmacologist 
Julie Dumond 
University of North 
Carolina, Chapel Hill 
Statistician Yunda Huang 
SCHARP, Fred Hutch 
Product 
developer 
representatives 
Julie Ledgerwood 
VRC 
Statistical 
research 
associate 
Xue Han 
SCHARP, Fred Hutch 
 Barney Graham 
VRC 
Clinical safety 
specialist 
Lauryn Takisaki 
HVTN Core, Fred 
Hutch 
 Martin Gaudinski 
VRC 
Clinical 
research 
manager 
Phil Andrew 
HPTN LOC, FHI360 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 14 of 142 
 Lucio Gama 
VRC 
Clinical trials 
manager 
Carissa Karg 
HVTN Core, Fred 
Hutch 
HVTN 
Laboratory 
program reps 
On Ho 
HVTN Laboratory 
Program, Fred Hutch 
Clinical data 
manager 
Ingrid Durenberger 
SCHARP, Fred Hutch 
 John Hural 
HVTN Laboratory 
Program, Fred Hutch 
Senior clinical 
data manager 
Gina Escamilla 
SCHARP, Fred Hutch 
HPTN 
Laboratory 
program rep 
Vanessa Cummings 
HPTN Laboratory 
Program, JHU 
SDMC 
Associate 
director of lab 
science 
April Randhawa 
SCHARP, Fred Hutch 
HVTN 
regulatory 
affairs associate 
Meg Brandon 
HVTN Core, Fred Hutch 
Protocol 
development 
manager 
Carter Bentley 
HVTN Core, Fred 
Hutch 
Clinic 
coordinators 
Rotrease Regan 
The Ponce de Leon 
Center CRS 
HVTN 
Community 
engagement 
unit 
representative 
Gail Broder  
HVTN Core, Fred 
Hutch 
 Elvin Fontana-Martinez 
Boston-Brigham CRS 
HPTN 
Community 
program 
associate 
Jontraye Davis 
HPTN LOC, FHI360 
Community 
Advisory Board 
(CAB) members 
Jamel Young 
The Ponce de Leon 
Center CAB 
Technical 
editor 
Richa Chaturvedi 
HVTN Core, Fred 
Hutch 
 Gary Daffin 
Fenway and Brigham & 
Women’s CAB 
  
Community 
educator/ 
recruiters 
Jorge Benitez 
Columbia Physicians and 
Surgeons 
  
 Noshima Darden-Tabb 
University of North 
Carolina, Chapel Hill 
  

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 15 of 142 
4 
Background 
4.1 
Rationale for trial concept 
Effective biomedical interventions are urgently needed to reduce the acquisition 
of HIV. The global HIV-1 epidemic continues and while many countries have 
made progress toward reducing HIV incidence, micro-epidemics of infection 
continue to occur in nearly all regions, even in countries possessing the full toolkit 
of proven prevention approaches (4-7). UNAIDS estimates that there were 2.1 
million new HIV infections worldwide in 2015 (8). Multiple advances in 
prevention, including treatment as prevention (TasP) (9) and pre- or postexposure 
prophylaxis (PrEP or PEP) (10, 11), have been made in recent years. However, 
these are hampered by side effects, cost, access, and significant adherence 
challenges, and thus remain imperfect tools to end the ongoing HIV epidemic. A 
biomedical HIV prevention approach that exhibits sustained activity over an 
extended time period, that has a safety profile acceptable for healthy persons, and 
whose effectiveness is less dependent upon consistent adherence, is still needed. 
Ultimately, an effective vaccine will be necessary to better control the HIV 
pandemic (12, 13). 
An alternative approach to prevention and treatment of infectious diseases is 
passive administration of antibodies, a strategy that has been employed for more 
than 100 years against diverse disease targets (14, 15). Hyperimmune serum is 
still used for hepatitis A and B prophylaxis (16, 17) and for PEP for rabies (18), 
measles (19), varicella zoster (20), and other infectious diseases (15). 
Furthermore, palivizumab, a monoclonal antibody directed against the F protein 
of respiratory syncytial virus (RSV), has been used for more than 15 years to 
prevent RSV infection in high-risk infants (21). 
Over the past several years, there has been a concerted and notably successful 
effort to isolate broadly neutralizing antibodies (bNAbs) to HIV-1 from 
chronically infected individuals (22-38). Subsequent studies have provided 
considerable insight into the sites these antibodies target on HIV-1 and the 
mechanisms by which they neutralize the virus (25, 26, 35, 39). This research has 
informed efforts to design recombinant protein immunogens that can elicit such 
antibodies (40-43), prompting optimism that vaccines that elicit bNAbs against 
HIV-1 can be developed (41, 44). In addition, the availability of bNAbs against 
HIV opens the exciting possibility of antibody mediated prevention (AMP) of 
HIV infection (45). 
4.2 
VRC01 
The Vaccine Research Center (VRC) at the National Institute of Allergy and 
Infectious Diseases (NIAID) at the National Institutes of Health (NIH) developed 
VRC01, a potent and broadly neutralizing HIV-1 human mAb targeted against the 
HIV-1 CD4 binding site. VRC01 is currently in clinical trials under IND 113,611 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 16 of 142 
[prevention indication] and IND 126,001 and IND 126,664 [therapeutic 
indication]. VRC01 was originally discovered in an individual infected with HIV-
1 for more than 15 years and whose immune system controlled the virus without 
ART (24, 46). 
In in vitro studies, 90% of 190 HIV-1 pseudoviruses across all clades tested 
demonstrated sensitivity to neutralization by VRC01. VRC01 has a 50% 
inhibitory concentration (IC50) of < 50 mcg/mL against 91% of primary HIV-1 
isolates and IC50 < 1 mcg/mL against 72% of HIV-1 isolates.  
Clinical studies of VRC01 started in September 2013. VRC01 has been tested in 
HIV-infected adults under VRC 601 (47), in healthy adults under VRC 602 (48) 
and HVTN 104 (49), and has been found to be safe and well tolerated at 
5-40 mg/kg administered intravenously (IV) and at 5 mg/kg subcutaneously (SC) 
in both HIV-infected (47) and HIV-uninfected adult populations (48). A study in 
infants born from HIV-1 infected mothers is ongoing under IMPAACT P1112 
[NCT02256631]. 
The efficacy of VRC01 in the prevention of HIV-1 infection is currently being 
evaluated in 2 phase 2b studies. HVTN 704/HPTN 085, a phase 2b clinical trial of 
VRC01 administered every 8 weeks for 72 weeks (10 infusions) IV to HIV-
uninfected men and transgender persons who have sex with men, started in April 
2016 [NCT02716675] while HVTN 703/HPTN 081, a phase 2b clinical trial of 
VRC01 administered every 8 weeks for 72 weeks (10 infusions) IV to HIV-
uninfected women in sub-Saharan Africa, began in May 2016 [NCT02568215]. 
Studies evaluating potential treatment indications for VRC01 were initiated in 
2015 in HIV-1 infected adults. The safety and virological effect of VRC01 
administration during a brief analytical treatment interruption (ATI) was assessed 
in ACTG A5340 (50). A study evaluating the effect of VRC01 on the HIV-1 
proviral reservoir (ACTG A5342; NCT02411539) was recently completed. Two 
additional studies evaluating the safety and therapeutic efficacy of VRC01 during 
acute HIV infection (RV398; NCT02591420) and during an ATI in patients who 
initiated ART during acute HIV infection (RV397; NCT02664415) were launched 
in 2016. 
Cumulatively, as of July 2017, across all phase 1 trials and in the two phase 2b 
AMP studies, VRC01 has been administered by either IV or SC routes to more 
than 2300 HIV-uninfected and HIV-infected adults and 33 HIV-uninfected 
infants. 
The majority of unsolicited adverse events (AEs) in all studies have been no 
greater than Grade 2 in severity. Overall, VRC01 administration in the dose range 
from 1 to 40 mg/kg IV and at 5 and 40 mg/kg SC has been assessed as well-
tolerated and safe for further evaluation. 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 17 of 142 
However, the relatively short half-life of VRC01 limits the feasibility of wider 
implementation of this mAb to treat HIV infection, or as part of a global public 
health strategy to prevent HIV-1 acquisition. 
4.3 
VRC01LS 
Recently, the VRC developed a VRC01 variant, designated VRC01LS, which was 
designed to have a longer half-life by exploiting the functions of the neonatal Fc 
receptor (FcRn). The FcRn regulates the half-life of IgG antibodies through pH-
dependent binding to IgG Fc regions, which favors binding at low pH (eg, 
lysosomal compartments and vaginal lumen) and release at neutral pH (eg, 
peripheral blood) (51, 52). The FcRn is expressed in endothelial cells of the 
vasculature and some myeloid cells, where it can rescue IgG from lysosomal 
degradation by binding these molecules within this low pH compartment, then 
releasing them back into circulation (53, 54). In the intestinal epithelium, the 
FcRn transports IgG bi-directionally; it transports IgG into the intestinal lumen 
and it recycles complexed antibody back to the tissue to support the induction of 
immunity, tolerance and/or susceptibility (55-58). In the genital tract, FcRn is 
expressed on columnar epithelial cells lining the human penile urethra and the 
endocervix, as well as on reserve epithelial cells lining the vagina. Thus, the tissue 
distribution of FcRn enables the delivery of IgG to relevant mucosal 
compartments and may thereby contribute to protection or susceptibility; the latter 
possibility has been suggested in the case of non-neutralizing Abs, which may 
mediate the transmission of bound, infectious particles via FcRn transport 
pathways (55, 59, 60). 
The LS mutation (M428L/N434S) to the constant region of the VRC01 antibody 
enhances its binding affinity for FcRn at low pH, yet does not affect its release at 
pH 7.4 (61). Thus, the LS modification was found to alter antibody turnover in 
nonhuman primate (NHP) models, with increased persistence in serum and slower 
decay in rectal and cervicovaginal tissue. Intravenous administration of VRC01LS 
also afforded increased protection against intra-rectal challenge with simian-
human immunodeficiency virus (SHIV) (61). Consequently, the increased 
persistence of anti-HIV neutralizing antibodies in mucosal tissue could have 
significant advantages in preventing HIV acquisition, as increased maintenance at 
the portals of entry might allow for consistent protective levels with less frequent 
administrations and/or reduced dosing. 
VRC 606 was the first study of the VRC-HIVMAB080-00-AB (VRC01LS) 
monoclonal antibody (mAb) in healthy adults. VRC01LS was deemed safe and 
well tolerated at doses of 5-40 mg/kg IV and at 5 mg/kg SC (see Section 4.9.2.1). 
VRC01LS is also being studied in the ongoing HVTN 116 clinical trial 
[NCT02797171]. 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 18 of 142 
4.4 
VRC07-523LS 
The VRC has also developed VRC07-523LS, a highly potent and broadly 
neutralizing HIV-1 human mAb targeted against the HIV-1 CD4 binding site. 
Numerous HIV-1 neutralizing mAbs from the VRC01 family, including VRC07 
(“07” denotes sequential numbering when discovered), have now been isolated 
from the same individual (donor 45) who, as noted above, was infected with HIV-
1 for more than 15 years and whose immune system controlled the virus without 
ART (62). Through advances in B-cell immunology and structure-guided 
optimization techniques, VRC07-523 (“523” denotes sequential numbering when 
engineered variant generated), and later VRC07-523LS (“LS” denotes 2 specific 
amino acid mutations), were developed with potency and breadth greater than 
those of early antibodies (62). 
Briefly, the VRC07 (wild-type) heavy chain was identified by deep sequencing of 
heavy chain transcripts from peripheral blood B cells isolated from donor 45 (24) 
based on its similarity to the VRC01 mAb and paired with the VRC01 (wild-type) 
light chain (62). To increase neutralization potency and breadth, a series of amino 
acid mutations were introduced; mutations that resulted in autoreactivity were 
rejected (62). The mutations that together define the 523 designation are a glycine 
to histidine mutation at residue 54 of the heavy chain, a deletion of the first two 
amino acids, glutamate and isoleucine, from the light chain, and a valine to serine 
mutation at the third amino acid residue of the light chain (62). The LS 
designation specifies methionine to leucine (L) and asparagine to serine (S) 
(M428L/N434S, referred to as LS) changes within the C-terminus of the heavy 
chain constant region. The LS mutation was introduced by site-directed 
mutagenesis to increase the binding affinity for the neonatal Fc-receptor (FcRn), 
resulting in increased recirculation of functional IgG (61, 63) and thereby 
increasing plasma half-life. 
VRC07-523LS was found to be 5-to 8-fold more potent than VRC01 (see Figure 
4-1), with an inhibitory concentration IC50 < 50 mcg/mL against 96% of HIV-1 
pseudoviruses representing the major circulating HIV-1 clades, and an IC50 < 1 
mcg/mL against 92% of HIV-1 viruses tested (62). Compared with other VRC07 
derivatives, VRC07-523LS displayed minimal levels of autoreactivity.  
 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 19 of 142 
 
Figure 4-1 VRC07-523LS neutralizes a higher fraction of HIV-1 isolates at a lower 
concentration than VRC01 (data courtesy of Kshitij Wagh and Bette Korber) 
In vivo proof-of-concept studies in rhesus macaques showed that VRC07-523LS 
is about 5-fold more potent than VRC01LS and has a 2-fold longer half-life (9.8 
days) than VRC07 (4.9 days) after a single dose of mAb at 10 mg/kg administered 
IV (62). The increased neutralization potency and breadth in vitro and prolonged 
half-life of VRC07-523LS correlated with improved protection against SHIV 
challenge in vivo (Figure 4-2; see also Section 4.8). Taken together, these data 
suggest that VRC07-523LS has considerable potential for prevention of HIV-1 
infection in humans. 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 20 of 142 
 
Figure 4-2 The increased neutralization potency of VRC07-523LS correlates with protection 
at lower antibody levels in a SHIV-rhesus macaque model compared with VRC01LS. (A) 
Rhesus macaques were administered 0.2 mg/kg (n = 4) or 0.05 mg/kg (n = 4) of VRC07-523LS or 
0.3 mg/kg of VRC01LS (n = 12), challenged with SHIV-BaLP4 intrarectally on day 5, and plasma 
concentrations of VRC07-523LS and VRC01LS were assayed by ELISA. (B) Regression model 
based on plasma mAb concentration at the time of infection. From (62). 
4.5 
Trial design rationale 
4.5.1 
Dose and schedule 
With the exception of IM administration, the VRC07-523LS doses and intervals 
between doses in this trial are based on human studies of VRC01 (Section 4.9.1), 
preclinical and clinical studies of VRC01LS (Sections 4.3 and 4.9.2), and 
preclinical and clinical studies of VRC07-523LS (Sections 4.4, 4.8, and 4.9.3). As 
pre-clinical dosing via the IM route has been conducted at the 2.5 mg/kg dose, 
this is the dose administered IM in this protocol. For comparison to other routes, 
the IM dosing schedule defaults to that of the IV and SC administration (see 
Section 6.1.2). 
PK data obtained in this study that assesses a range of doses and routes of 
administration, together with the data obtained in VRC 605 and in other trials of 
VRC07-523LS, will allow population PK analysis and predictive dose-regimen 
selection modeling. 
In addition, the study design allows comparisons between different dose/route 
groups, including the following:  
 2.5 mg/kg IV vs. 5mg/kg IV vs. 20 mg/kg IV (Groups 1, 2, and 3);  
 2.5 mg/kg SC vs 5 mg/kg SC (Groups 4 and 5);  
 5 mg/kg IV vs 5 mg/kg SC (Groups 2 and 5); and 
 2.5 mg/kg SC vs IV vs IM (Groups 1, 4, and 6). 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 21 of 142 
4.5.2 
Rationale for the exclusion of placebo recipients in IV and SC 
treatment groups 
Substantial safety data have already been collected over several trials on closely 
related products, including VRC01 and VRC01LS. These studies have 
demonstrated the safety and tolerability of the IV and SC administration of these 
products at doses similar to or greater than those proposed in this study. For 
example, in VRC 606, the doses for VRC01LS in HIV-uninfected participants 
ranged between 1 and 40 mg/kg for IV administrations, and 5 mg/kg for SC 
injections. Moreover, in multiple studies, including VRC 601, VRC 602, HVTN 
104, RV397, RV398, A5340, and A5342, doses for VRC01 in HIV-uninfected 
and/or HIV-infected participants ranged between 1 and 40 mg/kg for IV 
administrations, and between 5 and 40 mg/kg for SC injections.  
One of the largest of the phase 1 trials, HVTN 104, evaluated VRC01 in 88 
participants. Twenty-eight percent of IV infusions and 14% of SC injections were 
associated with mild pain or tenderness, with 55% of VRC01 recipients and 50% 
of placebo recipients experiencing mild pain and/or tenderness at the infusion or 
injection site at some point during the trial. Over 75% of IV infusions and SC 
injections in HVTN 104 were associated with no systemic reactogenicity; 56% of 
VRC01 recipients and 75% of placebo recipients experienced systemic 
reactogenicity at some point during the trial. Reactogenicity, when present, was 
typically mild or moderate (Mayer et al, PLoS Medicine, manuscript submitted).  
As well, mAbs against other pathogens have been licensed at similar or higher 
dose levels. For example, the prevention of severe RSV in infants is generally 
treated via monthly IM injection of a dose of 15 mg/kg throughout the RSV 
season (21). Other investigational mAbs directed at pathogens that have been 
safely taken into efficacy trials include a Clostridium difficile anti-toxin mAb 
administered at a 10 mg/kg dosage (64) and a mAb directed at hepatitis C virus 
administered at a 50 mg/kg dosage (65), much higher than the dose levels 
proposed in this study. 
Furthermore, the inclusion of placebo recipients would provide limited power to 
compare the rates of safety and tolerability events between active and placebo 
arms unless they were included in large numbers in each of the 5 IV and SC 
groups (66). For instance, with 20 participants in the active treatment arm of any 
of these groups, the study would need 20 placebo recipients per group to achieve 
~80% power to detect a difference between the rates of AE/SAE in the active vs. 
placebo arms if the true AE/SAE rates in the placebo and in the active arm were 
4% and 34%, respectively. These calculations assume a one-sided test comparing 
two independent binomial proportions with a significant level (type-1 error) of 
5%. 
In addition, drug serum concentration levels will only be present in VRC07-
523LS recipients and participants’ baseline samples can serve as controls for 
serum level assessments. Thus, the inclusion of placebo groups is not necessary 
for the PK objectives of this trial. Data from multiple groups will be evaluated 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 22 of 142 
concurrently by laboratory staff who will remain blinded to group assignment, 
which would help to avoid group-specific bias in the assessment of various drug 
activity endpoints. 
IM administration of an anti-HIV mAb will be evaluated for the first time in 
humans in this study. Since reactions to IM administration may not be comparable 
to those of IV or SC administration, a small number of placebo recipients have 
been included in the IM group to blind post-administration safety and tolerability 
assessments. 
4.6 
Plans for future product development and testing 
This study is the next step in the characterization of VRC07-523LS and is 
designed to identify an optimal dose and route of administration of the antibody 
as well as to determine if anti-drug antibodies (ADA) or side effects emerge with 
more prolonged administration of the antibody.  
This study will further characterize and compare the pharmacokinetics of IV and 
SC routes of administration at multiple doses. In addition, this study will provide 
the first characterization of the safety and pharmacokinetics of an anti-HIV mAb 
administered IM, which may ultimately prove to be a more feasible and 
acceptable route of administration than IV or SC. 
The breadth of information obtained is expected to inform further study of 
VRC07-523LS, including its potential for combination with other mAbs 
undergoing early study at doses, intervals, and routes that could be combined with 
one or more of the regimens evaluated here. 
Furthermore, since the site and mode of activity of VRC07-523LS are similar to 
those of VRC01, it should be possible to infer the potential HIV preventive 
efficacy of different regimens of VRC07-523LS from the PK and neutralizing 
values found in this study, as well as from the efficacy levels determined in the 
ongoing phase 2b efficacy studies of VRC01. This information will contribute 
greatly to the design of future bNAb efficacy trials. 
4.7 
Preclinical safety studies of VRC07-523LS 
4.7.1 
In vitro safety studies  
Several in vitro preclinical safety studies were performed with VRC07-523LS to 
assess potential off-target binding. To measure potential anti-phospholipid cross-
reactivity, binding of VRC07-523LS to cardiolipin was assessed using an 
enzyme-linked immunosorbent assay (ELISA) and demonstrated minimal binding 
compared with 4E10, an earlier-generation HIV-1 specific mAb which binds 
strongly to cardiolipin. VRC07-523LS was also tested for cross-reactivity against 
a panel of various nuclear antigens using a licensed systemic lupus erythematosus 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 23 of 142 
diagnostic test kit (Luminex AtheNA Multi-Lyte® ANA-II test) and did cross-
react with a small subset of nuclear antigens consistent with some reactivity with 
nuclear antigens. In addition, VRC07-523LS was assessed for anti-phospholipid 
properties in a clinical activated partial thromboplastin time (aPTT) assay and 
compared to the anti-HIV mAbs 4E10 and VRC01 as well as palivizumab; only 
4E10 showed evidence of antiphospholipid activity. By immunohistochemistry, 
VRC07-523LS displayed minimal binding to HEp-2 cells at 50 mcg/mL and no 
binding at 25 mcg/mL (62). 
A tissue cross-reactivity (TCR) study was performed in accordance with “Good 
Laboratory Practice (GLP) for Nonclinical Laboratory Studies” to determine the 
potential cross-reactivity of VRC07-523LS with cryosections of human and 
Sprague-Dawley rat tissues. VRC07-523LS staining was similar between the 
human and rat tissues examined, although staining tended to be somewhat more 
intense and frequent in the human tissue compared to the Sprague-Dawley rat 
tissues. According to ICH S6(R1), monoclonal antibody binding to cytoplasmic 
sites generally is considered of little to no toxicologic significance. See the 
Investigator’s Brochure for further details. 
4.7.2 
In vivo toxicology studies  
4.7.2.1 
Repeat dose IV and SC toxicity study in Sprague-Dawley rats 
A repeat dose IV and SC toxicity study (IITRI Project NO. 2517-001-002) with 
VRC07-523LS was performed in male and female Sprague-Dawley rats in 
accordance with Good Laboratory Practice (GLP) for Nonclinical Laboratory 
Studies. Treatment with VRC07-523LS at doses up to 400 mg/kg/dose IV or 40 
mg/kg/dose SC with three doses at 10 day intervals was generally well tolerated 
as most findings were reversible and no longer seen at the end of the recovery 
period. Additionally, histologic changes were not observed in the GLP repeat 
dose toxicology study in the cell types with staining observed in the GLP tissue 
cross reactivity (TCR) study. The no observed adverse effect levels (NOAELs) 
for this study were 400 mg/kg IV and 40 mg/kg SC. See the Investigator’s 
Brochure for further details. 
4.7.2.2 
Local tolerance of VRC07-523LS administered IM to Sprague-Dawley rats 
A GLP local tolerance study (IITRI Project N0. 2749-001) was performed 
to evaluate tissue reactions of VRC-HIVMAB075-00-AB (VRC07-523 
LS). Sprague-Dawley rats (five rats/sex in each group) were administered a 
single intramuscular (IM) injection of either the control (Final Formulation 
Buffer) or the MAb at a dose of 2.5 mg/kg on Day 1. Rats were then 
subjected to necropsy on Day 7 (6 days after dosing). Experimental 
endpoints included moribundity/mortality, daily clinical signs of toxicity, 
and injection site (Draize) reactogenicity scoring; body weights; plasma 
fibrinogen levels, serum alpha-2- macroglobulin (A2M) levels; gross 
pathology at necropsy; and microscopic pathology of the skeletal muscle 
injection sites. 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 24 of 142 
No treatment-related findings were noted locally at the injection site 
through injection site reactogenicity observations, limb evaluations, and 
gross and microscopic pathology. No evidence of systemic toxicity was 
also noted following a single IM injection of the HIV MAb as there were 
no adverse clinical findings seen and no alterations in body weights and 
serum A2M levels. There were statistically significant changes in plasma 
fibrinogen levels in the MAb-treated group (compared to the controls); 
however, these findings were considered to be of minimal toxicological 
significance. 
4.8 
Preclinical PK and challenge studies of VRC07-523LS  
When administered IV at a single dose of 10 mg/kg to male rhesus macaques 
(n = 4), the half-life of VRC07-523LS was 9.8 days, a 2-fold increase compared 
to VRC07 (4.9 days) (62). Plasma concentrations of VRC07-523LS exceeded 10 
mcg/mL at day 14 and remained greater than 2 mcg/mL at day 28 (62). Detectable 
concentrations (> 10 ng/mL) of VRC07-523LS were measured in rectal secretions 
for at least 14 days (last collection point) in the 2 animals tested (62). 
In a different study, VRC07-523LS was administered SC at a single dose of 10 
mg/kg to male (n = 2) and female (n = 4) rhesus macaques. The half-life was 
about 14 days and it persisted at least 49 days (last collection point) in rectal, 
vaginal, and nasal secretions. See the Investigator’s Brochure for further details. 
When administered IV at a single dose of 10 mg/kg to male and female 
cynomolgus macaques (n = 4), the half-life of VRC07-523LS was about 12 days 
(Figure 4-3B). In all 4 animals, plasma concentrations of VRC07-523LS exceeded 
10 mcg/mL at day 14 and were greater than 3 mcg/mL at day 28, and VRC07-
523LS was detectable at 28 days (last collection point) in rectal and vaginal 
secretions and tissues. See the Investigator’s Brochure for further details. 
In a SHIV challenge study, VRC07-523LS was administered to male (n = 3) and 
female (n = 3) rhesus macaques at a dose of 20 mg/kg IV and the plasma 
concentrations monitored by ELISA (Figure 4-3A). 6/6 animals were protected 
from SHIV-SF162P3 challenge on Day 5 after receiving a single dose of VRC07-
523LS at 20 mg/kg IV. The average plasma concentration of VRC07-523LS on 
the day of the challenge was 114.2 mcg/mL. See the Investigator’s Brochure for 
further details. 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 25 of 142 
 
Figure 4-3 (A) VRC07-523LS was administered to male (n = 3) and female (n = 3) rhesus 
macaques at a dose of 20 mg/kg IV in a SHIV challenge study; all were protected against 
infection. (B) VRC07-523LS PK was measured in male (n = 2) and female (n = 2) cynomolgus 
macaques following a single administration of 10 mg/kg IV. Plasma concentrations were 
monitored by ELISA in both studies. 
An additional challenge study assessed whether the increased neutralization 
potency observed with VRC07-523LS in vitro would confer greater protection in 
vivo compared to VRC01LS. 7/12 male rhesus macaques were protected from 
SHIV-BaLP4 intrarectal challenge after receiving VRC01LS at 0.3 mg/kg IV, 
whereas 3/4 male rhesus macaques were protected after receiving VRC07-523LS 
at 0.2 mg/kg IV. VRC07-523LS showed a > 5-fold increase in potency compared 
to VRC01LS, consistent with its ability to better neutralize viruses in vitro (62). 
4.9 
Clinical studies 
4.9.1 
Clinical studies of VRC01 
4.9.1.1 
VRC 601 
VRC 601 (NCT01950325) was the first study of the VRC01 mAb in HIV-infected 
participants (47). It was a dose-escalation study to examine safety, tolerability, 
dose, PK, and anti- antibody immune responses. VRC 601 opened in September 
2013 as a single site study at the NIH Clinical Center, Bethesda, Maryland and in 
total, 23 HIV-infected participants, including 15 aviremic ARV-treated 
participants and 8 viremic non-ARV treated participants, were infused with one or 
two doses of VRC01 at doses up to 40 mg/kg IV. 
All IV infusions and SC injections were well tolerated with no serious adverse 
events (SAEs) or dose limiting toxicity. VRC 601 demonstrated evidence of 
VRC01-mediated antiviral effect. Analysis of the VRC 601 viral load data 
obtained from 8 viremic adults shows that VRC01 has a statistically significant in 
vivo virological effect on HIV viral load when administered as a single 40 mg/kg 
IV dose (Figure 4-4) (47). None of these adults were taking ART when enrolled 
into the study and none had started ART during the time period when the viral 
load data were collected. Six of the eight adult participants had ≥1 log10 
VRC07-523LS (20 mg/kg IV) 
VRC07-523LS (10 mg/kg IV) 
(A) 
(B) 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 26 of 142 
copies/mL decrease in viral load and two participants had a viral load drop of 0.26 
and 0.18 log10 copies/mL respectively. These interim data indicate the following 
for a single dose of VRC01 at 40 mg/kg IV: a statistically significant decline in 
viral load postinfusion at days 5 to 16; a median time of 5 days to reach ≥ 0.5-
log10 decrease in viral load; and a median time of 7 days to greatest decrease in 
viral load postinfusion. 
 
Figure 4-4 The effect of VRC01 on plasma viral load after infusion. Plasma virus load over time 
for eight viremic participants before and after infusion with VRC01 (day 0, indicated by arrow). Limit 
of detection of the assay is indicated with a tick at 20 copies/mL (47).  
In VRC 601, participants were administered a single dose of VRC01 at 40 mg/kg 
and, therefore, a sustained effect on viral load was not expected. These data 
demonstrate a VRC01 mediated anti-viral effect and led to the hypothesis that 
repetitive dosing could have a beneficial clinical effect. This hypothesis was 
tested in two similar clinical trials, ACTG A5340 and NIH 15-I-0140, in which 
aviremic patients on stable ART underwent an ATI after receiving VRC01 at a 
dose of 40 mg/kg (50). No product-related safety concerns were identified in the 
24 participants enrolled. Viral rebound occurred despite VRC01 serum 
concentrations well above 50 mcg/mL with a mean time to rebound of 4 to 6 
weeks (50). While the mean time to rebound was statistically significantly 
different from historical controls in previous ACTG ATI studies at 4 weeks, there 
was no difference at 8 weeks. VRC01 was also found to exert selection pressure 
on emergent viruses (Figure 4-5). 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 27 of 142 
 
Figure 4-5 Viral suppression mediated by VRC01. Kaplan-Meier curve of plasma viremia 
suppression (< 200 copies/mL) after VRC01 administration in A5340 and NIH trial participants as 
compared with historical ACTG trials who underwent interruption of therapy without other 
immunotherapeutic interventions (50). 
4.9.1.2 
VRC 602 
VRC 602 was a dose-escalation study of the VRC01 mAb in HIV-uninfected 
adults to examine safety, tolerability, dose, and PK of VRC01 (48). There were 3 
open-label, dose escalation groups for IV administration and 1 double-blinded, 
placebo-controlled group for SC administration as shown in Table 4-1. 
Table 4-1 VRC 602 study schema 
VRC 602 Groups 
VRC01 Administration Schedule 
Group 
Initial 
Enrollments  
Additional 
Enrollments 
Day 0 
Week 4 
1 
3 
2 
5 mg/kg IV 
5 mg/kg IV 
2 
3 
2 
20 mg/kg IV 
20 mg/kg IV 
3 
3 
2 
40 mg/kg IV 
40 mg/kg IV 
4 
SC administration 
4A 
3 
2 
5 mg/kg SC 
5 mg/kg SC 
4B 
3 
2 
Placebo SC 
Placebo SC 
Total 
25 
20 participants treated with VRC01 at different dosage 
levels and 5 participants treated with placebo 
administered SC 
IV doses administered in 100 mL of normal saline over 1 hr. 
First SC dose administered at about 15 mL/hr via SC infusion pump; participant option for 
second dose administration (Week 4) by direct SC injection with needle and syringe. 
All IV infusions and SC injections were well tolerated with no SAEs or dose 
limiting toxicity (48). PK analysis from VRC 602 revealed a VRC01 terminal 
half-life of 15 days across all IV infused dose groups. After the first infusion, 28-

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 28 of 142 
day trough levels were 35 mcg/mL and 57 mcg/mL for the 20 mg/kg and 40 
mg/kg dose groups, respectively. Following the second infusion, the 28-day 
trough values rose to 57 mcg/mL and 89 mcg/mL for the 20 mg/kg and 40 mg/kg 
dose groups, respectively (48). In addition, postinfusion VRC01 retained the 
expected neutralizing activity in serum and no anti-VRC01 antibodies were 
detected (48). 
4.9.1.3 
HVTN 104 
HVTN 104 was a phase 1 clinical trial designed to evaluate the safety and drug 
levels of VRC01 administered in multiple IV or SC doses and different dosing 
schedules to 88 healthy, HIV-uninfected adults at 6 HVTN CRSs in 4 US cities: 
Boston, New York, Philadelphia, and Cleveland. The first participant enrolled in 
HVTN 104 on September 9, 2014 and study product administration for all 
participants was complete as of November 30, 2015. The study had 5 arms (Table 
4-2): Group 1 evaluated the IV administration of a 40 mg/kg loading dose, with 5 
subsequent 20 mg/kg doses given at 4 week intervals. Groups 2, 4, and 5 
evaluated 3 infusions of 40 mg/kg, 10 mg/kg, or 30 mg/kg, respectively, given 8 
weeks apart. Group 3 evaluated 5 mg/kg given every 2 weeks subcutaneously for 
22 weeks after an initial IV administration at 40 mg/kg in order to inform the 
design of perinatal prophylaxis studies. 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 29 of 142 
Table 4-2 HVTN 104 study schema 
Dose 
Groups 
Study product administration schedule in months (days) 
Group 
N 
0 
0.5 (14) 
1 (28) 
1.5 (42) 
2 (56) 
2.5 (70) 
3 (84) 
3.5 (98) 
4 (112) 
4.5 (126) 
5 (140) 
5.5 (154) 
1 
20 
VRC01 
40mg/kg IV 
 
VRC01 
20mg/kg 
IV 
 
VRC01 
20mg/kg IV 
 
VRC01 
20mg/kg IV 
 
VRC01 
20mg/kg IV 
 
VRC01 
20mg/kg IV 
 
2 
20 
VRC01 
40mg/kg IV 
 
 
 
VRC01 
40mg/kg IV 
 
 
 
VRC01 
40mg/kg IV 
 
 
 
3 
20 
VRC01 
40mg/kg IV 
VRC01 
5mg/kg SC 
VRC01 
5mg/kg 
SC 
VRC01 
5mg/kg 
SC 
VRC01 
5mg/kg 
SC 
VRC01 
5mg/kg 
SC 
VRC01 
5mg/kg 
SC 
VRC01 
5mg/kg 
SC 
VRC01 
5mg/kg 
SC 
VRC01 
5mg/kg 
SC 
VRC01 
5mg/kg 
SC 
VRC01 
5mg/kg 
SC 
4 
IV placebo 
for VRC01  
SC placebo 
for VRC01  
SC placebo 
for 
VRC01 
SC 
placebo 
for 
VRC01 
SC placebo 
for 
VRC01 
SC 
placebo 
for 
VRC01 
SC placebo 
for 
VRC01 
SC 
placebo 
for 
VRC01 
SC placebo 
for 
VRC01 
SC 
placebo 
for 
VRC01 
SC placebo 
for 
VRC01 
SC 
placebo 
for 
VRC01 
4 
12 
VRC01 
10mg/kg IV 
 
 
 
VRC01 
10mg/kg IV 
 
 
 
VRC01 
10mg/kg IV 
 
 
 
5 
12 
VRC01 
30mg/kg IV 
 
 
 
VRC01 
30mg/kg IV 
 
 
 
VRC01 
30mg/kg IV 
 
 
 
Total 
88 Intravenous (IV) doses administered in 100 mL of normal saline over 1 hr 
Subcutaneous (SC) doses administered by needle and syringe injection 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 30 of 142 
Secondary aims of HVTN 104 were to: (1) evaluate the kinetics of in vitro 
neutralization in serum of a single VRC01 sensitive virus isolate (TZM.bl assay); 
(2) determine whether anti-idiotypic antibody (AIA) could be detected and 
whether there was a correlation of VRC01 levels and AIA levels in serum; (3) 
determine if measurable levels of VRC01 could be found in genital, rectal, and 
oral secretions; (4) evaluate the kinetics of in vitro neutralization in mucosal 
secretions of a single VRC01 sensitive virus isolate; and (5) assess binding of 
VRC01 to multiple Env proteins. 
A total of 249 IV infusions and 208 SC injections of VRC01 were administered in 
HVTN 104. The infusions and injections were well tolerated, with 28% of 
infusions and 14% of injections associated with mild pain and/or tenderness. 55% 
of VRC01 and 50% of placebo recipients experienced mild pain and/or tenderness 
at the infusion or injection site sometime during the trial. One participant 
experienced moderate pain and/or tenderness following an SC injection of 
VRC01. Mild infusion site erythema/induration reactions were reported for 2 
VRC01 participants and 1 placebo recipient. Two moderate erythema/induration 
reactions were reported, 1 following IV VRC01 and 1 following VRC01 SC 
injection. For 76% of the infusions and injections administered in the trial, no 
systemic reactogenicity symptoms were reported. 56% of VRC01 and 75% of 
placebo recipients experienced systemic reactogenicity symptoms following at 
least one study product administration. These were all graded as mild in the 
placebo recipients. Among VRC01 recipients who experienced any systemic 
symptoms, the maximum severity was mild in 70%, moderate in 23%, and severe 
in 6% (3 participants). The most commonly reported symptoms were 
malaise/fatigue (30%), headaches (32%), and myalgias (26%).The severe 
systemic reactogenicity symptoms reported in 3 VRC01 recipients in HVTN 104 
are detailed as follows: 
 One participant developed severe malaise, myalgia, headache and chills, mild 
nausea, and moderate arthralgia symptoms within 3 days after the first 
infusion of study product. The participant had a concomitant AE of laboratory 
confirmed influenza A infection diagnosed on Day 2 and was treated with 
ibuprofen. Symptoms resolved by Day 7. 
 One participant reported a viral illness AE of moderate intensity beginning 3 
days prior to the 9th SC injection (10th study product administration), 
characterized by nausea and vomiting, sore throat, runny nose but no fevers; a 
household contact was also ill. At baseline on Day 0 of the 9th SC injection, 
mild malaise/fatigue was still present. At the early assessment timepoint on 
Day 0, mild malaise/fatigue was still present and was accompanied by grade 1 
nausea. Within 3 days of the injection, the participant developed severe 
malaise, myalgia, headache, chills, and arthralgia; these all resolved on Day 6, 
which was the date the AE for viral illness was resolved. There was no 
reported use of concomitant medications for these symptoms. 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 31 of 142 
 One participant reported severe malaise/fatigue on the day of the first 
infusion, resolving spontaneously the next day. During this reactogenicity 
period, this participant also reported a grade 1 headache on Day 1, resolving 
the next day. 
There were no study product discontinuations due to reactogenicity symptoms. 
There were 235 AEs occurring in 70 participants (79.5%), with similar rates of 
occurrence across all treatment groups (81% among VRC01 recipients; 75% in 
placebo recipients). 74% of AEs were graded as mild, 22.5% as moderate, and 
3.4% as severe. Only 9 AEs (3.8% of all AEs) occurring in 8 participants were 
deemed product-related by the investigators; all were mild and transient. Those 
occurring following VRC01 administration included elevations of hepatic 
transaminases (aspartate aminotransferase [AST] and alanine aminotransferase 
[ALT] in 1 individual), elevated creatinine, neutropenia, localized injection site 
pruritus, diarrhea, generalized rash, and Varicella zoster infection. No VRC01-
related hypersensitivity reactions or Cytokine Release Syndrome symptoms were 
observed during the study. 
Study product administration was discontinued in 8 participants. Reasons for 
discontinuing study product included: AEs (3 participants, see Section 4.9.1.4), 
relocation from study site (2), unable to adhere to visit schedule (1), unable to 
contact (1), and pregnancy (1). In summary, VRC01 was well-tolerated when 
administered IV or SC.  
Figure 4-6 shows individual-specific serum VRC01 levels among per-protocol 
(PP) participants who received all planned infusions and/or injections within 
protocol-specified visit windows in HVTN 104. Particularly, Groups 4 and 5 
evaluated the dose and intervals selected for the phase 2b efficacy trials.  
As measured by ELISA, average (geometric mean) serum VRC01 levels in T1 
three days after the first (40 mg/kg) and second (20 mg/kg) IV infusion were 422 
and 260 mcg/mL, respectively. Average peak levels 1 hour after the last infusion 
were 796 mcg/mL. Average trough levels 28 days post infusion were 69 mcg/mL 
after the first infusion and 51, 46, 45, 43 and 46 mcg/mL after infusions 2-6, 
respectively. VRC01 remained detectable (≥ 1.1 mcg/mL) in 6/9 (67%) of per 
protocol participants 12 weeks after the last IV infusion in T1. 
These levels are similar to those modeled for the phase 2b efficacy trials (HVTN 
704/HPTN 085 and HVTN 703/HPTN 081) and they show the desired overlap in 
concentrations achieved with the two doses selected for these trials. 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 32 of 142 
 
Figure 4-6 Individual-specific VRC01 serum levels among HVTN 104 participants who 
received all planned infusions/injections of VRC01/placebo. A double tick on the x-axis 
denotes a time interval of 3 days, representing visit days 3, 17, 31, 59, 115, and/or 157. T1: 20 
mg/kg IV, q 4 weeks with 40 mg/kg IV loading; T2: 40 mg/kg IV, q 8 weeks; T3 (P3): 5 mg/kg SC, q 
2 weeks with 40 mg/kg IV loading; T4: 10 mg/kg IV, q 8 weeks; T5: 30 mg/kg IV, q 8 weeks. Note: 
For T1, peak and pre-trough serum concentrations were not measured postinfusion at days 17, 59, 
70, 98, 115, 126, 143, 145, and 159; for T3, peak serum concentrations were not measured 
postinjection at days 31, 59, 115, and 143; for T2, T4, and T5, peak serum concentrations were 
measured post-third infusion at day 115 only in a subset of participants who also provided mucosal 
samples. 
4.9.1.4 
Safety summary of VRC01 
As of February 23, 2016, approximately 130 adult participants have received one 
or more VRC01 administrations in unblinded VRC01 studies, including 23 in 
VRC 601, 23 in VRC 602 (5 additional participants received placebo), and 84 in 
HVTN 104 (4 additional participants received placebo). 249 VRC01 infusions 
and 208 SC injections were given in HVTN 104. 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 33 of 142 
Cumulatively, there have been no expedited safety reports to the FDA or study 
safety pauses for AEs and no reactions during VRC01 or placebo/control product 
administration that resulted in an incomplete administration.  
VRC01 SC or IV administrations are generally associated with mild or moderate 
local reactions of pruritus, redness, and pain/tenderness, which resolve within a 
few minutes to a few hours after the administration is completed. When present, 
most systemic reactions after administration of VRC01 SC or IV are mild and 
include malaise, myalgia, headache, chills, nausea, and joint pain. 
Unsolicited AEs of grade 3 or higher severity and deemed related to study product 
were not reported in these trials. 
Other AEs attributed to study product administration have included mild or 
moderate AST elevation, ALT elevation, creatinine elevation, and decreased 
neutrophil count. Mild or moderate elevated transaminases were reported in 4 of 
21 (19%) HIV-infected participants in VRC 601 (all of whom were taking 
ARVs). These laboratory changes resolved spontaneously and did not require 
discontinuation of study product administration. Among HIV-uninfected 
participants in VRC 602 or HVTN 104, 1 participant had grade 1 (mild) 
transiently elevated ALT assessed as possibly attributed to VRC01 in the VRC 
602 study and 2 participants had grade 1 (mild) transiently elevated ALT/AST 
values assessed as related to VRC01 in HVTN 104. These 3 participants all 
received VRC01. 
In HVTN 104, there were 3 product discontinuations for AEs, 2 of which were 
deemed related to study product infusion or injection. One discontinuation was for 
a 20-minute episode of chest tightness occurring approximately 25 minutes after 
SC injection of placebo in a participant who is a chronic smoker on nicotine 
replacement while continuing to smoke. One discontinuation was in a participant 
who reported a generalized rash that began three days after SC injection of 
VRC01, and resolved within 4 hours with ibuprofen and the application of an 
inert cream. The third discontinuation was in a young, otherwise healthy 
participant who experienced a brief episode of syncope, deemed not related to 
study product, approximately 4 hours after IV infusion of VRC01. In addition, 
one person in HVTN 104 had study product discontinued due to pregnancy 
occurring during the trial. 
Of note, the safety experience with VRC01 has remained consistent whether 1 or 
2 doses were administered, as in VRC 601 and 602, or multiple doses were 
administered, as in HVTN 104. There were no observed trends toward recurrence 
of lab abnormalities or AEs deemed related to study product, nor observed 
increases in frequency or severity of local or systemic reactogenicity symptoms 
with multiple administrations of VRC01 in these trials. 
The ongoing efficacy trials (HVTN 704/HPTN 085 and HVTN 703/HPTN 081) 
have accumulated significant additional VRC01 clinical experience; but these 
trials remain blinded and, thus, do not yet contribute to the unblinded VRC01 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 34 of 142 
safety profile. However, in the ongoing blinded phase of these trials, urticaria or 
similar reactions have been reported at an overall frequency of about 1%. These 
reactions have been treated by stopping the infusion and providing supportive 
care, including anti-histamine and steroid therapy, as indicated, and no serious 
health consequences have been reported. No participants who experienced 
urticaria have been rechallenged. 
Overall, VRC01 administration in the dose range from 10 to 40 mg/kg IV and at 5 
mg/kg SC has been assessed as well-tolerated and safe for further evaluation. 
4.9.2 
Clinical studies of VRC01LS 
4.9.2.1 
VRC 606 
VRC01LS began evaluation in the VRC 606 study in November 2015. As of 
August 4, 2017, 39 healthy HIV-uninfected subjects had been enrolled and had 
received a total of 73 administrations of VRC01LS (35 IV and 38 SC) in this 
dose-escalation study to examine safety, tolerability, dose, and pharmacokinetics 
of VRC01LS. There were 4 open-label, dose escalation groups (Groups 1-4) to 
assess VRC01LS administered IV and SC once per participant and 2 open-label 
groups (Groups 5 and 6) to assess VRC01LS at 5 mg/kg SC or at 20 mg/kg IV 
administered every 12 weeks for a total of 3 administrations per participant. 
VRC01LS SC administrations were sometimes associated with mild local 
reactions including pain and swelling, which typically resolved within 24 hours. 
The solicited local and systemic signs and symptoms following administration of 
VRC01LS were generally none to mild. There have been no SAEs attributed to 
VRC01LS administration. Grade 1 AEs attributed to study product administration 
include two cases of diarrhea, one case of dizziness, which resolved without 
clinical sequelae, one case of erythema at the injection site, and one case of 
induration at the injection site. No other study product-related AEs have been 
reported. 
Overall, VRC01LS administration in the dose range from 1 to 40 mg/kg IV and at 
5 mg/kg SC have been assessed as well-tolerated and safe for further evaluation. 
An additional study of VRC01LS, HVTN 116 [NCT02797171], is currently 
recruiting with 36 of 74 participants enrolled as of October 15, 2017. 
Serum VRC01LS concentrations as high as 20 mcg/mL were observed in VRC 
606 at 165 days (approximately 24 weeks) after a 5 mg/kg IV infusion and were, 
on average, over 65 mcg/mL at 165 days after a 20 mg/kg IV infusion. VRC01LS 
concentrations remained, on average, above 10 mcg/mL at 165 days after 5 mg/kg 
SC (Figure 4-7). 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 35 of 142 
 
Figure 4-7 VRC01LS serum concentrations in VRC 606 compared to VRC01 serum 
concentrations with IV and SC administration 
Correlation of mAb concentration with neutralization and effector functions is not 
yet known; however, these levels are considerably higher than seen in VRC01 at 
similar timepoints. VRC01LS concentration on Day 84 after a single 5mg/kg SC 
administration was, on average, over 10 times greater than VRC01 concentration 
on Day 84 after a single 5mg/kg SC VRC01 administration. The difference is 
even more marked when comparing VRC01 concentrations on Day 84 after a 
single 20 mg/kg IV infusion to VRC01LS concentrations on Day 84 after a single 
20 mg/kg IV infusion: VRC01LS concentrations are over 40 times higher than 
those of VRC01 (Gaudinski et al, PLoS Medicine, manuscript submitted). 
4.9.3 
Clinical studies of VRC07-523LS; VRC 605 
A phase 1 open-label, dose-escalation study of VRC07-523LS, VRC 605 
(NCT03015181), is underway in healthy, HIV-uninfected adults to evaluate the 
safety and pharmacokinetics of 1 to 3 administrations of the antibody. The doses 
being evaluated are a single administration of 1 mg/kg and 5 mg/kg IV and SC, 
and 20 mg/kg and 40 mg/kg IV, and three administrations (q 12 weeks) of 5 
mg/kg SC and 20 mg/kg IV VRC07-523LS (Table 4-3).  
Study objectives include evaluating the safety and tolerability of the study 
regimen and the pharmacokinetics of each dose level through 24 weeks after the 
last dose; determining the presence or absence of detectable ADA to VRC07-
523LS; and evaluating for evidence of functional activity of VRC07-523LS. 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 36 of 142 
Table 4-3 VRC 605 study schema 
Group 
Participants 
Administration Schedule 
Day 0 
Week 12 
Week 24 
1 
3 
1 mg/kg IV 
 
 
2 
3 
5 mg/kg IV 
 
 
3 
3 
5 mg/kg SC 
 
 
4 
3 
20 mg/kg IV 
 
 
5 
3 
40 mg/kg IV 
 
 
6 
5 
5 mg/kg SC 
5 mg/kg SC 
5 mg/kg SC 
7 
5 
20 mg/kg IV 
20 mg/kg IV 
20 mg/kg IV 
Total 
25 
 
# One participant enrolled into Group 1 then withdrew prior to receiving VRC07-523LS, so an 
additional participant was enrolled into the group. 
As of January 15, 2018, the VRC 605 study is fully enrolled. Twenty-five (25) of 
26 participants have received at least 1 dose of VRC07-523LS (12 SC and 25 IV 
administrations). One participant withdrew prior to receiving the study product. 
Overall, 15 of 25 participants who received the product (60%) have had at least 
one AE with the maximum severity being grade 1 for 7 participants, grade 2 for 6 
participants, grade 3 for 1 participant and grade 4 for 1 participant. The grade 3 
AE was for an elevated creatinine 56 day after the last product administration. 
This was most likely related to dehydration following exercise. The creatinine 
value was determined to be a grade 3 based on the DAIDS Table parameter of an 
increase of 1.5 to 2 times the baseline value, which was still well within the 
institutional normal range. The grade 4 AE was for elevated liver enzymes likely 
related to a starting a concomitant medication, fluoxetine, known to cause 
hepatotoxicity, and not related to VRC07-523LS. VRC07-523LS administrations 
were discontinued for this participant due to the concomitant illness. While the 
participant was being followed for safety, liver enzymes tests fluctuated again 
after starting citalopram which reinforced that the event was most likely caused 
by an underlying sensitivity to selective serotonin reuptake inhibitor (SSRI) 
medications. This grade 4 laboratory abnormality was not considered life-
threatening as it was not clinically significant as there were no hospitalization, 
jaundice, coagulopathy, bleeding, or ascites. Six (6) mild or moderate AEs were 
assessed as related to study product including mild dizziness, 4 occasions of 
infusion reactions (1 mild and 3 moderate, reported for 2 participants), and mild 
abdominal pain. All AEs assessed as related to the study product have resolved 
without residual effects. 
Figure 4-8 displays interim VRC07-523LS PK results in VRC 605. 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 37 of 142 
B 
 
C 
A 
 
 
 
Figure 4-8 Interim VRC 605 PK results for VRC07-523LS with VRC01LS comparators. (A) 5 
mg/kg IV (Group 2 in this trial); administrations completed. (B) 5 mg/kg SC (Group 5 in this 
trial); administrations ongoing. (C) 20 mg/kg IV (Group 3 in this trial); administrations 
ongoing. 
4.10 
Potential risks of study products and administration 
There is limited human experience with administration of VRC07-523LS. VRC 
605 is evaluating VRC07-523LS prior to the start of HVTN 127/HPTN 087 and 
thus far there have been no SAEs or Grade 3 or higher related AEs. In addition, 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 38 of 142 
the similar CD4-binding site mAb VRC01 has been given to over 2300 
participants in several phase 1 and phase 2 clinical trials. More than 8,000 
infusions of 10 mg/kg and 30 mg/kg VRC01 have been given to HIV-uninfected 
adults in HVTN 704/HPTN 085 and HVTN 703/HPTN 081. Both VRC01 and 
VRC01LS are being tested in an ongoing phase 1 study (HVTN 116). 
Standard infusion reactions to mAb administration are typically mild but may 
include fever, flushing, chills, rigors, nausea, vomiting, pain, headache, dizziness, 
shortness of breath, hypertension, pruritus, rash, urticaria, diarrhea, tachycardia or 
chest pain (67). Most infusion reactions appear to result from antibody-antigen 
interactions resulting in cytokine release (67). Administration of mAbs may have 
a risk of severe reactions, such as acute anaphylaxis, serum sickness, angioedema, 
bronchospasm, hypotension, and hypoxia, the generation of anti-drug antibodies; 
they may also be associated with an increased risk of infections. However, these 
reactions are rare and more often associated with mAbs targeted to human 
proteins (67) or with the use of murine mAbs, which have a risk of eliciting 
human anti-mouse antibodies (68). Infusion of mAbs directed against cell surface 
targets on lymphocytes may cause a reaction known as “cytokine release 
syndrome”, with clinical manifestations including fatigue, headache, urticaria, 
pruritus, bronchospasm, dyspnea, sensation of tongue or throat swelling, rhinitis, 
nausea, vomiting, flushing, fever, chills, hypotension, tachycardia, and asthenia 
(69). Cases of cytokine release syndrome occur most often in the first few hours 
after the first mAb dose, 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 (69).  
Since VRC07-523LS targets a viral antigen rather than human cell surface 
antigens and is a human mAb, severe infusion reactions are expected to be rare.  
Most infusion-related events occur within the first 24 hours after beginning 
administration. Delayed allergic reactions to a mAb may include a serum sickness 
type of reaction, 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 are noted to be more common with chimeric types of mAb (68). 
Reactions related to the rate of infusion have been described for several FDA-
licensed mAbs. With licensed therapeutic mAbs, cytokine-mediated infusion 
reactions, including cytokine release syndrome, are typically managed by 
temporarily stopping the infusion, administering histamine blockers and restarting 
the infusion at a slower rate (70). Supportive treatment may also be indicated for 
some signs and symptoms. 
The published experience with mAbs administered by the SC route is limited but 
there is experience with the SC route of administration of immunoglobulins, such 
as Hizentra® (CSL Behring LLC, Kankakee, IL), 20% immune serum globulin, 
for patients with primary immunodeficiency diseases. Comparison of the safety 
and PK of intravenous immunoglobulin (IVIG) to subcutaneous immunoglobulin 
(SCIG) has been reported. The SC route of administration has a good safety 
profile. Tissue reactions are common but usually mild and tend to decline over 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 39 of 142 
time with repeated administrations (71). The package insert for Hizentra® notes 
that the most common adverse reactions (observed in ≥ 5% of study participants) 
in clinical trials were local reactions (such as swelling, redness, heat, pain and 
itching at the infusion site), headache, vomiting, pain, and fatigue. 
The published experience with mAb administered by the IM route is also limited 
but there is experience with the IM route of administration for palivizumab 
(Synagis®) (72). Monthly IM administration of palivizumab at a dose of 15 
mg/kg is safe, well-tolerated, and effective at preventing RSV infection in high-
risk infants. Compliance with monthly IM dosing of palivizumab has been 
reported to be high in clinical practice (73). 
To date, the clinical trial safety experience with VRC01-class mAbs has been 
reassuring. 
 In HVTN 104, IV administration of VRC01 was generally well-tolerated with 
mild pain and/or tenderness commonly reported at the site of the IV infusion. 
Mild to moderate systemic reactogenicity symptoms were reported by VRC01 
recipients following at least one of the infusions, but there was no clear 
relationship with frequency or severity to the dose of VRC01 (49). 
 In HVTN 104, SC administration of VRC01 was generally well-tolerated and 
associated with mild to moderate local pain and/or tenderness, but there was 
no difference in the frequency or severity between VRC01 recipients and 
placebo recipients (49). Erythema and/or induration at the SC injection sites 
were generally less than 25 cm2 whether VRC01 or placebo was injected (49). 
 No hypersensitivity reactions or cytokine release syndrome symptoms were 
reported in HVTN 104 (49).  
 The ongoing blinded HVTN 704/HPTN 085 and HVTN 703/HPTN 081 trials 
have reported an approximately 1% rate of urticaria or similar reactions. 
 In the ongoing VRC 605 trial of VRC07-523LS, there have been no SAEs and 
no safety pauses. The maximum severity of AEs has been Grade 1 (for 17 
events) and Grade 2 (for 6 events, including 2 infusion reactions). 
 Severe reactions associated with mAb administration, such as acute 
anaphylaxis, serum sickness, anti-drug antibodies, and increased risk of 
infections have not been observed to date in trials of VRC01-class mAbs. 
VRC07-523LS is an antibody to an HIV protein. Therefore, it may be 
theoretically possible for a standard antibody-based HIV diagnostic test to detect 
VRC07-523LS for a short time period postinfusion or postinjection. However, in 
HVTN 104, VRC01 did not cause a positive test result in several standard 
antibody-based HIV-1/2 diagnostic tests used in the US (49). In vitro testing of 
blood samples with VRC01 concentrations as high as 1,600 mcg/mL have been 
evaluated with several common HIV antibody-based test kits and no antibody-

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 40 of 142 
induced seroreactivity has been demonstrated. The issue of seroreactive results to 
HIV-1/2 screening assays as a result of mAb administration will also be evaluated 
in the ongoing HVTN 704/HPTN 085 and HVTN 703/HPTN 081 studies to 
further inform this risk. 
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. 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. Risk will be minimized by using sterile technique and universal 
precautions. 
Risks of Intravenous Infusion: The placement of an intravenous catheter can allow 
for the development of bacteremia because of the contact between the catheter 
and unsterile skin when it is inserted. This will be prevented through careful 
decontamination of local skin prior to catheter placement and through the use of 
infection control practices during infusion. Product contamination will be 
prevented by the use of aseptic technique in the pharmacy and universal 
precautions during product administration. 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 41 of 142 
5 
Objectives and endpoints 
5.1 
Primary objectives and endpoints 
Primary objective 1:  
To evaluate the safety and tolerability of different doses of VRC07-523LS 
administered IV, SC, and IM by repeat dosing every 16 weeks for a total of 5 
administrations to healthy adults 
Primary endpoint 1:  
Local and systemic Solicited AEs, laboratory measures of safety, Unsolicited 
AEs, SAEs, and AEs of special interest (AESI)  
Early discontinuation of administration and reason(s) for discontinuation and 
early study termination 
Primary objective 2:  
To evaluate the serum concentrations of VRC07-523LS administered IV, SC, and 
IM over a total of 6 regimens  
Primary endpoint 2:  
Serum concentrations of VRC07-523LS in each group at specific timepoints from 
baseline through the final scheduled study visit, as measured by binding activity 
among participants who received all scheduled product administrations 
5.2 
Secondary objectives and endpoints 
Secondary objective 1: 
To develop predictive population pharmacokinetic models of VRC07-523LS 
administered IV, SC, and IM 
Secondary endpoint 1: 
Data on serum concentrations of VRC07-523LS at all available timepoints for all 
groups in all participants regardless of how many product administrations they 
received 
Secondary objective 2: 
To determine whether ADA can be detected and whether there is a correlation of 
VRC07-523LS levels and ADA levels in serum 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 42 of 142 
Secondary endpoint 2: 
Serum concentration of ADA in each group measured at multiple timepoints from 
baseline through the final study visit 
Secondary objective 3: 
To determine whether serum neutralizing activity is maintained at consistent 
levels after each product administration 
Secondary endpoint 3: 
Magnitude and breadth of serum neutralizing activity in each group measured 
against a panel of Tier 2 viruses that exhibit a range of known sensitivities to 
VRC07-523LS 8 weeks after each product administration 
Secondary objective 4: 
To determine whether serum neutralizing activity agrees with measured serum 
concentrations 
Secondary endpoint 4: 
Magnitude of neutralization compared to serum concentration and known IC50 of 
VRC07-523LS for each isolate 8 weeks after each product administration 
5.3 
Exploratory objectives 
Exploratory objective 1: 
To evaluate the magnitude and breadth of serum IgG binding activity at each dose 
level  
Exploratory objective 2: 
To evaluate additional non-neutralizing functional humoral activities (eg, 
antibody-dependent cellular cytotoxicity [ADCC], antibody-dependent cellular 
phagocytosis [ADCP], virion capture) in serum with reagents that have known 
reactivity with VRC07-523LS 
Exploratory objective 3: 
To conduct analyses related to furthering the understanding of HIV, monoclonal 
antibodies, immunology, vaccines, and clinical trial conduct 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 43 of 142 
6 
Statistical considerations 
6.1 
Accrual and sample size calculations 
Recruitment will target enrolling 124 healthy, HIV-uninfected adult participants. 
The study design includes 6 treatment groups. Table 3-1 provides an overview of 
the sample sizes, routes of administration, doses, and schedules of administration 
for these treatment groups. All groups will be open to enrollment at the same 
time. Participants will be randomly assigned to the 6 groups.  
Groups 1, 2, and 3 entail multiple IV administrations of one of three doses of 
VRC07-523LS (2.5, 5, and 20 mg/kg, respectively). Participants will receive one 
administration of VRC07-523LS every 16 weeks, for a total of 5 administrations. 
The first and last administrations will be delivered at baseline (Week 0) and at 
Week 64 post-baseline, respectively. Recruitment will target 20 participants in 
each treatment group.  
Groups 4, and 5 entail multiple SC administrations of one of two doses of 
VRC07-523LS (2.5 mg/kg in Group 4, and 5 mg/kg in Group 5). Participants will 
receive one administration of VRC07-523LS every 16 weeks, for a total of 5 
administrations. The first and last administrations will be delivered at baseline 
(Week 0) and at Week 64 post-baseline, respectively. Recruitment will target 20 
participants in each treatment group.  
Group 6 entails multiple IM administrations of either one dose level of VRC07-
523LS (2.5 mg/kg) or a placebo. Participants will receive one administration 
every 16 weeks, for a total of 5 administrations. The first and last administrations 
will be delivered at baseline (Week 0) and at Week 64 post-baseline, respectively. 
Recruitment will target 24 participants in this treatment group, and use a 
randomization ratio of 5:1 to assign 20 participants to the VRC07-523LS arm and 
4 participants to the placebo arm.  
Participants will be followed for 112 weeks from the day they receive their first 
product administration. 
To ensure that both men and women will be adequately represented in the trial, 
the trial will enroll at least approximately 40% of each sex assigned at birth 
overall. 
Since enrollment is concurrent with receiving the first study product 
administration, all participants will provide some safety data. However, for PK 
and functional analyses, it is possible that data may be missing for various 
reasons, such as participants terminating from the study early, problems in 
shipping specimens, low cell viability of processed peripheral blood mononuclear 
cells (PBMCs) or high assay background. Immunogenicity data from 17 phase 1 
and 2 phase 2a HVTN vaccine trials, which began enrolling after June 2005 (data 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 44 of 142 
as of September 2014), indicate that 17% is a reasonable estimate for the rate of 
missing data. In HVTN 104 (phase 1 trial of VRC01), approximately 10-15% of 
drug concentration data were missing at the primary timepoints. Therefore, the 
sample size calculations in Section 6.1.2 account for 10-20% enrolled participants 
having missing data for the primary endpoint. 
6.1.1 
Sample size calculations for safety 
The goal of the safety evaluation for this study is to identify safety concerns 
associated with product administration. The ability of the study to detect SAEs 
(see Section 11.2.3) can be expressed by the true event rate above which at least 1 
SAE would likely be observed and the true event rate below which no events 
would likely be observed. Specifically, for each treatment group of size n = 20, 
there is at least 90% chance of observing at least 1 event if the true rate of such an 
event is 10.9% or more; and there is at least 90% chance of observing no events if 
the true rate is 0.5% or less. For active IV administration arms (n = 60) combined, 
there is at least 90% chance of observing at least 1 event if the true rate of such an 
event is 3.8% or more; and there is at least 90% chance of observing no events if 
the true rate is 0.17% or less. For active SC administration arms (n = 40) 
combined, there is at least 90% chance of observing at least 1 event if the true rate 
of such an event is 5.6% or more; and there is at least 90% chance of observing no 
events if the true rate is 0.26% or less. For all active arms combined (n = 120), 
there is at least 90% chance of observing at least 1 event if the true rate of such an 
event is 1.91% or more; and there is at least 90% chance of observing no events if 
the true rate is 0.087% or less. As a reference, in HVTN vaccine trials from 
December 2000 through April 2014, about 4% of participants who received 
placebos experienced an SAE. 
Binomial probabilities of observing 0, 1 or more, and 2 or more events among 
arms of sizes 20, 40, 60 and 120 are presented in Table 6-1 for a range of possible 
true AE rates. These calculations provide a more complete picture of the 
sensitivity of this study design to identify potential safety problems with VRC07-
523LS. 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 45 of 142 
Table 6-1 Probability of observing 0 events, 1 or more events, and 2 or more events, among 
arms of size 20, 40, 60, and 120 for a range of true event rates 
True event rate (%) 
arm size 
0 events 
1+ events 
2+ events 
1 
20 
0.82 
0.18 
0.02 
40 
0.67 
0.33 
0.06 
60 
0.55 
0.45 
0.12 
120 
0.30 
0.70 
0.34 
4 
20 
0.44 
0.56 
0.19 
40 
0.20 
0.80 
0.48 
60 
0.09 
0.91 
0.70 
120 
<0.01 
>0.99 
0.96 
10 
20 
0.12 
0.88 
0.61 
40 
0.01 
0.99 
0.92 
60 
<0.01 
>0.99 
0.99 
120 
<0.01 
>0.99 
>0.99 
20 
20 
0.01 
0.99 
0.93 
40 
<0.01 
>0.99 
>0.99 
60 
<0.01 
>0.99 
>0.99 
120 
<0.01 
>0.99 
>0.99 
30 
20 
<0.01 
>0.99 
0.99 
40 
<0.01 
>0.99 
>0.99 
60 
<0.01 
>0.99 
>0.99 
120 
<0.01 
>0.99 
>0.99 
An alternative way of describing the statistical properties of the study design is in 
terms of the 95% confidence interval for the true rate of an AE based on the 
observed data. Table 6-2 shows the 2-sided 95% confidence intervals for the 
probability of an event based on a particular observed rate. Calculations are done 
using the score test method (74). If none of the 20 participants for each individual 
treatment group experience a safety event, the 95% 2-sided upper confidence 
bound for the true rate of such events in the total VRC07-523LS-treated 
population is 16.1%. 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 46 of 142 
Table 6-2 Two-sided 95% confidence intervals based on observing a particular rate of safety 
endpoints for arms of size 20, 40, 60, and 120 
Observed event rate 
95% Confidence interval (%) 
0/20 
[0 ; 16.1] 
1/20 
[0.89 ; 23.6] 
2/20 
[2.79 ; 30.1] 
0/40 
[0 ; 8.76] 
1/40 
[0.44 ; 12.9] 
2/40 
[1.38; 16.5] 
0/60 
[0 ; 6.02] 
1/60 
[0.30 ; 8.9] 
2/60 
[0.92; 11.4] 
0/120 
[0 ; 3.1] 
1/120 
[0.2 ; 4.6] 
2/120 
[0.15 ; 5.9] 
6.1.2 
Sample size calculations for serum levels of VRC07-523LS 
Primary Objective 2 of this study is to evaluate serum concentrations of VRC07-
523LS at several timepoints following multiple IV, SC, and IM administrations. 
This objective is descriptive in nature, and will be accomplished by estimating the 
mean VRC07-523LS serum concentration within each active arm at specific 
timepoints following administration. The precision with which a true mean 
concentration can be estimated from observed data depends on the standard 
deviation (SD) of the measurements and the sample size. Table 6-3 displays two-
sided 95% confidence intervals for the mean drug concentration for several values 
of the observed average drug concentration. The construction of these confidence 
intervals assumed sample sizes of n = 16, 18, and 20 per arm, reflecting an 
attrition rate of 20%, 10%, and 0% compared to a planned treatment group size of 
20 participants. The calculations assumed that log-transformed serum 
concentrations are approximately normally distributed. For instance, with an 
observed mean loge serum level of loge(5) mcg/mL and assuming a standard 
deviation of 0.5 for their log-transformed values, a two-sided 95% confidence 
interval for the true mean drug concentration level is (3.8 , 6.5) (in mcg/mL) with 
an effective sample size of 16 participants. 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 47 of 142 
Table 6-3 Two-sided 95% confidence intervals based on observing a particular average drug 
level in participants in any of the active arms, taking attrition into consideration (n = 16, 18, 
20) 
Observed 
average loge-
serum level (loge 
mcg/mL) 
SD of loge-
drug levels 
(loge 
mcg/mL) 
95% confidence interval (mcg/mL) 
n = 16 
n = 18 
n = 20 
loge(0.5) 
0.5 
(0.4 , 0.7) 
(0.4 , 0.6) 
(0.4 , 0.6) 
loge(1) 
(0.8 , 1.3) 
(0.8 , 1.3) 
(0.8 , 1.3) 
loge(3) 
(2.3 , 3.9) 
(2.3 , 3.8) 
(2.4 , 3.8) 
loge(5) 
(3.8 , 6.5) 
(3.9 , 6.4) 
(4.0 , 6.3) 
loge(10) 
(7.7 , 13.1) 
(7.8 , 12.8) 
(7.9 , 12.6) 
loge(20) 
(15.3 , 26.1) 
(15.6 , 25.7) 
(15.8 , 25.3) 
loge(30) 
(23.0 , 39.1) 
(23.4 , 38.5) 
(23.7 , 37.9) 
loge(40) 
(30.6 , 52.2) 
(31.2 , 51.3) 
(31.6 , 50.6) 
loge(50) 
(38.3, 65.3) 
(39.0, 64.1) 
(39.6, 63.2) 
loge(100) 
(76.6, 130.5) 
(78.0, 128.2) 
(79.1, 126.4) 
loge(250) 
(191.5, 326.3) 
(195.0, 320.6) 
(197.8, 315.9) 
loge(500) 
(383.1, 652.6) 
(389.9, 641.1) 
(395.7, 631.8) 
loge(1000) 
(766.1, 1305.3) 
(779.9, 1282.3) 
(791.4, 1263.7) 
loge(0.5) 
1 
(0.3 , 0.9) 
(0.3 , 0.8) 
(0.3 , 0.8) 
loge(1) 
(0.6 , 1.7) 
(0.6 , 1.6) 
(0.6 , 1.6) 
loge(3) 
(1.8 , 5.1) 
(1.8 , 4.9) 
(1.9 , 4.8) 
loge(5) 
(2.9 , 8.5) 
(3.0 , 8.2) 
(3.1 , 8.0) 
loge(10) 
(5.9 , 17.0) 
(6.1 , 16.4) 
(6.3 , 16.0) 
loge(20) 
(11.7 , 34.1) 
(12.2 , 32.9) 
(12.5 , 31.9) 
loge(30) 
(17.6 , 51.1) 
(18.3 , 49.3) 
(18.8 , 47.9) 
loge(40) 
(23.5 , 68.2) 
(24.3 , 65.8) 
(25.0 , 63.9) 
loge(50) 
(29.3, 85.2) 
(30.4, 82.2) 
(31.3, 79.8) 
loge(100) 
(58.7, 170.4) 
(60.8, 164.4) 
(62.6, 159.7) 
loge(250) 
(146.7, 426.0) 
(152.0, 411.1) 
(156.6, 399.2) 
loge(500) 
(293.5, 851.9) 
(304.1, 822.1) 
(313.1, 798.4) 
loge(1000) 
(586.9, 1703.8) 
(608.2, 1644.3) 
(626.2, 1596.8) 
The values of the observed average and SD of the loge serum concentrations 
reported in Table 6-3 were selected to cover the range of values that we expect in 
the proposed study and chosen on the basis of model-based predictions of serum 
concentration data following multiple IV and SC administrations of VRC07-
523LS. These predictions were generated through Monte Carlo simulations of a 
population PK model adapted from a previously developed population PK model 
of VRC01 serum concentrations (48, 49). In these simulations, the PK parameters 
(eg, absorption and distribution rates) of VRC07-523LS were assumed to be all 
identical to those of VRC01 with the exception of the terminal elimination rate 
which was set to either 1/2, 1/5, or 1/10 of that of VRC01 (estimated half-life = 
15 days). These assumptions were motivated by experimental observations in 
preclinical macaque studies with VRC07-523LS and VRC 606 using VRC01LS 
which suggested that the half-life of VRC07-523LS could be approximately at 
least twice as long as that of VRC01. Thus, 3 scenarios were considered in these 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 48 of 142 
simulations in which the terminal half-life of VRC07-523LS was set to either 30 
days, or 75 days, or 150 days. We simulated the serum concentration trajectories 
of 4,000 hypothetical individuals using the population PK model. Because body 
weight was found to be significantly associated with some of the PK parameters 
of VRC01 (eg, its clearance) in the HVTN 104 study, the body weights of the 
4,000 hypothetical individuals were randomly drawn with replacement from the 
sample of body weights collected in the HVTN 104 study. The mean and variance 
of log-transformed serum concentrations were next computed up to 48 weeks 
after the last administration of VRC07-523LS for the 20 mg/kg IV and 2.5 mg/kg 
SC treatment groups proposed in this study (Groups 3 and 4). For example, 
assuming a half-life of 30 days for VRC07-523LS, the model predicted mean 
loge-serum concentrations at 24 weeks post last IV and SC administration in 
Groups 3 and 4 of loge(2.4) and loge(0.7) mcg/mL, respectively. Assuming a half-
life of 75 days for VRC07-523LS, the predicted mean loge-serum concentrations 
at 24 weeks post last IV and SC administration in Groups 3 and 4 were estimated 
as loge(33.2) and loge(3.7) mcg/mL, respectively. Assuming a half-life of 150 
days for VRC07-523LS, the predicted mean serum concentrations at 24 weeks 
post the last IV and SC administration in Groups 3 and 4 were estimated as 
loge(102.0) and loge(12.4) mcg/mL, respectively. The scenarios presented in 
Table 6-3 are expected to cover the range of values of VRC07-523LS serum 
concentrations that will be measured at the sampling times in Groups 1 - 5.  
Serum concentration data following IM administrations of 2.5 mg/kg VRC07-
523LS (Group 6) were not simulated due to the lack of a population PK model 
describing this route of administration in a related product. The mean and 
variance of serum concentrations are expected to fall within the range of values 
predicted for serum concentration data following IV and SC administrations of 
2.5 mg/kg VRC07-523LS (Groups 1 and 4). 
6.2 
Randomization  
A participant’s randomization assignment will be computer generated and 
provided to the CRS pharmacist through a Web-based randomization system. All 
groups will be enrolled simultaneously. The randomization will be done in blocks. 
This will ensure balanced randomization across Groups 1 through 5, with proper 
weights used to accelerate enrollment in Group 6 relative to Groups 1 through 5 
so that enrollment progresses concurrently in all arms. 
At each institution, the pharmacist with primary responsibility for dispensing 
study products is charged with maintaining security of the treatment assignments 
(except in emergency situations as specified in the Study Specific Procedures 
[SSP]). 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 49 of 142 
6.3 
Blinding 
Participants and CRS staff will be unblinded to participant group assignments 
(Groups 1 through 6); and to participant treatment assignments (Groups 1 through 
5).  
In Group 6, participants and CRS staff (except for CRS pharmacists) will be 
blinded to treatment assignment (ie, VRC07-523LS versus placebo). As the 
differing viscosities of VRC07-523LS and normal saline risk unblinding CRS 
staff (despite the use of syringe overlays [Section 8.3.1.3]), Group 6 participants 
will have study product administered and AE assessment/reporting performed by 
different CRS staff members. Study product assignments are accessible to those 
CRS pharmacists, DAIDS protocol pharmacists and contract monitors, and 
SDMC staff who are required to know this information in order to ensure proper 
trial conduct. Any discussion of study product assignment between pharmacy 
staff and any other CRS staff is prohibited. 
The SMB members are unblinded to treatment assignment for all 6 groups in 
order to conduct review of trial safety. 
If a participant in Group 6 leaves the trial prior to study completion, the 
participant will be told he or she must wait until all Group 6 participants are 
unblinded to learn his or her treatment assignment.  
Emergency unblinding decisions will be made by the site investigator. If time 
permits, the HVTN 127/HPTN 087 PSRT should be consulted before emergency 
unblinding occurs. 
  
6.4 
Statistical analyses 
This section describes the final study analysis, unblinded as to group and 
treatment arm assignment.  
Analyses for primary endpoints will be performed using SAS and R. All other 
descriptive and inferential statistical analyses will be performed using SAS, 
StatXact, or R statistical software. Additional software may be used to perform 
population PK analyses (eg, NONMEM). 
No formal multiple comparison adjustments will be employed for multiple 
primary endpoints. However, multiplicity adjustments will be made for certain 
secondary endpoints or assay data when the endpoint is viewed as a collection of 
hypotheses (eg, testing multiple peptide pools to determine a positive response; 
comparison of PK parameters across multiple treatment groups). 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 50 of 142 
6.4.1 
Analysis variables 
The analysis variables consist of baseline participant characteristics, safety, 
VRC07-523LS serum concentrations, ADA, and drug functionality for primary- 
and secondary-objective analyses. 
6.4.2 
Baseline comparability 
Treatment arms will be compared for baseline participant characteristics using 
descriptive statistics. 
6.4.3 
Safety/tolerability analysis 
All data from enrolled participants will be analyzed according to the initial 
randomization assignment regardless of how many administrations they received. 
The analysis is a modified intent-to-treat analysis (MITT) in that individuals who 
are randomized but not enrolled do not contribute data and hence are excluded 
from subsequent analysis.  
Since enrollment is concurrent with receiving the first study product 
administration, all participants will have received at least 1 study product 
administration and therefore will provide some safety data. 
6.4.3.1 
Solicited AEs 
The number and percentage of participants experiencing each type of Solicited 
AE sign or symptom will be tabulated by severity, attribution and treatment arm 
and the percentages displayed graphically by arm. For a given sign or symptom, 
each participant’s Solicited AEs will be counted once under the maximum 
severity for all infusion/injection visits. In addition to the individual types of 
events, the maximum severity of local pain or tenderness, induration or erythema, 
and of systemic symptoms will be calculated. Appropriate tests (eg, Kruskal-
Wallis or Wilcoxon rank-sum tests) will be used to test for differences in severity 
between arms. 
6.4.3.2 
SAEs and Unsolicited AEs 
Unsolicited AEs will be summarized using MedDRA System Organ Class and 
preferred terms. Tables will show by treatment arm the number and percentage of 
participants experiencing an Unsolicited AE within a System Organ Class or 
within preferred term category by severity or by relationship to study product. For 
the calculations in these tables, a participant with multiple Unsolicited AEs within 
a category will be counted once under the maximum severity or the strongest 
recorded causal relationship to study product. Formal statistical testing comparing 
arms is not planned since interpretation of differences must rely heavily upon 
clinical judgment. 
A listing of SAEs reported to the DAIDS Regulatory Support Center (RSC) 
Safety Office will provide details of the events including severity, relationship to 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 51 of 142 
study product, time between onset and last study product administration, and 
number of study product administrations received. A separate listing will do the 
same for AESI. A list of AESI to be reported for this protocol is provided in 
Appendix H. 
6.4.3.3 
Local laboratory values  
Box plots of local laboratory values will be generated for baseline values and for 
values measured during the course of the study by treatment arm and visit. Each 
box plot will show the first quartile, the median, and the third quartile. Outliers 
(values outside the box plot) will also be plotted. If appropriate, horizontal lines 
representing boundaries for abnormal values will be plotted. 
For each local laboratory measure, summary statistics will be presented by 
treatment arm and timepoint, as well as changes from baseline for postenrollment 
values. In addition, the number (percentage) of participants with local laboratory 
values recorded as meeting Grade 1 AE criteria or above as specified in the 
Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse 
Events (see Section 11.2.2) will be tabulated by treatment arm for each poststudy 
product administration timepoint. Reportable clinical laboratory abnormalities 
without an associated clinical diagnosis will also be included in the tabulation of 
AEs described above. 
6.4.3.4 
Reasons for study product discontinuation and early study termination 
The number and percentage of participants who discontinue study product 
administration and who terminate the study early will be tabulated by reason and 
treatment arm. 
6.4.4 
Serum concentration and population PK analysis of VRC07-523LS 
6.4.4.1 
General approach 
The primary goal of the statistical analyses is to document serum concentrations 
of VRC07-523LS over time following multiple IV, SC, and IM administrations.  
The primary analyses of serum concentrations of VRC07-523LS (Primary 
Objective 2) will be restricted to participants who received all scheduled 
administrations per protocol. Serum concentration data that appear unreliable, or 
from specimens collected outside of the visit window, or from HIV-infected 
participants postinfection may be excluded. 
The primary analysis of serum concentrations of VRC07-523LS will be 
performed using univariate statistics (eg, sample mean, standard deviation, 
standard error for the mean). Data will be displayed graphically using appropriate 
visualization techniques (eg, boxplots, histograms, spaghetti plots). Summary 
statistics and visualizations will be produced per treatment group and per 
timepoint. 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 52 of 142 
Additional analyses, addressing Secondary Objective 1, will estimate population 
PK parameters of VRC07-523LS, compare PK parameters across treatment 
groups, and assess whether any associations exist between PK parameters and 
participant’s baseline covariates (eg, body weight, age, or gender). Data from 
enrolled participants will be analyzed according to the initial randomization 
assignment regardless of how many administrations they received (MITT 
analysis). Serum concentration data that appear unreliable, or from HIV-infected 
participants postinfection may be excluded. Serum concentration data from 
specimens collected outside of the visit window may be included in population 
PK analysis that account for the actual specimen collection time and the actual 
time of each product administration. Since the exact date of HIV infection is 
unknown, any serum level data from blood draws 4 weeks prior to an infected 
participant’s last seronegative sample and thereafter may be excluded. All data 
from HIV-infected participants who have no seronegative samples postenrollment 
may be excluded from the analysis.  
The objective of the analysis of Secondary Objective 1 is to develop a population 
PK model of VRC07-523LS serum concentrations in healthy, HIV-uninfected 
adults. This analysis will be conducted using a population PK approach. The 
proposed models will describe the pharmacokinetics of VRC07-523LS at the 
individual level using a compartmental approach. Based on a previous population 
PK analysis of the serum concentrations of VRC01, we anticipate that a two-
compartmental model can characterize the kinetics of the serum concentrations of 
VRC07-523LS. In the event the modeling assumptions appear violated, we will 
consider other compartmental models. Serum concentrations from study 
participants will be described using a non-linear mixed effects model. 
Comparisons of PK parameters across treatment groups, doses, or routes of 
administration, will be performed using either likelihood ratio or Wald tests. 
Additional exploratory analyses will be performed to identify baseline covariates 
potentially associated with PK parameters of VRC07-523LS. Estimates of PK 
parameters, including area-under-the-curve (AUC), maximum concentration 
(Cmax), time to Cmax (Tmax), clearance (CL), volume of distribution (V), 
elimination rates and half-life, will be derived from these analyses. 
6.4.5 
ADA and drug functionality analysis 
The goal of the statistical analyses for the Secondary Objectives 2 – 4 and for the 
Exploratory Objectives will be to document drug functionality endpoints 
following multiple IV, SC, and IM administrations of VRC07-523LS, and to 
assess whether any association exists between ADA and VRC07-523LS serum 
levels.  
For Secondary Objective 2 regarding ADA, data from enrolled participants will 
be used according to the initial randomization assignment regardless of how many 
administrations they received (MITT). For Secondary Objectives 3 and 4 
regarding drug functionality, data from enrolled participants who received all 
scheduled administrations per-protocol will be used. Assay results that are 
unreliable or from HIV-infected participants postinfection will be excluded. 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 53 of 142 
Univariate and bivariate descriptive analyses of continuous assay data (eg, serum 
concentration of VRC07-523LS) will be performed using mean, median, standard 
deviation, range, skewness, Spearman’s and Pearson’s correlation coefficients, for 
example. Graphical displays of the data based on appropriate techniques (eg, 
boxplots, histograms, kernel density estimates, probability plots, two- or three-
dimensional scatterplots, spaghetti plots) will be generated to visually explore 
distributional properties of the data as well as potential pairwise associations. 
Statistics and graphical displays will be produced for each treatment arm across 
timepoints.  
Comparisons of continuous assay data between treatment groups or timepoints 
will be primarily performed using nonparametric rank-based tests (eg, Wilcoxon 
rank-sum test, Friedman nonparametric two-way analysis of variance (ANOVA). 
In the event the data appear normally distributed, the results of these tests may be 
compared to those produced by parametric tests (eg, two-sample t-tests with 
unequal variances). Appropriate data transformations (eg, square-root, 
logarithmic) may be applied prior to testing hypotheses in order for key 
distributional assumptions [eg, normality, homoscedasticity (ie, constancy of 
variance)] to be satisfied. 
Analysis of longitudinal data may be performed using mixed effects models or 
generalized estimating equations (GEE). These approaches allow describing 
outcome responses over several timepoints while accounting for potential inter-
subject heterogeneity.  
Analyses of categorical variables (eg, binary) will be conducted by constructing 
frequency tables. One such table will be produced for each treatment group and 
each timepoint. Crude response rates will be presented with their corresponding 
95% confidence interval estimates calculated using the score test method (74). 
Associations between categorical variables will be assessed using Fisher’s exact 
or Chi-squared tests. 
To achieve unbiased statistical estimation and inferences with nonparametric tests 
and generalized linear models fit by GEE methods, missing data need to be 
missing completely at random (MCAR). MCAR assumes that the probability of 
an observation being missing does not depend upon the observed responses or 
upon any unobserved covariates but may depend upon covariates included in the 
model (eg, missing more among whites than nonwhites). In situations where data 
are missing in no more than 20% of the participants, we will use nonparametric 
tests and GEE methods on which violations of the MCAR assumption are 
expected to have limited impact. We will consider including any of the available 
baseline predictors of the missing outcomes as covariates in statistical models. 
When the frequency of missing data is more substantial, methods that require the 
MCAR assumption may give misleading results. In this situation, statistical 
analyses will be performed using parametric generalized linear models fitted 
using the method of maximum likelihood which provides unbiased estimation and 
inferences under the parametric modeling assumptions and the assumption that 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 54 of 142 
the missing data are missing at random (MAR). MAR assumes that the 
probability of an observation being missing may depend upon the observed 
responses and upon observed covariates, but not upon any unobserved factors. 
Thus, this assumption is less stringent than the MCAR assumption. Generalized 
linear models for response rates will use a binomial error distribution and for 
quantitative endpoints, a normal error distribution. We will assess repeated 
immunogenicity measurement using linear mixed effects models. If 
immunological outcomes are left- and/or right- censored, we will use Hughes’ 
(75) linear mixed effects models to accommodate censoring. In addition, 
secondary analyses of repeated immunogenicity measurements may be done using 
weighted GEE (76) methods, which are valid under MAR. We will again consider 
including any of the available baseline predictors of the missing outcomes as 
covariates in statistical models. 
6.4.6 
Analyses and data sharing prior to end of scheduled follow-up visits 
Any analyses conducted prior to the end of the scheduled follow-up visits should 
not compromise the integrity of the trial in terms of participant retention or safety 
endpoint assessments. In particular, early analyses by treatment assignment 
require careful consideration and should be made available on a need to know 
basis in accordance with Section 6.4.6.1. Interim blinded safety data should not be 
shared outside of the SMB, HVTN 127/HPTN 087 PSRT, the protocol team 
leadership, the study product developer, and the study sponsor and/or its 
designee(s) for their regulatory reporting unless approved by the protocol and 
Networks’ leadership. 
6.4.6.1 
Safety analyses 
During the course of the trial, unblinded analyses of safety data will be prepared 
approximately every 4 months for review by the SMB. Ad hoc safety reports may 
also be prepared for SMB review at the request of the HVTN 127/HPTN 087 
PSRT. The HVTN and HPTN leadership must approve any other requests for 
unblinded safety data prior to the end of the scheduled follow-up visits. 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 55 of 142 
7 
Selection and withdrawal of participants 
Participants will be healthy, HIV-uninfected (seronegative) adults who 
comprehend the purpose of the study and have provided written informed consent. 
Volunteers will be recruited and screened; those determined to be eligible, based 
on the inclusion and exclusion criteria, will be enrolled in the study. Final 
eligibility determination will depend on information available at the time of 
enrollment, including results of screening laboratory tests, medical history, 
physical examinations, and answers to self-administered and/or interview 
questions.  
Investigators should always use good clinical judgment in considering a 
volunteer’s overall fitness for trial participation. Some volunteers may not be 
appropriate for enrollment even if they meet all inclusion/exclusion criteria. 
Medical, psychiatric, occupational, or other conditions may make evaluation of 
safety and/or immunogenicity difficult, and some volunteers may be poor 
candidates for retention. 
Determination of eligibility, taking into account all inclusion and exclusion 
criteria, must be made within 56 days prior to enrollment unless otherwise noted 
in Sections 7.1 and 7.2. 
7.1 
Inclusion criteria 
General and Demographic Criteria 
1. Age of 18 to 50 years 
2. Access to a participating CRS and willingness to be followed for the planned 
duration of the study 
3. Ability and willingness to provide informed consent 
4. Assessment of understanding: volunteer demonstrates understanding of this 
study and completes a questionnaire prior to first study product administration 
with verbal demonstration of understanding of all questionnaire items answered 
incorrectly 
5. Agrees not to enroll in another study of an investigational research agent until 
completion of the last required protocol clinic visit 
6. Good general health as shown by medical history, physical exam, and screening 
laboratory tests 
HIV-Related Criteria: 
7. Willingness to receive HIV test results 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 56 of 142 
8. Willingness to discuss HIV infection risks and amenable to HIV risk reduction 
counseling.  
9. Assessed by the clinic staff as being at ‘low risk’ for HIV infection and 
committed to maintaining behavior consistent with those criteria through the last 
required protocol clinic visit (see Appendix I).  
Laboratory Inclusion Values 
Hemogram/CBC 
10. Hemoglobin ≥ 11.0 g/dL for volunteers who were assigned female sex at birth, ≥ 
13.0 g/dL for volunteers who were assigned male sex at birth. For transgender 
participants who have been on hormone therapy for more than 6 consecutive 
months, determine hemoglobin eligibility based on the gender with which they 
identify (ie, a transgender female who has been on hormone therapy for more than 
6 consecutive months should be assessed for eligibility using the hemoglobin 
parameters for volunteers assigned female sex at birth). 
11. White blood cell count = 2,500 to 12,000 cells/mm3 
12. WBC differential either within institutional normal range or with site physician 
approval 
13. Platelets = 125,000 to 550,000/mm3 
Chemistry 
14. Chemistry panel: ALT < 1.25 times the institutional upper limit of normal and 
creatinine ≤ institutional upper limits of normal. 
Virology 
15. Negative HIV-1 and -2 blood test: US volunteers must have a negative FDA-
approved enzyme immunoassay (EIA) or chemiluminescent microparticle 
immunoassay (CMIA). Non-US sites may use locally available assays that have 
been approved by HVTN and HPTN Laboratory Operations. 
16. Negative Hepatitis B surface antigen (HBsAg)  
17. Negative anti-Hepatitis C virus antibodies (anti-HCV), or negative HCV 
polymerase chain reaction (PCR) if the anti-HCV is positive 
Urine 
18. Negative or trace urine protein 
Reproductive Status 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 57 of 142 
19. Volunteers who were assigned female sex at birth: negative serum or urine beta 
human chorionic gonadotropin (β-HCG) pregnancy test performed prior to study 
product administration on the day of initial study infusion/injection. Persons who 
are NOT of reproductive potential due to having undergone total hysterectomy or 
bilateral oophorectomy (verified by medical records), are not required to undergo 
pregnancy testing. 
20. Reproductive status: A volunteer who was assigned female sex at birth must: 
 Agree to use effective contraception (see Appendix B) for sexual activity that 
could lead to pregnancy from at least 21 days prior to enrollment through the 
last required protocol clinic visit. Effective contraception is defined as using 
the following methods: 
 Condoms (male or female) with or without a spermicide, 
 Diaphragm or cervical cap with spermicide, 
 Intrauterine device (IUD), 
 Hormonal contraception, or 
 Any other contraceptive method approved by the HVTN 127/HPTN 087 
PSRT 
 Successful vasectomy in any partner assigned male sex at birth 
(considered successful if a volunteer reports that a male partner has [1] 
documentation of azoospermia by microscopy, or [2] a vasectomy more 
than 2 years ago with no resultant pregnancy despite sexual activity 
postvasectomy); 
 Or not be of reproductive potential, such as having reached menopause (no 
menses for 1 year) or having undergone hysterectomy, bilateral 
oophorectomy, or tubal ligation; 
 Or plan to be sexually abstinent until at least 6 months following the last study 
product administration. 
21. Volunteers who were assigned female sex at birth must also agree not to seek 
pregnancy through alternative methods, such as artificial insemination or in 
vitro fertilization until after the last required protocol clinic visit 
7.2 
Exclusion criteria 
General 
1. Weight > 115 kg  

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 58 of 142 
2. Blood products received within 120 days before first study product 
administration, unless eligibility for earlier enrollment is determined by the 
HVTN 127/HPTN 087 PSRT  
3. Investigational research agents received within 30 days before first study 
product administration 
4. Intent to participate in another study of an investigational research agent or 
any other study that requires non-Network HIV antibody testing during the 
planned duration of the HVTN 127/HPTN 087 study  
5. Pregnant or breastfeeding 
Vaccines and other Injections 
6. HIV vaccine(s) received in a prior HIV vaccine trial. For volunteers who have 
received control/placebo in an HIV vaccine trial, the HVTN 127/HPTN 087 
PSRT will determine eligibility on a case-by-case basis. 
7. Previous receipt of humanized or human mAbs, whether licensed or 
investigational; the HVTN 127/HPTN 087 PSRT will determine eligibility on a 
case-by-case basis. 
Immune System  
8. Immunosuppressive medications received within 30 days before first injection 
or infusion (Not exclusionary: [1] corticosteroid nasal spray; [2] inhaled 
corticosteroids; [3] topical corticosteroids for mild, uncomplicated dermatitis; or 
[4] a single course of oral/parenteral prednisone or equivalent at doses < 2 
mg/kg/day and length of therapy < 11 days with completion at least 30 days prior 
to enrollment) 
9. Serious adverse reactions to VRC07-523LS formulation components, 
including history of anaphylaxis and related symptoms such as hives, respiratory 
difficulty, angioedema, and/or abdominal pain  
10. Immunoglobulin received within 90 days before first injection or infusion, unless 
eligibility for earlier enrollment is determined by the HVTN 127/HPTN 087 
PSRT 
11. Autoimmune disease (Not excluded from participation: Volunteer with mild, 
stable and uncomplicated autoimmune disease that does not require 
immunosuppressive medication and that, in the judgment of the site investigator, 
is likely not subject to exacerbation and likely not to complicate Solicited and 
Unsolicited AE assessments) 
12. Immunodeficiency 
Clinically significant medical conditions  

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 59 of 142 
13. Clinically significant medical condition, physical examination findings, 
clinically significant abnormal laboratory results, or past medical history with 
clinically significant implications for current health. A clinically significant 
condition or process includes but is not limited to: 
 A process that would affect the immune response, 
 A process that would require medication that affects the immune response, 
 Any contraindication to repeated injections, infusions, or blood draws, 
including inability to establish venous access, 
 A condition that requires active medical intervention or monitoring to avert 
grave danger to the volunteer’s health or well-being during the study period, 
 A condition or process (eg, chronic urticaria or recent injection or infusion 
with evidence of residual inflammation) for which signs or symptoms could 
be confused with reactions to the study product, or 
 Any condition specifically listed among the exclusion criteria. 
14. Any medical, psychiatric, occupational, or other condition that, in the 
judgment of the investigator, would interfere with, or serve as a contraindication 
to, protocol adherence, assessment of safety or Solicited AEs, or a volunteer’s 
ability to give informed consent 
15. Psychiatric condition that precludes compliance with the protocol. 
Specifically excluded are persons with psychoses within the past 3 years, ongoing 
risk for suicide, or history of suicide attempt or gesture within the past 3 years. 
16. Current anti-tuberculosis (TB) therapy 
17. Asthma other than mild or moderate, well-controlled asthma. (Symptoms of 
asthma severity as defined in the most recent National Asthma Education and 
Prevention Program (NAEPP) Expert Panel report).  
Exclude a volunteer who: 
 Uses a short-acting rescue inhaler (typically a beta 2 agonist) daily, or 
 Uses high dose inhaled corticosteroids, or 
 In the past year has had either of the following: 
 Greater than 1 exacerbation of symptoms treated with oral/parenteral 
corticosteroids; 
 Needed emergency care, urgent care, hospitalization, or intubation for 
asthma. 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 60 of 142 
18. Diabetes mellitus type 1 or type 2 (Not excluded: type 2 cases controlled with 
diet alone or a history of isolated gestational diabetes.) 
19. Hypertension: 
 If a person has been found to have elevated blood pressure or hypertension 
during screening or previously, exclude for blood pressure that is not well 
controlled. Well-controlled blood pressure is defined as consistently ≤ 140 
mm Hg systolic and ≤ 90 mm Hg diastolic, with or without medication, with 
only isolated, brief instances of higher readings, which must be ≤ 150 mm Hg 
systolic and ≤ 100 mm Hg diastolic. For these volunteers, blood pressure must 
be ≤ 140 mm Hg systolic and ≤ 90 mm Hg diastolic at enrollment. 
 If a person has NOT been found to have elevated blood pressure or 
hypertension during screening or previously, exclude for systolic blood 
pressure ≥ 150 mm Hg at enrollment or diastolic blood pressure ≥ 100 mm Hg 
at enrollment. 
20. Bleeding disorder diagnosed by a doctor (eg, factor deficiency, coagulopathy, or 
platelet disorder requiring special precautions) 
21. Malignancy (Not excluded from participation: Volunteer who has had 
malignancy excised surgically and who, in the investigator’s estimation, has a 
reasonable assurance of sustained cure, or who is unlikely to experience 
recurrence of malignancy during the period of the study) 
22. Seizure disorder: History of seizure(s) within past three years. Also exclude if 
volunteer has used medications in order to prevent or treat seizure(s) at any time 
within the past 3 years. 
23. Asplenia: any condition resulting in the absence of a functional spleen 
24. History of hereditary angioedema, acquired angioedema, or idiopathic 
angioedema. 
7.3 
Participant departure from study product administration schedule or 
withdrawal 
This section concerns an individual participant’s departure from the study product 
administration schedule. Pause rules for the trial are described in Section 11.3. 
7.3.1 
Delaying study product administration for a participant 
Under certain circumstances, a participant’s scheduled infusion or injection will 
be delayed. The factors to be considered in such a decision include but are not 
limited to the following:  
 Within 7 days prior to any study product administration 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 61 of 142 
 Receipt of systemic glucocorticoids (eg, prednisone or other 
glucocorticoids) or other immunomodulators (other than nonsteroidal anti-
inflammatory drugs [NSAIDs]) 
 Preinfusion or preinjection abnormal vital signs or clinical symptoms that may 
mask assessment of study product reaction. 
 Intercurrent illness that is not expected to resolve prior to the next scheduled 
study product administration which is assessed by the site principal 
investigator (or designee) to require delay or withdrawal from the study 
product administration schedule. The investigator may consult the HVTN 
127/HPTN 087 PSRT. 
 Pregnancy: study product administration will be stopped while a participant is 
pregnant. If the participant is no longer pregnant or breast-feeding and study 
product administration can be performed within an appropriate visit window, 
study product administration may resume with unanimous consent of the 
HVTN 127/HPTN 087 PSRT. 
Infusions and injections should not be administered outside the visit window 
period specified in the HVTN 127/HPTN 087 SSP. 
In order to avoid administration delays and missed injections or infusions, 
participants who plan to receive systemic glucocorticoids should be counseled to 
schedule receipt of these substances, when possible, outside the intervals 
indicated above. The effects of these substances on safety and their interactions 
with study product are unknown. 
7.3.2 
Participant departure from study product administration schedule 
Every effort should be made to follow the study product administration schedule 
per the protocol. If a participant misses a study product administration and the 
visit window period for the study product administration has passed, that study 
product cannot be given. The participant should be asked to continue study visits. 
The participant should resume the study product administration schedule with the 
next study product administration unless there are circumstances that require 
further delay or permanent discontinuation of study product administration (see 
Sections 7.3.1 and 7.3.3). 
7.3.3 
Discontinuing study product administration for a participant 
Under certain circumstances, an individual participant’s study product 
administrations will be permanently discontinued. Specific events that will result 
in stopping a participant’s study product administration schedule include: 
 Co-enrollment in a study with an investigational research agent (rare 
exceptions allowing for the continuation of study product administrations may 
be granted with the unanimous consent of the HVTN 127/HPTN 087 PSRT) 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 62 of 142 
 Clinically significant condition (ie, a condition that affects the immune system 
or for which continued study product administration and/or blood draws may 
pose additional risk), including but not limited to the following: 
 Any grade 4 local or systemic Solicited or Unsolicited AE that is 
subsequently considered to be related to study product; 
 Any grade 3 clinical AE (exception: fever and subjective local and 
systemic symptoms) that is subsequently considered to be related to study 
product (upon review, the HVTN 127/HPTN 087 PSRT may allow 
continuation of study product administration if the participant has grade 3 
erythema and/or induration); 
 Any grade 3 or 4 lab abnormality confirmed by a repeated value that is 
subsequently considered to be related to study product; 
 SAE that is subsequently considered to be related to study product 
administration; or 
 Clinically significant hypersensitivity or infusion related reaction 
including but not limited to type 1 hypersensitivity reaction, urticaria, or 
serum sickness associated with study product. Consultation with the 
HVTN 127/HPTN 087 PSRT is required prior to subsequent infusion 
following any hypersensitivity reaction associated with study product; or 
 Investigator determination in consultation with Protocol Team leadership (eg, 
for repeated nonadherence to study staff instructions) 
Participants discontinuing study product should be counseled on the importance 
of continuing with the study and strongly encouraged to participate in follow-up 
visits and protocol-related procedures per the protocol for the remainder of the 
trial, unless medically contraindicated. 
In addition, study product administration will be stopped for participants 
diagnosed with HIV infection. HIV-infected participants will not continue in the 
trial (see Sections 7.3.4). 
7.3.4 
Participant termination from the study 
Under certain circumstances, an individual participant may be terminated from 
participation in this study. Specific events that will result in early termination 
include: 
 Participant refuses further participation, 
 Participant relocates and remote follow-up or transfer to another CRS is not 
possible, 
 CRS determines that the participant is lost to follow-up,  
 Participant becomes HIV infected, or  

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 63 of 142 
 Investigator decides, in consultation with Protocol Team leadership, to 
terminate participation (eg, if participant exhibits inappropriate behavior 
toward clinic staff). 
 Any condition where termination from the study is required by applicable 
regulations. 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 64 of 142 
8 
Study product preparation and administration 
CRS pharmacists should consult the Pharmacy Guidelines and Instructions for 
DAIDS Clinical Trials Networks for standard pharmacy operations. The protocol 
schema is shown in Table 3-1. See the Investigator’s Brochure for further 
information about study products. 
8.1 
Study product regimen 
The schedule of study product administration is shown in Section 3 and additional 
information is given below.  
Group 1 
Treatment 1 (T1): VRC07-523LS (VRC-HIVMAB075-00-AB) 2.5 mg/kg to be 
administered IV at weeks 0, 16, 32, 48, and 64. 
Group 2  
Treatment 2 (T2): VRC07-523LS (VRC-HIVMAB075-00-AB) 5 mg/kg to be 
administered IV at weeks 0, 16, 32, 48, and 64. 
Group 3 
Treatment 3 (T3): VRC07-523LS (VRC-HIVMAB075-00-AB) 20 mg/kg to be 
administered IV at weeks 0, 16, 32, 48, and 64. 
Group 4  
Treatment 4 (T4): VRC07-523LS (VRC-HIVMAB075-00-AB) 2.5 mg/kg to be 
administered SC at weeks 0, 16, 32, 48, and 64.  
Group 5  
Treatment 5 (T5): VRC07-523LS (VRC-HIVMAB075-00-AB) 5 mg/kg to be 
administered SC at weeks 0, 16, 32, 48, and 64. 
Group 6 
Treatment 6 (T6): VRC07-523LS (VRC-HIVMAB075-00-AB) 2.5 mg/kg to be 
administered IM at weeks 0, 16, 32, 48 and 64. 
OR 
Placebo 6 (P6): Sodium Chloride for Injection USP, 0.9% to be administered IM 
at weeks 0, 16, 32, 48 and 64. 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 65 of 142 
8.2 
Study product formulation  
VRC07-523LS (Labeled as VRC07-523LS HIV MAb Drug Product VRC-
HIVMAB075-00-AB) 
VRC07-523LS will be supplied as 10 mL glass vials with a 6.25 ± 0.1 mL fill 
volume and 3 mL glass vials with a 2.25 mL ± 0.1 mL fill volume, at a 
concentration of 100 ± 10 mg/mL. Each vial contains a clear, colorless to yellow 
isotonic, sterile solution essentially free of visible particles; some opaque or 
translucent particles may be present. The formulation buffer is composed of 50 mM 
histidine, 50 mM sodium chloride, 5% sucrose and 2.5% sorbitol at pH 6.8.  
Vials are intended for single use only and thus do not contain a preservative. 
VRC07-523LS product label designates the long-term storage as -35°C to -15°C 
(-31F to 5F). Clinical site storage in a qualified, continuously monitored, 
temperature-controlled freezer with temperature excursions between -45°C to -
10°C (-49F to 14F) is acceptable. 
Following thaw, VRC07-523LS vials may be stored for up to 24 hours at 
controlled room temperature (maximum 27°C) and/or up to 2 weeks (14 days) 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 at controlled room temperature (maximum 27°C) for a 
minimum of 30 minutes and may be held at room temperature for up to 8 hours 
prior to product preparation. 
8.3 
Preparation of study products 
Prior to preparation of the first dose (enrollment visit), a new prescription will be 
sent to the pharmacy. The prescription MUST contain the participant’s weight (in 
kg) based upon the participant’s weight (in kg) at the most recent visit where 
weight was measured (this includes screening) and randomization code (this may 
NOT be communicated verbally). If this information is NOT on the prescription, 
the prescription will be returned to the clinic from the pharmacy to be completed 
appropriately prior to the pharmacist beginning preparation of study product. 
Subsequent visit weights based upon the participant’s weight (in kg) at the most 
recent visit where weight was measured must be communicated to the pharmacy 
in writing prior to the day of the visit.  
Any changes in weight of more than 10% (between the prior weight and the 
weight on the day of the study product administration visit) will require an 
updated visit weight. A new prescription, which includes the new weight, must be 
written so that product can be prepared based on that weight change. 
Pharmacists should keep in mind that the preparation instructions below are 
considered medium risk per USP 38 General Chapter Physical Tests / <797> 
Pharmaceutical Compounding - Sterile, and should follow the requirements of 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 66 of 142 
their country, their institution, and their pharmacy regulatory authority regarding 
these procedures. 
8.3.1 
VRC07-523LS 
VRC07-523LS 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 room temperature or storage at 2°C to 8°C. 
Ensure that only the required vials are present in the preparation unit during 
dilution and that medication labels are strictly segregated to avoid mix-ups. 
Thawing instructions (all groups): 
1. Thaw vial(s) for a minimum of 1 hour at controlled room temperature 
(maximum 27°C) after removing from the freezer.  
Following thaw, unopened vials of VRC07-523LS may be stored for up to 24 
hours at controlled room temperature (maximum 27°C) and/or up to 2 weeks 
(14 days) at 2°C to 8°C. 
2. Keep the material at room temperature during the entire preparation period 
until use, up to the maximum storage times described in Section 8.2.  
3. Prior to preparation for administration, vials should be swirled for 30 seconds 
with sufficient force to resuspend any visible particles, yet avoiding foaming. 
DO NOT SHAKE THE VIALS. If the particles are observed, return the vials 
to 2°C to 8°C storage. If the particles redissolve within the maximum storage 
times described in Section 8.2 for 2°C to 8°C storage, the vials may be used 
for product preparation. If particles continue to be observed, do not use the 
vialed product for SC or IV administration. 
Refrigerated product must be equilibrated at controlled room temperature 
(maximum 27°C) for a minimum of 30 minutes before preparation and must 
be used within 8 hours of any subsequent return to room temperature.  
4. If the thawed material is not administered within 24 hours of thaw, follow the 
storage information provided in Section 8.2. 
8.3.1.1 
Intravenous infusion preparation instructions (T1, T2, and T3): 
After thawing, if product was refrigerated again at 2°C to 8°C, vials of VRC07-
523LS should be equilibrated to controlled room temperature (maximum 27°C) 
for a minimum of 30 minutes and may be held at room temperature for up to 8 
hours prior to product preparation.  
1. Calculate the total milligrams of VRC07-523LS required based on the 
participant’s weight (in kg) and the randomized treatment group of either 2.5 
mg/kg, 5 mg/kg or 20 mg/kg. Remove the total number of vials required from 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 67 of 142 
storage based on a 6 mL or 2 mL withdrawal volume containing 600 mg or 
200 mg of VRC07-523LS, respectively.  
2. Gently swirl thawed vials for 30 seconds to avoid foaming. DO NOT SHAKE 
VIALS. Keep the vials upright at all times until ready to withdraw the 
contents. Do not invert the vial during inspection. 
3. Observe vials for particles. If particles are observed, refer to the thawing 
instructions described above in Section 8.3.1. 
4. Using aseptic technique, add the calculated volume of VRC07-523LS (total 
calculated milligrams of VRC07-523LS) to an appropriately sized IV 
container (bag/glass bottle) containing 100 mL of Sodium Chloride Injection, 
USP 0.9% that will also permit the addition of the required calculated volume 
of VRC07-523LS. Alternatively, if the pharmacist is using an IV container 
(bag/glass bottle) that cannot accommodate the full VRC07-523LS dose 
volume plus 100 mL of Sodium Chloride Injection, USP 0.9%, please refer to 
the Study Products Considerations section of the SSP for further preparation 
instructions.  
5. After product preparation in IV container (bag/glass bottle), the prepared VRC07-
523LS may be stored at 2°C to 8°C up to 24 hours or at room temperature 
(maximum 30°C) for a maximum of 8 hours total including the infusion time. 
Product may not be stored in direct sunlight. If stored at 2°C to 8°C, prepared 
product must be equilibrated at room temperature (maximum 30°C) for a 
minimum of 30 minutes prior to product administration. 
6. Label the IV container (bag/glass bottle) as follows: 
 Participant identifier, 
 Participant weight (in kg) 
 Randomized dose of VRC07-523LS of either 2.5 mg/kg, 5 mg/kg, or 
20 mg/kg and the total amount (mg) of VRC07-523LS added to the 
Sodium Chloride Injection, USP 0.9% 
 Final volume of the IV container (bag/glass bottle) 
 Lot number 
The prepared IV label should also be labeled with a DO NOT INFUSE after 
date and time, as follows: 
 24 hours if stored at 2°C to 8°C 
 8 hours, including completion of infusion, if stored at controlled room 
temperature (not to exceed 27°C) 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 68 of 142 
 Product may not be stored in direct sunlight 
Any unused portion of a VRC07-523LS vial will not be used for another 
participant. Any empty vials, unused portion of entered vials, or unused IV 
solution which contains study product should be discarded in a biohazard 
containment bag and incinerated or autoclaved in accordance with institutional or 
pharmacy policy. 
8.3.1.2 
Subcutaneous injection preparation instructions (T4 and T5): 
1. Calculate the total milligrams of VRC07-523LS required based on the 
participant’s weight (in kg) and the randomized treatment group of either 2.5 
mg/kg or 5 mg/kg. Remove the total number of vials required from storage 
based on a 6 mL of 2 mL withdrawal volume containing 600 mg or 200 mg of 
VRC07-523LS, respectively.  
2. Gently swirl thawed vials for 30 seconds to avoid foaming. DO NOT SHAKE 
VIALS. Keep the vials upright at all times until ready to withdraw the 
contents. Do not invert the vial during inspection. 
3. Observe vials for particles. If particles are observed, refer to the thawing 
instructions described above in Section 8.3.1. 
4. Using aseptic technique, withdraw the needed volume of VRC07-523LS (total 
calculated milligrams of VRC07-523LS) from the vial(s) into 1 to 4 syringes 
using a 5 micron filter needle (see SSP for needle/filter specifications and 
details). A new filter needle must be used when withdrawing product from 
vial for each syringe. The filter needle must be discarded prior to dispensing. 
Cap syringe(s) and affix a needle suitable for SC injection for administration. 
5. After product preparation in syringe(s), the prepared VRC07-523LS may be 
stored at 2°C to 8°C up to 24 hours or at room temperature (maximum 30°C) 
for a maximum of 4 hours total including the administration time. Product 
may not be stored in direct sunlight. If stored at 2°C to 8°C, prepared product 
must be equilibrated at room temperature (maximum 30°C) for a minimum of 
30 minutes prior to product administration. 
6. Label the syringe (or bag containing multiple syringes) as follows: 
 Participant identifier 
 Participant weight (in kg) 
 Randomized dose of VRC07-523LS of either 2.5 mg/kg or 5 mg/kg 
and total amount (mg) of VRC07-523LS in syringe(s) 
 Lot number 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 69 of 142 
The prepared syringe/bag labels should also be labeled with a DO NOT 
administer after time and date, as follows: 
 within 4 hours of preparation, including the administration time, when 
stored at controlled room temperature (maximum 30°C) 
 Product may not be stored in direct sunlight 
Any unused portion of a VRC07-523LS vial will not be used for another 
participant. Any empty vials, unused portion of entered vials, or unused IV 
solution which contains study product should be discarded in a biohazard 
containment bag and incinerated or autoclaved in accordance with institutional or 
pharmacy policy.  
8.3.1.3 
Intramuscular injection preparation instructions (T6 and P6) 
1. Calculate the total milligrams of VRC07-523LS required based on the 
participant’s weight and the randomized treatment group of 2.5 mg/kg and the 
total number of vials required based on a 6 mL or 2 mL withdrawal volume 
containing 600 mg or 200 mg of VRC07-523LS, respectively. 
2. Gently swirl thawed vials for 30 seconds to avoid foaming. DO NOT SHAKE 
VIALS. Keep the vials upright at all times until ready to withdraw the 
contents. Do not invert the vial during inspection. 
3. Observe vials for particles. If particles are observed, refer to the thawing 
instructions described above in Section 8.3.1. 
4. Using aseptic technique, withdraw the needed volume of VRC07-523LS (total 
calculated milligrams of VRC07-523LS) from the vial(s) into 1 to 4 syringes 
using a 5 micron filter needle (see SSP for needle/filter specifications and 
details). A new filter needle must be used when withdrawing product from 
vial for each syringe. The filter needle must be discarded prior to dispensing.  
For Placebo, using aseptic technique, draw the appropriate amount of Sodium 
Chloride for Injection USP, 0.9% into the appropriate number of syringes, 
based upon the equivalent weight-based dose calculated for the active arm. 
5. Cover each syringe (barrel and adapter hub) with an overlay to maintain the 
blind, due to the fact that VRC07-523LS appearance may be clear, colorless to 
yellow, which can possibly un-blind clinicians administering the IM placebo 
saline product which is clear. Cap syringe(s) and affix a needle suitable for IM 
injection for administration.  
6. After product preparation in syringe(s), the prepared VRC07-523LS may be 
stored at 2°C to 8°C up to 24 hours or at room temperature (maximum 30°C) 
for a maximum of 4 hours total including the administration time. Product 
may not be stored in direct sunlight. If stored at 2°C to 8°C, prepared product 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 70 of 142 
must be equilibrated at room temperature (maximum 30°C) for a minimum of 
30 minutes prior to product administration. 
7. Label the syringe (or bag containing multiple syringes) as follows: 
 Participant identifier 
 Participant weight (in kg) 
 “VRC705-523LS 2.5mg/kg or placebo for IM administration” 
The prepared syringe/bag labels should also be labeled with a DO NOT 
administer after time and date, as follows: 
 within 4 hours of preparation, including the administration time, when 
stored at controlled room temperature (maximum 30°C) 
 Product may not be stored in direct sunlight 
Any unused portion of a VRC07-523LS vial will not be used for another 
participant. Any empty vials, unused portion of entered vials, or unused IV 
solution which contains study product should be discarded in a biohazard 
containment bag and incinerated or autoclaved in accordance with 
institutional or pharmacy policy.  
8.4 
Administration 
8.4.1 
VRC07-523LS (Intravenously) 
For Groups T1, T2, and T3 - Prior to infusion, if the IV container (bag/glass 
bottle) containing the prepared solution has been stored at 2°C to 8°C, the 
prepared IV container (bag/glass bottle) must be equilibrated to room temperature 
(maximum of 30°C) for 30 minutes or longer and may be held for up to 8 hours, 
including equilibration time and completion of product administration. (NOTE: 
This 8 hour period may NOT exceed the DO NOT INFUSE after date and time on 
the IV bag label.) 
The IV container (bag/glass bottle) prepared by the pharmacy will include the 
weight that was used for preparation of the IV container (bag/glass bottle). The 
clinician responsible for administration will check the IV container (bag/glass 
bottle) label and confirm that the participant identifier is correct and that the 
weight on the IV container (bag/glass bottle) label is within 10% of the 
participant’s current actual weight (refer to Section 8.3 for more information). 
The entire contents of the prepared investigational study product solution will 
typically be administered IV over about 15 to 60 minutes using a volumetric 
pump. The total time needed to administer the dose may be longer based on 
factors such as participant tolerance. For a 30 minute administration, the rate of 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 71 of 142 
infusion may range from 10-20 mg/kg/hr with the lowest dose group to 80-160 
mg/kg/hr with the highest dose group. The mL/hr infusion rate may vary based on 
the total volume needed to administer a full dose.  
An in-line filter infusion set must be used for IV product administration. In-line 
filters must comply with the specifications described in the HVTN 127/HPTN 
087 SSP. When the in-line filter is added to the tubing, prime the administration 
set with normal saline for injection. CRS staff may prime the administration set 
with VRC07-523LS only during normal saline shortage. Flush the administration 
set with about 30 mL or appropriate volume of normal saline at the end of product 
administration. 
8.4.2 
VRC07-523LS (Subcutaneously) 
For Groups T4 and T5 - Syringes prepared by the pharmacy will contain the 
total amount (mg) of VRC07-523LS, undiluted, in up to 4 syringes depending on 
the volume needed to administer the total calculated dose.  
If more than one syringe is needed, the zip lock bag containing the syringes will 
show the total volume to be administered. The clinician responsible for 
administration will check the syringe/bag label(s) and confirm that the participant 
identifier is correct and that the weight on the syringe/bag label(s) is within 10% 
of the participant’s current actual weight (refer to Section 8.3 for more 
information).  
The filter needle(s) used during preparation must be discarded prior to dispensing 
and replaced with a needle suitable for SC injection at the time of administration.  
Proper SC technique must be used to ensure administration into the SC fatty layer 
of the abdomen, inner thigh, or upper arm and a slow push to minimize 
discomfort or the excessive distention of overlying skin. All SC injections must 
be at least 2 inches apart. 
When preparing a dose in a syringe and administering the dose, consideration 
should be given to the volume of solution in the needle before and after the dose 
is administered. Particularly if the needle used to withdraw the product is replaced 
prior to product administration, consideration should be given to conserving the 
full dose of product. The pharmacy and clinic staff members are encouraged to 
work together to administer the dose specified in the protocol.  
8.4.3 
VRC07-523LS (Intramuscularly) 
For Group T6/P6- Syringes prepared by the pharmacy will contain the total 
amount (mg) of VRC07-523LS undiluted or placebo, in up to 4 syringes 
depending on the volume needed to administer the total calculated dose.  
If more than one syringe is needed, the zip lock bag containing the syringes will 
show the total volume to be administered. The clinician responsible for 
administration will check the syringe/bag label(s) and confirm that the participant 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 72 of 142 
identifier is correct and that the weight on the syringe/bag label(s) is within 10% 
of the participant’s current actual weight (refer to Section 8.3 for more 
information).  
The filter needle(s) used during preparation must be discarded prior to dispensing 
and replaced with a needle suitable for IM injection at the time of administration.  
Proper IM technique shall be used to ensure administration into gluteus or deltoid. 
All IM injections must be at least 2 inches apart. 
When preparing a dose in a syringe and administering the dose, consideration 
should be given to the volume of solution in the needle before and after the dose 
is administered. Particularly if the needle used to withdraw the product is replaced 
prior to product administration, consideration should be given to conserving the 
full dose of product. The pharmacy and clinic staff members are encouraged to 
work together to administer the dose specified in the protocol. 
8.5 
Acquisition of study products 
VRC-HIVMAB075-00-AB (VRC07-523LS) is provided by the VRC/NIAID. 
Filter needles, in-line filter infusion sets and Sodium Chloride for Injection USP, 
0.9% should be obtained by the CRS. Please refer to the study product 
considerations section of the SSPs for product specific reference numbers.  
Once a CRS is protocol registered, the pharmacist can obtain study products from 
the NIAID Clinical Research Products Management Center (CRPMC) by 
following the ordering procedures given in Pharmacy Guidelines and Instructions 
for DAIDS Clinical Trials Networks. 
8.6 
Pharmacy records 
The CRS pharmacist is required to maintain complete records of all study 
products. The pharmacist of record is responsible for maintaining randomization 
codes and randomization confirmation notices for each participant in a secure 
manner. 
8.7 
Final disposition of study products 
All unused study products must be returned to the CRPMC after the study is 
completed or terminated unless otherwise instructed by the CRPMC. The 
procedures and relevant form are included in the Pharmacy Guidelines and 
Instructions for DAIDS Clinical Trials Networks.  

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 73 of 142 
9 
Clinical procedures 
The schedules of clinical procedures are shown in Appendix G. 
9.1 
Informed consent 
Informed consent is the process of working with participants so that they fully 
understand what will and may happen to them while participating in a research 
study. The informed consent form documents that a participant (1) has been 
informed about the potential risks, benefits, and alternatives to participation, and 
(2) is willing to participate in the study. Informed consent encompasses all written 
or verbal study information CRS staff provide to the participant, before and 
during the trial. CRS staff will obtain informed consent of participants according 
to HVTN and HPTN policies and procedures. 
The informed consent process continues throughout the study. Key study concepts 
should be reviewed periodically with the participant and the review should be 
documented. At each study visit, CRS staff should consider reviewing the 
procedures and requirements for that visit and for the remaining visits. 
Additionally, if any new information is learned that might affect the participants’ 
decisions to stay in the trial, this information will be shared with trial participants. 
If necessary, participants will be asked to sign revised informed consent forms. 
A CRS may employ recruitment efforts prior to the participant consenting. For 
example, some CRSs use a telephone script to prescreen people before they come 
to the clinic for a full screening visit. Participants must sign a screening or 
protocol-specific consent before any procedures are performed to determine 
eligibility. CRSs must submit recruitment and prescreening materials to their 
IRB/EC and any applicable RE for human subjects protection review and 
approval. 
Note: As defined in the DAIDS Protocol Registration Manual, an RE is “Any 
group other than the local IRB/EC responsible for reviewing and/or approving a 
clinical research protocol and site-specific ICFs [informed consent forms] prior to 
implementation at a site.” CRSs are responsible for knowing the requirements of 
their applicable REs. 
9.1.1 
Screening consent form 
Without a general screening consent, screening for a specific study cannot take 
place until the site receives protocol registration from the DAIDS RSC Protocol 
Registration Office. 
Some CRSs have approval from their IRB/EC and any applicable RE to use a 
general screening consent form that allows screening for an unspecified HIV 
prevention clinical trial. In this way, CRS staff can continually screen potential 
participants and, when needed, proceed quickly to obtain protocol-specific 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 74 of 142 
enrollment consent. Sites conducting general screening or prescreening approved 
by their IRB/EC and any applicable RE may use the results from this screening to 
determine eligibility for this protocol, provided the tests are conducted within the 
time periods specified in the eligibility criteria.  
9.1.2 
Protocol-specific consent forms 
The protocol-specific consent forms describe the study products to be used and all 
aspects of protocol participation, including screening and enrollment procedures. 
A sample protocol-specific consent form for the main study is located in 
Appendix A. A separate sample consent form for other uses of specimens is 
located in Appendix C. 
Each CRS is responsible for developing a protocol-specific consent form(s) for 
local use, based on the sample protocol-specific consent forms in Appendix A and 
Appendix C. The consent form(s) must be developed in accordance with 
requirements of the following: 
 CRS’s IRB/EC and any applicable REs, 
 CRS’s institution, and 
 Elements of informed consent as described in Title 45, CFR Part 46 and Title 
21 CFR, Part 50, and in the International Conference on Harmonisation (ICH) 
E6, Good Clinical Practice: Consolidated Guidance 4.8.  
Study sites are strongly encouraged to have their local CABs review their sites-
specific consent forms. This review should include, but should not be limited to, 
issues of cultural competence, local language considerations, and the level of 
understandability. 
The sample informed consent forms include instructions throughout the 
documents for developing specific content. 
Regarding protocol registration, sites should follow procedures outlined in the 
current version of the DAIDS Protocol Registration Manual. 
9.1.3 
Assessment of Understanding 
Study staff are responsible for ensuring that participants fully understand the 
study before enrolling them. This process involves reviewing the informed 
consent form with the participant, allowing time for the participant to reflect on 
the procedures and issues presented, and answering all questions completely.  
An Assessment of Understanding is used to document the participant’s 
understanding of key concepts in this clinical trial. The participant must complete 
the Assessment of Understanding before enrollment. Staff may provide assistance 
in reading and understanding the questions and responses, if necessary. 
Participants must verbalize understanding of all questions answered incorrectly. 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 75 of 142 
This process and the participant’s understanding of the key concepts should be 
recorded in source documentation at the site. 
IRB/EC and any applicable RE may require that a participant has signed either a 
screening or protocol-specific consent document prior to administering the 
Assessment of Understanding. The consent process (including the use of the 
Assessment of Understanding) should be explained thoroughly to the IRB/EC and 
any applicable RE, whose recommendations should be followed. 
9.2 
Pre-enrollment procedures 
Screening may occur over the course of several contacts/visits, up to and 
including before study product administration on day 0. All inclusion and 
exclusion criteria must be assessed within 56 days before enrollment, unless 
otherwise specified in the eligibility criteria (or below in this section). 
After the appropriate informed consent has been obtained and before enrollment, 
the following procedures are performed: 
 Medical history, documented in the case history record 
 Assessment of whether the volunteer is at low risk for HIV infection (see 
Appendix I) 
 Complete physical examination, including height, weight, vital signs, and 
clinical assessments of head, ears, eyes, nose, and throat; neck; lymph nodes; 
heart; chest; abdomen; extremities; neurological function; and skin 
 Assessment of concomitant medications the volunteer is taking, including 
prescription and nonprescription drugs, vitamins, topical products, 
alternative/complementary medicines (eg, herbal and health food 
supplements), recreational drugs, vaccinations, and allergy shots 
 Laboratory tests as defined in the inclusion and exclusion criteria, including: 
 Screening HIV,  
 HBsAg, 
 Anti-HCV Abs, 
 Syphilis, 
 CBC with differential and platelets, 
 Chemistry panel (ALT, creatinine), 
 Urine dipstick (urinalysis if indicated; see Section 9.7), 
 Urine or serum pregnancy test (volunteers who were assigned female sex 
at birth); Persons who are not of reproductive potential due to having 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 76 of 142 
undergone total hysterectomy with bilateral oophorectomy (verified by 
medical records), are not required to undergo pregnancy testing;  
 Administration of behavioral risk assessment questionnaire 
 Obtaining of volunteer demographics in compliance with the NIH Policy on 
Reporting Race and Ethnicity Data: Subjects in Clinical Research, Aug. 8, 
2001 (available at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-01-
053.html) 
 Counseling on HIV testing and risk reduction, performed in compliance with 
the US Centers for Disease Control and Prevention (CDC)’s current 
guidelines or other local guidelines for HIV counseling, testing, and referral as 
described in Section 9.5 
 Discussion of pregnancy prevention. A pregnant or breastfeeding person may 
not be enrolled in this trial. Specific criteria and assessment of contraception 
and pregnancy status are described in study inclusion criteria. Discussion of 
pregnancy prevention includes advising a participant who was assigned 
female sex at birth and who reports no current sexual activity that could lead 
to that participant becoming pregnant to have a plan to begin adequate birth 
control. This plan would be put to use if, during the study, the participant 
becomes sexually active in a way that could lead to that participant becoming 
pregnant. 
9.2.1 
Use of screening results from another HVTN or HPTN study 
If a participant screens for an HVTN or HPTN study at the same CRS but then 
does not join that study, screening results from that effort may be applied to the 
screening for this protocol, as long as the screening was done under participant 
consent, the participant has signed a consent form to begin screening for this 
study, and the tests were conducted within the time periods specified in the 
eligibility criteria (see Sections 7.1 and 7.2). 
9.3 
Enrollment and study product administration visits 
Enrollment is simultaneous with first study product administration. The CRS 
requests the randomization assignment via a Web-based randomization system. In 
general, the interval between randomization and enrollment should not exceed 4 
working days. However, circumstances may require a participant’s enrollment 
visit to be changed. This may exceed the 4-day randomization time limit. 
At all infusion/injection visits, the following procedures are performed before 
study product administration: 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 77 of 142 
 Abbreviated physical examination, including weight, vital signs, and a 
symptom-directed evaluation by history and/or appropriate physical exam 
based on participant self-reported symptoms or complaints; 
 Assessment of baseline Solicited AEs; 
 Assessment of concomitant medications (as described in Section 9.2); 
 Assessment of any new or unresolved Unsolicited AEs/intercurrent illnesses;  
 CBC with differential and platelets, 
 Chemistry panel (see Section 9.2), and 
 Urine or serum pregnancy test (for participants who were assigned female sex 
at birth). Persons who are NOT of reproductive potential due to having 
undergone total hysterectomy or bilateral oophorectomy (verified by medical 
records), are not required to undergo pregnancy testing. 
Following completion of all procedures in the preceding list, and if results 
indicate that study product administration may proceed, study product is prepared 
and administered (see Sections 8.3 and 8.4). 
Administration of all infusions and injections during a study product 
administration visit must be accomplished within 1 calendar day. 
Immediately following infusion/injection, the participant remains in the clinic for 
observation. See the HVTN 127/HPTN 087 SSP for details regarding infusion 
visit protocols and subsequent infusion observation and Solicited AE assessment 
procedures that CRSs must follow. The CRS will make arrangements to be in 
contact with the participant during the Solicited AE period (as described in 
Section 9.8 and the SSP). 
The following procedures will be performed at all infusion/injection visits. These 
procedures may be performed prior to or following study product administration:  
 Risk reduction counseling (as described in Section 9.5);  
 For participants capable of becoming pregnant, pregnancy prevention 
assessment (as described in Section 9.2 and 9.6); and 
The following procedure will be performed at all infusion/injection visits 
following study product administration: 
  Acceptability questionnaire. 
Additional procedures will be performed at scheduled visits as specified in 
Appendix G:  

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 78 of 142 
 HIV infection assessment including pretest counseling and HIV diagnostic 
testing. A subsequent follow-up contact is conducted to provide post-test 
counseling and to report results to participant; 
 Behavioral risk assessment questionnaire; 
 Assessment of new or unresolved social impacts (site staff will ask participant 
about the status of any unresolved social impacts and if s/he has experienced 
any new social impacts as a result of the trial participation). 
 Social impact questionnaire; 
 Confirm that participants received HIV test results from previous visit. If not, 
provide test results and post-test counseling as appropriate; and 
 Specimen collection (should be completed prior to study product 
administration). 
9.4 
Follow-up visits 
Procedures will be performed at scheduled follow-up visits as specified in 
Appendix G:  
 Assessment of new or unresolved social impacts (site staff will ask participant 
about the status of any unresolved social impacts and if s/he has experienced 
any new social impacts as a result of the trial participation); 
 Assessment of new or continuing concomitant medications (as described in 
Section 9.2); and 
 Assessment of new or unresolved AEs/intercurrent illnesses or AESIs (as 
described in Section 11.2.2 and Appendix H); 
 Risk reduction counseling (as described in Section 9.5);  
 Pregnancy prevention assessment (as described in Sections 9.2 and 9.6); and 
 Behavioral risk assessment questionnaire; 
 Administration of the social impact assessment questionnaire (types of 
impacts assessed involve personal relationships, health insurance, life 
insurance, educational or employment opportunities, housing, immigration, or 
travel); 
 Ask participants in Group 6 whether they believe they received the active 
study product or the control; 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 79 of 142 
 HIV infection assessment including pre-test counseling and HIV diagnostic 
testing. A subsequent follow-up contact is conducted to provide post-test 
counseling and to report results to participant; 
 Confirm that participants received HIV test results from previous visit. If not, 
provide test results and post-test counseling as appropriate; 
 Abbreviated physical examination including weight, vital signs, and a 
symptom-directed evaluation by history and/or appropriate physical exam 
based on participant self-reported symptoms or complaints; 
 Complete physical examination, including weight, vital signs, and clinical 
assessments of head, ears, eyes, nose, and throat; neck; lymph nodes; heart; 
chest; abdomen; extremities; neurological function; and skin; 
 Specimen collection; 
 Clinical laboratory tests including: 
 CBC with differential, 
 Chemistry panel (see Section 9.2), and 
 Urine dipstick (urinalysis if appropriate; see Section 9.7); and 
 Urine or serum pregnancy test (for participants who were assigned female sex 
at birth). Persons who are NOT of reproductive potential due to having 
undergone total hysterectomy or bilateral oophorectomy (verified by medical 
records), are not required to undergo pregnancy testing. 
9.5 
HIV counseling and testing 
HIV counseling will be performed in compliance with the CDC’s guidelines or 
other local guidelines for HIV counseling and referral. HIV testing will be 
performed in accordance with the protocol-specific HIV testing algorithm 
following enrollment. 
Participants will be counseled routinely during the trial on the avoidance of HIV 
infection.  
Potential participants identified as being HIV infected during screening are not 
enrolled. All participants who become HIV infected during the study will be 
terminated from this study. Potential and enrolled participants identified as HIV 
infected will be referred for medical treatment, counseling, and management of 
the HIV infection. These individuals may also be referred to appropriate ongoing 
clinical trials or observational studies. 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 80 of 142 
9.5.1 
Study product-related seroreactivity 
Tests of human sera containing monoclonal antibodies similar to VRC07-523LS 
have been tested using a variety of commercially available HIV test kits without 
any indication of reactivity. For this reason, we do not anticipate that receipt of 
the study product will cause a reactive result on currently available HIV test kits. 
However, this remains a theoretical possibility.  
Because this possibility cannot be categorically eliminated, study staff will advise 
study participants to confine their HIV testing while in the study to that provided 
through the CRS. Staff will also inform study participants of the likelihood of 
routine HIV testing being offered or performed outside the study CRS at 
emergency rooms, clinics, and medical offices, and will inform participants of 
their right to opt out of HIV testing outside the study site. CRS staff should 
inform study participants if local and/or state/regional policies and regulations 
permit medical providers to perform HIV testing without first informing patients. 
If this is the case, then CRS staff should advise study participants that they may 
decline testing preemptively. CRS staff should also inform participants if positive 
results must be reported to local public health authorities. CRS staff should 
provide participants with CRS contact information and should encourage 
participants to ask medical providers to contact the CRS. The CRS can verify that 
the participant is in an HIV mAb clinical trial and should only be tested at the 
study CRS. 
9.6 
Contraception status 
Contraception status is assessed and documented at screening and study product 
administration visits for a participant who was assigned female sex at birth and 
who is sexually active in a way that could cause that participant to become 
pregnant. Prior to enrollment and throughout the study, staff will ask participants 
to verbally confirm their use of adequate contraceptive methods. A participant 
who was assigned female sex at birth and is sexually active in a way that could 
cause that participant to become pregnant should be reminded at all scheduled 
clinic visits of the importance of using contraception and should be referred to 
specific counseling, information, and advice as needed. (Specific contraception 
requirements are listed in Section 7.1). This reminder should be documented in 
the participant’s study record. 
Self-reported infertility—including having undergone hysterectomy, bilateral 
oophorectomy, or tubal ligation—must be documented in the participant’s study 
record. 
9.7 
Urinalysis 
Urine dipstick testing may be performed in the clinic or the lab. The following 
analytes should be analyzed and recorded: specific gravity, protein, 
blood/hemoglobin, pH, urobilinogen, bilirubin, ketones, leucocyte esterase, 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 81 of 142 
nitrite, and glucose. The examination is performed on urine obtained by clean 
catch. Urine microscopy is required when the protein result is 1+, 2+, 3+, or 4+ 
(or semi-quantitative 30, 100, 300, or 2000 g/L) and/or the blood/hemoglobin 
result is trace, 1+, 2 +, 3+, or 4+, but not required (unless otherwise clinically 
indicated) if the dipstick result is abnormal due to non-urinary bleeding. 
If the dipstick performed for screening is transiently abnormal with an 
exclusionary result (eg, 2+ proteinuria), then repeat the dipstick and, if within the 
eligibility limits specified in the protocol, the participant may be enrolled (see 
SSP for further detail). 
A follow-up urine test should be deferred if a participant is experiencing non-
urinary bleeding (eg, menstruation), but should be performed as soon as possible. 
If a follow-up dipstick is abnormal due to non-urinary bleeding (eg, a 
participant’s menstrual period), document in the comment section of the CRF and 
repeat the dipstick once the participant is no longer experiencing non-urinary 
bleeding. In this case, a urine microscopy is not required (see SSP for further 
detail). If a follow-up dipstick is abnormal due to infection, document this issue in 
the participant’s source documentation and provide appropriate treatment and/or 
referral. 
9.8 
Assessments of Solicited AEs  
For all participants, baseline assessments are performed before each infusion or 
injection and assessments for Solicited AEs are performed after each infusion or 
injection. All Solicited AEs are graded according to the Division of AIDS Table 
for Grading the Severity of Adult and Pediatric Adverse Events, Corrected 
Version 2.1 dated July 2017, except as noted in Section 11.2.2. 
The Solicited AE assessment period is 3 full days following each infusion or 
injection per the assessment schedule shown in Table 9-1. Participants are 
instructed to record symptoms using a memory tool. The site staff and the 
participant will be in contact after the 3-day Solicited AE assessment period, or 
sooner if indicated. See SSP for further detail. In general, a participant who self-
reports any reaction following infusion/injection that is greater than mild is seen 
by a clinician within 48 hours after onset, unless the reaction is improving and/or 
has completely resolved. Clinic staff will follow new or unresolved Solicited AEs 
present at day 3 to resolution. 
Solicited AEs are reported using CRFs that correspond to the time of assessment 
in Table 9-1. Solicited AE assessments include assessments of systemic and local 
symptoms, and study product-related lesions. Events not listed on a CRF, or with 
an onset after the Solicited AE assessment period (day of infusion/injection and 3 
full days after), or those SAEs/Unsolicited AEs requiring expedited reporting to 
DAIDS, are recorded on an AE Log. 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 82 of 142 
Table 9-1 Schedule of Solicited AE assessments 
Day 
Time 
Performed by 
0a 
Baseline: before infusion or injection 
CRS clinician 
 
Early: 25-60 minutes after infusion or 
injection 
CRS clinician 
 
Between early assessment and 11:59pm 
day 0 
CRS clinician or participant 
1-3b 
Between 12:00am and 11:59pm on the 
respective day 
CRS clinician or participant 
a Day of infusion or injection 
b New or unresolved Solicited AEs present on day 3 are followed until resolution 
9.8.1 
Assessment of systemic and local symptoms 
Systemic symptoms to be assessed as solicited AEs in this trial include increased 
body temperature, chills, malaise and/or fatigue, headache, myalgia, arthralgia, 
nausea, urticaria, non-exertional dyspnea, non-exertional tachycardia (assessed by 
CRS staff, not by the participant), generalized pruritus, facial flushing, and 
unexplained diaphoresis. Local symptoms include pain or tenderness at the 
infusion/injection site. Additionally, in participants receiving SC injection local 
pruritus will be assessed. The daily maximum severity reached for each symptom 
during the assessment period is reported (see SSP).  
Body temperature is measured by oral or infrared thermometry. All temperatures 
must be measured by non-axillary thermometry. This includes temperatures taken 
in the clinic, as well as temperatures taken by participants during the solicited AE 
assessment period. Temperature is reported in degrees Celsius. If temperature is 
measured in Fahrenheit, the conversion to Celsius should be documented in the 
participant’s chart note. A measurement is taken once daily during the assessment 
period and should be repeated if participant is feeling feverish. 
9.8.2 
Assessment of infusion/injection site 
Typical infusion and injection site reactions are erythema/redness and 
induration/swelling. The maximum horizontal and maximum vertical 
measurements for all infusion/injection site reactions are recorded. 
All infusion/injection site reactions are monitored until resolution. Areas greater 
than 25 cm2 are followed daily; otherwise, the frequency of follow-up is based on 
clinician judgment. 
9.9 
Visit windows and missed visits 
Visit windows are defined in SSP. For a visit not performed within the window 
period, a Missed Visit form is completed.  
If a participant misses a scheduled visit, CRS staff should attempt to bring the 
participant in as soon as possible to complete the required safety assessments and 
other procedures. See the SSP for more details. If a participant missed an 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 83 of 142 
infusion/injection visit or if study product administration must be permanently 
discontinued, see Section 7.3.2 and Section 7.3.3 for resolution. 
9.10 
Early termination visit 
In the event of early participant termination, site staff should consider if the 
following assessments are appropriate: a final physical examination, clinical 
laboratory tests (including urine dipstick, CBC with differential, ALT, and 
creatinine), pregnancy testing, social impact assessment, and HIV test. 
9.11 
Pregnancy 
If a participant becomes pregnant during the course of the study, no more 
infusions or injections of study product will be given, but remaining visits and 
study procedures should be completed unless medically contraindicated or 
applicable regulations require termination from the study. If the participant 
terminates from the study prior to the pregnancy outcome, the site should make 
every effort to keep in touch with the participant in order to ascertain the 
pregnancy outcome. Pregnancies and pregnancy outcomes will be reported. 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 84 of 142 
10 
Laboratory 
10.1 
CRS laboratory procedures 
The HVTN 127/HPTN 087 Site Lab Instructions and SSP provide further 
guidelines for operational issues concerning the clinical and processing 
laboratories. These documents include guidelines for general specimen collection, 
special considerations for phlebotomy, specimen labeling, whole blood 
processing, HIV screening/diagnostic testing, and general screening and safety 
testing. 
Tube types for blood collection are specified in Appendix F. For tests performed 
locally, the local lab may assign appropriate tube types. 
In specific situations, the blood collection tubes may be redirected to another 
laboratory or may require study-specific processing techniques. In these cases, 
laboratory special instructions will be posted on the protocol-specific section of 
the HVTN website. 
Of note, all assays described below are performed as research assays and are not 
approved for use in medical care. Results from these assays are not made 
available to participants or medical professionals to guide treatment decisions. 
10.2 
Total blood volume 
Required blood volumes per visit are shown in Appendix F. Not shown is any 
additional blood volume that would be required if a safety lab needs to be 
repeated, or if a serum pregnancy test needs to be performed. The additional 
blood volume would likely be minimal. The total blood volume drawn for each 
participant will not exceed 500 mL in any 56-day (8-week) period. 
10.3 
VRC07-523LS concentrations 
VRC07-523LS concentrations will be measured in serum. The binding assay may 
employ the VRC01 Fab specific 5C9 mAb or another suitable protein. 5C9 is an 
anti-idiotype antibody cloned from a single B cell that was sorted by flow 
cytometry using a VRC01 scFv probe. 5C9 also captures VRC07-523LS given the 
homology of the proteins. Serum concentrations of VRC07-523LS will be based 
upon the concentrations of sample dilutions falling within the linear range of the 
standard curve.  

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 85 of 142 
10.4 
Endpoint assays: humoral 
10.4.1 
Neutralizing antibody assay 
HIV-1–specific neutralizing antibody (nAb) assays will be performed on serum 
samples from study participants taken at postadministration timepoints and at 
baseline. The TZM-bl assay (77, 78) will test neutralization of a panel of Tier 2 
viruses that exhibit a range of known sensitivities to VRC07-523LS. The viruses 
will be selected from a global panel and/or clade-specific panels (79, 80).  
10.4.2 
ADA detection assay 
Anti-VRC07-523LS antibody assays will be performed on select serum samples 
from study participants collected at baseline and after antibody administration. 
ADA will be measured by using the Meso Scale Discovery (MSD) platform with 
VRC07-523LS as the target antigen.  
10.4.3 
ADA functional assay 
A functional ADA assay will be used to confirm any positive activity that is 
observed in the ADA detection assay (MSD). Functional activity will measure a 
reduction in VRC07-523LS neutralizing activity against a qualified virus in the 
TZM-bl assay.  
10.4.4 
Binding antibody multiplex assay (BAMA) 
HIV-1–specific total binding IgG may be assessed on serum samples from study 
participants collected at baseline and after antibody administration with reagents 
that have known reactivity with VRC07-523LS. 
10.5 
Exploratory studies 
Samples may be used for other testing and research related to furthering the 
understanding of HIV immunology, antibody mediated prevention, or vaccines. In 
addition, cryopreserved samples may be used to perform additional assays to 
support standardization and validation of existing or newly developed methods.  
10.6 
Specimen storage and other use of specimens  
The Networks store specimens from all study participants indefinitely, unless a 
participant requests that specimens be destroyed or if required by IRB/EC, or RE.  
Other use of specimens is defined as studies not covered by the protocol or the 
informed consent form for the main study (see Appendix A).  
This research may relate to HIV, vaccines, monoclonal antibodies, the immune 
system, and other diseases. This could include genetic testing and, potentially, 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 86 of 142 
genome-wide studies. This research is done only to the extent authorized in each 
study site’s informed consent form, or as otherwise authorized under applicable 
law. Other research on specimens will occur only after review and approval by the 
HVTN, the HPTN, the IRB/EC of the researcher requesting the specimens, and 
the CRS’s IRBs/ECs/REs if required.  
As part of consenting for the study, participants document their initial decision to 
allow or not allow their specimens to be used in other research, and they may 
change their decision at any time. The participant’s initial decision about other 
use of their specimens, and any later change to that decision, is recorded by their 
CRS in a Web-based tool that documents their current decisions for other use of 
their specimens. The Networks will only allow other research to be done on 
specimens from participants who allow such use.  
CRSs must notify HVTN Regulatory Affairs if institutional or local governmental 
requirements pose a conflict with or impose restrictions on specimen storage or 
other use of specimens. 
10.7 
Biohazard containment 
As the transmission of HIV and other blood-borne pathogens can occur through 
contact with contaminated needles, blood, and blood products, appropriate 
precautions will be employed by all personnel in the drawing of blood and 
shipping and handling of all specimens for this study, as currently recommended 
by the CDC and the NIH or other applicable agencies. 
All dangerous goods materials, including Biological Substances, Category A or 
Category B, must be transported according to instructions detailed in the 
International Air Transport Association Dangerous Goods Regulations. 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 87 of 142 
11 
 Safety monitoring and safety review 
11.1 
Safety monitoring and oversight 
11.1.1 
HVTN 127/HPTN 087 PSRT 
The HVTN 127/HPTN 087 PSRT is composed of the following members: 
 DAIDS medical officer representatives 
 Protocol chairs  
 Protocol Team leader 
 Core medical monitor 
 Clinical safety specialist 
The clinician members of HVTN 127/HPTN 087 PSRT are responsible for 
decisions related to participant safety. 
The Protocol Team clinic coordinator, clinical data manager, study product 
developer representative, clinical research manager, clinical trials manager, and 
others may also be included in HVTN 127/HPTN 087 PSRT meetings. 
11.1.2 
HVTN SMB 
The SMB is a multidisciplinary group consisting of biostatisticians, clinicians, 
and experts in HIV vaccine and drug research that, collectively, has experience in 
the conduct and monitoring of vaccine and drug trials. Members of the SMB are 
not directly affiliated with the protocols under review.  
The SMB reviews safety data, unblinded as to treatment arm, approximately 
every 4 months. The reviews consist of evaluation of cumulative Solicited AEs, 
Unsolicited AEs, laboratory safety data, and individual reports of AEs requiring 
expedited reporting to DAIDS. The SMB conducts additional special reviews at 
the request of the HVTN 127/HPTN 087 PSRT.  
Study sites will receive SMB summary minutes and are responsible for 
forwarding them to their IRB/EC and any applicable RE. 
11.1.3 
Roles and responsibilities in safety monitoring  
The roles and responsibilities of the SDMC in relation to safety monitoring 
include: 
 Maintaining a central database management system for clinical data; 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 88 of 142 
 Providing reports of clinical data to appropriate groups such as the HVTN 
127/HPTN 087 PSRT and HVTN SMB (see Section 11.1.2); 
The roles and responsibilities of the HVTN CSS or HVTN Core designee in 
relation to safety monitoring include: 
 Daily monitoring of clinical data for events that meet the safety pause and 
HVTN 127/HPTN 087 PSRT AE review criteria (see Section 11.3); 
 Notifying CRSs and other groups when safety pauses or planned holds are 
instituted and lifted (see Section 11.3); 
 Querying CRSs for additional information regarding reported clinical data; 
and 
 Providing support to the HVTN 127/HPTN 087 PSRT. 
11.2 
Safety reporting 
11.2.1 
Submission of safety forms to SDMC 
Site staff must submit all safety forms (eg, Solicited AEs, Unsolicited AEs, 
urinalysis, local lab results, and concomitant medications) before the end of the 
next business day, excluding federal or bank holidays. The forms should not be 
held in anticipation of additional information at a later date. If additional 
information is received at a later date, the forms should be updated and 
resubmitted before the end of the next business day after receiving the new 
information. For the case of a longer site holiday closure, site staff must submit 
the data by the end of the 5th day (local time) after receiving the information even 
if this day is a holiday. 
For example: If the site becomes aware of an AE on Thursday (Day 0), the site 
must submit the data by the end of the next business day, on Friday. If there is a 
longer site holiday closure, then this AE may be reported no later than the end of 
the fifth day, Monday (Day 4). If Monday is a holiday as well, all safety forms 
still need to be submitted by the end of Monday (Day 4). 
11.2.2 
AE reporting 
An AE is any untoward medical occurrence in a clinical investigation participant 
administered a study product/procedure(s) and which does not necessarily have a 
causal relationship with this treatment. An AE can therefore be any unfavorable 
and unintended sign (including an abnormal laboratory finding), symptom, or 
disease temporally associated with the use of an investigational study 
product/procedure(s), whether or not related to the investigational study 
product/procedure(s).  

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 89 of 142 
The study Unsolicited AE reporting period is from study enrollment of a trial 
participant to (and including) the Week 80 visit (v16.0) 
Only AESI are reported to the SDMC after the completion of that visit (bulleted 
above) to the end of trial participation for each participant (see Appendix H). 
All AEs are graded according to the Division of AIDS (DAIDS) Table for 
Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 
2.1, July 2017, available on the RSC website at http://rsc.tech-res.com/clinical-
research-sites/safety-reporting/daids-grading-tables, except: 
 Unintentional weight loss is required to be reported as an AE only if it is 
considered to be potentially deleterious to the participant’s health (see HVTN 
127/HPTN 087 SSP) 
 Infusion Site Erythema or Redness and Infusion Site Induration or Swelling 
will not consider interference with usual social and functional activities such 
that: 
 Grade 1 is: 2.5 to < 5 cm in diameter OR 6.25 to < 25 cm2 surface area; 
 Grade 2 is: ≥ 5 to < 10 cm in diameter OR ≥ 25 to < 100 cm2 surface area; 
 Grade 3 is: ≥ 10 cm in diameter OR ≥ 100 cm2 surface area OR Ulceration 
OR Secondary infection OR Phlebitis OR Sterile abscess OR Drainage; 
 Grade 4 is: Potentially life-threatening consequences (eg, abscess, 
exfoliative dermatitis, necrosis involving dermis or deeper tissue); 
 Injection Site Erythema or Redness and Injection Site Induration or Swelling 
will not consider interference with usual social and functional activities such 
that: 
 Grade 1 is: 2.5 to < 5 cm in diameter OR 6.25 to < 25 cm2 surface area; 
 Grade 2 is: ≥ 5 to < 10 cm in diameter OR ≥ 25 to < 100 cm2 surface area; 
 Grade 3 is: ≥ 10 cm in diameter OR ≥ 100 cm2 surface area OR Ulceration 
OR Secondary infection OR Phlebitis OR Sterile abscess OR Drainage; 
 Grade 4 is: Potentially life-threatening consequences (eg, abscess, 
exfoliative dermatitis, necrosis involving dermis or deeper tissue); 
 Infusion reactions (see HVTN 127/HPTN 087 SSP) 
All AEs are reported to the SDMC on the appropriate CRF. Clinic staff should 
evaluate every AE to determine if (1) the AE meets the requirements for 
expedited reporting to DAIDS (see Section 11.2.3), (2) if the AE meets the 
criteria for a safety pause/prompt AE review (see Section 11.3), and (3) if the AE 
is listed as an AESI. A list of AESI to be reported in this protocol is provided in 
Appendix H. 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 90 of 142 
Sites are expected to notify HVTN clinical safety staff of any serious safety 
concern requiring their attention (Table 11-1). Telephone numbers and email 
addresses are found on the protocol home page on the HVTN 127/HPTN 087 
protocol-specific site (https://members.hvtn.org/protocols/hvtn127-hptn087). 
Concerns requiring immediate attention should be communicated by calling the 
clinical safety phone. 
In the case of email notification, clinical safety staff will reply during working 
hours (HVTN Core local time) to confirm that the email has been received and 
reviewed. If email service is not available, the CRS should notify clinical safety 
staff of the event by telephone, then submit CRFs. 
In addition, site investigators are required to submit AE information in accordance 
with IRB/EC and any applicable RE requirements.  
11.2.3 
Expedited reporting of AEs to DAIDS 
Requirements, definitions and methods for expedited reporting of AEs are 
outlined in Version 2.0 (January 2010) of the Manual for Expedited Reporting of 
Adverse Events to DAIDS (DAIDS EAE Manual), which is available on the RSC 
website at http://rsc.tech-res.com/clinical-research-sites/safety-reporting/manual. 
The SAE Reporting Category will be used for this study.  
The internet-based DAIDS Adverse Experience Reporting System (DAERS) must 
be used for expedited AE (EAE) reporting to DAIDS. In the event of system 
outages or technical difficulties, expedited AE reports may be submitted via the 
DAIDS EAE Form. This form is available on the DAIDS RSC website at 
http://rsc.tech-res.com/clinical-research-sites/safety-reporting/daids/paper-eae-
reporting. 
For questions about DAERS, please contact CRMSsupport@niaid.nih.gov or 
from within the DAERS application itself. 
For questions about EAE reporting, please contact the DAIDS RSC Safety Office 
at (DAIDSRSCSafetyOffice@tech-res.com). 
The study products for which expedited reporting are required are:  
 VRC-HIVMAB075-00-AB (VRC07-523LS) 
While the participant is in the study, from enrollment to the end of trial 
participation for that participant, the SAE Reporting Category will be used.  
After the end of trial participation for that participant, unless otherwise noted, 
only Suspected, Unexpected Serious Adverse Reactions (SUSARs) as defined in 
Version 2.0 of the DAIDS EAE Manual must be reported to DAIDS, if the study 
staff become aware of the events. All AESI will be considered unexpected, and, if 
deemed related to the study products, will be reported as SUSARs, if applicable.  

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 91 of 142 
The NIAID/DAIDS will report all unexpected SAEs related to the study products 
observed in this clinical trial to the FDA in accordance with 21 CFR 312.32 (IND 
Safety Reports). However, because safety is a primary study endpoint, the 
Sponsor Medical Officer will not routinely be unblinded to study treatment 
assignment when there is an assessment of relatedness of the SAE with the study 
product(s); and the safety report will be sent to the FDA based on the blinded 
attribution assessment. In addition, the NIAID/DAIDS or designee(s) will prepare 
and file expedited reports to other appropriate regulatory authorities within the 
timelines required by pertinent national regulatory agencies.  
If the PSRT believes unblinding is appropriate (eg, if unblinding to treatment 
assignment will assist with the clinical management of the SAE), the PSRT will 
consult the independent HVTN SMB for a recommendation. In the event the 
HVTN SMB determines that unblinding is indicated, the SMB will inform the 
individual who requested unblinding (eg, site physician) of the participant’s 
treatment assignment in such a manner as to maintain the study blind of the PSRT 
and study team. For additional impact and management of SAEs on the study, see 
Section 11.3. 
CRS Investigators of Record (IoRs)/designees will submit AE information and 
any other relevant safety information to their IRBs/ECs in accordance with 
IRB/EC requirements. 
11.3 
Safety pause and prompt PSRT AE review 
When a trial is placed on safety pause, all enrollment and study product 
administration related to the event that triggered the pause will be held until 
further notice. The AEs that will lead to a safety pause or prompt HVTN 
127/HPTN 087 PSRT AE review are summarized in Table 11-1. Study product 
administration may be suspended for safety concerns other than those described in 
the table, or before pause rules are met, if, in the judgment of the HVTN 
127/HPTN 087 PSRT, participant safety may be threatened. Criteria for an 
individual participant’s departure from the schedule of study product 
administration are listed in Section 7.3. 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 92 of 142 
Table 11-1 AE notification and safety pause/AE review rules 
Event and 
relationship to study 
products 
Severity 
CRS actiona 
HVTN Core actionb 
SAE, related 
Grade 5 or 
Grade 4 
Phone immediately, email 
and submit forms 
immediately 
Immediate pause 
SAE, not related 
Grade 5 
Phone immediately, email 
and submit forms 
immediately 
Immediate PSRT notification 
SAE, related 
Grade 3 
Email and submit forms 
immediately 
Immediate PSRT notification and 
prompt PSRT AE review to 
consider pause 
AEc, related 
Grade 4 or 
3 
Email and submit forms 
immediately 
Immediate PSRT notification and 
prompt PSRT AE review to 
consider pause 
a Phone numbers and email addresses are found on the Protocol home page on the HVTN Members’ site 
(https://members.hvtn.org/protocols/hvtn127-hptn087). 
b HVTN CSS or HVTN Core designee 
c Does not include subjective Solicited AEs (injection or infusion site pain/tenderness, fatigue/malaise, 
headache, non-exertional dyspnea, generalized pruritus, facial flushing, unexplained diaphoresis). 
For all safety pauses, HVTN Core notifies the HVTN 127/HPTN 087 PSRT, 
HVTN Regulatory Affairs, DAIDS Pharmaceutical Affairs Branch (PAB), 
DAIDS Regulatory Affairs Branch (RAB), DAIDS Safety and Pharmacovigilance 
Team (SPT), and participating CRSs. When an immediate safety pause is 
triggered, HVTN Core notifies the SMB.  
Once a trial is paused, the HVTN 127/HPTN 087 PSRT reviews safety data and 
decides whether the pause can be lifted or permanent discontinuation of study 
product administration is appropriate, consulting the SMB if necessary. HVTN 
Core notifies the participating CRSs, HVTN Regulatory Affairs, DAIDS PAB, 
DAIDS RAB, and DAIDS SPT of the decision regarding resumption or 
discontinuation of study product administration. Based on the HVTN 127/HPTN 
087 PSRT assessment, DAIDS RAB notifies the FDA as needed. 
If an immediate HVTN 127/HPTN 087 PSRT notification or prompt HVTN 
127/HPTN 087 PSRT AE review is triggered, HVTN Core notifies the HVTN 
127/HPTN 087 PSRT as soon as possible during working hours (HVTN Core 
local time)—or, if the information was received during off hours, by the morning 
of the next workday. If a prompt HVTN 127/HPTN 087 PSRT AE review cannot 
be completed within 72 hours of notification (excluding weekends and US federal 
holidays), an automatic safety pause occurs. 
The HVTN and HPTN require that each CRS submit to its IRB/EC and any 
applicable RE protocol-related safety information (such as IND safety reports, 
notification of study product holds due to the pause rules, unanticipated problems 
involving risks to participants or others, and notification of other unplanned safety 
pauses). CRSs must also follow all applicable RE reporting requirements. 
In addition, all other AEs are reviewed routinely by the HVTN 127/HPTN 087 
PSRT (see Section 11.4.2). 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 93 of 142 
11.4 
Review of cumulative safety data 
Routine safety review occurs at the start of enrollment and then throughout the 
study. 
Reviews proceed from a standardized set of protocol-specific safety data reports. 
These reports are produced by the SDMC and include queries to the CRSs. Events 
are tracked by internal reports until resolution.  
11.4.1 
Daily review 
Blinded daily safety reviews are routinely conducted by HVTN Core for events 
requiring expedited reporting to DAIDS, and events that meet safety pause criteria 
or prompt HVTN 127/HPTN 087 PSRT AE review criteria. 
11.4.2 
Weekly review 
During the study product administration phase of the trial, the HVTN 127/HPTN 
087 PSRT reviews clinical safety reports on a weekly basis and conducts calls to 
review the data as appropriate. Following the visit 8 weeks post-final study 
product administration, less frequent reporting and safety reviews may be 
conducted at the discretion of the HVTN 127/HPTN 087 PSRT. The HVTN CSS 
or HVTN Core designee reviews reports of clinical and laboratory AEs. Events 
identified during the review that are considered questionable, inconsistent, or 
unexplained are referred to the CRS clinic coordinator for verification. 
11.5 
Study termination 
This study may be terminated early by the determination of the HVTN 127/HPTN 
087 PSRT, a pertinent national regulatory authority, NIH, Office for Human 
Research Protections (OHRP), or study product developer(s). In addition, the 
conduct of this study at an individual CRS may be terminated by the 
determination of the IRB/EC and any applicable RE. 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 94 of 142 
12 
Protocol conduct 
This protocol and all actions and activities connected with it will be conducted in 
compliance with the principles of GCP (ICHe6), the HVTN and HPTN network-
specific Manuals of Operations, and DAIDS Clinical Research Policies and 
Standard Procedures Documents, including procedures for the following: 
 Protocol registration, activation, and implementation; 
 Informed consent, screening, and enrollment; 
 Study participant reimbursement; 
 Clinical and safety assessments; 
 Safety monitoring and reporting; 
 Data collection, documentation, transfer, and storage; 
 Participant confidentiality; 
 Study follow-up and close-out; 
 Unblinding of staff and participants; 
 Quality control; 
 Protocol monitoring and compliance; 
 Advocacy and assistance to participants regarding negative social impacts 
associated with participation in the trial; 
 Risk reduction counseling;  
 Specimen collection, processing, and analysis;  
 Exploratory and ancillary studies and sub-studies, and 
 Destruction of specimens. 
Any policies or procedures that vary from DAIDS, HVTN, or HPTN standards or 
require additional instructions (eg, instructions for randomization specific to this 
study) will be described in the HVTN 127/HPTN 087 SSP.  

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 95 of 142 
12.1 
Social impacts 
It is possible that participants’ involvement in the study could result in social 
impacts. For example, a participant’s involvement in the study could become 
known to others, and a social harm may result (ie, because participants could be 
perceived as being HIV infected or at “high risk” for HIV infection). Participants 
could be treated unfairly, or could have problems being accepted by their families 
and/or communities. Alternatively, a social benefit may result (eg, a participant 
could feel good helping others). 
Social harms are negative social impact events and social benefits are positive 
social impact events that a participant reports as affecting them as a result of 
being involved in a research study. It is not the researcher’s opinion of how they 
perceive an event has affected a participant. Social impacts will be collected and 
reported on CRFs during scheduled visits (see Appendix G). A social harm that is 
reported by the participant and judged by the IoR/designee to be serious or 
unexpected will be reported to the responsible site’s IRB at least annually, or 
according to their individual requirements. In the event that a participant reports a 
social harm, every effort will be made by study staff to provide appropriate care 
and counseling to the participant as necessary, and/or referral to appropriate 
resources for the safety and wellbeing of the participant. While maintaining 
participant confidentiality, study sites may engage their Community Advisory 
Board (CAB) in exploring the social context surrounding instances of social 
harms to minimize the potential occurrence of such an impact. 
12.2 
Emergency communication with study participants 
As in all clinical research, this study may generate a need to reach participants 
quickly to avoid imminent harm, or to report study findings that may otherwise 
concern their health or welfare. 
When such communication is needed, the CRS will request that its IRB/EC and 
any applicable RE expedite review of the message. If this review cannot be 
completed in a timeframe consistent with the urgency of the required 
communication, the site can contact the participant without IRB/EC approval if 
such communication is necessary to avoid imminent harm to the study participant. 
The CRS must notify the IRB/EC and any applicable RE of the matter as soon as 
possible. 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 96 of 142 
13 
Version history 
The Protocol Team may modify the original version of the protocol. 
Modifications are made to Network protocols via clarification memos, letters of 
amendment, or full protocol amendments.  
The version history of, and modifications to, Protocol HVTN 127/HPTN 087 are 
described below. 
Protocol history and modifications 
Date: March 8, 2018 
Protocol version: Version 2.0 
Protocol modification: Full Protocol Amendment 1 
Item 1 
Added on Title page: IND number 
Item 2 
Revised on Title page and in Section 3, Appendices A, C, and J: Study title 
Item 3 
Added: Intramuscular injection (IM) study arm 
Item 4 
Revised: Product administration and follow-up visit schedules 
Item 5 
Updated in Section 4.9.3: Clinical studies of VRC07-523LS; VRC 605 
Item 6 
“Pharmacokinetics” removed in Section 6.1.2, Sample size calculations for 
serum levels of VRC07-523LS 
Item 7 
Updated in Section 6.4.6: Analyses and data sharing prior to end of 
scheduled follow-up visits 
Item 8 
Updated in Sections 7, Appendix B, and Appendix D: Use of “sex assigned 
at birth” 
Item 9 
Removed in Section 9.1.2, Protocol-specific consent forms: Instruction to 
follow protocol-specific memo regarding when to start using site-specific 
consent forms 
Item 10 Clarified in Sections 9.3 and 9.4: HIV assessment procedure includes HIV 
diagnostic testing 
Item 11 Clarified in Section 9.8 Assessments of Solicited AEs: CRS clinician 
assessment 
Item 12 Clarified in Section 9.8.1, Assessment of systemic and local symptoms: 
Thermometry 
Item 13 Clarified in Section 9.8.2, Assessment of infusion/injection site: 
Infusion/injection site reaction measurements 
Item 14 Updated in Section 10.1, CRS laboratory procedures: Special instructions 
and research assays 
Item 15 Clarified in Section 11.2.1, Submission of safety forms to SDMC: Submittal 
deadlines 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 97 of 142 
Item 16 Revised in Section 11.2.2, AE reporting: Unsolicited AE reporting period 
Item 17 Clarified in Section 11.2.3, Expedited reporting of AEs to DAIDS: 
Unblinding procedures 
Item 18 Added in Section 11.3, Safety pause and prompt PSRT AE review: 
Submission of unanticipated problems to IRB/EC 
Item 19 Clarified in Section 12.2, Emergency communication with study 
participants: Circumstances under which communication is allowed prior to 
IRB/EC approval 
Item 20 Clarified in Appendix A, Item 8: Visit intervals 
Item 21 Clarified in Appendix A, Item 14: Sample testing 
Item 22 Clarified in Appendix A Item 16 and Appendix C: Other research on stored 
samples 
Item 23 Added in Appendix A and in Appendix C: Participants may change their 
minds regarding use of samples and data in other studies 
Item 24 Clarified in footnote to Appendix A and Appendix C signature blocks: 
Witness requirement 
Item 25 Clarified in Appendix B, Approved birth control methods (for sample 
informed consent form): Condom use for HIV and STI prevention 
Item 26 Revised in Appendix D: Table of procedures (for sample informed consent 
form) 
Item 27 Revised in Appendix E: Product administration schedule graphic 
Item 28 Revised in Appendix F: Laboratory procedures table 
Item 29 Revised in Appendix G: Procedures at CRS table 
Item 30 Clarified in Appendix H, Adverse events of special interest (AESI): Update 
provisions 
Item 31 Added as Appendix I: Low risk guidelines for the US and Switzerland 
Item 32 Updated and corrected in Section 3.1: Protocol team 
Item 33 Updated: Section and appendix numbers  and cross-references 
Item 34 Corrected: Acronyms, spelling and grammatical errors, page layout, and 
stylistic inconsistencies 
Date: November 28, 2017 
Protocol version: Version 1.0 
Protocol modification: Original protocol 
 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 98 of 142 
14 
Document references (other than literature 
citations) 
Other documents referred to in this protocol, and containing information relevant 
to the conduct of this study, include: 
 Assessment of Understanding. Accessible through the HVTN protocol-
specific website. 
 Current CDC Guidelines 
 Revised Recommendations for HIV Testing of Adults, Adolescents, and 
Pregnant Women in Health-Care Settings. Available at 
http://www.cdc.gov/mmwr/PDF/rr/rr5514.pdf  
 Revised Guidelines for HIV Counseling, Testing, and Referral. Available 
at http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5019a1.htm 
 Division of AIDS (DAIDS) Clinical Research Policies and Standard 
Procedures Documents. Available at 
https://www.niaid.nih.gov/research/daids-clinical-research-policies-standard-
procedures  
 Division of AIDS Protocol Registration Manual. Available at 
https://www.niaid.nih.gov/sites/default/files/prmanual.pdf  
 Division of AIDS Table for Grading the Severity of Adult and Pediatric 
Adverse Events. Corrected Version 2.1, July 2017. Available at http://rsc.tech-
res.com/clinical-research-sites/safety-reporting/daids-grading-tables 
 The Manual for Expedited Reporting of Adverse Events to DAIDS. Version 
2.0, January 2010. Available at http://rsc.tech-res.com/clinical-research-
sites/safety-reporting/manual 
 HVTN Certificate of Confidentiality. Accessible through the HVTN website. 
 HVTN 127/HPTN 087 Special Instructions. Accessible through the HVTN 
protocol-specific website. 
 HVTN 127/HPTN 087 Study Specific Procedures. Accessible through the 
HVTN protocol-specific website. 
 HVTN 127/HPTN 087 Site Lab Instructions. Accessible through the HVTN 
protocol-specific website. 
 HVTN Manual of Operations. Accessible through the HVTN website. 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 99 of 142 
 Dangerous Goods Regulations (updated annually), International Air Transport 
Association. Available for purchase at 
http://www.iata.org/ps/publications/dgr/Pages/index.aspx 
 Lab assay algorithm (available upon request) 
 International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use (ICH) E6, Guideline for Good Clinical 
Practice: Section 4.8, Informed consent of trial subjects. Available at 
http://www.ich.org/products/guidelines/efficacy/article/efficacy-
guidelines.html 
 HVTN 127/HPTN 087 Participants’ Bill of Rights and Responsibilities. 
Accessible through the HVTN protocol-specific website. 
 NIH Policy on Reporting Race and Ethnicity Data: Subjects in Clinical 
Research. Available at http://grants1.nih.gov/grants/guide/notice-files/NOT-
OD-01-053.html 
 Pharmacy Guidelines and Instructions for DAIDS Clinical Trials Networks, 
July 2008. 
 Requirements for Source Documentation in DAIDS Funded and/or Sponsored 
Clinical Trials. Available at 
https://www.niaid.nih.gov/sites/default/files/daids-sourcedocpolicy.pdf  
 Title 21, Code of Federal Regulations, Part 50. Available at 
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFR
Part=50 
 Title 45, Code of Federal Regulations, Part 46. Available at 
http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.html 
See Section 16 for literature cited in the background and statistics sections of this 
protocol. 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 100 of 142 
15 
Acronyms and abbreviations 
Ab 
antibody 
ACD 
acid citrate dextrose 
ADA 
anti-drug antibody 
ADCC 
antibody dependent cellular cytotoxicity 
ADCP 
antibody dependent cellular phagocytosis 
AE 
adverse event 
AESI 
adverse events of special interest 
AIA 
anti-idiotypic antibody 
ALT 
alanine aminotransferase 
AMP 
antibody mediated prevention 
ANOVA analysis of variance 
aPTT 
activated partial thromboplastin time 
ART 
antiretroviral therapy 
AST 
aspartate aminotransferase 
ATI 
analytic treatment interruption 
AUC 
area under the curve 
BAMA 
binding antibody multiplex assay 
β-HCG 
beta human chorionic gonadotropin 
bNAb 
broadly neutralizing antibody 
CAB 
Community Advisory Board 
CBC 
complete blood count 
CDC 
US Centers for Disease Control and Prevention 
CFR 
Code of Federal Regulations 
CIOMS 
Council for International Organizations of Medical Sciences 
CL 
clearance 
Cmax 
maximum concentration 
CMIA 
chemiluminescent microparticle immunoassay 
CRF 
case report form 
CRPMC 
NIAID Clinical Research Products Management Center 
CRS 
clinical research site 
CSR 
central specimen repository 
CSS 
Clinical Safety Specialist 
DAERS 
DAIDS Adverse Experience Reporting System 
DAIDS 
(NIAID, NIH) Division of AIDS  
DEHP 
di(2-ethylhexyl)phthalate 
DHHS 
US Department of Health and Human Services 
EAE 
expedited AE 
EC 
ethics committee 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 101 of 142 
EDTA 
ethylenediaminetetraacetic acid 
EIA 
enzyme immunoassay 
ELISA 
enzyme-linked immunosorbent assay 
Fc  
fragment crystallizable 
 
FcRn 
neonatal Fc receptor 
FDA 
US Food and Drug Administration 
Fred Hutch 
Fred Hutchinson Cancer Research Center 
GCP 
Good Clinical Practice 
GEE 
generalized estimating equation 
GINA 
Genetic Information Nondiscrimination Act 
GLP 
Good Laboratory Practice 
HBsAg 
hepatitis B surface antigen 
HCV 
hepatitis C virus 
Hg 
mercury 
HIPAA 
Health Insurance Portability and Accountability Act 
HIV 
human immunodeficiency virus 
HPTN 
HIV Prevention Trials Network 
HVTN 
HIV Vaccine Trials Network 
ICF 
informed consent form 
ICH 
International Council for Harmonisation of Technical Requirements 
for Pharmaceuticals for Human Use 
IgG 
immunoglobulin G 
IND 
Investigational New Drug 
IoR 
Investigator of Record 
IRB 
institutional review board 
IUD 
intrauterine device 
IVIG 
intravenous immunoglobulin 
IV 
intravenous 
mAb 
monoclonal antibody 
MAR 
missing at random 
MCAR 
missing completely at random 
MedDRA Medical Dictionary for Regulatory Activities 
MITT 
modified intent-to-treat 
MSD 
Meso Scale Discovery 
nAb 
neutralizing antibody 
NAEPP 
National Asthma Education and Prevention Program 
NHP 
nonhuman primate 
NIAID 
National Institute of Allergy and Infectious Diseases (US NIH) 
NIH 
US National Institutes of Health 
NSAID 
nonsteroidal anti-inflammatory drug 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 102 of 142 
NOAEL 
no observed adverse effects level 
OHRP 
US Office for Human Research Protections 
PAB 
DAIDS Pharmaceutical Affairs Branch 
PBMC 
peripheral blood mononuclear cell 
PCR 
polymerase chain reaction 
PEP 
post-exposure prophylaxis 
PES 
polyethersulfone 
PI 
Principal Investigator 
PK 
pharmacokinetic 
PP 
per protocol 
PrEP 
pre-exposure prophylaxis 
PSRT 
Protocol Safety Review Team 
RAB 
DAIDS Regulatory Affairs Branch 
RE 
regulatory entity 
RSC 
(DAIDS) Regulatory Support Center 
RSV 
respiratory syncytial virus 
SAE 
serious adverse event 
SC 
subcutaneous 
SCHARP Statistical Center for HIV/AIDS Research and Prevention 
SCIG 
subcutaneous immunoglobulin 
SD 
standard deviation 
SDMC 
statistical and data management center 
SHIV 
simian human immunodeficiency virus 
SMB 
Safety Monitoring Board 
SPT 
DAIDS Safety and Pharmacovigilance Team 
SSP 
Study Specific Procedures 
SST 
serum-separating tube 
SUSAR 
suspected unexpected serious adverse reaction 
TasP 
treatment as prevention 
TB 
tuberculosis 
TCR 
tissue cross reactivity 
Tmax 
time to Cmax 
USP 
United States Pharmacopeia  
UW-VSL University of Washington Virology Specialty Laboratory 
V 
volume of distribution 
VITL 
Vaccine Research Center- Immunology Testing Laboratory 
VRC 
Vaccine Research Center (NIAID) 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 103 of 142 
16 
Literature cited 
1. UNAIDS. Ethical considerations in biomedical HIV prevention trials. 2007 
7/2007. 
2. The National Commission for the Protection of Human Subjects of 
Biomedical and Behavioral Research. The Belmont Report: Ethical Principles 
and Guidelines for the Protection of Human Subjects of Research. 1979 
4/18/1979. 
3. Council for International Organizations of Medical Sciences (CIOMS). 
International ethical guidelines for biomedical research involving human 
subjects. Bull Med Ethics. 2002(182):17-23. 
4. UNAIDS. Report on the Global AIDS Epidemic, 2012 country progress 
reports 2013 [updated 2013. Available from: 
http://www.unaids.org/en/dataanalysis/knowyourresponse/countryprogressre
ports/2012countries/. 
5. UNAIDS. Global Report: Report on the global AIDS epidemic 2013. 2013 
2013. Report No.: UNAIDS / JC2502/1/E. 
6. WHO/UNICEF/UNAIDS. Global Report on HIV Treatment 2013: Results, 
Impact and Opportunities. 2014. 
7. UNAIDS. Local Epidemics Issues Brief. 2014 2014. 
8. UNAIDS. Global AIDS Update. 2016. 
9. Cohen MS, Chen YQ, McCauley M, Gamble T, Hosseinipour MC, 
Kumarasamy N, et al. Prevention of HIV-1 infection with early antiretroviral 
therapy. N Engl J Med. 2011;365(6):493-505. 
10. Grant RM, Lama JR, Anderson PL, McMahan V, Liu AY, Vargas L, et al. 
Preexposure chemoprophylaxis for HIV prevention in men who have sex 
with men. N Engl J Med. 2010;363(27):2587-99. 
11. Grant RM, Smith DK. Integrating Antiretroviral Strategies for Human 
Immunodeficiency Virus Prevention: Post- and Pre-Exposure Prophylaxis 
and Early Treatment. Open Forum Infect Dis. 2015;2(4):ofv126. 
12. Fauci AS, Marston HD. Ending AIDS--is an HIV vaccine necessary? N Engl 
J Med. 2014;370(6):495-8. 
13. Gray GE, Laher F, Lazarus E, Ensoli B, Corey L. Approaches to preventative 
and therapeutic HIV vaccines. Curr Opin Virol. 2016;17:104-9. 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 104 of 142 
14. Hey A. History and Practice: Antibodies in Infectious Diseases. Microbiol 
Spectr. 2015;3(2):AID-0026-2014. 
15. Graham BS, Ambrosino DM. History of passive antibody administration for 
prevention and treatment of infectious diseases. Curr Opin HIV AIDS. 
2015;10(3):129-34. 
16. Winokur PL, Stapleton JT. Immunoglobulin prophylaxis for hepatitis A. Clin 
Infect Dis. 1992;14(2):580-6. 
17. Fiore AE, Wasley A, Bell BP. Prevention of hepatitis A through active or 
passive immunization: recommendations of the Advisory Committee on 
Immunization Practices (ACIP). MMWR Recomm Rep. 2006;55(RR-7):1-
23. 
18. Manning SE, Rupprecht CE, Fishbein D, Hanlon CA, Lumlertdacha B, 
Guerra M, et al. Human rabies prevention--United States, 2008: 
recommendations of the Advisory Committee on Immunization Practices. 
MMWR Recomm Rep. 2008;57(RR-3):1-28. 
19. McLean HQ, Fiebelkorn AP, Temte JL, Wallace GS, Centers for Disease C, 
Prevention. Prevention of measles, rubella, congenital rubella syndrome, and 
mumps, 2013: summary recommendations of the Advisory Committee on 
Immunization Practices (ACIP). MMWR Recomm Rep. 2013;62(RR-04):1-
34. 
20. Centers for Disease C, Prevention. Updated recommendations for use of 
VariZIG--United States, 2013. MMWR Morb Mortal Wkly Rep. 
2013;62(28):574-6. 
21. Simoes EA. Immunoprophylaxis of respiratory syncytial virus: global 
experience. Respir Res. 2002;3 Suppl 1:S26-33. 
22. Li Y, Migueles SA, Welcher B, Svehla K, Phogat A, Louder MK, et al. 
Broad HIV-1 neutralization mediated by CD4-binding site antibodies. Nat 
Med. 2007;13(9):1032-4. 
23. Simek MD, Rida W, Priddy FH, Pung P, Carrow E, Laufer DS, et al. Human 
immunodeficiency virus type 1 elite neutralizers: individuals with broad and 
potent neutralizing activity identified by using a high-throughput 
neutralization assay together with an analytical selection algorithm. J Virol. 
2009;83(14):7337-48. 
24. Wu X, Yang ZY, Li Y, Hogerkorp CM, Schief WR, Seaman MS, et al. 
Rational design of envelope identifies broadly neutralizing human 
monoclonal antibodies to HIV-1. Science. 2010;329(5993):856-61. 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 105 of 142 
25. Zhou T, Georgiev I, Wu X, Yang ZY, Dai K, Finzi A, et al. Structural basis 
for broad and potent neutralization of HIV-1 by antibody VRC01. Science. 
2010;329(5993):811-7. 
26. Gray ES, Taylor N, Wycuff D, Moore PL, Tomaras GD, Wibmer CK, et al. 
Antibody specificities associated with neutralization breadth in plasma from 
human immunodeficiency virus type 1 subtype C-infected blood donors. J 
Virol. 2009;83(17):8925-37. 
27. Gray ES, Madiga MC, Hermanus T, Moore PL, Wibmer CK, Tumba NL, et 
al. The neutralization breadth of HIV-1 develops incrementally over four 
years and is associated with CD4+ T cell decline and high viral load during 
acute infection. J Virol. 2011;85(10):4828-40. 
28. Corti D, Langedijk JP, Hinz A, Seaman MS, Vanzetta F, Fernandez-
Rodriguez BM, et al. Analysis of memory B cell responses and isolation of 
novel monoclonal antibodies with neutralizing breadth from HIV-1-infected 
individuals. PLoS ONE. 2010;5(1):e8805. 
29. Walker LM, Huber M, Doores KJ, Falkowska E, Pejchal R, Julien JP, et al. 
Broad neutralization coverage of HIV by multiple highly potent antibodies. 
Nature. 2011;477(7365):466-70. 
30. Scheid JF, Mouquet H, Ueberheide B, Diskin R, Klein F, Oliveira TY, et al. 
Sequence and structural convergence of broad and potent HIV antibodies that 
mimic CD4 binding. Science. 2011;333(6049):1633-7. 
31. Binley JM, Lybarger EA, Crooks ET, Seaman MS, Gray E, Davis KL, et al. 
Profiling the specificity of neutralizing antibodies in a large panel of plasmas 
from patients chronically infected with human immunodeficiency virus type 
1 subtypes B and C. J Virol. 2008;82(23):11651-68. 
32. Sather DN, Armann J, Ching LK, Mavrantoni A, Sellhorn G, Caldwell Z, et 
al. Factors associated with the development of cross-reactive neutralizing 
antibodies during human immunodeficiency virus type 1 infection. J Virol. 
2009;83(2):757-69. 
33. Falkowska E, Ramos A, Feng Y, Zhou T, Moquin S, Walker LM, et al. 
PGV04, an HIV-1 gp120 CD4 binding site antibody, is broad and potent in 
neutralization but does not induce conformational changes characteristic of 
CD4. J Virol. 2012;86(8):4394-403. 
34. Walker LM, Phogat SK, Chan-Hui PY, Wagner D, Phung P, Goss JL, et al. 
Broad and potent neutralizing antibodies from an African donor reveal a new 
HIV-1 vaccine target. Science. 2009;326(5950):285-9. 
35. Walker LM, Simek MD, Priddy F, Gach JS, Wagner D, Zwick MB, et al. A 
limited number of antibody specificities mediate broad and potent serum 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 106 of 142 
neutralization in selected HIV-1 infected individuals. PLoS Pathog. 
2010;6(8):e1001028. 
36. McLellan JS, Pancera M, Carrico C, Gorman J, Julien JP, Khayat R, et al. 
Structure of HIV-1 gp120 V1/V2 domain with broadly neutralizing antibody 
PG9. Nature. 2011;480(7377):336-43. 
37. Kong L, Lee JH, Doores KJ, Murin CD, Julien JP, McBride R, et al. 
Supersite of immune vulnerability on the glycosylated face of HIV-1 
envelope glycoprotein gp120. Nat Struct Mol Biol. 2013;20(7):796-803. 
38. Huang J, Ofek G, Laub L, Louder MK, Doria-Rose NA, Longo NS, et al. 
Broad and potent neutralization of HIV-1 by a gp41-specific human antibody. 
Nature. 2012;491(7424):406-12. 
39. Stamatatos L, Morris L, Burton DR, Mascola JR. Neutralizing antibodies 
generated during natural HIV-1 infection: good news for an HIV-1 vaccine? 
Nat Med. 2009;15(8):866-70. 
40. Walker LM, Burton DR. Rational antibody-based HIV-1 vaccine design: 
current approaches and future directions. Curr Opin Immunol. 
2010;22(3):358-66. 
41. Burton DR, Ahmed R, Barouch DH, Butera ST, Crotty S, Godzik A, et al. A 
Blueprint for HIV Vaccine Discovery. Cell Host Microbe. 2012;12(4):396-
407. 
42. Burton DR, Stanfield RL, Wilson IA. Antibody vs. HIV in a clash of 
evolutionary titans. Proc Natl Acad Sci U S A. 2005;102(42):14943-8. 
43. Kwong PD, Mascola JR. Human antibodies that neutralize HIV-1: 
identification, structures, and B cell ontogenies. Immunity. 2012;37(3):412-
25. 
44. Georgiev IS, Gordon JM, Zhou T, Kwong PD. Elicitation of HIV-1-
neutralizing antibodies against the CD4-binding site. Curr Opin HIV AIDS. 
2013;8(5):382-92. 
45. Pegu A, Hessell AJ, Mascola JR, Haigwood NL. Use of broadly neutralizing 
antibodies for HIV-1 prevention. Immunol Rev. 2017;275(1):296-312. 
46. Wu X, Wang C, O'Dell S, Li Y, Keele BF, Yang Z, et al. Selection pressure 
on HIV-1 envelope by broadly neutralizing antibodies to the conserved CD4-
binding site. J Virol. 2012;86(10):5844-56. 
47. Lynch RM, Boritz E, Coates EE, DeZure A, Madden P, Costner P, et al. 
Virologic effects of broadly neutralizing antibody VRC01 administration 
during chronic HIV-1 infection. Sci Transl Med. 2015;7(319):319ra206. 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 107 of 142 
48. Ledgerwood JE, Coates EE, Yamshchikov G, Saunders JG, Holman L, 
Enama ME, et al. Safety, pharmacokinetics and neutralization of the broadly 
neutralizing HIV-1 human monoclonal antibody VRC01 in healthy adults. 
Clin Exp Immunol. 2015;182(3):289-301. 
49. Huang Y, Zhang L, Ledgerwood J, Grunenberg N, Bailer R, Isaacs A, et al. 
Population pharmacokinetics analysis of VRC01, an HIV-1 broadly 
neutralizing monoclonal antibody, in healthy adults. MAbs. 2017:1-9. 
50. Bar KJ, Sneller MC, Harrison LJ, Justement JS, Overton ET, Petrone ME, et 
al. Effect of HIV Antibody VRC01 on Viral Rebound after Treatment 
Interruption. N Engl J Med. 2016;375(21):2037-50. 
51. Pyzik M, Rath T, Lencer WI, Baker K, Blumberg RS. FcRn: The Architect 
Behind the Immune and Nonimmune Functions of IgG and Albumin. J 
Immunol. 2015;194(10):4595-603. 
52. Roopenian DC, Akilesh S. FcRn: the neonatal Fc receptor comes of age. Nat 
Rev Immunol. 2007;7(9):715-25. 
53. Roopenian DC, Christianson GJ, Sproule TJ, Brown AC, Akilesh S, Jung N, 
et al. The MHC class I-like IgG receptor controls perinatal IgG transport, IgG 
homeostasis, and fate of IgG-Fc-coupled drugs. J Immunol. 
2003;170(7):3528-33. 
54. Akilesh S, Christianson GJ, Roopenian DC, Shaw AS. Neonatal FcR 
expression in bone marrow-derived cells functions to protect serum IgG from 
catabolism. J Immunol. 2007;179(7):4580-8. 
55. Gupta S, Gach JS, Becerra JC, Phan TB, Pudney J, Moldoveanu Z, et al. The 
Neonatal Fc receptor (FcRn) enhances human immunodeficiency virus type 1 
(HIV-1) transcytosis across epithelial cells. PLoS Pathog. 
2013;9(11):e1003776. 
56. Gupta S, Pegu P, Venzon DJ, Gach JS, Ma ZM, Landucci G, et al. Enhanced 
in vitro transcytosis of simian immunodeficiency virus mediated by vaccine-
induced antibody predicts transmitted/founder strain number after rectal 
challenge. J Infect Dis. 2015;211(1):45-52. 
57. Yoshida M, Kobayashi K, Kuo TT, Bry L, Glickman JN, Claypool SM, et al. 
Neonatal Fc receptor for IgG regulates mucosal immune responses to luminal 
bacteria. J Clin Invest. 2006;116(8):2142-51. 
58. Tzaban S, Massol RH, Yen E, Hamman W, Frank SR, Lapierre LA, et al. The 
recycling and transcytotic pathways for IgG transport by FcRn are distinct 
and display an inherent polarity. J Cell Biol. 2009;185(4):673-84. 
59. Li Z, Palaniyandi S, Zeng R, Tuo W, Roopenian DC, Zhu X. Transfer of IgG 
in the female genital tract by MHC class I-related neonatal Fc receptor 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 108 of 142 
(FcRn) confers protective immunity to vaginal infection. Proc Natl Acad Sci 
U S A. 2011;108(11):4388-93. 
60. Armitage CW, O'Meara CP, Harvie MC, Timms P, Blumberg RS, Beagley 
KW. Divergent outcomes following transcytosis of IgG targeting intracellular 
and extracellular chlamydial antigens. Immunol Cell Biol. 2014;92(5):417-
26. 
61. Ko SY, Pegu A, Rudicell RS, Yang ZY, Joyce MG, Chen X, et al. Enhanced 
neonatal Fc receptor function improves protection against primate SHIV 
infection. Nature. 2014;514(7524):642-5. 
62. Rudicell RS, Kwon YD, Ko SY, Pegu A, Louder MK, Georgiev IS, 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):12669-82. 
63. Zalevsky J, Chamberlain AK, Horton HM, Karki S, Leung IW, Sproule TJ, et 
al. Enhanced antibody half-life improves in vivo activity. Nat Biotechnol. 
2010;28(2):157-9. 
64. Lowy I, Molrine DC, Leav BA, Blair BM, Baxter R, Gerding DN, et al. 
Treatment with monoclonal antibodies against Clostridium difficile toxins. N 
Engl J Med. 2010;362(3):197-205. 
65. Chung RT, Gordon FD, Curry MP, Schiano TD, Emre S, Corey K, et al. 
Human monoclonal antibody MBL-HCV1 delays HCV viral rebound 
following liver transplantation: a randomized controlled study. Am J 
Transplant. 2013;13(4):1047-54. 
66. Huang Y, Karuna ST, Janes H, Frahm N, Nason M, Edlefsen PT, et al. Use of 
placebos in Phase 1 preventive HIV vaccine clinical trials. Vaccine. 
2015;33(6):749-52. 
67. LaCasce AC, MC; Burstein,H; Meyerhardt,JA. Infusion-related reactions to 
therapeutic monoclonal antibodies used for cancer therapy 2017 [Available 
from: https://www.uptodate.com/contents/infusion-related-reactions-to-
therapeutic-monoclonal-antibodies-used-for-cancer-
therapy?source=search_result&search=infusion%20reaction&selectedTitle=2
~150#H10. 
68. Hansel TT, Kropshofer H, Singer T, Mitchell JA, George AJ. The safety and 
side effects of monoclonal antibodies. Nat Rev Drug Discov. 2010;9(4):325-
38. 
69. Bugelski PJ, Achuthanandam R, Capocasale RJ, Treacy G, Bouman-Thio E. 
Monoclonal antibody-induced cytokine-release syndrome. Expert Rev Clin 
Immunol. 2009;5(5):499-521. 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 109 of 142 
70. Vogel WH. Infusion reactions: diagnosis, assessment, and management. Clin 
J Oncol Nurs. 2010;14(2):E10-E21. 
71. Haddad E, Barnes D, Kafal A. Home therapy with subcutaneous 
immunoglobulins for patients with primary immunodeficiency diseases. 
Transfus Apher Sci. 2012;46(3):315-21. 
72. Resch B. Product review on the monoclonal antibody palivizumab for 
prevention of respiratory syncytial virus infection. Hum Vaccin Immunother. 
2017:0. 
73. Frogel MP, Stewart DL, Hoopes M, Fernandes AW, Mahadevia PJ. A 
systematic review of compliance with palivizumab administration for RSV 
immunoprophylaxis. J Manag Care Pharm. 2010;16(1):46-58. 
74. Agresti A, Coull BA. Approximate is better than "exact" for interval 
estimation of binomial proportions. Am Stat. 1998;52(2):119-26. 
75. Hughes JP. Mixed effects models with censored data with application to HIV 
RNA levels. Biometrics. 1999;55(2):625-9. 
76. Rotnitzky A, Robins J. Analysis of semi-parametric regression models with 
non-ignorable non-response. Stat Med. 1997;16(1-3):81-102. 
77. Montefiori DC. Measuring HIV neutralization in a luciferase reporter gene 
assay. Methods Mol Biol. 2009;485:395-405. 
78. Ozaki DA, Gao H, Todd CA, Greene KM, Montefiori DC, Sarzotti-Kelsoe 
M. International technology transfer of a GCLP-compliant HIV-1 
neutralizing antibody assay for human clinical trials. PLoS ONE. 
2012;7(1):e30963. 
79. Seaman M, Janes H, Hawkins N, randpre L, Devoy C, Giri A, et al. Tiered 
Categorization of a Diverse Panel of HIV-1 Env Pseudoviruses for 
Assessment of Neutralizing Antibodies. J Virol. 2010;84(3):1439-52. 
80. DeCamp A, Hraber P, Bailer RT, Seaman MS, Ochsenbauer C, Kappes J, et 
al. Global panel of HIV-1 Env reference strains for standardized assessments 
of vaccine-elicited neutralizing antibodies. J Virol. 2014;88(5):2489-507. 
 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 110 of 142 
Appendix A 
Sample informed consent form 
Title: A multicenter, randomized, partially blinded phase 1 clinical trial to 
evaluate the safety and serum concentrations of a human monoclonal antibody, 
VRC-HIVMAB075-00-AB (VRC07-523LS), administered in multiple doses and 
routes to healthy, HIV-uninfected adults 
Protocol number: HVTN 127/HPTN 087 
Site: [Insert site name] 
Thank you for your interest in our research study. Please read this consent form or 
ask someone to read it to you. If you decide to join the study, we will ask you to 
sign or make your mark on this form. We will offer you a copy to keep. We will 
ask you questions to see if we have explained everything clearly. You can also 
ask us questions about the study.  
Research is not the same as treatment or medical care. The purpose of a research 
study is to answer scientific questions. 
About the study 
The HIV Vaccine Trials Network (HVTN), the HIV Prevention Trials Network 
(HPTN) and [Insert site name]  are doing a study to test the antibody against HIV 
called VRC07-523LS. HIV is the virus that causes AIDS. Antibodies are one of 
the ways the human body fights infection. Antibodies are natural proteins that the 
body can make to prevent infectious agents such as bacteria and viruses from 
making you sick. Researchers can also make antibodies in laboratories and give 
them to people intravenously (with an IV) or by injection. We will tell you more 
about these procedures below. Antibodies have been used successfully to prevent 
or treat some other health problems, such as a virus that causes respiratory 
infections in infants. 
About 124 people will take part in this study at multiple sites. The researcher in 
charge of this study at this clinic is [Insert name of site PI]. The US National 
Institutes of Health (NIH) is paying for the study.  
1. We are doing this study to answer several questions. 
 Is the VRC07-523LS antibody safe to give to people? 
 Are people able to take the antibody without becoming too uncomfortable? 
 How much of the antibody remains in the body as time passes? 
 How does the body’s response to the antibody change depending on the dose 
given?  
 Does the method of giving the antibody change the body’s response? 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 111 of 142 
2. The antibody cannot give you HIV. 
The study antibody is not made from actual HIV. It is impossible for the antibody 
to give you HIV. Also, it cannot cause you to give HIV to someone else. We do 
not know if the antibody will decrease, increase, or not change your chance of 
becoming infected with HIV if you are exposed to the virus. 
3. The study antibody is experimental. 
The formal name of the study antibody is VRC-HIVMAB075-00-AB. From here 
on, we will call it VRC07-523LS or the study antibody.  
VRC07-523LS is an experimental product. That means we do not know if it will 
be safe to use in people, or if it will work to prevent HIV infection. VRC07-
523LS is only used in research studies. 
VRC07-523LS was developed by Vaccine Research Center at the US National 
Institutes of Health (NIH).  
In laboratory and animal studies, the study antibody attached to and prevented 
infection by many kinds of HIV viruses from around the world. We do not know 
if it will act the same way when given to people. It will take many studies to learn 
if it will be useful for prevention of HIV or treatment of HIV. This study will not 
answer these questions. 
Risks of the VRC07-523LS antibody: 
This section lists the side effects we know about. There may be others that we 
don’t yet know about, even serious ones. We will tell you if we learn about any 
new side effects. 
The VRC07-523LS antibody has been tested for safety in animals. In animal 
studies, no safety problems were seen at doses 20 times higher than those used in 
this study. 
As of early August 2017, VRC07-523LS has been given by subcutaneous 
injection (given under the skin) or by intravenous infusion (IV) to 25 people in an 
ongoing clinical trial at the NIH Clinical Center. So far, the study antibody has 
not made people too uncomfortable or caused serious health problems. This is the 
first clinical trial that will test giving the antibody to people by intramuscular 
injection (given in the muscle). We will describe these procedures in Section 10 
of this form. 
As of July 2017, similar antibodies called VRC01 and VRC01LS have been given 
to people in 14 clinical studies in the United States, Peru, Brazil, Switzerland, 
Thailand, and in Sub-Saharan Africa. In these studies, more than 2400 adults and 
33 infants have gotten these study products. 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 112 of 142 
Many of these studies are still going on and we don’t know which people got the 
study antibody and which people got a placebo (a liquid with no antibody in it). 
After receiving the antibody or a placebo, many people said that they had mild 
pain, itching, or redness where the antibody or placebo was given to them. Of 
these people, some said they felt like they had the flu after getting the antibody, 
but that this feeling lasted a few hours at most. 
In a previous study, one person who got a study antibody by injection had a rash. 
One person had a brief fainting spell several hours after getting a study antibody 
by IV infusion. To be safe, no more injections or infusions were given to these 
people. Some participants had mild body discomfort, muscle pain, or joint pain 
after getting the study antibody.  
The study antibody has not been given to people by intramuscular injection 
before. It has been tested in rats at the same dose as in this study. No safety 
problems were seen in rats. Even if something looks like it is safe in animals, this 
may not be true for people. 
General risks of antibodies: 
Antibodies that are different from VRC07-523LS have been given to people for 
other illnesses. With those antibodies most side effects happen within the first 24 
hours. Those antibodies have caused fever, stuffy nose, redness in the face, 
feeling weak or having low energy, chills, shaking, nausea, vomiting, pain, 
headache, dizziness, trouble breathing, high or low blood pressure, itchiness, rash, 
hives, lip, tongue, throat or face swelling, diarrhea, racing heartbeat, or chest pain.  
Rarely, some antibodies have caused serious reactions that may be life-
threatening. Two such serious reactions are: 
 Anaphylaxis – a physical reaction that includes difficulty breathing, possibly 
leading to low blood oxygen, low blood pressure, hives or rash, and swelling 
in the mouth and face. This may occur soon after getting an antibody 
 Serum Sickness – a physical reaction that includes developing hives or a rash, 
fever, big lymph nodes, muscle and joint pains, chest discomfort and shortness 
of breath. This may occur several days to 3 weeks after getting an antibody 
Please tell us if you have ever experienced reactions similar to anaphylaxis or 
serum sickness, and the cause of the reactions if you remember. 
Rarely, antibodies licensed for treatment of other diseases have been linked to a 
blood disorder that interferes with blood clotting, to cancer, to damage to the heart 
muscle, and to the body’s immune system attacking healthy cells.  
These rare side effects and reactions have not been seen in other studies with 
VRC07-523LS or similar experimental antibodies.  

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 113 of 142 
Antibodies given to a person usually do not last in the body more than a few 
months. One of the goals of this study is to see how long VRC07-523LS will stay 
in the body. We don’t know yet how long it will last, but it may be several 
months.  
Joining the study 
4. It is completely up to you whether or not to join the study.  
Take your time in deciding. If it helps, talk to people you trust, such as your 
doctor, friends or family. If you decide not to join this study, or if you leave it 
after you have joined, your other care at this clinic and the benefits or rights you 
would normally have will not be affected. 
If you join this study, you may not be allowed to join some other kinds of HIV 
prevention studies now or in the future. You cannot be in this study while you are 
in another study where you get a study product. Also during the study, you should 
not donate blood or tissue. 
If you choose not to join this study, you may be able to join another study. 
Site: Remove item 5 if you use a separate screening consent that covers these 
procedures. 
5. If you want to join the study, we will screen you to see if you are eligible. 
Screening involves a physical exam, HIV test and health history. A physical exam 
may include, but is not limited to: 
 Checking your weight, temperature and blood pressure 
 Looking in your mouth and throat 
 Listening to your heart and lungs 
 Feeling your abdomen (stomach and liver) 
 Checking your veins to see how easy it might be to start an IV 
We will also do blood and urine tests. These tests tell us about some aspects of 
your health, such as how healthy your kidneys, liver, and immune system are. We 
will also test you for syphilis, hepatitis B, and hepatitis C. We will ask you about 
medications you are taking. We will ask you about behaviors that might put you 
at risk for getting HIV.  
If you are able to become pregnant, we will test you for pregnancy. If you have 
had your uterus or ovaries removed (a hysterectomy or oophorectomy), verified 
by medical records, you are not required to have a pregnancy test. 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 114 of 142 
We will review the screening results with you. The screening results may show 
you are not eligible to join the study, even if you want to.  
Site: adapt the following section so it is applicable to the care available at your site 
6. If we find that you have a health problem during screening or during the 
study, we will tell you about the care that we can give here for free. 
For the care that we cannot give, we will explain how we will help you get care 
elsewhere. For health problems that are unrelated to the study, we will not pay for 
care. 
7. If you are able to become pregnant, you must agree to use birth control to 
join this study. 
Site: If you want to include Appendix B, Approved birth control methods (for sample 
informed consent form), in this consent form, paste it below and delete paragraph 
below. 
You should not become pregnant during the study because we do not know how 
the study antibody could affect the developing baby. You must agree to use 
effective birth control from 21 days before your first injection or IV infusion 
through your last scheduled clinic visit. We will talk to you about effective birth 
control methods. They are listed on a handout that we will give to you.  
Being in the study 
If you meet the study requirements and want to join, here is what will happen: 
Site: Modify the number of visits and range of visit lengths to be site-specific. This is 
to account for variation in screening protocols and in the number of possible follow-
up visits between protocol-mandated visits. 
8. You will come to the clinic for 19 scheduled visits for a little over 2 years.  
Most of the visits will be about 8 weeks apart. We will also ask you to come to 
the clinic about 3 days after the first injection or infusion and then again about 6 
days after to draw your blood. We will do this so that we can look at how your 
body responds to the study product. 
Visits can last from [#] to [#] hours. 
You may have to come for more visits if you have a lab or health issue. 
We may contact you after the main study ends (for example, to tell you about the 
study results). 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 115 of 142 
9. We will give you [Site: Insert compensation] for each study visit you 
complete. 
This amount is to cover the costs of [Site: Insert text] 
Site: Insert any costs to participants (eg, birth control costs for female participants 
who could become pregnant). 
US sites: Include the following paragraph: 
Payments you receive for being in the study may be taxable. We may need to ask 
you for your Social Security number for tax reasons. 
You do not have to pay anything to be in this study. 
10. We will give you the study products by IV or injection.  
There are 6 groups in this study. People in the different groups will get the study 
products either by IV or by injection. The amount of antibody is different in the 
different groups. In one group, some people will get a placebo. 
When getting an IV, a sterile needle is used to place a small plastic tube into a 
vein in your arm. The tube is connected to a small bag of fluid that contains the 
antibody. An IV pump controls how fast the fluid drips from the bag, through the 
tube, and into your vein. The first IV will take about one hour. Other IVs will 
probably take about 15 to 30 minutes each, but could take up to an hour. 
When getting a subcutaneous (SC) injection, a sterile needle is put under the skin 
on your arm, abdomen, or thigh. For an intramuscular (IM) injection, a sterile 
needle is put directly into either your gluteus (buttock) or deltoid (upper arm) 
muscle. You will get up to 4 injections at each injection visit. You can ask the 
study staff more about this. 
Which group you are in and whether you get the study antibody by IV or SC or 
IM injection is completely random, like flipping a coin. Whether you get the 
study antibody or the placebo is also random. We have no say in which group you 
are assigned to.  
If you get IM injections, you will have to wait until everyone completes their final 
study visits to find out whether you got the antibody or the placebo. This could be 
several years. If you have a serious medical problem and need to know what you 
got before the end of the study, we can tell you. 
11. We will give the IVs and injections to all participants on the same schedule. 
You will get an IV or injections five times, about once every 4 months. 
 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 116 of 142 
IV and Injection Schedule 
Groups 
First IV or 
injection 
4 months 
later 
8 months 
later 
12 months 
later 
16 months 
later 
1 - 6 
X 
X 
X 
X 
X 
You will have to wait in the clinic for about an hour after the first IV or injection 
and for about half an hour after the other IVs or injections to see if there are any 
problems. Then for that night and for 3 more days, you will need to keep track of 
how you are feeling and if you have any symptoms. We will ask you the ways we 
can contact you. We will contact you about 3 days after each IV or injection to 
ask how you have been feeling. Contact the clinic staff if you have any issues or 
concerns after getting an IV or an injection. If you have a problem, we will 
continue to check on you until it goes away. 
12. In addition to giving you the study antibody or a placebo, we will: 
 Do regular HIV testing, as well as counseling on your results and on how to 
avoid getting HIV 
 Do physical exams 
 Do pregnancy tests if you are able to become pregnant 
 Ask questions about your health, including medications you may be taking 
 Ask questions about any personal problems or benefits you may have from 
being in the study 
 Take urine and blood samples. 
When we take blood, the amount will depend on the lab tests we need to do. It 
will be some amount between 34 mL and 160 mL (a little more than 2 tablespoon 
to 2/3 cup). Your body will make new blood to replace the blood we take out.  
Site: You may want to add a sentence to the end of the previous paragraph 
contextualizing the blood volumes described (eg, “To compare, people who donate 
blood in the US can give a total of about 500 mL in an 8-week period.”). Modify the 
example for cultural relevance and alter blood volumes as necessary. 
Site: Insert Appendix D, Table of procedures (for informed consent form) in this 
section or distribute it as a separate sheet if it is helpful to your study participants. 
You are not required to do either. 
We will be looking for side effects. We will review the results of these procedures 
and tests with you at your next visit, or sooner if necessary. If any of the results 
are important to your health, we will tell you.  

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 117 of 142 
13. We will counsel you on avoiding HIV infection. 
We will ask you personal questions about your HIV risk factors such as sexual 
behavior, alcohol, and drug use. We will talk with you about ways to keep your 
risk of getting HIV low.  
14. We will test your samples in this study. 
We will send your samples (without your name) to labs approved by the HVTN 
and HPTN for this study, which are located in the United States and South Africa. 
In rare cases, some of your samples may be sent to labs approved by the HVTN in 
other countries for research related to this study. 
The samples will be tested to: 
 Measure how much antibody is in your blood, and 
 See how your immune system responds to the study antibody. 
Researchers may also do genetic testing related to this study on your samples. 
Your genes are passed to you from your birth parents. They affect how you look 
and how your body works. The differences in people’s genes can help explain 
why some people get a disease while others do not. The genetic testing will only 
involve some of your genes, not all of your genes (your genome). The researchers 
will study only the genes related to the immune system and HIV and those that 
affect how people get HIV. 
If you become HIV infected, the researchers may look at all of the genes of the 
virus found in your samples. The researchers will use this information to learn 
more about HIV and the study product(s).  
In some cases, researchers may take cells from your samples and grow more of 
them over time, so that they can continue to contribute to this study.  
These tests done on your samples are for research purposes, not to check your 
health. The labs will not give the results to you or this clinic because their tests 
are not approved for use in making health care decisions. These labs are only 
approved to do research tests.  
When your samples are no longer needed for this study, the HVTN will continue 
to store them. 
Site: Delete next section if using separate consent for use of samples and information 
in other studies 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 118 of 142 
15. When samples are no longer needed for this study, the study sponsors want 
to keep them for use in other studies by HVTN, HPTN, or other researchers.  
This section gives you information so you can decide if you want your extra 
samples and information used in other studies. You will mark your decision at the 
end of the form. If you have any questions, please ask. 
Do I have to agree? No. You are free to say yes or no, or to change your mind 
after you sign this form. At your request, we will destroy all extra samples that we 
have. Your decision will not affect your being in this study or have any negative 
consequences here.  
Where are the samples stored? Extra samples are stored in a secure central place 
called a repository. Your samples will be stored in the HVTN repository in the 
United States. 
How long will the samples be stored? There is no limit on how long your extra 
samples will be stored. [Site: Revise the previous sentence to insert limits if your 
regulatory authority imposes them.] 
Will I be paid for the use of my samples? No. Also, a researcher may make a new 
scientific discovery or product based on the use of your samples. If this happens, 
there is no plan to share any money with you. The researcher is not likely to ever 
know who you are. 
Will I benefit from allowing my samples to be used in other studies? Probably not. 
Results from these other studies are not given to you, this clinic, or your doctor. 
They are not part of your medical record. The studies are only being done for 
research purposes. 
Will the HVTN or HPTN sell my samples and information? No, but the HVTN 
and HPTN may share your samples with other researchers. Once we share your 
samples and information, we may not be able to get them back. 
How do other researchers get my samples and information? When a researcher 
wants to use your samples and information, their research plan must be approved 
by the HVTN and HPTN. Also, the researcher’s institutional review board (IRB) 
or ethics committee (EC) will review their plan. [Site: If review by your 
institution’s IRB/EC/RE is also required, insert a sentence stating this.] IRBs/ECs 
protect the rights and well-being of people in research. If the research plan is 
approved, the HVTN will send your samples to the researcher’s location.  
What information is shared with other researchers? The samples and information 
will be labeled with a code number. Your name will not be part of the 
information. However, some information that we share may be personal, such as 
your race, ethnicity, sex, health information from the study, and HIV status. We 
may share information about the study product you received and how your body 
responded to the study product.  

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 119 of 142 
What kind of studies might be done with my extra samples and information? The 
studies will be related to HIV prevention or infection, the immune system and 
other diseases.  
Researchers may also do genetic testing on your samples.  
In some cases, researchers may take cells from your samples and grow more of 
them over time, so that they can continue to do research with them.  
If you agree, your samples could also be used for genome wide studies. In these 
studies, researchers will look at all of your genes (your genome). The researchers 
compare the genomes of many people, looking for common patterns of genes that 
could help them understand diseases. The researchers may put the information 
from the genome-wide studies into a protected database so that other researchers 
can access it, but your name and other personal information will not be included. 
Usually, no one would be able to look at your genome and link it to you as a 
person. However, if another database exists that also has information on your 
genome and your name, someone might be able to compare the databases and 
identify you. If others found out, it could lead to discrimination or other problems. 
The risk of this is very small. There may be other unknown risks. 
Who will have access to my information in studies using my extra samples?  
People who may see your information are: 
 Researchers who use your extra samples and information for other research 
 Government agencies that fund or monitor the research using your extra 
samples and information 
 Any regulatory agency that reviews clinical trials, 
 The researcher’s Institutional Review Board or Ethics Committee 
 The people who work with the researcher  
All of these people will do their best to protect your information. The results of 
any new studies that use your extra samples and information may be published. 
No publication will use your name or identify you personally. 
16. We will do our best to protect your private information. 
US sites: Check HIPAA authorization for conflicts with this section. 
Your study records and samples will be kept in a secure location. We will label all 
of your samples and most of your records with a code number, not your name or 
other personal information. However, it is possible to identify you, if necessary. 
We will not share your name with the lab that does the tests on your samples, or 
with anyone else who does not need to know your name. 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 120 of 142 
Clinic staff will have access to your study records. Your records may also be 
reviewed by groups who watch over this study to see that we are protecting your 
rights, keeping you safe, and following the study plan. These groups include: 
 The US National Institutes of Health and its study monitors, 
 The US Food and Drug Administration, 
 Any regulatory agency that reviews clinical trials, 
 [Insert name of local IRB/EC] , 
 [Insert name of local and/or national regulatory authority as appropriate], 
 The NIH Vaccine Research Center and people who work for them, 
 The HVTN, HPTN, and people who work for them,  
 The HVTN Safety Monitoring Board, and 
 The US Office for Human Research Protections. 
All reviewers will take steps to keep your records private. 
We cannot guarantee absolute privacy. At this clinic, we have to report the 
following information:  
Site: Include any public health or legal reporting requirements. Bulleted examples 
should include all appropriate cases (reportable communicable disease, risk of harm 
to self or others, etc.). 
 [Item 1] 
 [Item 2] 
 [Item 3] 
US sites: Include the following boxed text. You can remove the box. 
We have a Certificate of Confidentiality from the US government, to help protect 
your privacy. With the certificate, we do not have to release information about 
you to someone who is not connected to the study, such as the courts or police. 
Sometimes we can’t use the certificate. Since the US government funds this 
research, we cannot withhold information from it. Also, you can still release 
information about yourself and your study participation to others. 
The results of this study may be published. No publication will use your name or 
identify you personally. 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 121 of 142 
We may share information from the study with other researchers. We will not 
share your name or information that can identify you. 
A description of this clinical trial will be available on 
http://www.ClinicalTrials.gov. This website will not include information that can 
identify you. At most, the website will include a summary of the results. You can 
search this website at any time. 
17. We may stop your IVs or injections or take you out of the study at any time. 
We may do this even if you want to stay in the study and even if you were 
scheduled for more injections.  
This may happen if: 
 you do not follow instructions, 
 we think that staying in the study might harm you, 
 you get HIV, 
 you enroll in a different research study where you get another study product, 
or 
 the study is stopped for any reason. 
If we stop your injections, we may ask you to stay in the study to complete other 
study procedures. 
18. We will stop your IV infusions or injections if you become pregnant.  
We will encourage you to stay in the study if you choose. We will discuss your 
study options with you. 
If you leave the study while you are still pregnant, we will contact you after your 
due date to ask some questions about your pregnancy and delivery. 
19. If you get infected with HIV during the study, we will help you get care and 
support. 
You will not be able to stay in this study. We will counsel you about your HIV 
infection and about telling your partner(s). We will tell you where you can get 
support and medical care. Site: Modify the following sentence as appropriate. We 
will not provide or pay for any of your HIV care directly.  

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 122 of 142 
Other Risks 
20. There are other risks to being in this study. 
This section describes the other risks and restrictions we know about. There may 
also be unknown risks, even serious ones. We will tell you if we learn anything 
new that may affect your willingness to stay in the study. 
Risks of giving blood and receiving injections:  
In this study, we will do some routine medical procedures. These include taking 
blood from you and giving you injections. These procedures can cause bruising, 
pain, fainting, soreness, redness, swelling, itching, a sore, bleeding, and (rarely) 
muscle damage or infection where you got the injection. Giving blood can cause a 
low blood cell count (anemia), making you feel tired. 
Risks of IV infusion procedures: 
Getting an IV may cause stinging, discomfort, pain, soreness, redness, bruising, 
itching, rash and swelling where the needle goes into the skin. Rarely, needle 
sticks can result in a blood clot or infection. 
Personal problems/discrimination/testing HIV antibody positive: 
Some people who join HVTN and HPTN studies report personal problems or 
discrimination because of joining an HIV prevention study. Family or friends may 
worry, get upset or angry, or assume that you are infected with HIV or at high risk 
and treat you unfairly as a result. Rarely, a person has lost a job because the study 
took too much time away from work, or because their employer thought they had 
HIV.  
HIV testing 
HIV antibody tests are the usual way to test for HIV infections. We do not expect 
you to test positive on HIV antibody tests. We have used several common HIV 
antibody tests to test samples of blood containing very similar antibodies and 
none of them detected the antibody.  
To be absolutely safe we ask you to get HIV tests only at this clinic during the 
study. Our tests can always detect true HIV infection. They can also tell if 
someone is really not HIV infected. Since the antibodies do not last long in the 
body, we do not expect you to have any problems with HIV testing after the study 
ends. 
Although it has not been seen so far, getting VRC07-523LS may cause common 
HIV antibody tests to show that someone is HIV-negative, even if they are 
actually infected. 
Embarrassment/anxiety:  

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 123 of 142 
You may feel embarrassed when we ask about your HIV risks, such as having sex 
and using drugs. Also, waiting for your HIV test results or other health test results 
could make you feel anxious. You could feel worried if your test results show that 
you are infected with HIV. If you feel embarrassed or anxious, please tell us and 
we will try to help you. 
Risks of disclosure of your personal information: 
We will take several steps to protect your personal information. Although the risk 
is very low, it is possible that your personal information could be given to 
someone who should not have it. If that happened, you could face discrimination, 
stress, and embarrassment. We can tell you more about how we will protect your 
personal information if you would like it.  
Risks of genetic testing: 
It is unlikely, but the genetic tests done on your samples could show you may be 
at risk for certain diseases. If others found out, it could lead to discrimination or 
other problems. However, it is almost impossible for you or others to know your 
test results from the genetic testing. The results are not part of your study records 
and are not given to you.  
U.S. Sites, include the following paragraph In the very unlikely event that your 
genetic information becomes linked to your name, a federal law called the 
Genetic Information Nondiscrimination Act (GINA) helps protect you. GINA 
keeps health insurance companies and employers from seeing results of genetic 
testing when deciding about giving you health insurance or offering you work. 
GINA does not help or protect you against discrimination by companies that sell 
life, disability or long-term care insurance. 
Unknown risks:  
We do not know if the study antibody will increase, decrease, or not change your 
risk of becoming infected with HIV if exposed. If you get infected with HIV, we 
do not know how the study antibody might affect your HIV infection or how long 
it takes to develop AIDS. 
We do not know how the study antibody will affect a pregnant participant or a 
developing baby.  
Benefits 
21. The study may not benefit you. 
We do not expect getting the study antibody to benefit you in any way. However, 
being in the study might still help you in some ways. The counseling that you get 
as part of the study may help you avoid getting HIV. The lab tests and physical 
exams that you get while in this study might detect health problems you don’t yet 
know about.  

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 124 of 142 
This study may help in the search for a drug or a vaccine to prevent HIV. 
However, if the study antibody or a vaccine later gets approved and sold, there are 
no plans to share any money with you.  
Your rights and responsibilities 
22. If you join the study, you have rights and responsibilities. 
You have many rights that we will respect. You also have responsibilities. We list 
these in the Participant’s Bill of Rights and Responsibilities. We will give you a 
copy of it. 
Leaving the study 
23. Tell us if you decide to leave the study.  
You are free to leave the study at any time and for any reason. Your care at this 
clinic and your legal rights will not be affected, but it is important for you to let us 
know.  
We will ask you to come back to the clinic one last time for a physical exam, and 
we may ask to take some blood and urine samples. We will also ask about any 
personal problems or benefits you have experienced from being in the study. We 
believe these steps are important to protecting your health, but it is up to you 
whether to complete them. 
Injuries 
Sites: Approval from HVTN Regulatory Affairs (at vtn.core.reg@hvtn.org) is needed 
for any change (other than those that the instructions specifically request or those 
previously approved by HVTN Regulatory Affairs) to the boxed text 
24. If you get sick or injured during the study, contact us immediately. 
Your health is important to us. (Sites: adjust the following 2 sentences if 
applicable to the care available at your site) We will tell you about the care that 
we can give here. For the care that we cannot provide, we will explain how we 
will help you get care elsewhere. 
If you become sick or injured in this study, there is a process to decide if it is 
related to the study antibody and/or procedures. If it is, we call it a study-related 
injury. There are funds to pay for treatment of study-related injuries if certain 
conditions are met.  
The HVTN and HPTN have limited funds to pay medical costs for study-related 
injuries that it determines are reasonable. (Sites: insert locale- appropriate 
medical insurance language in the following sentence) If the injury is not study 
related, then you and your health insurance will be responsible for treatment costs. 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 125 of 142 
Some injuries are not physical. For example, you might be harmed emotionally by 
being in an HIV prevention study. Or you might lose wages because you cannot 
go to work. However, there are no funds to pay for these kinds of injuries, even if 
they are study related. 
You may disagree with the decision about whether your injury is study related. If 
you wish, independent experts will be asked to review the decision. You always 
have the right to use the court system if you are not satisfied. 
Questions  
25. If you have questions or problems at any time during your participation in 
this study, use the following important contacts. 
If you have questions about this study, contact 
[name or title and telephone number of the investigator or other study staff]. 
If you have any symptoms that you think may be related to this study, contact 
[name or title and telephone number of the investigator or other study staff]. 
This study has been reviewed and approved by a committee called the 
[name of local IRB/EC]. If you have questions about your rights as a research 
participant, or problems or concerns about how you are being treated in this study, 
contact [name or title and telephone number of person on IRB/EC] , at the 
committee. 
Your permissions and signature  
Site: Delete the following section if using a separate consent for use of samples and 
information in other studies 
26. In Section 15 of this form, we told you about possible other uses of your extra 
samples and information, outside this study. Please choose only one of the 
options below and write your initials or make your mark in the box next to it. 
Whatever you choose, the HVTN and HPTN keep track of your decision 
about how your samples and information can be used. You can change your 
mind after signing this form. 
 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 126 of 142 
 
I allow my extra samples and information to be used for other studies related 
to HIV prevention, the immune system, and other diseases. This may include 
genetic testing and keeping my cells growing over time.  
OR 
 
 
I agree to the option above and also to allow my extra samples and 
information to be used in genome wide studies. 
 
OR 
 
 
I do not allow my extra samples to be used in any other studies. This includes 
not allowing genetic testing, growing more of my cells, or genome wide 
studies.  
27. If you agree to join this study, you will need to sign or make your mark 
below. Before you sign or make your mark on this consent form, make sure 
of the following: 
 You have read this consent form, or someone has read it to you. 
 You feel that you understand what the study is about and what will happen to 
you if you join. You understand what the possible risks and benefits are. 
 You have had your questions answered and know that you can ask more. 
 You agree to join this study. 
You will not be giving up any of your rights by signing this consent form. 
 
 
 
 
 
 
 
Participant’s name (print) 
 
Participant’s signature or mark 
 
Date 
 
Time 
 
 
 
 
 
 
 
Clinic staff conducting consent 
discussion (print) 
 
Clinic staff signature 
 
Date 
 
Time 
For participants who are unable to read or write, a witness should complete the 
signature block below: 
 
 
 
 
 
 
 
Witness’s name (print) 
 
Witness’s signature  
 
Date 
 
Time 
*Witness is impartial and was present for the entire discussion of this consent form. 
 
 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 127 of 142 
Appendix B 
Approved birth control methods (for sample 
informed consent form) 
Site: Any change to the following boxed text requires approval from HVTN 
Regulatory Affairs at vtn.core.reg@hvtn.org. 
You should not become pregnant during the study because we do not know how 
the study antibody could affect the developing baby. 
You must agree to use effective birth control from 21 days before your first IV 
infusion or injection until after your last scheduled clinic visit.  
Effective birth control means using any of the following methods every time you 
have sex: 
 Birth control drugs that prevent pregnancy—given by pills, shots, patches, 
vaginal rings, or inserts under the skin; 
 Male or female condoms, with or without a cream or gel that kills sperm; 
 Diaphragm or cervical cap with a cream or gel that kills sperm; 
 Intrauterine device (IUD); or 
 Any other contraceptive method approved by the researchers. 
You do not have to use birth control if: 
 You are only having sex with a partner or partners who have had a vasectomy. 
(We will ask you some questions to confirm that the vasectomy was 
successful.); 
 You have reached menopause, with no menstrual periods for one year; 
 You have had a hysterectomy (your uterus removed); 
 You have had your ovaries removed; 
 You have a tubal ligation (your “tubes tied”) or confirmed successful 
placement of a product that blocks the fallopian tubes; 
 You are having sex only with a partner or partners assigned female sex at 
birth; 
 You only have oral sex; or, 
 You are sexually abstinent (no sex at all). 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 128 of 142 
Remember: If you are having sex, male and female condoms are the only birth 
control methods that also provide protection against HIV and other sexually 
transmitted infections. 
If you join the study, we will test you for pregnancy at some visits, including 
before each study injection. 
 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 129 of 142 
Appendix C 
Sample consent form for use of samples and 
information in other studies 
Title: A multicenter, randomized, partially blinded phase 1 clinical trial to 
evaluate the safety and serum concentrations of a human monoclonal antibody, 
VRC-HIVMAB075-00-AB (VRC07-523LS), administered in multiple doses and 
routes to healthy, HIV-uninfected adults 
Protocol number: HVTN 127/HPTN 087 
Site: [Insert site name] 
When samples are no longer needed for this study, the study sponsors want to 
keep them for use in other studies by HVTN, HPTN, or other researchers. This 
section gives you information so you can decide if you want your extra samples 
and information used in other studies. You will mark your decision at the end of 
the form. If you have any questions, please ask.  
1. Do I have to agree?  
No. You are free to say yes or no, or to change your mind after you sign this form. 
At your request, we will destroy all extra samples that we have. Your decision 
will not affect your being in this study or have any negative consequences here.  
2. Where are the samples stored?  
Extra samples are stored in a secure central place called a repository. Your 
samples will be stored in the HVTN repository in the United States. 
3. How long will the samples be stored?  
There is no limit on how long your extra samples will be stored. [Site: Revise the 
previous sentence to insert limits if your regulatory authority imposes them.] 
4. Will I be paid for the use of my samples?  
No. Also, a researcher may make a new scientific discovery or product based on 
the use of your samples. If this happens, there is no plan to share any money with 
you. The researcher is not likely to ever know who you are. 
5. Will I benefit from allowing my samples to be used in other studies?  
Probably not. Results from these other studies are not given to you, this clinic, or 
your doctor. They are not part of your medical record. The studies are only being 
done for research purposes. 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 130 of 142 
6. Will the HVTN or HPTN sell my samples and information?  
No, but the HVTN and HPTN may share your samples with other researchers. 
Once we share your samples and information, we may not be able to get them 
back. 
7. How do other researchers get my samples and information?  
When a researcher wants to use your samples and information, their research plan 
must be approved by the HVTN and HPTN. Also, the researcher’s institutional 
review board (IRB) or ethics committee (EC) will review their plan. [Site: If 
review by your institution’s IRB/EC/RE is also required, insert a sentence stating 
this.] IRBs/ECs protect the rights and well-being of people in research. If the 
research plan is approved, the HVTN will send your samples to the researcher’s 
location. 
8. What information is shared with other researchers?  
The samples and information will be labeled with a code number. Your name will 
not be part of the information. However, some information that we share may be 
personal, such as your race, ethnicity, gender, health information from the study, 
and HIV status. We may share information about the study product you received 
and how your body responded to the study product.  
9. What kind of studies might be done with my extra samples and information?  
The studies will be related to HIV prevention or infection, the immune system, 
and other diseases.  
Researchers may also do genetic testing on your samples.  
In some cases, researchers may take cells from your samples and grow more of 
them over time, so that they can continue to do research with them. 
If you agree, your samples could also be used for genome wide studies. In these 
studies, researchers will look at all of your genes (your genome). The researchers 
compare the genomes of many people, looking for common patterns of genes that 
could help them understand diseases. The researchers may put the information 
from the genome-wide studies into a protected database so that other researchers 
can access it, but your name and other personal information will not be included. 
Usually, no one would be able to look at your genome and link it to you as a 
person. However, if another database exists that also has information on your 
genome and your name, someone might be able to compare the databases and 
identify you. If others found out, it could lead to discrimination or other problems. 
The risk of this is very small. There may be other unknown risks. 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 131 of 142 
10. What are the risks of genetic testing?  
It is unlikely, but the genetic tests done on your samples could show you may be 
at risk for certain diseases. If others found out, it could lead to discrimination or 
other problems. However, it is almost impossible for you or others to know your 
test results from the genetic testing. The results are not part of your study records 
and are not given to you.  
U.S. Sites, include the following paragraph  
In the very unlikely event that your genetic information becomes linked to your 
name, a federal law called the Genetic Information Nondiscrimination Act 
(GINA) helps protect you. GINA keeps health insurance companies and 
employers from seeing results of genetic testing when deciding about giving you 
health insurance or offering you work. GINA does not help or protect you against 
discrimination by companies that sell life, disability or long-term care insurance.  
11. Who will have access to my information in studies using my extra samples? 
People who may see your information are: 
 Researchers who use your extra samples and information for other research 
 Government agencies that fund or monitor the research using your extra 
samples and information 
 Any regulatory agency that reviews clinical trials, 
 The researcher’s Institutional Review Board or Ethics Committee 
 The people who work with the researcher  
All of these people will do their best to protect your information. The results of 
any new studies that use your extra samples and information may be published. 
No publication will use your name or identify you personally. 
Questions  
12. If you have questions or problems about allowing your samples and 
information to be used in other studies, use the following important contacts. 
If you have questions about the use of your samples or information or if you want 
to change your mind about their use, contact 
[name or title and telephone number of the investigator or other study staff]. 
If you think you may have been harmed because of studies using your samples or 
information, contact 
[name or title and telephone number of the investigator or other study staff]. 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 132 of 142 
If you have questions about your rights as a research participant, contact 
[name or title and telephone number of person on IRB/EC . 
13. Please choose only one of the options below and write your initials or make 
your mark in the box next to it. Whatever you choose, the HVTN and HPTN 
keep track of your choice about how your samples and information can be 
used. You can change your mind after signing this form. 
 
 
I allow my extra samples and information to be used for other studies 
related to HIV prevention, the immune system, and other diseases. This 
may include genetic testing and keeping my cells growing over time.  
OR 
 
 
I agree to the option above and also to allow my extra samples and 
information to be used in genome wide studies. 
OR 
 
 
I do not allow my extra samples to be used in any other studies. This 
includes not allowing genetic testing, growing more of my cells, or 
genome wide studies.  
 
 
 
 
 
 
 
 
 
Participant’s name (print) 
 
Participant’s signature or mark 
 
Date 
 
Time 
 
 
 
 
 
 
 
Clinic staff conducting consent 
discussion (print) 
 
Clinic staff signature 
 
Date 
 
Time 
For participants who are unable to read or write, a witness should complete the 
signature block below: 
 
 
 
 
 
 
 
Witness’s name (print) 
 
Witness’s signature  
 
Date 
 
Time 
*Witness is impartial and was present for the entire discussion of this consent form

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 133 of 142 
Appendix D 
Table of procedures (for sample informed consent form) 
 
 
 
 
 
 
 
 
 
Weeks after first IV or injection 
Procedure 
Screening 
visit(s) 
First IV or 
injection visit 
3 days 
6 days 
4 
8 
12 
16 
24 
32 
40 
48 
56 
64 
72 
80 
88 
96 
104 
112 
IV infusion or injection 
 
√ 
 
 
 
 
 
√ 
 
√ 
 
√ 
 
√ 
 
 
 
 
 
 
Medical history 
√ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Complete physical 
√ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
√ 
Brief physical 
 
√ 
 
 
 
√ 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
 
 
 
 
 
 
Urine test 
√ 
 
 
 
 
√ 
 
 
 
 
 
 
 
 
√ 
 
 
 
 
 
Blood drawn 
√ 
√ 
√ √ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Pregnancy test* 
√ 
√ 
 
 
 
 
 
√ 
 
√ 
 
√ 
 
√ 
 
 
 
 
√ 
 
HIV testing and pretest counseling 
√ 
 
 
 
 
 
√ 
 
√ 
 
√ 
 
√ 
 
√ 
 
√ 
 
√ 
√ 
Risk reduction counseling 
√ 
√ 
 
 
 
√ 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
 
 
 
 
 
√ 
Interview/questionnaire 
√ 
√ 
 
 
 
√ 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
 
 
√ 
 
√ 
 
Not shown in this table is a time after all study participants have completed their last scheduled visit when you can find out what products you received. 
* For persons assigned female sex at birth and who are capable of becoming pregnant. Persons who have had a total hysterectomy (removal of the uterus) or removal of both ovaries (verified by 
medical records), are not required to have a pregnancy test.
1 yr 
2 yrs 
6 mos 
1½ yrs 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 134 of 142 
Appendix E 
Schema graphic (for sample informed consent 
form) 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 135 of 142 
Appendix F 
Laboratory procedures 
Visit:
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
Day:
D0
D3
D6
D28
D56
D84
D112
D168
D224
D280
D336
D392
D448
D504
D560
D616
D672
D728
D784
Week:
W0
W4
W8
W12
W16
W24
W32
W40
W48
W56
W64
W72
W80
W88
W96
W104
W112
Inf or 
Inj #1
Inf or Inj 
#2
Inf or Inj 
#3
Inf or Inj 
#4
Inf or 
Inj #5
Procedure
Ship to1
Assay location2
Tube 
Type4
Tube size
(vol. 
capacity)4
Total
BLOOD COLLECTION
Screening/Diagnostic
Screening HIV test
Local lab
Local lab
EDTA
5mL
5
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
5
HBsAg/anti-HCV
Local lab
Local lab
SST
5mL
5
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
5
Syphilis
Local lab
Local lab
SST
5mL
5
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
5
HIV diagnostics8
UW-VSL
UW-VSL
EDTA
10mL
—
—
—
—
—
—
10
—
10
—
10
—
10
—
10
—
10
—
10
20
90
Safety labs
CBC/ Differential
Local lab
Local lab
EDTA
5mL
5
5
—
—
—
5
—
5
5
5
5
5
5
5
5
—
—
—
5
—
60
Chemistry Panel5
Local lab
Local lab
SST
5mL
5
5
—
—
—
5
—
5
5
5
5
5
5
5
5
—
—
—
5
—
60
Drug levels
VRC07-523LS concentration
CSR
HVTN Labs / VITL
SST
8.5mL
—
8.5
8.5
8.5
8.5
8.5
8.5
8.5
8.5
8.5
8.5
8.5
8.5
8.5
8.5
8.5
8.5
8.5
8.5
8.5
161.5
Host genetics6
CSR
HVTN Labs
ACD
8.5mL
—
z
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
0
Humoral assays
ADA detection assay (MSD)
CSR
VITL
SST
8.5mL
—
y
—
—
—
—
—
y
—
y
—
y
—
y
—
y
y
y
y
y
0
ADA functional assay (NAb)
CSR
HVTN Labs
SST
8.5mL
—
y
—
—
—
—
—
y
—
y
—
y
—
y
—
y
y
y
y
y
0
Binding Ab assay
CSR
HVTN Labs
SST
8.5mL
—
y
—
—
—
y
—
—
y
—
y
—
y
—
y
—
y
—
—
—
0
Neutralizing Ab assay
CSR
HVTN Labs
SST
8.5mL
—
8.5
—
—
—
8.5
—
—
8.5
—
8.5
—
8.5
—
8.5
—
8.5
—
—
—
59.5
STORAGE
Serum 
CSR
—
SST
8.5mL
—
34
25.5
25.5
25.5
17
25.5
25.5
17
25.5
17
25.5
17
25.5
17
25.5
17
25.5
25.5
25.5
442
PBMC 
CSR
—
ACD
8.5mL
—
85
—
—
—
—
—
—
—
68
—
—
—
68
—
—
—
—
—
85
306
Visit total
25
146
34
34
34
44
44
44
54
112
54
44
54
112
54
34
44
34
54
139
1194
56-Day total
 
25
171
205
239
273
317
122
132
98
166
166
98
98
166
166
88
78
78
88
193
URINE COLLECTION
Urine dipstick9
Local lab
Local lab
X
—
—
—
—
X
—
—
—
—
—
—
—
—
X
—
—
—
—
—
Pregnancy Test7
Local lab
Local lab
X
X
—
—
—
—
—
X
—
X
—
X
—
X
—
—
—
—
X
—
Screening 
visit3
 
Inf = Infusion 
Inj = Injection 
1 CSR = central specimen repository; UW-VSL = University of Washington Virology Specialty Laboratory (Seattle, Washington, USA). 
2 HVTN Laboratories include: Fred Hutchinson Cancer Research Center (Seattle, Washington, USA); Duke University Medical Center (Durham, North Carolina, USA). 
Non-HVTN laboratories: VITL = Vaccine Research Center – Immunology Testing Laboratory (Gaithersburg, Maryland, USA). 
3 Screening may occur over the course of several contacts/visits up to and including day 0 prior to study product administration. 
4 Local labs may assign appropriate alternative tube types for locally performed tests. 
5 Chemistry panel is defined in Section 9.2 (pre-enrollment). 
6 Genotyping may be performed on enrolled participants using cryopreserved PBMC collected at baseline. 
7 For a participant who was assigned female sex at birth, pregnancy test must be performed on urine or blood specimens on the day of study product infusion/injection with 
negative results received prior to infusion/injection. Persons who have undergone total hysterectomy or bilateral oophorectomy (verified by medical records), are not required to 
undergo pregnancy testing. 
8 At an early termination visit for a withdrawn or terminated participant (see Section 9.10), blood should be drawn for HIV diagnostic testing, as shown for visit 23 above. 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 136 of 142 
9 And microscopy if needed. 
y = SST blood collected for neutralizing Ab assays and serum storage will also cover specimen needs for the anti-VRC07-523LS concentrations, ADA detection assay (MSD), 
ADA functional assay (NAb), and binding Ab assays; no separate blood draw is needed. 
z = ACD blood collected for PBMC storage will also cover specimen needs for host genetics assay; no separate blood draw is needed. 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 137 of 142 
Appendix G 
Procedures at CRS  
 
Visit 
011 
022 
03 
04 
05 
06 
07 
08 
09 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19 
20 
Post 
Day: 
 
D0 
D3 
D6 
D28 
D56 
D84 
D112 
D168 
D224 
D280 
D336 
D392 
D448 
D504 
D560 
D616 
D672 
D728 
D924 
 
Week: 
 
W0 
 
 
W4 
W8 
W12 
W16 
W24 
W32 
W40 
W48 
W56 
W64 
W72 
W80 
W88 
W96 
W104 
W112 
 
Procedure 
Scr
. 
Inf/ 
Inj1 
 
 
 
 
 
Inf/ 
Inj2 
 
Inf/ 
Inj3 
 
Inf/ 
Inj4 
 
Inf/ 
Inj5 
 
 
 
 
 
 
 
Study procedures3 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signed screening consent (if used) 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Assessment of understanding 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Signed protocol consent 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Medical history  
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Complete physical exam 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
X 
— 
Confirm eligibility, obtain demographics, randomize  
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Abbreviated physical exam 
— 
X 
— 
— 
— 
X 
— 
X 
X 
X 
X 
X 
X 
X 
— 
— 
— 
— 
— 
— 
— 
Risk reduction counseling 
X 
X 
— 
— 
— 
X 
— 
X 
X 
X 
X 
X 
X 
X 
— 
— 
— 
— 
— 
X 
— 
Contraception assessment4 
X 
X 
— 
— 
— 
X 
— 
X 
X 
X 
X 
X 
X 
X 
— 
— 
— 
— 
— 
X 
— 
Behavioral risk assessment questionnaire 
X 
— 
— 
— 
— 
— 
— 
— 
X 
— 
— 
X 
— 
— 
X 
— 
— 
— 
— 
X 
— 
Social impact assessment 
— 
X 
— 
— 
— 
X 
— 
X 
X 
X 
X 
X 
X 
X 
X 
— 
— 
X 
— 
X 
— 
Social impact assessment questionnaire 
— 
— 
— 
— 
— 
— 
— 
— 
X 
— 
— 
X 
— 
— 
X 
— 
— 
— 
— 
X 
— 
Acceptability questionnaire 
— 
X 
— 
— 
— 
— 
— 
X 
— 
X 
— 
X 
— 
X 
— 
— 
— 
— 
— 
— 
— 
Belief questionnaire5 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
X 
— 
Concomitant medications 
X 
X 
— 
— 
— 
X 
— 
X 
X 
X 
X 
X 
X 
X 
— 
— 
— 
— 
— 
X 
— 
Intercurrent illness/Unsolicited adverse experience 
— 
X 
— 
— 
— 
X 
— 
X 
X 
X 
X 
X 
X 
X 
X 
X 
— 
— 
— 
— 
— 
AESI 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
X 
X 
X 
X 
— 
HIV infection assessment6 
X 
— 
— 
— 
— 
— 
X 
— 
X 
— 
X 
— 
X 
— 
X 
— 
X 
— 
X 
X 
— 
Confirm HIV test results provided to participant 
— 
X 
— 
— 
— 
— 
— 
X 
— 
X 
— 
X 
— 
X 
— 
X 
— 
X 
— 
X 
X 
Study product administration 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Infusion/Injection7 
— 
X 
— 
— 
— 
— 
— 
X 
— 
X 
— 
X 
— 
X 
— 
— 
— 
— 
— 
— 
— 
Solicited AE assessment8 
— 
X 
— 
— 
— 
— 
— 
X 
— 
X 
— 
X 
— 
X 
— 
— 
— 
— 
— 
— 
— 
Local lab assessments 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Screening HIV test 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Hepatitis B, Hepatitis C 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Syphilis 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
CBC, differential 
X 
X 
— 
— 
— 
X 
— 
X 
X 
X 
X 
X 
X 
X 
X 
— 
— 
— 
— 
— 
— 
Chemistry panel9 
X 
X 
— 
— 
— 
X 
— 
X 
X 
X 
X 
X 
X 
X 
X 
— 
— 
— 
— 
— 
— 
Urine dipstick10 
X 
— 
— 
— 
— 
X 
— 
— 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
— 
— 
— 
Pregnancy (urine or serum HCG)11 
X 
X 
— 
— 
— 
— 
— 
X 
— 
X 
— 
X 
— 
X 
— 
— 
— 
— 
— 
— 
— 
Poststudy 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unblind participant 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
X 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 138 of 142 
1 Screening may occur over the course of several contacts/visits up to and including day 0 prior to study product administration. 
2 Specimens collected at Day 0 may be obtained within the 14 days prior to study product administration, except for a pregnancy test which must be performed on 
urine or blood specimens within 24 hours prior to study product administration with negative results received prior to study product administration. 
3 For specimen collection requirements, see Appendix F. 
4 Pregnancy prevention (contraception) assessment is required only for participants who were assigned female at birth and who are capable of becoming pregnant. 
For such participants, use of effective contraception is required from 21 days prior to the first study product administration until the last scheduled clinic visit. 
5 Group 6 participants only. 
6 Includes pre-test counseling and HIV testing. A subsequent follow-up contact is conducted to provide post-test counseling and to report results to participant. 
7 Blood draws required at study product administration visit must be performed prior to administration of study product; however, it is not necessary to have results 
prior to administration, except for results of a serum pregnancy test, if indicated. Lab tests may be drawn with the 3 days prior to study product administration. 
8 Solicited AE assessments performed daily for at least 3 days following study product administration (see Section 9.8). 
9 Chemistry panels are defined in Section 9.2. 
10 And microscopy if needed. 
11 For a participant who was assigned female sex at birth, pregnancy test must be performed on urine or blood specimens within 24 hours prior to study product 
infusion/injection with negative results received prior to infusion/injection. Persons who have undergone total hysterectomy or bilateral oophorectomy (verified 
by medical records), are not required to undergo pregnancy testing. 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 139 of 142 
Appendix H 
Adverse events of special interest (AESI) 
AEs of special interest (AESI) for this protocol include those listed below. Updates to 
AESI will be provided in the HVTN 127/HPTN 087 SSP. 
 Systemic lupus erythematosus (SLE)  
 Systemic scleroderma (SSD) (Systemic sclerosis [SSc]), including diffuse 
systemic form and CREST syndrome 
 Sjogren’s syndrome (SS) 
 Polymyositis/Dermatomyositis syndrome (PM/DM) 
 Raynaud’s syndrome 
 Antiphospholipid antibody syndrome (APS) 
 Idiopathic thrombocytopenic purpura (ITP) 
 Crohn’s disease 
 Ulcerative colitis 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 140 of 142 
Appendix I 
Low risk guidelines for the US and Switzerland 
 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 141 of 142 
 

HVTN 127/HPTN 087 Version 2.0 / March 8, 2018 
HVTN127-HPTN087_v2.0_FINAL / Page 142 of 142 
Appendix J 
Protocol Signature Page 
 
A multicenter, randomized, partially blinded phase 1 clinical trial to evaluate the 
safety and serum concentrations of a human monoclonal antibody, VRC-
HIVMAB075-00-AB (VRC07-523LS), administered in multiple doses and routes to 
healthy, HIV-uninfected adults 
I will conduct the study in accordance with the provisions of this protocol and all 
applicable protocol-related documents. I agree to conduct this study in compliance 
with United States (U.S.) Health and Human Service regulations (45 CFR 46); 
applicable U.S. Food and Drug Administration regulations; standards of the 
International Conference on Harmonization Guideline for Good Clinical Practice 
(E6); Institutional Review Board/Ethics Committee determinations; all applicable in-
country, state, and local laws and regulations; and other applicable requirements (eg, 
US National Institutes of Health, Division of AIDS) and institutional policies 
 
 
 
 
 
 
 
 
 
Investigator of Record Name (print) 
 
Investigator of Record Signature 
 
Date 
 
 
DAIDS Protocol Number: HVTN 127/HPTN 087 
DAIDS Protocol Version: Version 2.0 
Protocol Date: March 8, 2018